Variant summary: AIRE c.769C>T (p.Arg257X), also known as the "Finnish major mutation", results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 0.00075 in 248166 control chromosomes in the gnomAD database, including 1 homozygote. c.769C>T has been reported in the literature in multiple individuals affected with Autoimmune Polyglandular Syndrome Type 1 (example, Aaltonen_1997, Giordano_2012, Cervato_2010). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in lack of transcriptional regulation by mutant AIRE of KRT14, an AIRE-dependant gene as observed by a lack of mRNA expression in-vitro (example, Oftedal_2015). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
ClinVar Genomic variation as it relates to human health
NM_000383.4(AIRE):c.769C>T (p.Arg257Ter)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(23)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic
23
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000383.4(AIRE):c.769C>T (p.Arg257Ter)
Variation ID: 3307 Accession: VCV000003307.63
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 21q22.3 21: 44289773 (GRCh38) [ NCBI UCSC ] 21: 45709656 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 Oct 20, 2024 Jul 31, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000383.4:c.769C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000374.1:p.Arg257Ter nonsense NC_000021.9:g.44289773C>T NC_000021.8:g.45709656C>T NG_009556.1:g.8894C>T LRG_18:g.8894C>T LRG_18t1:c.769C>T LRG_18p1:p.Arg257Ter - Protein change
- R257*
- Other names
- -
- Canonical SPDI
- NC_000021.9:44289772:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00022
The Genome Aggregation Database (gnomAD), exomes 0.00075
The Genome Aggregation Database (gnomAD) 0.00105
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| AIRE | - | - |
GRCh38 GRCh37 |
1134 | 1275 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (15) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000179294.35 | |
| Pathogenic (7) |
criteria provided, multiple submitters, no conflicts
|
Jul 31, 2024 | RCV000378770.34 | |
|
AIRE-related disorder
|
Pathogenic (1) |
no assertion criteria provided
|
Apr 2, 2024 | RCV003421900.6 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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|---|---|---|---|---|---|
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Pathogenic
(Oct 14, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000231520.5
First in ClinVar: Jun 28, 2015 Last updated: Dec 15, 2018 |
Sex: mixed
|
|
|
Pathogenic
(Oct 14, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Polyglandular autoimmune syndrome, type 1
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001361217.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
Comment:
Variant summary: AIRE c.769C>T (p.Arg257X), also known as the "Finnish major mutation", results in a premature termination codon, predicted to cause a truncation of the … (more)
Variant summary: AIRE c.769C>T (p.Arg257X), also known as the "Finnish major mutation", results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 0.00075 in 248166 control chromosomes in the gnomAD database, including 1 homozygote. c.769C>T has been reported in the literature in multiple individuals affected with Autoimmune Polyglandular Syndrome Type 1 (example, Aaltonen_1997, Giordano_2012, Cervato_2010). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in lack of transcriptional regulation by mutant AIRE of KRT14, an AIRE-dependant gene as observed by a lack of mRNA expression in-vitro (example, Oftedal_2015). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
|
Pathogenic
(Dec 19, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Polyglandular autoimmune syndrome, type 1
Affected status: unknown
Allele origin:
unknown
|
Myriad Genetics, Inc.
Accession: SCV001194176.2
First in ClinVar: Apr 06, 2020 Last updated: Jul 04, 2020 |
Comment:
NM_000383.3(AIRE):c.769C>T(R257*) is classified as pathogenic in the context of type 1 autoimmune polyglandular syndrome. Sources cited for classification include the following: PMID 12050215, 20407228, 14974083, … (more)
NM_000383.3(AIRE):c.769C>T(R257*) is classified as pathogenic in the context of type 1 autoimmune polyglandular syndrome. Sources cited for classification include the following: PMID 12050215, 20407228, 14974083, 9398839, 9398840, 18708298 and 10677297. Classification of NM_000383.3(AIRE):c.769C>T(R257*) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening. (less)
|
|
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Pathogenic
(Aug 24, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Polyglandular autoimmune syndrome, type 1
Affected status: unknown
Allele origin:
germline
|
Johns Hopkins Genomics, Johns Hopkins University
Accession: SCV001431521.1
First in ClinVar: Sep 05, 2020 Last updated: Sep 05, 2020 |
Comment:
This AIRE variant (rs121434254) is rare (<0.1%) in a large population dataset (gnomAD: 218/279538 total alleles; 0.08%; 1 homozygote) and has an entry in ClinVar. … (more)
This AIRE variant (rs121434254) is rare (<0.1%) in a large population dataset (gnomAD: 218/279538 total alleles; 0.08%; 1 homozygote) and has an entry in ClinVar. This variant has been reported previously in a homozygous or compound heterozygous state in multiple unrelated individuals affected with APS1. This nonsense variant results in a premature stop codon in exon 6 of 14 likely leading to nonsense mediated decay and lack of protein production. This variant alone is not expected to cause APS1. We consider c.769C>T to be pathogenic. (less)
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|
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Pathogenic
(Jan 01, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Polyglandular autoimmune syndrome, type 1
Affected status: yes
Allele origin:
unknown
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001366339.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PP3,PP4,PVS1,PS3,PM2. This variant was detected in homozygous state.
|
|
|
Pathogenic
(Jun 05, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Polyglandular autoimmune syndrome, type 1
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
maternal
|
New York Genome Center
Study: CSER-NYCKidSeq
Accession: SCV001480457.1 First in ClinVar: Feb 20, 2021 Last updated: Feb 20, 2021 |
Comment:
The c.769C>T, p.Arg257Ter nonsense variant identified in the AIRE gene has been reported previously in both the homozygous and compound heterozygous state in multiple unrelated … (more)
The c.769C>T, p.Arg257Ter nonsense variant identified in the AIRE gene has been reported previously in both the homozygous and compound heterozygous state in multiple unrelated individuals with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) [PMID: 9398840; PMID: 25707324; PMID: 30863741; PMID: 31588815]. This variant is the most common Finnish pathogenic variant, present in 82% of Finnish APECED alleles, and is also common in the Northern Italian and Eastern European APECED patient populations [PMID: 9398840]. Functional studies have demonstrated that cells transfected with the p.Arg257Ter allele lack expression of mRNA from AIRE-dependent genes [PMID: 26084028]. This variant has 0.06%frequency (84 heterozygous) in gnomAD database indicating this is a rare allele. The detected nonsense substitution truncates the protein at codon 257, which is 289 amino acids from the end of the protein and expected to result in an absent protein product through nonsense-mediated mRNA decay [PMID: 24681721.] Based on the available evidence, the c.769C>T, p.Arg257Ter variant in the AIRE gene is classified as pathogenic. (less)
Clinical Features:
Recurrent bacterial infections (present) , Recurrent viral infections (present) , Recurrent fungal infections (present) , B lymphocytopenia (present) , Hepatitis (present) , Celiac disease (present) … (more)
Recurrent bacterial infections (present) , Recurrent viral infections (present) , Recurrent fungal infections (present) , B lymphocytopenia (present) , Hepatitis (present) , Celiac disease (present) , Onychomycosis (present) , Exocrine pancreatic insufficiency (present) , Nasal polyposis (present) (less)
Secondary finding: no
|
|
|
Pathogenic
(Sep 29, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Polyglandular autoimmune syndrome, type 1
Affected status: yes
Allele origin:
germline
|
Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV004175443.1
First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023 |
|
|
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Pathogenic
(Aug 14, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Polyglandular autoimmune syndrome, type 1
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002024184.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
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Pathogenic
(Jul 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV005089747.1
First in ClinVar: Aug 04, 2024 Last updated: Aug 04, 2024 |
|
|
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Pathogenic
(May 23, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV000840731.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
|
|
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Pathogenic
(Feb 14, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Polyglandular autoimmune syndrome, type 1
Affected status: yes
Allele origin:
germline
|
DASA
Accession: SCV002097300.1
First in ClinVar: Feb 20, 2022 Last updated: Feb 20, 2022 |
Comment:
The c.769C>T;p.(Arg257*) variant creates a premature translational stop signal in the AIRE gene. It is expected to result in an absent or disrupted protein product … (more)
The c.769C>T;p.(Arg257*) variant creates a premature translational stop signal in the AIRE gene. It is expected to result in an absent or disrupted protein product - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 3307; PMID: 9398840; 20718774; 22024611; 9398840) - PS4. The variant is present at low allele frequencies population databases (rs121434254 - gnomAD 0.005649%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. The p.(Arg257*) was detected in trans with a pathogenic variant (PMID: 9398840; 20718774; 22024611) - PM3. In summary, the currently available evidence indicates that the variant is pathogenic. (less)
Number of individuals with the variant: 1
Sex: male
Geographic origin: Brazil
|
|
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Pathogenic
(Mar 29, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Polyglandular autoimmune syndrome, type 1
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002805919.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
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Pathogenic
(Feb 17, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000329055.7
First in ClinVar: Dec 06, 2016 Last updated: Mar 04, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate lack of expression of mRNA from AIRE-dependent genes (Oftedal et al., 2015); R257X variant is the most common Finnish pathogenic variant, present in 82% of Finnish APECED alleles, and is also common in the Northern Italian and Eastern European APECED patient populations (Finnish-German APECED Consortium 1997; Heino et al., 2001); This variant is associated with the following publications: (PMID: 22162465, 20718774, 24948345, 16965330, 11524733, 15886230, 11524731, 11298085, 22024611, 18616706, 9921903, 19807739, 12050215, 19863576, 25707324, 27065010, 27048654, 26891119, 14582926, 24158785, 18274776, 28458664, 30018023, 12951636, 11207636, 31588815, 30863741, 31956453, 33225392, 34078422, 34426522, 24493573, 32441320, 34235359, 26084028, 9398840) (less)
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Pathogenic
(Sep 14, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
APECED
Affected status: yes
Allele origin:
germline
|
National Institute of Allergy and Infectious Diseases - Centralized Sequencing Program, National Institutes of Health
Accession: SCV004036182.1
First in ClinVar: Sep 30, 2023 Last updated: Sep 30, 2023 |
|
|
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Pathogenic
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Polyglandular autoimmune syndrome, type 1
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000832482.7
First in ClinVar: Oct 10, 2018 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg257*) in the AIRE gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg257*) in the AIRE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AIRE are known to be pathogenic (PMID: 11524731, 26141571). This variant is present in population databases (rs121434254, gnomAD 0.5%), including at least one homozygous and/or hemizygous individual. This premature translational stop signal has been observed in individual(s) with autoimmune polyendocrinopathy with candidiasis and ectodermal dysplasia (APECED) (PMID: 9398840, 20718774, 22024611). It is commonly reported in individuals of Finnish ancestry (PMID: 9398840). ClinVar contains an entry for this variant (Variation ID: 3307). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
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Pathogenic
(Feb 01, 2024)
|
criteria provided, single submitter
Method: curation
|
Polyglandular autoimmune syndrome, type 1
Affected status: no
Allele origin:
germline
|
Laboratory of Medical Genetics, National & Kapodistrian University of Athens
Accession: SCV005051833.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
|
|
|
Pathogenic
(Apr 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001247536.26
First in ClinVar: May 12, 2020 Last updated: Oct 20, 2024 |
Comment:
AIRE: PVS1, PM3:Strong, PM2:Supporting, PS3:Supporting
Number of individuals with the variant: 3
|
|
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Pathogenic
(Sep 16, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Polyglandular autoimmune syndrome type 1
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV001452113.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001978034.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
|
|
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001980556.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
|
|
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Pathogenic
(Nov 01, 2009)
|
no assertion criteria provided
Method: literature only
|
AUTOIMMUNE POLYENDOCRINOPATHY SYNDROME, TYPE I
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000023628.3
First in ClinVar: Apr 04, 2013 Last updated: Jul 09, 2022 |
Comment on evidence:
Nagamine et al. (1997) and the Finnish-German APECED Consortium (1997) identified a C-to-T transition in the AIRE gene, resulting in an arg257-to-ter (R257X) substitution. This … (more)
Nagamine et al. (1997) and the Finnish-German APECED Consortium (1997) identified a C-to-T transition in the AIRE gene, resulting in an arg257-to-ter (R257X) substitution. This was the predominant mutation in Finnish APECED (APS1; 240300) patients, accounting for 10 of 12 alleles studied by Nagamine et al. (1997). The consortium stated that it accounted for 82% of the Finnish disease alleles, and that all occurred on the same haplotype. The C-to-T transition involved nucleotide 889 in exon 6. The same mutation was found in an Italian (heterozygote) and a German (homozygote) patient with different haplotypes. In 5 of 16 patients with APS1 from the U.S., Wang et al. (1998) found the R257X mutation in exon 6 of the AIRE gene. To understand the complexity of the APECED phenotype, Halonen et al. (2002) studied the AIRE and HLA class II genotypes in a series of patients with APECED. The only association between the phenotype and the AIRE genotype was the higher prevalence of candidiasis in the patients with the most common mutation, arg257 to ter, than in those with other mutations. The authors concluded that AIRE mutation has little influence on the APECED phenotype, whereas, in contrast to earlier reports, HLA class II is a significant determinant. Among 14 unrelated Polish patients with APECED, Stolarski et al. (2006) found that the R257X mutation was the most common: 7 patients were homozygous and 6 were heterozygous, yielding a frequency of 71% in the studied cohort. The mutation resulted from an 8473C-T transition. In a patient previously diagnosed by Brodehl et al. (1967) with isolated hypercystinuria (see 220100) who was subsequently found to have APS1, Eggermann et al. (2007) identified compound heterozygosity for the common mutations R257X and 964del13 (607358.0003). Two older sibs had died from hypocalcemic tetany. In a 23-year-old Indian man with APS1, who died of septicemia, Zaidi et al. (2009) identified homozygosity for the R257X mutation in the AIRE gene. In addition to the cardinal features of APS1, this patient also had enamel hypoplasia, pitted nails, gallstones, sicca syndrome, primary hypothyroidism, chronic sinusitis and otitis media, nasal polyps, and hyposplenia. (less)
