TMEM67 transmembrane protein 67 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TMEM67provided by HGNC
Official Full Name: transmembrane protein 67provided by HGNC
Primary source: HGNC:HGNC:28396
See related: Ensembl:ENSG00000164953 MIM:609884; AllianceGenome:HGNC:28396
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MKS3; JBTS6; NPHP11; TNEM67; MECKELIN
Summary: The protein encoded by this gene localizes to the primary cilium and to the plasma membrane. The gene functions in centriole migration to the apical membrane and formation of the primary cilium. Multiple transcript variants encoding different isoforms have been found for this gene. Defects in this gene are a cause of Meckel syndrome type 3 (MKS3) and Joubert syndrome type 6 (JBTS6). [provided by RefSeq, Nov 2008]
Expression: Broad expression in testis (RPKM 4.7), thyroid (RPKM 3.1) and 23 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 8q22.1

Exon count:: 35

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (93754844..93832653)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (94879829..94957683)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (94767072..94831466)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Two novel TMEM67 variations in a Chinese family with recurrent pregnancy loss: a case report.
Title: Two novel TMEM67 variations in a Chinese family with recurrent pregnancy loss: a case report.
TMEM67 is required for the gating function of the transition zone that controls entry of membrane-associated proteins ARL13B and INPP5E into primary cilia.
Title: TMEM67 is required for the gating function of the transition zone that controls entry of membrane-associated proteins ARL13B and INPP5E into primary cilia.
Association of novel TMEM67 variants with mild phenotypes of high gamma-glutamyl transpeptidase cholestasis and congenital hepatic fibrosis.
Title: Association of novel TMEM67 variants with mild phenotypes of high gamma-glutamyl transpeptidase cholestasis and congenital hepatic fibrosis.
TACC3 promotes prostate cancer cell proliferation and restrains primary cilium formation.
Title: TACC3 promotes prostate cancer cell proliferation and restrains primary cilium formation.
This study confirms the diagnosis of Joubert syndrome in a Vietnamese family and expands the mutational spectrum of TMEM67 sequence variations.
Title: Novel compound heterozygous TMEM67 variants in a Vietnamese family with Joubert syndrome: a case report.
Study identified two novel heterozygous mutations (p.Gly132Ala and p.Tyr920ThrfsX40) in the TMEM67 gene in a patient with COACH syndrome. Co-injection into zebrafish embryos of tmem67 morpholinos and RNAs encoding the two mutations show no rescue of the hydrocephalus phenotype. These findings indicate that the two mutations may cause COACH syndrome via altered Wnt signaling, at least in part.
Title: Functional validation of novel MKS3/TMEM67 mutations in COACH syndrome.
Compound heterozygous mutations in TMEM67 cause RHYNS syndrome ranging from early lethality to adults with liver fibrosis.
Title: Biallelic variants in the ciliary gene TMEM67 cause RHYNS syndrome.
Kidney disease occurs in up to one third of patients with Joubert syndrome, most commonly in those with mutations in CEP290, TMEM67, and AHI1.
Title: Prospective Evaluation of Kidney Disease in Joubert Syndrome.
The authors results suggest that Asn242Ser in TMEM67 is a founder mutation in the Iranian population, which might explain a significant proportion of JS cases from eastern Iran.
Title: A Common Ancestral Asn242Ser Mutation in TMEM67 Identified in Multiple Iranian Families with Joubert Syndrome.
Low expression of TMEM67 is associated with lymph node metastasis in urothelial carcinoma of the bladder.
Title: Low expression of TMEM67 is a critical predictor of poor prognosis in human urothelial carcinoma of the bladder.

Submit: New GeneRIF Correction See all GeneRIFs (27)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Bardet-Biedl syndrome 14 MedGen: C2673874 OMIM: 615991 GeneReviews: Bardet-Biedl Syndrome Overview	not available
COACH syndrome 1 MedGen: C5435651 OMIM: 216360 GeneReviews: Not available	not available
Joubert syndrome 6 MedGen: C1853153 OMIM: 610688 GeneReviews: Joubert Syndrome	not available
Meckel syndrome, type 3 MedGen: C1846357 OMIM: 607361 GeneReviews: Not available	not available
Nephronophthisis 11 MedGen: C3150796 OMIM: 613550 GeneReviews: Nephronophthisis-Related Ciliopathies	not available
RHYNS syndrome MedGen: C1865794 OMIM: 602152 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

D8S1128 (e-PCR), detects polymorphism
- UniSTS:811

D8S2279 (e-PCR)
- UniSTS:473907

RH102566 (e-PCR)
- UniSTS:96900

RH102073 (e-PCR)
- UniSTS:96407

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables filamin binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables unfolded protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in ERAD pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cilium assembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in cilium assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cilium assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of centrosome duplication	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in non-canonical Wnt signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of MKS complex	ISS Inferred from Sequence or Structural Similarity more info
located_in centrosome	IDA Inferred from Direct Assay more info	PubMed
located_in ciliary membrane	IDA Inferred from Direct Assay more info	PubMed
located_in ciliary membrane	TAS Traceable Author Statement more info
is_active_in ciliary transition zone	IBA Inferred from Biological aspect of Ancestor more info
located_in ciliary transition zone	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic vesicle membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: meckelin

Names: meckel syndrome type 3 protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009190.1 RefSeqGene

Range

5001..69391

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_688

mRNA and Protein(s)

NM_001142301.1 → NP_001135773.1 meckelin isoform 2

See identical proteins and their annotated locations for NP_001135773.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) has an alternate splice pattern in the 5' coding region. The resulting isoform (2) has a shorter and distinct N-terminus, compared to isoform 1.

Source sequence(s)

AC010834, AK092244, BC032835, BM310097, DC368894

UniProtKB/TrEMBL

A0A804HL43

Conserved Domains (1) summary

pfam09773
Location:87 → 914

Meckelin; Meckelin (Transmembrane protein 67)
NM_153704.6 → NP_714915.3 meckelin isoform 1 precursor

See identical proteins and their annotated locations for NP_714915.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer protein (isoform 1).

Source sequence(s)

AC010834, AK308071, BC031220, BC054338, BM310097

Consensus CDS

CCDS6258.2

UniProtKB/Swiss-Prot

B3KRU5, B3KT47, G5E9H2, Q3ZCX3, Q5HYA8, Q7Z5T8, Q8IZ06

UniProtKB/TrEMBL

A0A0C4DFP8

Related

ENSP00000389998.3, ENST00000453321.8

Conserved Domains (1) summary

pfam09773
Location:168 → 995

Meckelin; Meckelin (Transmembrane protein 67)

RNA

NR_024522.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) has an alternate splice pattern in the 3' UTR. The predicted protein is not represented because the transcript is a candidate for nonsense-mediated decay (NMD).

Source sequence(s)

AC010834, AK308071, BC031220, BC032835

Related

ENST00000684149.1