TMEM237

Chr 2

transmembrane protein 237

Also known as: ALS2CR4, JBTS14

NCBI Gene: 65062ENSG00000155755UniProt: Q96Q45

The protein encoded by this gene is a tetraspanin protein that is thought to be involved in WNT signaling. Defects in this gene are a cause of Joubert syndrome-14. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

Primary Disease Associations & Inheritance

UniProtJoubert syndrome 14
566
ClinVar variants
77
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TMEM237
🧬
Gene-Disease Validity (ClinGen)
Joubert syndrome 14 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
77 Pathogenic / Likely Pathogenic· 267 VUS of 566 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.25LOEUF
pLI 0.000
Z-score 0.64
OE 0.86 (0.60–1.25)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.09Z-score
OE missense 0.98 (0.87–1.11)
189 obs / 192.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.86 (0.60–1.25)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.87–1.11)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.61
0≤1.21.6
LoF obs/exp: 20 / 23.3Missense obs/exp: 189 / 192.7Syn Z: 2.55

ClinVar Variant Classifications

566 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic54
Likely Pathogenic23
VUS267
Likely Benign166
Benign36
Conflicting20
54
Pathogenic
23
Likely Pathogenic
267
VUS
166
Likely Benign
36
Benign
20
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
0
41
0
54
Likely Pathogenic
16
0
7
0
23
VUS
5
169
88
5
267
Likely Benign
0
1
120
45
166
Benign
0
1
33
2
36
Conflicting
—20
Total3417128952566

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TMEM237 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TMEM237-related Joubert syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — TMEM237
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genotype-phenotype correlates in Joubert syndrome: A review.
Gana S et al.·Am J Med Genet C Semin Med Genet
2022Review
[Phenotype and genotype analysis of a pedigree affected with Joubert syndrome due to variant of TMEM237 gene].
Cui S et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2021
Clinical and Molecular Diagnosis of Joubert Syndrome and Related Disorders.
Radha Rama Devi A et al.·Pediatr Neurol
2020
Enhanced diagnostic yield in Meckel-Gruber and Joubert syndrome through exome sequencing supplemented with split-read mapping.
Watson CM et al.·BMC Med Genet
2016
Novel pathogenic variants and multiple molecular diagnoses in neurodevelopmental disorders.
Trinh J et al.·J Neurodev Disord
2019
A case series of joubert syndrome evaluated with whole exome sequencing and the utility of optical genome mapping in the diagnosis.
Kiraz A et al.·Neurogenetics
2025Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools