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NM_021926.4(ALX4):c.653G>A (p.Arg218Gln) AND Parietal foramina 2

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Nov 8, 2012
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000005318.6

Allele description [Variation Report for NM_021926.4(ALX4):c.653G>A (p.Arg218Gln)]

NM_021926.4(ALX4):c.653G>A (p.Arg218Gln)

Gene:
ALX4:ALX homeobox 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11p11.2
Genomic location:
Preferred name:
NM_021926.4(ALX4):c.653G>A (p.Arg218Gln)
HGVS:
  • NC_000011.10:g.44275472C>T
  • NG_015809.1:g.39695G>A
  • NM_021926.4:c.653G>AMANE SELECT
  • NP_068745.2:p.Arg218Gln
  • LRG_1256t1:c.653G>A
  • LRG_1256:g.39695G>A
  • LRG_1256p1:p.Arg218Gln
  • NC_000011.9:g.44297022C>T
  • Q9H161:p.Arg218Gln
Protein change:
R218Q; ARG218GLN
Links:
UniProtKB: Q9H161#VAR_010785; OMIM: 605420.0003; dbSNP: rs104894193
NCBI 1000 Genomes Browser:
rs104894193
Molecular consequence:
  • NM_021926.4:c.653G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Parietal foramina 2 (PFM2)
Identifiers:
MONDO: MONDO:0012309; MedGen: C1865044; Orphanet: 60015; OMIM: 609597

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000025496OMIM
no assertion criteria provided
Pathogenic
(Feb 1, 2006)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

SCV000056259GeneReviews
no assertion criteria provided
pathologic
(Nov 8, 2012)
not providedcuration

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providednot providednot providednot providednot providednot providednot providednot providedcuration
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Haploinsufficiency of the human homeobox gene ALX4 causes skull ossification defects.

Mavrogiannis LA, Antonopoulou I, Baxová A, Kutílek S, Kim CA, Sugayama SM, Salamanca A, Wall SA, Morriss-Kay GM, Wilkie AO.

Nat Genet. 2001 Jan;27(1):17-8.

PubMed [citation]
PMID:
11137991

Enlarged parietal foramina caused by mutations in the homeobox genes ALX4 and MSX2: from genotype to phenotype.

Mavrogiannis LA, Taylor IB, Davies SJ, Ramos FJ, Olivares JL, Wilkie AO.

Eur J Hum Genet. 2006 Feb;14(2):151-8.

PubMed [citation]
PMID:
16319823
PMCID:
PMC1477589

Details of each submission

From OMIM, SCV000025496.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In affected members of 2 unrelated families with parietal foramina-2 (PFM2; 609597), Mavrogiannis et al. (2001) identified a heterozygous c.653G-A transition in the ALX4 gene, resulting in an arg218-to-gln (R218Q) substitution. The mutation substituted a highly conserved residue in the N-terminal arm of the homeodomain that contacts the minor groove of DNA. In mouse, the identical mutation underlies the Strong luxoid allele, Alx4(lst), and abolishes DNA binding and transcriptional activation in vitro, with no detectable dominant-negative effect.

In a review of 7 patients from 2 unrelated families with parietal foramina due to the R218Q mutation, Mavrogiannis et al. (2006) found that the patients had disproportionately wide defects compared to patients with other mutations. The authors postulated a dominant-negative effect.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From GeneReviews, SCV000056259.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

Converted during submission to Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1not providednot providednot providednot providedAssert pathogenicitynot providednot providednot providednot provided

Last Updated: Apr 23, 2022