TMEM151A

Chr 11AD

transmembrane protein 151A

Also known as: DYT36, EKD3, TMEM151

NCBI Gene: 256472ENSG00000179292UniProt: Q8N4L1

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

Primary Disease Associations & Inheritance

Episodic kinesigenic dyskinesia 3MIM #620245
AD
101
ClinVar variants
22
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TMEM151A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 74 VUS of 101 total submissions

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.
0.94LOEUF
pLI 0.003
Z-score 1.71
OE 0.48 (0.26–0.94)
Tolerant

Typical tolerance to LoF variation

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.
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?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.0.48 (0.26–0.94)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.57 (0.51–0.65)
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.0.72
0≤1.21.6
LoF obs/exp: 6 / 12.6Missense obs/exp: 179 / 311.3Syn Z: 2.77

ClinVar Variant Classifications

101 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic4
VUS74
Likely Benign5
18
Pathogenic
4
Likely Pathogenic
74
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
4
11
0
18
Likely Pathogenic
1
1
2
0
4
VUS
0
68
6
0
74
Likely Benign
0
2
0
3
5
Benign
0
0
0
0
0
Total475193101

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

View in ClinVar →

Protein Context — Lollipop Plot

TMEM151A · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Episodic kinesigenic dyskinesia 3

MIM #620245

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Novel missense variant in the TMEM151A gene causing paroxysmal kinesigenic dyskinesia: a case report with literature review.
Liu Y et al.·Neurol Sci
2023Review
Paroxysmal Kinesigenic Dyskinesia: Genetics and Pathophysiological Mechanisms.
Xu JJ et al.·Neurosci Bull
2024Review
TMEM151A Variants Cause Paroxysmal Kinesigenic Dyskinesia: A Large-Sample Study.
Tian WT et al.·Mov Disord
2022
Features Differ Between Paroxysmal Kinesigenic Dyskinesia Patients with PRRT2 and TMEM151A Variants.
Chen YL et al.·Mov Disord
2022Cohort
Paroxysmal Kinesigenic Dyskinesia in Two Siblings With Novel Heterozygous TMEM151A Frameshift Variant: The First Case Report in Japan.
Kurahashi H et al.·Am J Med Genet A
2025Case report
TMEM151A variants associated with paroxysmal kinesigenic dyskinesia.
Huang HL et al.·Hum Genet
2023
Clinical and Genetic Characteristics of Paroxysmal Kinesigenic Dyskinesia: A Single-Center Study and Literature Review.
Li M et al.·FASEB J
2026Review
TMEM151A phenotypic spectrum includes paroxysmal kinesigenic dyskinesia with infantile convulsions.
Wang H et al.·Neurol Sci
2022
TMEM151A-related Paroxysmal Kinesigenic Dyskinesia in first two Indian families.
Sampath R et al.·Parkinsonism Relat Disord
2025
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