GPR137B

Chr 1

G protein-coupled receptor 137B

Also known as: TM7SF1

GPR137B encodes a lysosomal integral membrane protein that regulates mTORC1 signaling complex localization and activity by interacting with Rag GTPases, and controls lysosomal morphology and autophagy. Mutations cause autosomal recessive developmental delays and seizures. This gene shows minimal constraint against loss-of-function variants based on population data.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.32
Clinical SummaryGPR137B
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
1.32LOEUF
pLI 0.000
Z-score 0.46
OE 0.89 (0.611.32)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.24Z-score
OE missense 1.05 (0.941.17)
229 obs / 219.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.89 (0.611.32)
00.351.4
Missense OE1.05 (0.941.17)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 18 / 20.2Missense obs/exp: 229 / 219.0Syn Z: 0.22
DN
0.7228th %ile
GOF
0.73top 25%
LOF
0.3939th %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

GPR137B · 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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