GPRC5B

Summary

GPRC5B (G protein-coupled receptor class C group 5 member B, HGNC:13308) is a protein-coding gene on chromosome 16p12.3, encoding G-protein coupled receptor family C group 5 member B (Q9NZH0). G-protein coupled receptor involved in the regulation of cell volume.

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.

Source: NCBI Gene 51704 — RefSeq curated summary.

At a glance

• Gene–disease (curated): megalencephalic leukoencephalopathy with subcortical cysts 1 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 34
• Clinical variants (ClinVar): 80 total — 2 pathogenic
• Phenotypes (HPO): 20
• Druggable target: yes
• MANE Select transcript: NM_016235

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13308
Approved symbol	GPRC5B
Name	G protein-coupled receptor class C group 5 member B
Location	16p12.3
Locus type	gene with protein product
Status	Approved
Aliases	RAIG-2
Ensembl gene	ENSG00000167191
Ensembl biotype	protein_coding
OMIM	605948
Entrez	51704

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 19 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000300571, ENST00000535671, ENST00000562348, ENST00000562469, ENST00000564449, ENST00000566822, ENST00000568214, ENST00000569102, ENST00000569479, ENST00000569847, ENST00000570142, ENST00000893187, ENST00000893188, ENST00000893189, ENST00000893190, ENST00000893191, ENST00000893192, ENST00000893193, ENST00000893194, ENST00000918495, ENST00000965674

RefSeq mRNA: 2 — MANE Select: NM_016235 NM_001304771, NM_016235

CCDS: CCDS10581

Canonical transcript exons

ENST00000300571 — 4 exons

Exon	Start	End
ENSE00001110790	19861837	19861973
ENSE00001110792	19856691	19860544
ENSE00001308588	19884727	19884848
ENSE00003604789	19871816	19872846

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 99.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.2653 / max 1744.1204, expressed in 1199 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156603	31.7841	1190
156604	0.3598	186
156602	0.2611	74
156592	0.2500	100
156594	0.2002	99
207794	0.1754	115
156593	0.1518	59
156606	0.0540	33
156607	0.0289	10

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
medial globus pallidus	UBERON:0002477	99.87	gold quality
globus pallidus	UBERON:0001875	99.82	gold quality
inferior olivary complex	UBERON:0002127	99.80	gold quality
inferior vagus X ganglion	UBERON:0005363	99.70	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.69	gold quality
middle frontal gyrus	UBERON:0002702	99.58	gold quality
lateral globus pallidus	UBERON:0002476	99.55	gold quality
medulla oblongata	UBERON:0001896	99.52	gold quality
subthalamic nucleus	UBERON:0001906	99.44	gold quality
superior vestibular nucleus	UBERON:0007227	99.39	gold quality
ventral tegmental area	UBERON:0002691	99.37	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.35	gold quality
spinal cord	UBERON:0002240	99.33	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.33	gold quality
pons	UBERON:0000988	99.21	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.21	gold quality
corpus callosum	UBERON:0002336	99.21	gold quality
putamen	UBERON:0001874	99.20	gold quality
cranial nerve II	UBERON:0000941	99.15	gold quality
midbrain	UBERON:0001891	99.11	gold quality
substantia nigra	UBERON:0002038	99.08	gold quality
amygdala	UBERON:0001876	99.07	gold quality
caudate nucleus	UBERON:0001873	99.05	gold quality
hypothalamus	UBERON:0001898	99.05	gold quality
nucleus accumbens	UBERON:0001882	99.02	gold quality
substantia nigra pars compacta	UBERON:0001965	98.98	gold quality
Ammon’s horn	UBERON:0001954	98.83	gold quality
CA1 field of hippocampus	UBERON:0003881	98.71	gold quality
parotid gland	UBERON:0001831	98.69	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.69	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	250.72
E-MTAB-5061	yes	26.40
E-HCAD-35	yes	23.86
E-GEOD-84465	yes	23.29
E-GEOD-81547	yes	23.21
E-HCAD-10	yes	20.48
E-MTAB-9388	yes	14.81
E-ANND-3	yes	10.94
E-ENAD-27	yes	6.10

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

72 targeting GPRC5B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-1207-5P	99.49	69.11	2983

Literature-anchored findings (GeneRIF, showing 9)

• this study proposes that increased expression of GPRC5B contributes to the reduced insulin secretion and beta-cell viability observed in type-2 diabetes. (PMID:24404583)
• Caveolin-1 prevents palmitate-induced NF-kappaB signaling by inhibiting GPRC5B-phosphorylation. (PMID:30086884)
• We also found a novel association of rs12446632 near GPRC5B, which is highly expressed in adipose tissue and the central nervous system, with adult HDL cholesterol. (PMID:30947744)
• The GPRC5B is up-regulated by inflammatory signals and mechanical stress in NRCF, while GPRC5B modulates the inflammatory response of cardiac fibroblasts and the degradation of extracellular matrix-proteins in the mice heart. (PMID:31104767)
• GPRC5b is a novel podocyte-specific receptor that regulates inflammatory response in the glomerulus bymodulating the NF-kB signaling pathway. Upregulation of Gprc5b in human glomerulopathies suggests that it may play a role in their pathogenesis. (PMID:31285284)
• Orphan G Protein-Coupled Receptor GPRC5B Controls Smooth Muscle Contractility and Differentiation by Inhibiting Prostacyclin Receptor Signaling. (PMID:31941358)
• Identification of the GlialCAM interactome: the G protein-coupled receptors GPRC5B and GPR37L1 modulate megalencephalic leukoencephalopathy proteins. (PMID:34100078)
• Multi-Omics Analysis for Transcriptional Regulation of Immune-Related Targets Using Epigenetic Data: A New Research Direction. (PMID:35046932)
• GPRC5B (G protein-coupled receptor class C group 5 member B) suppresses glucose starvation-induced apoptosis in head-and-neck squamous cell carcinoma. (PMID:36682796)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gprc5bb	ENSDARG00000075141
danio_rerio	gprc5ba	ENSDARG00000077080
mus_musculus	Gprc5b	ENSMUSG00000008734
rattus_norvegicus	Gprc5b	ENSRNOG00000016013

Paralogs (3): GPRC5A (ENSG00000013588), GPRC5D (ENSG00000111291), GPRC5C (ENSG00000170412)

Protein

Protein identifiers

G-protein coupled receptor family C group 5 member B — Q9NZH0 (reviewed: Q9NZH0)

Alternative names: A-69G12.1, Retinoic acid-induced gene 2 protein

All UniProt accessions (6): Q9NZH0, H3BN33, H3BQV9, H3BSJ1, H3BT47, H3BT93

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor involved in the regulation of cell volume.

Subcellular location. Cell membrane. Cytoplasmic vesicle membrane.

Tissue specificity. Expression is high in kidney, pancreas, and testis, medium in brain, heart, prostate, small intestine, and spleen, low in liver, placenta, skeletal muscle, colon, ovary, and thymus, and not detectable in lung and peripheral leukocyte. According to PubMed:10945465, highly expressed in most brain areas examined, with the highest levels observed in corpus callosum, caudate nucleus, putamen, substantia nigra, thalamus, hippocampus, and spinal cord as well as in dorsal root ganglia (DRG). Expressed in glia limitans, ependymal cells, astrocyte cell bodies, the perivascular region in astrocyte endfeet, but not in neurons. In the periphery, expression levels are relatively low, compared to the CNS, with the strongest expression detected in pancreas, testis, uterus, and stomach.

Disease relevance. Megalencephalic leukoencephalopathy with subcortical cysts 3 (MLC3) [MIM:620447] An autosomal dominant disorder characterized by increased head circumference apparent in infancy, followed by progressive motor and cognitive decline in early childhood. Affected individuals either do not achieve walking or lose independent ambulation in the first or second decades. Cognitive impairment is variable and accompanied by poor speech and dysarthria. Most patients have early-onset seizures, which may be mild or refractory. Brain imaging shows unremitting megalencephalic leukoencephalopathy with subcortical cysts and swelling of the cerebral white matter. The disease is caused by variants affecting the gene represented in this entry.

Induction. By all-trans retinoic acid (ATRA).

Similarity. Belongs to the G-protein coupled receptor 3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NZH0-1	1	yes
Q9NZH0-2	2

RefSeq proteins (2): NP_001291700, NP_057319* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017978	GPCR_3_C	Domain
IPR051753	RA-inducible_GPCR3	Family

Pfam: PF00003

UniProt features (24 total): topological domain 8, transmembrane region 7, sequence variant 2, signal peptide 1, chain 1, region of interest 1, modified residue 1, glycosylation site 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZH0-F1	74.39	0.40

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 354

Glycosylation sites (1): 30

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 275 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, E2F_Q4, BROWNE_HCMV_INFECTION_4HR_UP, GCM_MAP4K4, E2F_Q4_01, WALLACE_PROSTATE_CANCER_RACE_UP, GCM_PTPRD, E2F4DP1_01, MODULE_64, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOCC_CELL_SURFACE, AP2_Q3, COLIN_PILOCYTIC_ASTROCYTOMA_VS_GLIOBLASTOMA_UP

GO Biological Process (10): cell volume homeostasis (GO:0006884), intracellular signal transduction (GO:0035556), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of neuron differentiation (GO:0045666), positive regulation of inflammatory response (GO:0050729), positive regulation of macrophage cytokine production (GO:0060907), positive regulation of protein tyrosine kinase activity (GO:0061098), positive regulation of canonical Wnt signaling pathway (GO:0090263)

GO Molecular Function (5): G protein-coupled receptor binding (GO:0001664), G protein-coupled receptor activity (GO:0004930), protein kinase binding (GO:0019901), protein kinase activator activity (GO:0030295), protein tyrosine kinase binding (GO:1990782)

GO Cellular Component (12): obsolete extracellular space (GO:0005615), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), plasma membrane (GO:0005886), cell surface (GO:0009986), cytoplasmic vesicle membrane (GO:0030659), signaling receptor complex (GO:0043235), membrane raft (GO:0045121), extracellular exosome (GO:0070062), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
signal transduction	2
nuclear lumen	2
cytoplasm	2
regulation of cell size	1
cellular homeostasis	1
intracellular anatomical structure	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
neuron differentiation	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
inflammatory response	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of inflammatory response	1
macrophage cytokine production	1
regulation of macrophage cytokine production	1
positive regulation of myeloid leukocyte cytokine production involved in immune response	1
protein tyrosine kinase activity	1
positive regulation of protein kinase activity	1
positive regulation of peptidyl-tyrosine phosphorylation	1
regulation of protein tyrosine kinase activity	1
positive regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
signaling receptor binding	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
kinase binding	1
protein kinase activity	1
kinase activator activity	1
protein kinase regulator activity	1

Protein interactions and networks

STRING

947 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPRC5B	IQCK	Q8N0W5	660
GPRC5B	FANCL	Q9NW38	625
GPRC5B	V9GXZ4	V9GXZ4	586
GPRC5B	TNNI3K	Q59H18	575
GPRC5B	SEC16B	Q96JE7	572
GPRC5B	TMEM160	Q9NX00	570
GPRC5B	ZNF608	Q9ULD9	570
GPRC5B	NEGR1	Q7Z3B1	566
GPRC5B	GPR158	Q5T848	564
GPRC5B	GNPDA2	Q8TDQ7	534
GPRC5B	NUDT3	O95989	528
GPRC5B	GPR156	Q8NFN8	528
GPRC5B	DNAJC27	Q9NZQ0	516
GPRC5B	GPR139	Q6DWJ6	508
GPRC5B	FAIM2	Q9BWQ8	479

IntAct

46 interactions, top by confidence:

A	B	Type	Score
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
RCAN1	PPP3CB	psi-mi:“MI:0914”(association)	0.660
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
GPRC5B	STXBP3	psi-mi:“MI:0914”(association)	0.530
TMEM171	THAP12	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
CD226	MEN1	psi-mi:“MI:0914”(association)	0.530
CSGALNACT2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
CHRND	TPST2	psi-mi:“MI:0914”(association)	0.530
KIAA2013	TMBIM6	psi-mi:“MI:0914”(association)	0.530
TSG101	GPRC5B	psi-mi:“MI:0407”(direct interaction)	0.440
GPRC5B	HSP90B1	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
GPRC5B	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	GPRC5B	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	GPRC5B	psi-mi:“MI:0915”(physical association)	0.400
GPRC5B	HTR2C	psi-mi:“MI:0915”(physical association)	0.370
FUCA2	GPRC5B	psi-mi:“MI:0915”(physical association)	0.370
TMEM120A	GPRC5B	psi-mi:“MI:0915”(physical association)	0.370
GPRC5B	C11orf71	psi-mi:“MI:0915”(physical association)	0.370
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
ADGRE5	TMEM223	psi-mi:“MI:0914”(association)	0.350
CD70	GXYLT2	psi-mi:“MI:0914”(association)	0.350
TNFRSF1A	KHNYN	psi-mi:“MI:0914”(association)	0.350

BioGRID (119): GPRC5B (Affinity Capture-MS), GPRC5B (Affinity Capture-MS), GPRC5B (Affinity Capture-MS), GPRC5B (Affinity Capture-MS), GPRC5B (Affinity Capture-MS), GPRC5B (Affinity Capture-MS), MPP7 (Affinity Capture-MS), GPRC5B (Affinity Capture-MS), GPRC5B (Affinity Capture-MS), GPRC5B (Affinity Capture-MS), GPRC5B (Affinity Capture-MS), GPRC5B (Affinity Capture-MS), STXBP1 (Affinity Capture-MS), STX4 (Affinity Capture-MS), SDCBP (Affinity Capture-MS)

ESM2 similar proteins: A2VE58, A3KQ86, A6H7B0, A6NC51, A6NDP7, A6NFC5, B1AQL3, B2RZ87, E9Q9H8, O14894, O43761, P0C5X8, P30408, P47987, Q08AU7, Q08DL4, Q13021, Q1HG44, Q2KIG8, Q2KJ98, Q3UUA0, Q49LS7, Q4VV71, Q58CW5, Q5RE43, Q5RFC1, Q5XGR0, Q63175, Q63ZU3, Q64302, Q6DFR5, Q7TQJ1, Q7Z7N9, Q8BHJ6, Q8K177, Q8R191, Q91X49, Q923Z0, Q96DZ7, Q9BSK0

Diamond homologs: Q2YDG0, Q3KRC4, Q8BHL4, Q8K3J9, Q8NFJ5, Q923Z0, Q9JIL6, Q9NQ84, Q9NZD1, Q9NZH0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

80 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	60
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2573133	NM_016235.3(GPRC5B):c.523ATC[3] (p.Ile176_Ala177insIle)	Pathogenic
2573134	NM_016235.3(GPRC5B):c.528_530dup (p.Ala177_Val178insAla)	Pathogenic

SpliceAI

692 predictions. Top by Δscore:

Variant	Effect	Δscore
16:19861835:A:AC	donor_gain	1.0000
16:19861835:ACGGT:A	donor_gain	1.0000
16:19861836:C:CG	donor_gain	1.0000
16:19861836:CG:C	donor_gain	1.0000
16:19861836:CGGT:C	donor_gain	1.0000
16:19861836:CGGTC:C	donor_gain	1.0000
16:19862002:CAT:C	acceptor_gain	1.0000
16:19862004:T:TC	acceptor_gain	1.0000
16:19871811:TTTA:T	donor_loss	1.0000
16:19871814:A:C	donor_loss	1.0000
16:19884721:ACTT:A	donor_loss	1.0000
16:19884722:CTTA:C	donor_loss	1.0000
16:19884723:TTA:T	donor_loss	1.0000
16:19884724:TAC:T	donor_loss	1.0000
16:19884725:A:AC	donor_gain	1.0000
16:19884725:A:AT	donor_loss	1.0000
16:19884726:C:CA	donor_loss	1.0000
16:19884726:C:CC	donor_gain	1.0000
16:19861828:GATAC:G	donor_loss	0.9900
16:19861829:ATACT:A	donor_loss	0.9900
16:19861830:TACT:T	donor_loss	0.9900
16:19861831:ACTTA:A	donor_loss	0.9900
16:19861832:CT:C	donor_loss	0.9900
16:19861833:TT:T	donor_loss	0.9900
16:19861834:TAC:T	donor_loss	0.9900
16:19861836:CGG:C	donor_gain	0.9900
16:19861971:GAG:G	acceptor_gain	0.9900
16:19861974:C:CC	acceptor_gain	0.9900
16:19861974:CTGGG:C	acceptor_loss	0.9900
16:19861975:T:G	acceptor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000166718 (16:19865322 G>A), RS1000276436 (16:19869203 C>A,T), RS1000344869 (16:19859536 G>A), RS1000361769 (16:19877255 CT>C,CTT), RS1000417351 (16:19877656 G>A,C), RS1000464141 (16:19875404 G>A), RS1000502824 (16:19868437 A>G), RS1000552772 (16:19864187 G>A,T), RS1000699492 (16:19875966 A>G,T), RS1000726305 (16:19874231 A>G), RS1000751996 (16:19876199 G>A), RS1000860912 (16:19887716 T>C), RS1001172157 (16:19856675 T>A), RS1001202529 (16:19874030 G>A,C), RS1001222492 (16:19863591 A>C,G)

Disease associations

OMIM: gene MIM:605948 | disease phenotypes: MIM:620447

GenCC curated gene-disease

Disease	Classification	Inheritance
megalencephalic leukoencephalopathy with subcortical cysts 3	Strong	Autosomal dominant
megalencephalic leukoencephalopathy with subcortical cysts 1	Strong	Autosomal dominant

Mondo (2): megalencephalic leukoencephalopathy with subcortical cysts 3 (MONDO:0957533), megalencephalic leukoencephalopathy with subcortical cysts 1 (MONDO:0024555)

Orphanet (0):

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000256	Macrocephaly
HP:0000716	Depression
HP:0000726	Dementia
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001270	Motor delay
HP:0001332	Dystonia
HP:0002015	Dysphagia
HP:0002061	Lower limb spasticity
HP:0002063	Rigidity
HP:0002070	Limb ataxia
HP:0002312	Clumsiness
HP:0002333	Motor deterioration
HP:0002505	Loss of ambulation
HP:0003593	Infantile onset
HP:0006986	Upper limb spasticity
HP:0031936	Delayed ability to walk
HP:6000461	Cerebral subcortical cyst

GWAS associations

34 associations (top):

Study	Trait	p-value
GCST000830_17	Body mass index	3.000000e-21
GCST001762_667	Obesity-related traits	5.000000e-06
GCST001953_34	Obesity	4.000000e-09
GCST001953_40	Obesity	2.000000e-10
GCST001953_55	Obesity	4.000000e-12
GCST002541_106	Menarche (age at onset)	1.000000e-08
GCST002783_18	Body mass index	1.000000e-13
GCST002783_364	Body mass index	2.000000e-19
GCST002783_499	Body mass index	1.000000e-18
GCST002783_94	Body mass index	2.000000e-10
GCST004065_34	Waist circumference	1.000000e-09
GCST004065_38	Waist circumference	5.000000e-13
GCST004065_40	Waist circumference	9.000000e-07
GCST004066_125	Hip circumference	1.000000e-11
GCST004066_16	Hip circumference	4.000000e-10
GCST004557_109	Body mass index	5.000000e-06
GCST004557_140	Body mass index	3.000000e-07
GCST004557_210	Body mass index	3.000000e-06
GCST004557_241	Body mass index	6.000000e-11
GCST004557_30	Body mass index	3.000000e-10
GCST004557_68	Body mass index	1.000000e-06
GCST004558_138	Body mass index (joint analysis main effects and physical activity interaction)	5.000000e-06
GCST004558_161	Body mass index (joint analysis main effects and physical activity interaction)	1.000000e-10
GCST004558_27	Body mass index (joint analysis main effects and physical activity interaction)	6.000000e-10
GCST004559_105	Body mass index in physically active individuals	1.000000e-09
GCST004559_194	Body mass index in physically active individuals	3.000000e-06
GCST004559_23	Body mass index in physically active individuals	3.000000e-09
GCST006802_2	Body mass index	2.000000e-06
GCST007485_15	Anthropometric traits	1.000000e-07
GCST007490_24	Anthropometric traits (multi-trait analysis)	2.000000e-15

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004703	age at menarche
EFO:0008002	physical activity measurement
EFO:0004324	body weights and measures
EFO:0004338	body weight
EFO:0004344	birth weight
EFO:0008202	L-Selectin measurement
EFO:0009819	comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523926 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Class C Orphans

CTD chemical–gene interactions

57 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects methylation, decreases expression, affects cotreatment, increases abundance	5
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	4
Aflatoxin B1	affects expression, increases expression, increases methylation	4
bisphenol A	decreases expression, increases expression	3
perfluorooctane sulfonic acid	decreases expression, increases expression	3
Valproic Acid	affects expression, decreases expression	3
trichostatin A	affects cotreatment, decreases expression	2
Decitabine	affects expression, decreases expression, decreases reaction	2
Vorinostat	decreases expression, affects cotreatment	2
Acetaminophen	increases expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Progesterone	affects cotreatment, decreases expression, increases expression	2
tert-Butylhydroperoxide	increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
methyleugenol	increases expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	increases expression, affects cotreatment	1
sulforaphane	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
nefazodone	affects cotreatment, increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
incobotulinumtoxinA	decreases expression	1
(+)-JQ1 compound	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4883477	Binding	PRESTO-Tango GPCRome screening (GPRC5B)	Data for DCP probe UCSF924

Cellosaurus cell lines

1 cell lines: 1 telomerase immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C3K9	N/Tert-1 GPRC5B	Telomerase immortalized cell line	Male

Clinical trials (associated diseases)

2 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project