GALR2

protein-coding

galanin receptor 2, the group of Galanin receptors

Gene summary

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]

MANE transcript

NM_003857.4

Inheritance

—

ClinVar variants

U:63B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.97

Max pathogenic AF

—

Genomic locus

chr17:76,074,781-76,077,537

External References & Databases

Ensembl (ENSG00000182687)

Transcript & Mutation Effects

hg38 • Region Span ~2.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GALR2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 67

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003857.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			63 clinvar	5 clinvar	2 clinvar	70
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	63	6	2	71

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003857.4	RefSeq	NP_003848.1	2	MANE Select
ENST00000329003.4	Ensembl	ENSP00000329684.3	2	MANE Select
ENST00001139905.1	Ensembl	ENSP00000807214.1	2	Standard
XM_011525427.4	RefSeq	XP_011523729.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neuroactive ligand-receptor interaction - Homo sapiens (human)
Peptide GPCRs
GPCRs, Class A Rhodopsin-like
Signaling by GPCR
Signal Transduction

Biological Process

muscle contraction
cell surface receptor signaling pathway
G protein-coupled receptor signaling pathway
adenylate cyclase-modulating G protein-coupled receptor signaling pathway
adenylate cyclase-activating G protein-coupled receptor signaling pathway

Molecular Function

galanin receptor activity
protein binding
G protein-coupled peptide receptor activity
peptide hormone binding
neuropeptide binding

Cellular Component

plasma membrane
integral component of plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000329003
Coding exons: 2
Length: 2748
Individuals with no LoFs: 125605
Homozygous LoFs: 0
Heterozygous LoFs: 30
Defined: 125635
p: 0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.388	212	228	0.928	0.0000104	2399
Missense (PolyPhen)		84	88.464	0.94954		1019
Synonymous	-0.0978	111	110	1.01	0.00000528	898
Loss of Function	0.0685	8	8.21	0.974	3.58e-7	74

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00027	0.00025	rare
Latino/Admixed American	0.000088	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00038	0.00038	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.000033	0.000033	rare
Other	0.00034	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for the hormone galanin and GALP. Receptor for the hormone spexin-1 (PubMed:24517231). The activity of this receptor is mediated by G proteins that activate the phospholipase C/protein kinase C pathway (via G(q)) and that inhibit adenylyl cyclase (via G(i)). {ECO:0000269|PubMed:24517231, ECO:0000269|PubMed:25691535, ECO:0000269|PubMed:9480833, ECO:0000269|PubMed:9685625, ECO:0000269|PubMed:9832121, ECO:0000269|PubMed:9880084}.;

Recessive Scores

pRec: 0.159

Intolerance Scores

LoFtool: 0.549
RVIS EVS: 1.17
RVIS percentile EVS: 92.7

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.215

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium