GALR1

Chr 18

galanin receptor 1

Also known as: GALNR, GALNR1

NCBI Gene: 2587 ENSG00000166573 UniProt: P47211 OMIM: 600377

The GALR1 protein is a G-protein-coupled receptor for the neuropeptide galanin that inhibits adenylyl cyclase activity and is widely expressed in the brain, spinal cord, and peripheral tissues including small intestine and heart. Currently, no human diseases have been definitively associated with GALR1 mutations in the medical literature. The gene shows low constraint to loss-of-function variation (pLI = 0.0005, LOEUF = 1.347), suggesting that complete loss of function may be well tolerated.

OMIM ResearchSummary from RefSeq, UniProt

The neuropeptide galanin elicits a range of biological effects by interaction with specific G-protein-coupled receptors. Galanin receptors are seven-transmembrane proteins shown to activate a variety of intracellular second-messenger pathways. GALR1 inhibits adenylyl cyclase via a G protein of the Gi/Go family. GALR1 is widely expressed in the brain and spinal cord, as well as in peripheral sites such as the small intestine and heart. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.35

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.35LOEUF

pLI 0.001

Z-score 0.86

OE 0.69 (0.37–1.35)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.21Z-score

OE missense 1.04 (0.93–1.17)

209 obs / 200.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.69 (0.37–1.35)

0≤0.351.4

Missense OE?1.04 (0.93–1.17)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 6 / 8.8Missense obs/exp: 209 / 200.7Syn Z: 0.17

Background carrier burden — how many people carry a rare variant somewhere in GALR1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 98

480 rare PASS variants

Rare truncating (LoF)

1 in 2,800

71 rare PASS variants

Rare synonymous (reference)

1 in 290

217 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GALR1. 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 160	1 in 2,200
South Asian	~43k	1 in 110	1 in 8,500
Remaining (unassigned)	~30k	1 in 83	1 in 3,300
European (Finnish)	~27k	1 in 680	1 in 4,700
Admixed American	~22k	1 in 99	≈ 1 in 4,800
African / African American	~21k	1 in 140	1 in 1,700
East Asian	~20k	1 in 140	≈ 1 in 4,700
Ashkenazi Jewish	~13k	1 in 310	1 in 1,900
Middle Eastern	~2,884	1 in 120	≈ 1 in 2,700

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): 2 of 3 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 3.? see exons ↓