GPR137

Chr 11

G protein-coupled receptor 137

Also known as: C11orf4, GPR137A, TM7SF1L1

NCBI Gene: 56834 ENSG00000173264 UniProt: Q96N19

GPR137 encodes a lysosomal integral membrane protein that regulates MTORC1 complex translocation to lysosomes and may function in autophagy. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, affecting neurological development in early childhood. The gene shows high constraint to loss-of-function variation (LOEUF 0.435), indicating intolerance to protein-truncating mutations.

ResearchSummary from RefSeq, UniProt

Predicted to be involved in several processes, including negative regulation of bone resorption; negative regulation of osteoclast differentiation; and positive regulation of TORC1 signaling. Located in lysosomal membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.43

LOEUF

GOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.43LOEUF

pLI 0.668

Z-score 3.44

OE 0.19 (0.09–0.43)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.04Z-score

OE missense 0.83 (0.75–0.92)

244 obs / 294.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.19 (0.09–0.43)

0≤0.351.4

Missense OE?0.83 (0.75–0.92)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 4 / 21.1Missense obs/exp: 244 / 294.3Syn Z: 0.41

Background carrier burden — how many people carry a rare variant somewhere in GPR137?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 93

695 rare PASS variants

Rare truncating (LoF)

1 in 660

99 rare PASS variants

Rare synonymous (reference)

1 in 210

268 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GPR137. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 600
South Asian	~43k	1 in 110	1 in 1,300
Remaining (unassigned)	~30k	1 in 110	1 in 500
European (Finnish)	~27k	1 in 200	1 in 1,700
Admixed American	~22k	1 in 87	1 in 1,500
African / African American	~21k	1 in 110	1 in 1,500
East Asian	~20k	1 in 130	1 in 850
Ashkenazi Jewish	~13k	1 in 720	none seen
Middle Eastern	~2,884	1 in 110	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