TMEM237: Transmembrane Protein 237 in Joubert Syndrome and Ciliopathies
Essential component of the ciliary transition zone, mutations linked to Joubert syndrome and related disorders
Gene Information Card
| Symbol | TMEM237 |
|---|---|
| Full Name | Transmembrane Protein 237 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q33.1 |
| NCBI Gene ID | 65062 ncbi.nlm.nih.gov/gene/65062 |
| Ensembl ID | ENSG00000155755 |
| UniProt ID | Q96QK1 |
| OMIM ID | 614423 |
| HGNC ID | 25032 |
| Aliases | ALS2CR4, JBTS14, FLJ22175 |
Description
TMEM237 (Transmembrane Protein 237) encodes a protein localized to the ciliary transition zone, a critical region for ciliary signaling and protein trafficking. It is part of the MKS module, interacting with other ciliopathy-associated proteins such as TMEM216, TMEM67, and CEP290. Loss-of-function mutations in TMEM237 disrupt ciliogenesis and lead to Joubert syndrome type 14 (JBTS14), characterized by cerebellar vermis hypoplasia, intellectual disability, and often renal and retinal involvement.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Joubert syndrome 14 (JBTS14) | Loss of TMEM237 function disrupts ciliary transition zone assembly, impairing ciliary signaling and causing neurodevelopmental defects. | OMIM #614424; multiple families with biallelic mutations |
| Meckel-Gruber syndrome (MKS) | Biallelic TMEM237 mutations can cause a severe ciliopathy phenotype overlapping with MKS, including encephalocele, polydactyly, and cystic kidneys. | Case reports in ClinVar and literature |
| Nephronophthisis (NPHP) | TMEM237 mutations have been associated with renal cystic disease, often as part of a syndromic ciliopathy. | ClinVar; limited evidence from individual cases |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 14.2 | Medium |
| Kidney | 10.5 | Medium |
| Brain | 8.3 | Low |
| Liver | 6.1 | Low |
| Lung | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 12.0 | Embryonic kidney cell line |
| HeLa | 9.8 | Cervical carcinoma cell line |
| HepG2 | 7.5 | Hepatocellular carcinoma cell line |
| SH-SY5Y | 6.2 | Neuroblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.748C>T (p.Arg250*) | Nonsense | Rare | Premature stop; loss of function |
| c.1A>G (p.Met1?) | Start loss | Rare | No protein translation |
| c.1063_1064del (p.Leu355Valfs*3) | Frameshift | Rare | Truncated protein; loss of function |
| c.1184T>C (p.Leu395Pro) | Missense | Rare | Likely disrupts protein folding |
Mutation functional classification
Loss of Function (LOF)
Majority of reported TMEM237 mutations are loss-of-function (nonsense, frameshift, splice-site), leading to truncated or absent protein and impaired ciliary transition zone function.
Gain of Function (GOF)
No gain-of-function mutations reported for TMEM237.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is recessive.
View complete mutation data：
Gene Ontology (GO)
| • ciliary transition zone (GO:0035869) | • protein binding (GO:0005515) |
| • integral component of membrane (GO:0016021) | • cilium assembly (GO:0060271) |
| • smoothened signaling pathway (GO:0007224) | • cell projection organization (GO:0030030) |
Pathways
• Ciliopathy (MKS/Joubert syndrome) pathway
• Hedgehog signaling pathway (ciliary dependent)
Protein Summary
TMEM237 is a 402-amino acid transmembrane protein with four predicted transmembrane domains. It localizes to the ciliary transition zone and interacts with other MKS complex proteins (e.g., TMEM216, TMEM67, CEP290). The protein is essential for proper ciliary membrane composition and signaling, particularly in the Hedgehog pathway. Loss of TMEM237 leads to ciliary defects and syndromic ciliopathies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TMEM237 Knockout HEK293 Cell Line | EDJ-KQ15826 | Human | 65062 | Details Get a Quote |
| TMEM237 Knockout A-549 Cell Line | EDJ-KQ49040 | Human | 65062 | Details Get a Quote |
| TMEM237 Knockout HCT 116 Cell Line | EDJ-KQ49041 | Human | 65062 | Details Get a Quote |
| TMEM237 Knockout HeLa Cell Line | EDJ-KQ49042 | Human | 65062 | Details Get a Quote |
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