TMEM138

Chr 11AR

transmembrane protein 138

Also known as: HSPC196

This gene encodes a multi-pass transmembrane protein required for ciliogenesis, the formation of primary cilia that are essential for cellular signaling pathways. Mutations cause Joubert syndrome 16, an autosomal recessive neurodevelopmental disorder characterized by cerebellar vermis hypoplasia, developmental delay, and distinctive brain malformations. The gene has relatively low constraint against loss-of-function variants (pLI 0.05), consistent with its recessive inheritance pattern where heterozygous carriers are typically unaffected.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.111 OMIM phenotype
Clinical SummaryTMEM138
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Gene-Disease Validity (ClinGen)
ciliopathy · ARModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Low constraint (pLI 0.05) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — TMEM138
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.11LOEUF
pLI 0.047
Z-score 1.40
OE 0.43 (0.191.11)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.47Z-score
OE missense 0.86 (0.711.04)
75 obs / 87.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.43 (0.191.11)
00.351.4
Missense OE0.86 (0.711.04)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 3 / 7.0Missense obs/exp: 75 / 87.4Syn Z: -0.16
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongTMEM138-related Joubert syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.80top 25%
GOF
0.78top 25%
LOF
0.2190th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TMEM138 · 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
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