The GALR3 protein is a G protein-coupled receptor for the hormones galanin and spexin-1, which regulate cognition, memory, pain processing, hormone secretion, and feeding behavior. This gene shows very low constraint against loss-of-function variants (pLI 0.0001, LOEUF 1.71), and no established Mendelian diseases have been linked to GALR3 mutations in current medical literature.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.71
Clinical SummaryGALR3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
24 unique Pathogenic / Likely Pathogenic· 66 VUS of 95 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.71LOEUF
pLI 0.000
Z-score 0.18
OE 0.93 (0.501.71)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.21Z-score
OE missense 0.95 (0.831.09)
139 obs / 146.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.93 (0.501.71)
00.351.4
Missense OE0.95 (0.831.09)
00.61.4
Synonymous OE1.15
01.21.6
LoF obs/exp: 6 / 6.5Missense obs/exp: 139 / 146.3Syn Z: -1.00
DN
0.7327th %ile
GOF
0.87top 5%
LOF
0.2872th %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

95 submitted variants in ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic2
VUS66
Likely Benign3
Conflicting1
22
Pathogenic
2
Likely Pathogenic
66
VUS
3
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
2
0
2
VUS
0
65
1
0
66
Likely Benign
0
3
0
0
3
Benign
0
0
0
0
0
Conflicting
1
Total06825094

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

View in ClinVar →

Protein Context — Lollipop Plot

GALR3 · 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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