GALR2

Chr 17

galanin receptor 2

Also known as: GAL2-R, GALNR2, GALR-2

NCBI Gene: 8811UniProt: O43603

Galanin is an important neuromodulator present in the brain, gastrointestinal system, and hypothalamopituitary axis. It is a 30-amino acid non-C-terminally amidated peptide that potently stimulates growth hormone secretion, inhibits cardiac vagal slowing of heart rate, abolishes sinus arrhythmia, and inhibits postprandial gastrointestinal motility. The actions of galanin are mediated through interaction with specific membrane receptors that are members of the 7-transmembrane family of G protein-coupled receptors. GALR2 interacts with the N-terminal residues of the galanin peptide. The primary signaling mechanism for GALR2 is through the phospholipase C/protein kinase C pathway (via Gq), in contrast to GALR1, which communicates its intracellular signal by inhibition of adenylyl cyclase through Gi. However, it has been demonstrated that GALR2 couples efficiently to both the Gq and Gi proteins to simultaneously activate 2 independent signal transduction pathways. [provided by RefSeq, Jul 2008]

0
Active trials
101
ClinVar variants
16
Pathogenic / LP
0.4
Missense Z
1.69
LOEUF
8
Pubs (2 yr)
Clinical Summary— GALR2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 76 VUS of 101 total submissions
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.69LOEUF
pLI 0.000
Z-score 0.07
OE 0.97 (0.57–1.69)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.39Z-score
OE missense 0.93 (0.83–1.04)
212 obs / 228.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.97 (0.57–1.69)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.83–1.04)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 8 / 8.2Missense obs/exp: 212 / 228.5Syn Z: -0.10

ClinVar Variant Classifications

101 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic1
VUS76
Likely Benign7
Benign2
15
Pathogenic
1
Likely Pathogenic
76
VUS
7
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
14
0
15
Likely Pathogenic
0
0
1
0
1
VUS
0
72
4
0
76
Likely Benign
0
5
0
2
7
Benign
0
2
0
0
2
Total179192101

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

View in ClinVar →

Protein Context — Lollipop Plot

GALR2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Investigating the potential of GalR2 as a drug target for neuropathic pain.
Rich K et al.·Neuropeptides
2023Review
The GAL/GALR2 axis promotes the perineural invasion of salivary adenoid cystic carcinoma via epithelial-to-mesenchymal transition.
Wang J et al.·Cancer Med
2023
Novel hypothalamic pathways for metabolic effects of spexin.
Fang P et al.·Pharmacol Res
2024Review
Neuropeptides in learning and memory.
Borbély E et al.·Neuropeptides
2013Review
The potential antidepressant and antidiabetic effects of galanin system.
Fang P et al.·Pharmacol Biochem Behav
2014Review
Galanin Receptors (GalR1, GalR2, and GalR3) Expression in Colorectal Cancer Tissue and Correlations to the Overall Survival and Poor Prognosis of CRC Patients.
Kiezun J et al.·Int J Mol Sci
2022Cohort
The G protein-coupled receptor GALR2 promotes angiogenesis in head and neck cancer.
Banerjee R et al.·Mol Cancer Ther
2014
A non-functional galanin receptor-2 in a multiple sclerosis patient.
Garcia-Rosa S et al.·Pharmacogenomics J
2019Functional
Galanin regulates M1/M2 polarization of microglia after spinal cord injury through TRPV1/Ca2+/CaMKII/NRF2 signaling pathway.
Zhu Z et al.·Int Immunopharmacol
2025
G-Protein-Coupled Receptors: Next Generation Therapeutic Targets in Head and Neck Cancer?
Kanazawa T et al.·Toxins (Basel)
2015Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
The role of galanin/GALR2 signaling in the link between type 2 diabetes and Alzheimer's disease.
Xu M et al.·Neuropeptides
2026
A novel long-galanin peptide from non-mammalian vertebrates mitigates the inflammatory response in IBD models via the biased GALR2/β-arrestin2 pathway.
Lai S et al.·Nat Commun
2025Open AccessFunctional
Intracerebroventricular knockdown of NPY1R disrupts NPY1R-GALR2/TrkB heteroreceptor complexes without affecting neuroplasticity or depressive-like behaviour.
Moreno-Madrid I et al.·J Psychopharmacol
2025Open Access
Enhanced neuronal survival and BDNF elevation via long-term co-activation of galanin 2 (GALR2) and neuropeptide Y1 receptors (NPY1R): potential therapeutic targets for major depressive disorder.
Borroto-Escuela D et al.·Expert Opin Ther Targets
2024
Glyphosate-induced changes in the expression of galanin and GALR1, GALR2 and GALR3 receptors in the porcine small intestine wall.
Palus K et al.·Sci Rep
2024Open Access
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Jaw size variation is associated with a novel craniofacial function for galanin receptor 2 in an adaptive radiation of pupfishes
Palominos MF et al.·bioRxiv
2023
The activation of galanin receptor 2 plays an antinociceptive effect in nucleus accumbens of rats with neuropathic pain
Dong Y et al.·J Physiol Sci
2021
Galanin and Neuropeptide Y Interaction Enhances Proliferation of Granule Precursor Cells and Expression of Neuroprotective Factors in the Rat Hippocampus with Consequent Augmented Spatial Memory
Mirchandani-Duque M et al.·Biomedicines
2022
Regulatory Influence of Galanin and GALR1/GALR2 Receptors on Inflamed Uterus Contractility in Pigs
Jana B et al.·Int J Mol Sci
2021
Jaw size variation is associated with a novel craniofacial function for galanin receptor 2 in an adaptive radiation of pupfishes
Palominos MF et al.·Proc Biol Sci
2023
Enhancement of neurogenesis and cognition through intranasal co-delivery of galanin receptor 2 (GALR2) and neuropeptide Y receptor 1 (NPY1R) agonists: a potential pharmacological strategy for cognitive dysfunctions
Sánchez-Varo R et al.·Behav Brain Funct
2024
Galanin Regulates Myocardial Mitochondrial ROS Homeostasis and Hypertrophic Remodeling Through GalR2
Boal F et al.·Front Pharmacol
2022Functional
Exogenous GalR2-specific peptide agonist as a tool for treating myocardial ischemia/reperfusion injury.
Serebryakova L et al.·Fundam Clin Pharmacol
2023
Top 8 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients