TMEM52B

Chr 12

transmembrane protein 52B

Also known as: C12orf59

NCBI Gene: 120939ENSG00000165685UniProt: Q4KMG9

TMEM52B encodes a transmembrane protein located in extracellular exosomes, though its specific cellular function remains unclear. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy or early childhood. The gene shows minimal constraint against loss-of-function variants, consistent with a recessive inheritance pattern.

Summary from RefSeq
Research Assistant →
0
Active trials
2
Pubs (1 yr)
38
P/LP submissions
0%
P/LP missense
1.55
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— TMEM52B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
38 unique Pathogenic / Likely Pathogenic· 38 VUS of 81 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
1.55LOEUF
pLI 0.001
Z-score 0.57
OE 0.76 (0.40–1.55)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.31Z-score
OE missense 1.09 (0.93–1.28)
106 obs / 97.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.76 (0.40–1.55)
0≤0.351.4
Missense OE1.09 (0.93–1.28)
0≤0.61.4
Synonymous OE0.91
0≤1.21.6
LoF obs/exp: 5 / 6.6Missense obs/exp: 106 / 97.4Syn Z: 0.47
DN
0.7131th %ile
GOF
0.76top 25%
LOF
0.2484th %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

81 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic2
VUS38
Likely Benign1
36
Pathogenic
2
Likely Pathogenic
38
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
36
0
36
Likely Pathogenic
0
0
2
0
2
VUS
0
35
3
0
38
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total03641077

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

View in ClinVar →

Protein Context — Lollipop Plot

TMEM52B · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients