GPRC5B

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

Basic information

Region (hg38): 16:19856691-19886167

Links

ENSG00000167191 ∙ NCBI:51704 ∙ OMIM:605948 ∙ HGNC:13308 ∙ Uniprot:Q9NZH0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• megalencephalic leukoencephalopathy with subcortical cysts 1 (Strong), mode of inheritance: AD
• megalencephalic leukoencephalopathy with subcortical cysts 3 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Megalencephalic leukoencephalopathy with subcortical cysts 3	AD	General	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	Neurologic	37143309

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GPRC5B gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GPRC5B gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	2	3
missense			18		1	19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	18	1	3

Variants in GPRC5B

This is a list of pathogenic ClinVar variants found in the GPRC5B region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-19860510-T-G		not specified	Uncertain significance (Sep 09, 2024)
16-19860519-G-A		not specified	Uncertain significance (Jun 22, 2023)
16-19861855-G-A			Benign (Mar 19, 2018)
16-19861900-G-A			Likely benign (Apr 19, 2018)
16-19861904-G-A		not specified	Uncertain significance (Mar 03, 2022)
16-19861926-T-G		not specified	Uncertain significance (May 13, 2024)
16-19871863-C-T		not specified	Uncertain significance (Sep 07, 2022)
16-19871885-C-T		not specified	Uncertain significance (Dec 16, 2022)
16-19871914-G-A		not specified	Uncertain significance (Apr 28, 2022)
16-19871927-A-T		not specified	Uncertain significance (Sep 26, 2022)
16-19871984-C-T		not specified	Uncertain significance (Mar 04, 2024)
16-19871996-C-T		not specified	Uncertain significance (Aug 17, 2021)
16-19872059-G-T		not specified	Uncertain significance (Jan 04, 2022)
16-19872091-G-A		not specified	Uncertain significance (Feb 06, 2024)
16-19872176-C-T		not specified	Uncertain significance (Jun 06, 2022)
16-19872185-T-G		not specified	Uncertain significance (Jul 19, 2023)
16-19872233-T-C		not specified	Uncertain significance (May 06, 2024)
16-19872315-A-AGCG		Megalencephalic leukoencephalopathy with subcortical cysts 3	Pathogenic (Jul 19, 2023)
16-19872317-C-CGAT		Megalencephalic leukoencephalopathy with subcortical cysts 3	Pathogenic (Jul 19, 2023)
16-19872382-G-A		not specified	Uncertain significance (Nov 09, 2024)
16-19872391-C-T		not specified	Uncertain significance (Jul 31, 2024)
16-19872395-C-G		not specified	Uncertain significance (Oct 25, 2024)
16-19872404-G-A		not specified	Uncertain significance (Mar 26, 2024)
16-19872407-C-T			Benign (Apr 04, 2018)
16-19872514-A-G		not specified	Uncertain significance (May 30, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GPRC5B	protein_coding	protein_coding	ENST00000300571	3	28874

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0242	0.963	125731	0	17	125748	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.32	200	260	0.769	0.0000170	2602
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000206	0.000206
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000709	0.0000703
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

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.
• Pathway: GPCRs, Class C Metabotropic glutamate, pheromone (Consensus)

Recessive Scores

• pRec: 0.135

Intolerance Scores

• loftool: 0.107
• rvis_EVS: -0.82
• rvis_percentile_EVS: 11.88

Haploinsufficiency Scores

• pHI: 0.728
• hipred: Y
• hipred_score: 0.768
• ghis: 0.654

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.460

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gprc5b
• Phenotype: homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: G protein-coupled receptor signaling pathway;locomotory behavior;positive regulation of neuron projection development;activation of protein kinase activity;glucose homeostasis;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of neuron differentiation;positive regulation of inflammatory response;positive regulation of macrophage cytokine production;positive regulation of protein tyrosine kinase activity;positive regulation of canonical Wnt signaling pathway
• Cellular component: extracellular space;nucleus;nucleolus;cytosol;plasma membrane;cell surface;integral component of membrane;cytoplasmic vesicle membrane;intracellular membrane-bounded organelle;receptor complex;extracellular exosome
• Molecular function: G protein-coupled receptor binding;G protein-coupled receptor activity;protein kinase binding;protein kinase activator activity