GPR27

Chr 3

G protein-coupled receptor 27

Also known as: SREB1

NCBI Gene: 2850 ENSG00000170837 UniProt: Q9NS67

GPR27 encodes an orphan G protein-coupled receptor with 7 transmembrane domains that may function as an amine-like receptor, though its specific ligand and signaling pathway remain unknown. Currently, no human diseases have been definitively associated with GPR27 mutations in the medical literature. The gene shows moderate tolerance to loss-of-function variation (pLI 0.35, LOEUF 1.05), suggesting it may not be essential for normal human development.

ResearchSummary from RefSeq, UniProt

GPR27 is a member of the G protein-coupled receptors (GPCRs), a large family of receptors that have a similar structure characterized by 7 transmembrane domains. Activation of GPCRs by extracellular stimuli such as neurotransmitters, hormones, or light induces an intracellular signaling cascade mediated by heterotrimeric GTP-binding proteins, or G proteins.[supplied by OMIM, May 2010]

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

1.05

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

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.05LOEUF

pLI 0.347

Z-score 1.53

OE 0.22 (0.08–1.05)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.60Z-score

OE missense 0.64 (0.55–0.76)

102 obs / 158.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.22 (0.08–1.05)

0≤0.351.4

Missense OE?0.64 (0.55–0.76)

0≤0.61.4

Synonymous OE?1.23

0≤1.21.6

LoF obs/exp: 1 / 4.5Missense obs/exp: 102 / 158.8Syn Z: -1.65

Background carrier burden — how many people carry a rare variant somewhere in GPR27?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

570 rare PASS variants

Rare truncating (LoF)

1 in 7,400

51 rare PASS variants

Rare synonymous (reference)

1 in 170

395 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GPR27. 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 200	1 in 8,200
South Asian	~43k	1 in 210	1 in 5,200
Remaining (unassigned)	~30k	1 in 160	1 in 4,700
European (Finnish)	~27k	1 in 640	1 in 4,500
Admixed American	~22k	1 in 150	1 in 2,800
African / African American	~21k	1 in 240	≈ 1 in 6,500
East Asian	~20k	1 in 110	≈ 1 in 9,500
Ashkenazi Jewish	~13k	1 in 490	none seen
Middle Eastern	~2,884	1 in 230	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): 0 of 1 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 1.? see exons ↓