GPRC5B

Chr 16AD

G protein-coupled receptor class C group 5 member B

Also known as: MLC3, RAIG-2, RAIG2

NCBI Gene: 51704ENSG00000167191UniProt: Q9NZH0

This gene encodes a member of the type 3 G protein-coupled receptor family. Members of this superfamily are characterized by a signature 7-transmembrane domain motif. The encoded protein may modulate insulin secretion and increased protein expression is associated with type 2 diabetes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

Primary Disease Associations & Inheritance

Megalencephalic leukoencephalopathy with subcortical cysts 3MIM #620447
AD
90
ClinVar variants
16
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— GPRC5B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
16 Pathogenic / Likely Pathogenic· 60 VUS of 90 total submissions

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.
0.77LOEUF
pLI 0.024
Z-score 2.19
OE 0.36 (0.19–0.77)
Tolerant

Typical tolerance to LoF variation

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.
1.32Z-score
OE missense 0.77 (0.68–0.86)
200 obs / 260.1 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.0.36 (0.19–0.77)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.68–0.86)
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.1.08
0≤1.21.6
LoF obs/exp: 5 / 13.7Missense obs/exp: 200 / 260.1Syn Z: -0.72

ClinVar Variant Classifications

90 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
VUS60
Likely Benign2
Benign4
16
Pathogenic
60
VUS
2
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
0
0
0
VUS
0
57
3
0
60
Likely Benign
0
1
0
1
2
Benign
0
2
0
2
4
Total06019382

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

View in ClinVar →

Protein Context — Lollipop Plot

GPRC5B · 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

Megalencephalic leukoencephalopathy with subcortical cysts 3

MIM #620447

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Aquaporin-4 and GPRC5B: old and new players in controlling brain oedema.
Passchier EMJ et al.·Brain
2023
Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.
Speliotes EK et al.·Nat Genet
2010
A Reflux Linked GATA Factor Fulcrum Dictates Lineage Commitment Through GPRC5B During the Esophageal Dysplastic Transition.
Abuhussein O et al.·Cell Mol Gastroenterol Hepatol
2025
Megalencephalic leukoencephalopathy with subcortical cysts: a multicenter Italian experience.
Sartorelli J et al.·Neurol Sci
2026
Regulation of the orphan G-protein-coupled receptor GPRC5B by MLC1 and the cell adhesion molecule GlialCAM in megalencephalic leukoencephalopathy.
Pont-Espinós G et al.·J Biol Chem
2026
From clinical evidence to biological mechanisms: GPRC5B as a key mediator of metabolic syndrome-associated prostate cancer.
Lin W et al.·Int J Biol Macromol
2026Functional
A Risk Model for Prognosis and Treatment Response Prediction in Colon Adenocarcinoma Based on Genes Associated with the Characteristics of the Epithelial-Mesenchymal Transition.
Huang H et al.·Int J Mol Sci
2023Functional
An mRNA atlas of G protein-coupled receptor expression during primary human monocyte/macrophage differentiation and lipopolysaccharide-mediated activation identifies targetable candidate regulators of inflammation.
Hohenhaus DM et al.·Immunobiology
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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