TMEM167A

Chr 5

transmembrane protein 167A

Also known as: TMEM167, kish

TMEM167A encodes a protein involved in the early secretory pathway and is located in the Golgi apparatus. Mutations cause autosomal recessive intellectual disability with seizures and brain malformations. This gene is not highly constrained against loss-of-function variants, consistent with a recessive inheritance pattern affecting neurodevelopment.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.79
Clinical SummaryTMEM167A
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.79LOEUF
pLI 0.000
Z-score 0.04
OE 0.98 (0.501.79)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.41Z-score
OE missense 0.82 (0.611.09)
32 obs / 39.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.98 (0.501.79)
00.351.4
Missense OE0.82 (0.611.09)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 5 / 5.1Missense obs/exp: 32 / 39.2Syn Z: 0.14
DN
0.80top 25%
GOF
0.81top 10%
LOF
0.3163th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TMEM167A · 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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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC