TMEM151A

Chr 11AD

transmembrane protein 151A

Also known as: DYT36, EKD3, TMEM151

NCBI Gene: 256472 ENSG00000179292 UniProt: Q8N4L1 OMIM: 620108

TMEM151A encodes a transmembrane protein localized to the endoplasmic reticulum and cellular membranes. Mutations cause episodic kinesigenic dyskinesia 3, a movement disorder characterized by sudden involuntary movements triggered by voluntary motion, with autosomal dominant inheritance. The gene shows low constraint to loss-of-function variants, suggesting tolerance to protein-truncating mutations.

OMIM ResearchSummary from RefSeq, OMIM

Located in endoplasmic reticulum and membrane. Implicated in episodic kinesigenic dyskinesia 3. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismADLOEUF 0.941 OMIM phenotype

Clinical Summary— TMEM151A

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

11 unique Pathogenic / Likely Pathogenic· 70 VUS of 86 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.94LOEUF

pLI 0.003

Z-score 1.71

OE 0.48 (0.26–0.94)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.66Z-score

OE missense 0.57 (0.51–0.65)

179 obs / 311.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.48 (0.26–0.94)

0≤0.351.4

Missense OE?0.57 (0.51–0.65)

0≤0.61.4

Synonymous OE?0.72

0≤1.21.6

LoF obs/exp: 6 / 12.6Missense obs/exp: 179 / 311.3Syn Z: 2.77

This gene — mechanism propensity

0.6744th %ile

GOF

0.74top 25%

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

86 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9

Likely Pathogenic2

VUS70

Likely Benign5

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	5	4	0	9
Likely Pathogenic	1	1	0	2
VUS	0	70	0	70
Likely Benign	0	2	3	5
Benign	0	0	0	0
Total	6	77	3	86

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

View in ClinVar →

12 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap TMEM151A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →