TMEM158

Chr 3

transmembrane protein 158

Also known as: BBP, RIS1, p40BBP

NCBI Gene: 25907ENSG00000249992UniProt: Q8WZ71OMIM: 620257

TMEM158 encodes a cell surface receptor for brain injury-derived neurotrophic peptide that is upregulated during Ras pathway activation and cellular senescence. Biallelic mutations cause autosomal recessive hypomyelinating leukodystrophy with cerebellar atrophy and seizures, a severe neurological disorder affecting white matter development. The gene shows tolerance to loss-of-function variants in the general population.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 1.74
Clinical Summary— TMEM158
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.15) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 unique Pathogenic / Likely Pathogenic· 38 VUS of 45 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
1.74LOEUF
pLI 0.149
Z-score 0.67
OE 0.49 (0.17–1.74)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.09Z-score
OE missense 0.55 (0.40–0.77)
26 obs / 47.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.49 (0.17–1.74)
0≤0.351.4
Missense OE0.55 (0.40–0.77)
0≤0.61.4
Synonymous OE0.74
0≤1.21.6
LoF obs/exp: 1 / 2.0Missense obs/exp: 26 / 47.1Syn Z: 0.96
DN
0.4785th %ile
GOF
0.6442th %ile
LOF
0.54top 25%

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

45 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic1
VUS38
6
Pathogenic
1
Likely Pathogenic
38
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
1
0
1
VUS
0
37
1
0
38
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total0378045

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

View in ClinVar →

Protein Context — Lollipop Plot

TMEM158 · 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

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 5 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