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Pathogenic
(Apr 02, 2024)
|
no assertion criteria provided
Method: clinical testing
|
AIRE-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004117021.2
First in ClinVar: Nov 20, 2023 Last updated: Oct 08, 2024 |
Comment:
The AIRE c.769C>T variant is predicted to result in premature protein termination (p.Arg257*). This variant has been reported with a second AIRE variant in many … (more)
The AIRE c.769C>T variant is predicted to result in premature protein termination (p.Arg257*). This variant has been reported with a second AIRE variant in many unrelated individuals with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) (Nagamine et al. 1997. PubMed ID: 9398839; Finnish-German APECED Consortium. 1997. PubMed ID: 9398840; Björses et al. 2000. PubMed ID: 10677297; Stolarski et al. 2006. PubMed ID: 16965330; Podkrajsek et al. 2008. PubMed ID: 18682433; Orlova et al. 2010. PubMed ID: 20407228). In vitro experimental studies have demonstrated that this variant disrupts protein function (Björses et al. 2000. PubMed ID: 10677297; Halonen et al. 2004. PubMed ID: 14974083; Oftedal et al. 2015. PubMed ID: 26084028). This variant has also been observed in the heterozygous state without a second AIRE variant in some individuals with classic and atypical APECED with a proposed incomplete penetrance (Sedivá et al. 2002. PubMed ID: 12503856; Buzi et al. 2003. PubMed ID: 12843157; Orlova et al. 2010. PubMed ID: 20407228). However, there are many heterozygous individuals with no symptoms of APECED and an autosomal dominant mode of inheritance is not established. This variant is reported at a relatively high frequency (0.50% of alleles) in individuals of Finnish descent in gnomAD, but has been shown to be a founder mutation in this population (Finnish-German APECED Consortium. 1997. PubMed ID: 9398840). This variant is also interpreted as pathogenic or likely pathogenic by many labs in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/3309). Nonsense variants in AIRE are expected to be pathogenic. This variant is interpreted as pathogenic for autosomal recessive AIRE-related disorders. (less)
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Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Polyglandular autoimmune syndrome, type 1
Affected status: yes
Allele origin:
germline
|
Genomics England Pilot Project, Genomics England
Accession: SCV001760476.1
First in ClinVar: Jul 27, 2021 Last updated: Jul 27, 2021 |
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Comment:
Comment:
NM_000383.3(AIRE):c.769C>T(R257*) is classified as pathogenic in the context of type 1 autoimmune polyglandular syndrome. Sources cited for classification include the following: PMID 12050215, 20407228, 14974083, 9398839, 9398840, 18708298 and 10677297. Classification of NM_000383.3(AIRE):c.769C>T(R257*) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.
Comment:
This AIRE variant (rs121434254) is rare (<0.1%) in a large population dataset (gnomAD: 218/279538 total alleles; 0.08%; 1 homozygote) and has an entry in ClinVar. This variant has been reported previously in a homozygous or compound heterozygous state in multiple unrelated individuals affected with APS1. This nonsense variant results in a premature stop codon in exon 6 of 14 likely leading to nonsense mediated decay and lack of protein production. This variant alone is not expected to cause APS1. We consider c.769C>T to be pathogenic.
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PP3,PP4,PVS1,PS3,PM2. This variant was detected in homozygous state.
Comment:
The c.769C>T, p.Arg257Ter nonsense variant identified in the AIRE gene has been reported previously in both the homozygous and compound heterozygous state in multiple unrelated individuals with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) [PMID: 9398840; PMID: 25707324; PMID: 30863741; PMID: 31588815]. This variant is the most common Finnish pathogenic variant, present in 82% of Finnish APECED alleles, and is also common in the Northern Italian and Eastern European APECED patient populations [PMID: 9398840]. Functional studies have demonstrated that cells transfected with the p.Arg257Ter allele lack expression of mRNA from AIRE-dependent genes [PMID: 26084028]. This variant has 0.06%frequency (84 heterozygous) in gnomAD database indicating this is a rare allele. The detected nonsense substitution truncates the protein at codon 257, which is 289 amino acids from the end of the protein and expected to result in an absent protein product through nonsense-mediated mRNA decay [PMID: 24681721.] Based on the available evidence, the c.769C>T, p.Arg257Ter variant in the AIRE gene is classified as pathogenic.
Comment:
The c.769C>T;p.(Arg257*) variant creates a premature translational stop signal in the AIRE gene. It is expected to result in an absent or disrupted protein product - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 3307; PMID: 9398840; 20718774; 22024611; 9398840) - PS4. The variant is present at low allele frequencies population databases (rs121434254 - gnomAD 0.005649%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. The p.(Arg257*) was detected in trans with a pathogenic variant (PMID: 9398840; 20718774; 22024611) - PM3. In summary, the currently available evidence indicates that the variant is pathogenic.
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate lack of expression of mRNA from AIRE-dependent genes (Oftedal et al., 2015); R257X variant is the most common Finnish pathogenic variant, present in 82% of Finnish APECED alleles, and is also common in the Northern Italian and Eastern European APECED patient populations (Finnish-German APECED Consortium 1997; Heino et al., 2001); This variant is associated with the following publications: (PMID: 22162465, 20718774, 24948345, 16965330, 11524733, 15886230, 11524731, 11298085, 22024611, 18616706, 9921903, 19807739, 12050215, 19863576, 25707324, 27065010, 27048654, 26891119, 14582926, 24158785, 18274776, 28458664, 30018023, 12951636, 11207636, 31588815, 30863741, 31956453, 33225392, 34078422, 34426522, 24493573, 32441320, 34235359, 26084028, 9398840)
Comment:
This sequence change creates a premature translational stop signal (p.Arg257*) in the AIRE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AIRE are known to be pathogenic (PMID: 11524731, 26141571). This variant is present in population databases (rs121434254, gnomAD 0.5%), including at least one homozygous and/or hemizygous individual. This premature translational stop signal has been observed in individual(s) with autoimmune polyendocrinopathy with candidiasis and ectodermal dysplasia (APECED) (PMID: 9398840, 20718774, 22024611). It is commonly reported in individuals of Finnish ancestry (PMID: 9398840). ClinVar contains an entry for this variant (Variation ID: 3307). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Comment:
AIRE: PVS1, PM3:Strong, PM2:Supporting, PS3:Supporting
Comment:
The AIRE c.769C>T variant is predicted to result in premature protein termination (p.Arg257*). This variant has been reported with a second AIRE variant in many unrelated individuals with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) (Nagamine et al. 1997. PubMed ID: 9398839; Finnish-German APECED Consortium. 1997. PubMed ID: 9398840; Björses et al. 2000. PubMed ID: 10677297; Stolarski et al. 2006. PubMed ID: 16965330; Podkrajsek et al. 2008. PubMed ID: 18682433; Orlova et al. 2010. PubMed ID: 20407228). In vitro experimental studies have demonstrated that this variant disrupts protein function (Björses et al. 2000. PubMed ID: 10677297; Halonen et al. 2004. PubMed ID: 14974083; Oftedal et al. 2015. PubMed ID: 26084028). This variant has also been observed in the heterozygous state without a second AIRE variant in some individuals with classic and atypical APECED with a proposed incomplete penetrance (Sedivá et al. 2002. PubMed ID: 12503856; Buzi et al. 2003. PubMed ID: 12843157; Orlova et al. 2010. PubMed ID: 20407228). However, there are many heterozygous individuals with no symptoms of APECED and an autosomal dominant mode of inheritance is not established. This variant is reported at a relatively high frequency (0.50% of alleles) in individuals of Finnish descent in gnomAD, but has been shown to be a founder mutation in this population (Finnish-German APECED Consortium. 1997. PubMed ID: 9398840). This variant is also interpreted as pathogenic or likely pathogenic by many labs in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/3309). Nonsense variants in AIRE are expected to be pathogenic. This variant is interpreted as pathogenic for autosomal recessive AIRE-related disorders.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Variant summary: AIRE c.769C>T (p.Arg257X), also known as the "Finnish major mutation", results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 0.00075 in 248166 control chromosomes in the gnomAD database, including 1 homozygote. c.769C>T has been reported in the literature in multiple individuals affected with Autoimmune Polyglandular Syndrome Type 1 (example, Aaltonen_1997, Giordano_2012, Cervato_2010). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in lack of transcriptional regulation by mutant AIRE of KRT14, an AIRE-dependant gene as observed by a lack of mRNA expression in-vitro (example, Oftedal_2015). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
NM_000383.3(AIRE):c.769C>T(R257*) is classified as pathogenic in the context of type 1 autoimmune polyglandular syndrome. Sources cited for classification include the following: PMID 12050215, 20407228, 14974083, 9398839, 9398840, 18708298 and 10677297. Classification of NM_000383.3(AIRE):c.769C>T(R257*) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.
