TMEM237

Chr 2AR

transmembrane protein 237

Also known as: ALS2CR4, JBTS14

The protein is a tetraspanin component of the transition zone in primary cilia and is required for ciliogenesis and involved in WNT signaling. Mutations cause Joubert syndrome 14, a ciliopathy characterized by cerebellar vermis hypoplasia, developmental delay, and brainstem abnormalities. This gene follows autosomal recessive inheritance.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.251 OMIM phenotype
Clinical SummaryTMEM237
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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.
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ClinVar Variants
58 unique Pathogenic / Likely Pathogenic· 241 VUS of 500 total submissions
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GeneReview available — TMEM237
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.25LOEUF
pLI 0.000
Z-score 0.64
OE 0.86 (0.601.25)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.09Z-score
OE missense 0.98 (0.871.11)
189 obs / 192.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.86 (0.601.25)
00.351.4
Missense OE0.98 (0.871.11)
00.61.4
Synonymous OE0.61
01.21.6
LoF obs/exp: 20 / 23.3Missense obs/exp: 189 / 192.7Syn Z: 2.55

ClinVar Variant Classifications

500 submitted variants in ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic21
VUS241
Likely Benign153
Benign25
Conflicting14
37
Pathogenic
21
Likely Pathogenic
241
VUS
153
Likely Benign
25
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
0
20
0
37
Likely Pathogenic
21
0
0
0
21
VUS
5
169
62
5
241
Likely Benign
0
0
109
44
153
Benign
0
0
24
1
25
Conflicting
14
Total4316921550491

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