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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
TMEM237
transmembrane protein 237
Chromosome 2 Β· 2q33.1
NCBI Gene: 65062Ensembl: ENSG00000155755.20HGNC: HGNC:14432UniProt: Q96Q45
48PubMed Papers
21Diseases
0Drugs
44Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingregulation of Wnt signaling pathwaycilium assemblyciliumJoubert syndrome 14Joubert syndromeJoubert syndrome with oculorenal defectJoubert syndrome and related disorders
✦AI Summary

TMEM237 is a transmembrane protein that functions as a critical component of the ciliary transition zone (TZ), the gatekeeper structure at the base of primary cilia 1. It is essential for proper ciliogenesis and localizes to the TZ where it interacts with other ciliopathy-associated proteins including RPGRIP1L/MKS5, MKS-2/TMEM216, B9D1, and B9D2 1. TMEM237 regulates Wnt signaling pathway function and participates in the MKS module that controls ciliary composition and TZ integrity 12. Loss of TMEM237 function results in defective ciliogenesis and Wnt pathway deregulation, as demonstrated in zebrafish gastrulation models 1. Mutations in TMEM237 cause Joubert syndrome 14 (JBTS14), a primary ciliopathy characterized by cerebellar and brainstem malformation 13. TMEM237 mutations are frequently associated with renal involvement in Joubert syndrome patients, requiring close monitoring of renal function 3. Additionally, TMEM237 may contribute to dopaminergic neurodegeneration through Wnt pathway dysfunction in response to environmental pesticide exposure 4. The mutation spectrum includes nonsense mutations, splicing variants, and copy number deletions 56.

Sources cited
1
TMEM237 localizes to the ciliary transition zone, is required for ciliogenesis, regulates Wnt signaling, and functionally interacts with other TZ proteins
PMID: 22152675
2
TMEM237 mutations in Joubert syndrome are frequently associated with renal involvement requiring closer monitoring
PMID: 35238134
3
Compound heterozygous TMEM237 variants (nonsense and splicing mutations) cause Joubert syndrome and expands the variant spectrum
PMID: 34839509
4
TMEM237 (JBTS-14) is organized by TMEM107 within the MKS module and controls TZ subdomain architecture
PMID: 26595381
5
TMEM237 mutations including intergenic deletions contribute to Joubert and Meckel-Gruber syndrome phenotypes
PMID: 26729329
6
TMEM237 mammalian ortholog is necessary for Wnt pathway signaling in nervous system and modulates pesticide-induced dopaminergic neurodegeneration
PMID: 40644377
Disease Associationsβ“˜21
Joubert syndrome 14Open Targets
0.78Strong
Joubert syndromeOpen Targets
0.73Strong
Joubert syndrome with oculorenal defectOpen Targets
0.62Moderate
Joubert syndrome and related disordersOpen Targets
0.45Moderate
Meckel syndromeOpen Targets
0.43Moderate
eye diseaseOpen Targets
0.37Weak
Joubert syndrome with renal defectOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.27Weak
upper aerodigestive tract neoplasmOpen Targets
0.26Weak
genetic disorderOpen Targets
0.19Weak
Retinal dystrophyOpen Targets
0.11Weak
male reproductive system diseaseOpen Targets
0.04Suggestive
congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiencyOpen Targets
0.04Suggestive
hepatocellular carcinomaOpen Targets
0.03Suggestive
congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiencyOpen Targets
0.03Suggestive
urethral diseaseOpen Targets
0.03Suggestive
urinary system diseaseOpen Targets
0.03Suggestive
tricuspid valve diseaseOpen Targets
0.03Suggestive
cervical carcinomaOpen Targets
0.02Suggestive
ciliopathyOpen Targets
0.01Suggestive
Joubert syndrome 14UniProt
Pathogenic Variants44
NM_001044385.3(TMEM237):c.943+1G>TPathogenic
Joubert syndrome 14
β˜…β˜…β˜†β˜†2026
NM_001044385.3(TMEM237):c.52C>T (p.Arg18Ter)Pathogenic
Joubert syndrome 14|Joubert syndrome|not provided|Joubert syndrome and related disorders|TMEM237-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 18
NM_001044385.3(TMEM237):c.725G>A (p.Trp242Ter)Pathogenic
Joubert syndrome 14|Joubert syndrome and related disorders
β˜…β˜…β˜†β˜†2025β†’ Residue 242
NM_001044385.3(TMEM237):c.677+1G>APathogenic
Joubert syndrome 14
β˜…β˜…β˜†β˜†2025
NM_001044385.3(TMEM237):c.175C>T (p.Arg59Ter)Pathogenic
Joubert syndrome 14
β˜…β˜…β˜†β˜†2025β†’ Residue 59
NM_001044385.3(TMEM237):c.62del (p.Pro21fs)Pathogenic
Joubert syndrome|Joubert syndrome 14
β˜…β˜…β˜†β˜†2024β†’ Residue 21
NM_001044385.3(TMEM237):c.869+1G>APathogenic
Meckel-Gruber syndrome|Joubert syndrome 14
β˜…β˜…β˜†β˜†2024
NM_001044385.3(TMEM237):c.136+1G>TLikely pathogenic
Joubert syndrome 14|TMEM237-related disorder
β˜…β˜…β˜†β˜†2023
NM_001044385.3(TMEM237):c.553+1G>APathogenic
Joubert syndrome 14|Joubert syndrome and related disorders
β˜…β˜…β˜†β˜†2023
NM_001044385.3(TMEM237):c.869+1delPathogenic
Joubert syndrome 14
β˜…β˜…β˜†β˜†2021
NM_001044385.3(TMEM237):c.418C>T (p.Gln140Ter)Likely pathogenic
Joubert syndrome 14
β˜…β˜…β˜†β˜†2019β†’ Residue 140
NM_001044385.3(TMEM237):c.325C>T (p.Arg109Ter)Pathogenic
Joubert syndrome 14
β˜…β˜†β˜†β˜†2026β†’ Residue 109
NM_001044385.3(TMEM237):c.470_473dup (p.Thr159fs)Pathogenic
Joubert syndrome 14
β˜…β˜†β˜†β˜†2026β†’ Residue 159
NM_001044385.3(TMEM237):c.890C>G (p.Ser297Ter)Pathogenic
Joubert syndrome 14
β˜…β˜†β˜†β˜†2025β†’ Residue 297
NM_001044385.3(TMEM237):c.658dup (p.Thr220fs)Pathogenic
Joubert syndrome 14
β˜…β˜†β˜†β˜†2025β†’ Residue 220
NM_001044385.3(TMEM237):c.901C>T (p.Arg301Ter)Pathogenic
Joubert syndrome 14
β˜…β˜†β˜†β˜†2025β†’ Residue 301
NM_001044385.3(TMEM237):c.869+1G>TPathogenic
Joubert syndrome 14
β˜…β˜†β˜†β˜†2025
NM_001044385.3(TMEM237):c.1159+1G>TLikely pathogenic
Joubert syndrome 14
β˜…β˜†β˜†β˜†2024
NM_001044385.3(TMEM237):c.7_34del (p.Thr3fs)Likely pathogenic
Joubert syndrome 14
β˜…β˜†β˜†β˜†2024β†’ Residue 3
NM_001044385.3(TMEM237):c.137-2A>GLikely pathogenic
Joubert syndrome 14
β˜…β˜†β˜†β˜†2024
View on ClinVar β†—
Related Genes
NPHP4Protein interaction88%TCTN1Protein interaction87%TMEM216Protein interaction85%TCTN2Protein interaction81%B9D2Protein interaction78%TMEM231Protein interaction77%
Tissue Expression6 tissues
Brain
100%
Heart
98%
Ovary
78%
Bone Marrow
51%
Lung
38%
Liver
13%
Gene Interaction Network
Click a node to explore
TMEM237NPHP4TCTN1TMEM216TCTN2B9D2TMEM231
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q96Q45
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.32LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.02 [0.79–1.32]
RankingsWhere TMEM237 stands among ~20K protein-coding genes
  • #9,147of 20,598
    Most Researched48
  • #1,448of 5,498
    Most Pathogenic Variants44
  • #13,843of 17,882
    Most Constrained (LOEUF)1.32
Genes detectedTMEM237
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Genotype-phenotype correlates in Joubert syndrome: A review.
PMID: 35238134
Am J Med Genet C Semin Med Genet Β· 2022
1.00
2
PMID: 20301500
0.90
3
[Phenotype and genotype analysis of a pedigree affected with Joubert syndrome due to variant of TMEM237 gene].
PMID: 34839509
Zhonghua Yi Xue Yi Chuan Xue Za Zhi Β· 2021
0.80
4
Function of TRPC1 in modulating hepatocellular carcinoma progression.
PMID: 36797544
Med Oncol Β· 2023
0.70
5
TMEM237 is mutated in individuals with a Joubert syndrome related disorder and expands the role of the TMEM family at the ciliary transition zone.
PMID: 22152675
Am J Hum Genet Β· 2011
0.60