GPR88

protein-coding

G protein-coupled receptor 88, the group of G protein-coupled receptors, Class A orphans

Gene summary

The protein encoded by this gene is a G protein-coupled receptor found almost exclusively in the striatum, a brain structure that controls motor function and cognition. Defects in this gene have been associated with chorea, speech delay, and learning difficulties, as well as some neuropsychiatric disorders. [provided by RefSeq, Mar 2017]

MANE transcript

NM_022049.3

Inheritance

ClinVar variants

P:1U:58B:41

Top phenotype

Chorea, childhood-onset, with psychomotor retardation

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr1:100,538,139-100,542,021

External References & Databases

Ensembl (ENSG00000181656)

Transcript & Mutation Effects

hg38 • Region Span ~3.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

chorea, childhood-onset, with psychomotor retardationLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014839

Submitter: Ambry Genetics

chorea, childhood-onset, with psychomotor retardationLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0014839

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Chorea, childhood-onset, with psychomotor retardationAR

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: 27123486

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GPR88 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 77

not specifiedTotal: 35

Chorea, childhood-onset, with psychomotor retardationTotal: 1

GPR88-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022049.3. 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				39 clinvar	2 clinvar	41
missense			58 clinvar			58
nonsense	1 clinvar					1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	0	58	39	2	100

Highest pathogenic variant AF is 0.0000028451486

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022049.3	RefSeq	NP_071332.2	1	MANE Select
ENST00000315033.5	Ensembl	ENSP00000314223.4	1	MANE Select
ENST00001145372.1	Ensembl	ENSP00000806377.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

GPCRs, Other

Biological Process

G protein-coupled receptor signaling pathway
phototransduction
locomotory behavior
detection of visible light
neuronal action potential

Molecular Function

motor activity
G protein-coupled photoreceptor activity

Cellular Component

cellular_component
nucleus
cytoplasm
plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000315033
Coding exons: 1
Length: 3882
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.03	65	179	0.363	0.00000823	2284
Missense (PolyPhen)		17	52.367	0.32463		596
Synonymous	-0.371	99	94.4	1.05	0.00000456	933
Loss of Function	2.47	1	8.99	0.111	3.94e-7	83

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable G-protein coupled receptor implicated in a large repertoire of behavioral responses that engage motor activities, spatial learning, and emotional processing. May play a role in the regulation of cognitive and motor function. {ECO:0000250|UniProtKB:Q9EPB7, ECO:0000250|UniProtKB:Q9ESP4}.;

Recessive Scores

pRec: 0.111

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.307

Gene Damage Prediction

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