GPRC5B

protein-coding

G protein-coupled receptor class C group 5 member B, the group of G protein-coupled receptors, Class C orphans

Gene summary

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]

MANE transcript

NM_016235.3

Inheritance

ClinVar variants

U:67B:14

Top phenotype

Megalencephalic leukoencephalopathy with subcortical cysts 3

gnomAD constraint

pLI —, LoF o/e 0.36

Max pathogenic AF

—

Genomic locus

chr16:19,856,691-19,886,167

External References & Databases

Ensembl (ENSG00000167191)

Transcript & Mutation Effects

hg38 • Region Span ~29.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

megalencephalic leukoencephalopathy with subcortical cysts 3STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0957533

Submitter: PanelApp Australia

megalencephalic leukoencephalopathy with subcortical cysts 3LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0957533

Submitter: Ambry Genetics

megalencephalic leukoencephalopathy with subcortical cysts 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0024555

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Megalencephalic leukoencephalopathy with subcortical cysts 3AD

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 37143309

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GPRC5B variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 58

not providedTotal: 18

Megalencephalic leukoencephalopathy with subcortical cysts 3Total: 4

GPRC5B-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016235.3. 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				6 clinvar	1 clinvar	7
missense			66 clinvar	6 clinvar	1 clinvar	73
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	67	12	2	81

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016235.3	RefSeq	NP_057319.1	3	MANE Select
ENST00000300571.7	Ensembl	ENSP00000300571.2	3	MANE Select
NM_001304771.1	RefSeq	NP_001291700.1	4	Standard
ENST00000535671.5	Ensembl	ENSP00000442858.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

GPCRs, Class C Metabotropic glutamate, pheromone

Biological Process

G protein-coupled receptor signaling pathway
locomotory behavior
positive regulation of neuron projection development
activation of protein kinase activity
glucose homeostasis

Molecular Function

G protein-coupled receptor binding
G protein-coupled receptor activity
protein kinase binding
protein kinase activator activity

Cellular Component

extracellular space
nucleus
nucleolus
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000300571
Coding exons: 3
Length: 28874
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125748
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.32	200	260	0.769	0.0000170	2602
Missense (PolyPhen)		86	122.96	0.6994		1236
Synonymous	-0.717	131	121	1.08	0.00000926	876
Loss of Function	2.19	5	13.7	0.364	8.08e-7	121

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Unknown. This retinoic acid-inducible G-protein coupled receptor provide evidence for a possible interaction between retinoid and G-protein signaling pathways.;

Recessive Scores

pRec: 0.135

Intolerance Scores

LoFtool: 0.107
RVIS EVS: -0.82
RVIS percentile EVS: 11.88

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.460

Gene Damage Prediction

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