Comment:
This AIRE variant (rs121434254) is rare (<0.1%) in a large population dataset (gnomAD: 218/279538 total alleles; 0.08%; 1 homozygote) and has an entry in ClinVar. This variant has been reported previously in a homozygous or compound heterozygous state in multiple unrelated individuals affected with APS1. This nonsense variant results in a premature stop codon in exon 6 of 14 likely leading to nonsense mediated decay and lack of protein production. This variant alone is not expected to cause APS1. We consider c.769C>T to be pathogenic.
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PP3,PP4,PVS1,PS3,PM2. This variant was detected in homozygous state.
Comment:
The c.769C>T, p.Arg257Ter nonsense variant identified in the AIRE gene has been reported previously in both the homozygous and compound heterozygous state in multiple unrelated individuals with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) [PMID: 9398840; PMID: 25707324; PMID: 30863741; PMID: 31588815]. This variant is the most common Finnish pathogenic variant, present in 82% of Finnish APECED alleles, and is also common in the Northern Italian and Eastern European APECED patient populations [PMID: 9398840]. Functional studies have demonstrated that cells transfected with the p.Arg257Ter allele lack expression of mRNA from AIRE-dependent genes [PMID: 26084028]. This variant has 0.06%frequency (84 heterozygous) in gnomAD database indicating this is a rare allele. The detected nonsense substitution truncates the protein at codon 257, which is 289 amino acids from the end of the protein and expected to result in an absent protein product through nonsense-mediated mRNA decay [PMID: 24681721.] Based on the available evidence, the c.769C>T, p.Arg257Ter variant in the AIRE gene is classified as pathogenic.
Comment:
The c.769C>T;p.(Arg257*) variant creates a premature translational stop signal in the AIRE gene. It is expected to result in an absent or disrupted protein product - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 3307; PMID: 9398840; 20718774; 22024611; 9398840) - PS4. The variant is present at low allele frequencies population databases (rs121434254 - gnomAD 0.005649%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. The p.(Arg257*) was detected in trans with a pathogenic variant (PMID: 9398840; 20718774; 22024611) - PM3. In summary, the currently available evidence indicates that the variant is pathogenic.
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate lack of expression of mRNA from AIRE-dependent genes (Oftedal et al., 2015); R257X variant is the most common Finnish pathogenic variant, present in 82% of Finnish APECED alleles, and is also common in the Northern Italian and Eastern European APECED patient populations (Finnish-German APECED Consortium 1997; Heino et al., 2001); This variant is associated with the following publications: (PMID: 22162465, 20718774, 24948345, 16965330, 11524733, 15886230, 11524731, 11298085, 22024611, 18616706, 9921903, 19807739, 12050215, 19863576, 25707324, 27065010, 27048654, 26891119, 14582926, 24158785, 18274776, 28458664, 30018023, 12951636, 11207636, 31588815, 30863741, 31956453, 33225392, 34078422, 34426522, 24493573, 32441320, 34235359, 26084028, 9398840)
Comment:
This sequence change creates a premature translational stop signal (p.Arg257*) in the AIRE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AIRE are known to be pathogenic (PMID: 11524731, 26141571). This variant is present in population databases (rs121434254, gnomAD 0.5%), including at least one homozygous and/or hemizygous individual. This premature translational stop signal has been observed in individual(s) with autoimmune polyendocrinopathy with candidiasis and ectodermal dysplasia (APECED) (PMID: 9398840, 20718774, 22024611). It is commonly reported in individuals of Finnish ancestry (PMID: 9398840). ClinVar contains an entry for this variant (Variation ID: 3307). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Comment:
AIRE: PVS1, PM3:Strong, PM2:Supporting, PS3:Supporting
Comment:
The AIRE c.769C>T variant is predicted to result in premature protein termination (p.Arg257*). This variant has been reported with a second AIRE variant in many unrelated individuals with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) (Nagamine et al. 1997. PubMed ID: 9398839; Finnish-German APECED Consortium. 1997. PubMed ID: 9398840; Björses et al. 2000. PubMed ID: 10677297; Stolarski et al. 2006. PubMed ID: 16965330; Podkrajsek et al. 2008. PubMed ID: 18682433; Orlova et al. 2010. PubMed ID: 20407228). In vitro experimental studies have demonstrated that this variant disrupts protein function (Björses et al. 2000. PubMed ID: 10677297; Halonen et al. 2004. PubMed ID: 14974083; Oftedal et al. 2015. PubMed ID: 26084028). This variant has also been observed in the heterozygous state without a second AIRE variant in some individuals with classic and atypical APECED with a proposed incomplete penetrance (Sedivá et al. 2002. PubMed ID: 12503856; Buzi et al. 2003. PubMed ID: 12843157; Orlova et al. 2010. PubMed ID: 20407228). However, there are many heterozygous individuals with no symptoms of APECED and an autosomal dominant mode of inheritance is not established. This variant is reported at a relatively high frequency (0.50% of alleles) in individuals of Finnish descent in gnomAD, but has been shown to be a founder mutation in this population (Finnish-German APECED Consortium. 1997. PubMed ID: 9398840). This variant is also interpreted as pathogenic or likely pathogenic by many labs in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/3309). Nonsense variants in AIRE are expected to be pathogenic. This variant is interpreted as pathogenic for autosomal recessive AIRE-related disorders.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Delay in the Diagnosis of APECED: A Case Report and Review of Literature from Iran. | Jamee M | Immunological investigations | 2020 | PMID: 31588815 |
| Pure Red Cell Aplasia (PRCA) and Cerebellar Hypoplasia as Atypical Features of Polyglandular Autoimmune Syndrome Type I (APS-1): Two Sisters With the Same AIRE Mutation but Different Phenotypes. | Chinello M | Frontiers in pediatrics | 2019 | PMID: 30863741 |
| Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. | Kisand K | Journal of clinical immunology | 2015 | PMID: 26141571 |
| Dominant Mutations in the Autoimmune Regulator AIRE Are Associated with Common Organ-Specific Autoimmune Diseases. | Oftedal BE | Immunity | 2015 | PMID: 26084028 |
| Expanding the spectrum: chronic urticaria and autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. | Lundberg C | Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology | 2015 | PMID: 25707324 |
| Autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) in Sicily: confirmation that R203X is the peculiar AIRE gene mutation. | Giordano C | Journal of endocrinological investigation | 2012 | PMID: 22024611 |
| AIRE gene mutations and autoantibodies to interferon omega in patients with chronic hypoparathyroidism without APECED. | Cervato S | Clinical endocrinology | 2010 | PMID: 20718774 |
| Autoimmune polyglandular syndrome type 1 in Russian patients: clinical variants and autoimmune regulator mutations. | Orlova EM | Hormone research in paediatrics | 2010 | PMID: 20407228 |
| Two novel AIRE mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) among Indians. | Zaidi G | Clinical genetics | 2009 | PMID: 19807739 |
| Clinical and microstructural aberrations of enamel of deciduous and permanent teeth in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. | Pavlic A | Archives of oral biology | 2009 | PMID: 19246027 |
| Evaluation of the autoimmune regulator (AIRE) gene mutations in a cohort of Italian patients with autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) and in their relatives. | Cervato S | Clinical endocrinology | 2009 | PMID: 18616706 |
| Impaired dendritic cell maturation and cytokine production in patients with chronic mucocutanous candidiasis with or without APECED. | Ryan KR | Clinical and experimental immunology | 2008 | PMID: 19037923 |
| Radioimmunoassay for autoantibodies against interferon omega; its use in the diagnosis of autoimmune polyendocrine syndrome type I. | Oftedal BE | Clinical immunology (Orlando, Fla.) | 2008 | PMID: 18708298 |
| Detection of a complete autoimmune regulator gene deletion and two additional novel mutations in a cohort of patients with atypical phenotypic variants of autoimmune polyglandular syndrome type 1. | Podkrajsek KT | European journal of endocrinology | 2008 | PMID: 18682433 |
| Autoimmune polyendocrine syndrome type I in Slovakia: relevance of screening patients with autoimmune Addison's disease. | F Magitta N | European journal of endocrinology | 2008 | PMID: 18426830 |
| A novel mutation associated with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. | Bhui RD | Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology | 2008 | PMID: 18320920 |
| Sicilian family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and lethal lung disease in one of the affected brothers. | De Luca F | European journal of pediatrics | 2008 | PMID: 18274776 |
| Primary immune deficiency disorders presenting as autoimmune diseases: IPEX and APECED. | Moraes-Vasconcelos D | Journal of clinical immunology | 2008 | PMID: 18264745 |
| Posterior reversible encephalopathy syndrome in a child during an accelerated phase of a severe APECED phenotype due to an uncommon mutation of AIRE. | Capalbo D | Clinical endocrinology | 2008 | PMID: 18248641 |
| Isolated cystinuria (OMIM 238200) is not a separate entity but is caused by a mutation in the cystinuria gene SLC7A9. | Eggermann T | Clinical genetics | 2007 | PMID: 17539912 |
| Hereditary long QT syndrome due to autoimmune hypoparathyroidism in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome. | Meyer T | Journal of electrocardiology | 2007 | PMID: 17289071 |
| Autoimmune polyendocrine syndrome type 1 in Norway: phenotypic variation, autoantibodies, and novel mutations in the autoimmune regulator gene. | Wolff AS | The Journal of clinical endocrinology and metabolism | 2007 | PMID: 17118990 |
| Molecular background of polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome in a Polish population: novel AIRE mutations and an estimate of disease prevalence. | Stolarski B | Clinical genetics | 2006 | PMID: 16965330 |
| Anti-interferon autoantibodies in autoimmune polyendocrinopathy syndrome type 1. | Meager A | PLoS medicine | 2006 | PMID: 16784312 |
| Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. | Perheentupa J | The Journal of clinical endocrinology and metabolism | 2006 | PMID: 16684821 |
| Polymorphisms at +49A/G and CT60 sites in the 3' UTR of the CTLA-4 gene and APECED-related AIRE gene mutations analysis in sporadic idiopathic hypoparathyroidism. | Goswami R | International journal of immunogenetics | 2005 | PMID: 16313305 |
| APECED-causing mutations in AIRE reveal the functional domains of the protein. | Halonen M | Human mutation | 2004 | PMID: 14974083 |
| Fatal primary pulmonary hypertension in a 30-yr-old female with APECED syndrome. | Korniszewski L | The European respiratory journal | 2003 | PMID: 14582926 |
| Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome: time to review diagnostic criteria? | Buzi F | The Journal of clinical endocrinology and metabolism | 2003 | PMID: 12843157 |
| Immunological findings in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and their family members: are heterozygotes subclinically affected? | Sedivá A | Journal of pediatric endocrinology & metabolism : JPEM | 2002 | PMID: 12503856 |
| AIRE mutations and human leukocyte antigen genotypes as determinants of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype. | Halonen M | The Journal of clinical endocrinology and metabolism | 2002 | PMID: 12050215 |
| A novel mutation of the autoimmune regulator gene in an Italian kindred with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, acting in a dominant fashion and strongly cosegregating with hypothyroid autoimmune thyroiditis. | Cetani F | The Journal of clinical endocrinology and metabolism | 2001 | PMID: 11600535 |
| Novel AIRE mutations and P450 cytochrome autoantibodies in Central and Eastern European patients with APECED. | Cihakova D | Human mutation | 2001 | PMID: 11524733 |
| APECED mutations in the autoimmune regulator (AIRE) gene. | Heino M | Human mutation | 2001 | PMID: 11524731 |
| Autoimmune regulator AIRE: evidence for genetic differences between autoimmune hepatitis and hepatitis as part of the autoimmune polyglandular syndrome type 1. | Vogel A | Hepatology (Baltimore, Md.) | 2001 | PMID: 11343230 |
| Screening for an AIRE-1 mutation in patients with Addison's disease, type 1 diabetes, Graves' disease and Hashimoto's thyroiditis as well as in APECED syndrome. | Meyer G | Clinical endocrinology | 2001 | PMID: 11298085 |
| Autoimmune polyendocrine syndrome type 1 (APS I) in Norway. | Myhre AG | Clinical endocrinology | 2001 | PMID: 11207636 |
| Mutations in the AIRE gene: effects on subcellular location and transactivation function of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protein. | Björses P | American journal of human genetics | 2000 | PMID: 10677297 |
| Characterization of mutations in patients with autoimmune polyglandular syndrome type 1 (APS1). | Wang CY | Human genetics | 1998 | PMID: 9921903 |
| An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. | Finnish-German APECED Consortium | Nature genetics | 1997 | PMID: 9398840 |
| Positional cloning of the APECED gene. | Nagamine K | Nature genetics | 1997 | PMID: 9398839 |
| [An isolated defect of the tubular cystine reabsorption in a family with idiopathic hypoparathyroidism]. | Brodehl J | Klinische Wochenschrift | 1967 | PMID: 6031738 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=AIRE | - | - | - | - |
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Text-mined citations for rs121434254 ...
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Record last updated Oct 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.