TMEM67 Gene - Transmembrane Protein 67
Key player in ciliary function and associated with ciliopathies including Meckel-Gruber and Joubert syndromes
Gene Information Card
| Symbol | TMEM67 |
|---|---|
| Full Name | Transmembrane Protein 67 |
| Gene Type | Protein coding |
| Chromosomal Location | 8q22.1 |
| NCBI Gene ID | 91147 ncbi.nlm.nih.gov/gene/91147 |
| Ensembl ID | ENSG00000164953 |
| UniProt ID | Q5HYA8 |
| OMIM ID | 609884 |
| HGNC ID | 28396 |
| Aliases | MKS3, JBTS6, NPHP11, TNEM67 |
Description
TMEM67 (Transmembrane Protein 67) encodes a transmembrane protein localized to the primary cilium and involved in ciliary signaling and planar cell polarity. Mutations in this gene cause a spectrum of ciliopathies, including Meckel-Gruber syndrome type 3 (MKS3), Joubert syndrome type 6 (JBTS6), COACH syndrome, and nephronophthisis type 11 (NPHP11). The protein is essential for ciliary membrane composition and Hedgehog signaling.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Meckel-Gruber syndrome type 3 (MKS3) | Loss of TMEM67 disrupts ciliary function, leading to neural tube defects, cystic kidneys, and polydactyly | OMIM #607361 |
| Joubert syndrome type 6 (JBTS6) | Impaired ciliary signaling causes cerebellar vermis hypoplasia, hypotonia, and developmental delay | OMIM #610688 |
| COACH syndrome | TMEM67 mutations affect ciliary protein trafficking, resulting in liver fibrosis, coloboma, and ataxia | OMIM #216360 |
| Nephronophthisis type 11 (NPHP11) | Defective ciliary function leads to renal tubular atrophy and interstitial fibrosis | OMIM #613550 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Kidney | 8.2 | Medium |
| Brain | 6.1 | Low |
| Liver | 5.3 | Low |
| Lung | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 10.1 | Embryonic kidney cell line |
| HepG2 | 7.8 | Hepatocellular carcinoma |
| SH-SY5Y | 5.4 | Neuroblastoma |
| A549 | 4.9 | Lung carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.725A>G (p.Asn242Ser) | Missense | Rare | Alters protein localization to cilium |
| c.1471C>T (p.Arg491*) | Nonsense | Rare | Premature truncation, loss of function |
| c.1792G>A (p.Gly598Arg) | Missense | Rare | Disrupts ciliary membrane targeting |
| c.2281C>T (p.Arg761Trp) | Missense | Rare | Impaired protein stability |
Mutation functional classification
Loss of Function (LOF)
Most TMEM67 mutations are loss-of-function, leading to truncated or mislocalized protein, disrupting ciliary function.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • cilium (GO:0005929) | • ciliary basal body (GO:0036064) |
| • cilium assembly (GO:0060271) | • smoothened signaling pathway (GO:0007224) |
| • protein binding (GO:0005515) |
Pathways
• Ciliopathy pathway (KEGG: hsa05200)
• Hedgehog signaling pathway (KEGG: hsa04340)
Protein Summary
TMEM67 is a 995-amino acid transmembrane protein with multiple membrane-spanning domains. It localizes to the primary cilium and is required for ciliary membrane composition and Hedgehog signal transduction. The protein interacts with other ciliary proteins such as MKS1 and CC2D2A, and its dysfunction leads to impaired ciliogenesis and planar cell polarity defects.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TMEM67 Knockout HEK293 Cell Line | EDJ-KQ10705 | Human | 91147 | Details Get a Quote |
| TMEM67 Knockout HCT 116 Cell Line | EDJ-KQ36960 | Human | 91147 | Details Get a Quote |
| TMEM67 Knockout A-549 Cell Line | EDJ-KQ38262 | Human | 91147 | Details Get a Quote |
| TMEM67 Knockout HeLa Cell Line | EDJ-KQ38263 | Human | 91147 | Details Get a Quote |
