OXGR1

protein-coding

oxoglutarate receptor 1, the group of Oxoglutarate receptor

Gene summary

This gene encodes a G protein-coupled receptor (GPCR) that belongs to the oxoglutarate receptor family within the GPCR superfamily. The encoded protein is activated by the citric acid intermediate, oxoglutarate, as well as several cysteinyl leukotrienes, including leukotrienes E4, C4 and D4, which are implicated in many inflammatory disorders. In mice, a knock-out of this gene leads to middle ear inflammation, changes in the mucosal epithelium, and an increase in fluid behind the eardrum, and is associated with hearing loss. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

Previous symbols:

GPR99
GPR80

MANE transcript

NM_001346194.2

Inheritance

ClinVar variants

P:4U:60B:4

Top phenotype

Nephrolithiasis, calcium oxalate, 2, with nephrocalcinosis

gnomAD constraint

pLI —, LoF o/e 0.87

Max pathogenic AF

—

Genomic locus

chr13:96,985,713-96,994,730

External References & Databases

Ensembl (ENSG00000165621)

Transcript & Mutation Effects

hg38 • Region Span ~9.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

nephrolithiasis, calcium oxalate, 2, with or without nephrocalcinosisMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0958191

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Nephrolithiasis, calcium oxalate, 2, with nephrocalcinosisAD

Manifestation: Renal

Intervention: Renal

Rationale: The condition involves predisposition to nephrocalcinosis and nephrolithiasis, and management may help manage renal and related sequelae

Refs: 36571463

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to OXGR1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 61

Nephrolithiasis, calcium oxalate, 2, with or without nephrocalcinosisTotal: 6

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001346194.2. 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				1 clinvar		1
missense	1 clinvar	2 clinvar	60 clinvar	2 clinvar		65
nonsense						0
start loss						0
frameshift	1 clinvar				1 clinvar	2
splice donor/acceptor (+/-2bp)						0
Total	2	2	60	3	1	68

Highest pathogenic variant AF is 0.0012453763

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001346194.2	RefSeq	NP_001333123.1	1	MANE Select
ENST00000541038.2	Ensembl	ENSP00000437356.2	1	MANE Select
NM_001346195.2	RefSeq	NP_001333124.1	1	Standard
NM_001346196.2	RefSeq	NP_001333125.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by GPCR
Signal Transduction
Class A/1 (Rhodopsin-like receptors)
GPCR ligand binding
G alpha (i) signalling events

Biological Process

G protein-coupled receptor signaling pathway

Molecular Function

G protein-coupled receptor activity

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000298440
Coding exons: 1
Length: 9012
Individuals with no LoFs: 123023
Homozygous LoFs: 61
Heterozygous LoFs: 2663
Defined: 125747
p: 0.0109

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0875	182	185	0.982	0.00000957	2215
Missense (PolyPhen)		51	63.412	0.80427		772
Synonymous	0.390	70	74.3	0.942	0.00000404	681
Loss of Function	0.354	7	8.09	0.866	5.04e-7	96

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00092	0.00092	rare
Latino/Admixed American	0.019	0.018	notable
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.066	0.066	notable
Finnish	0.027	0.028	notable
European (Non-Finnish)	0.0019	0.0019	notable
South Asian	0.0020	0.0019	notable
Other	0.0055	0.0056	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for alpha-ketoglutarate. Seems to act exclusively through a G(q)-mediated pathway (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.114

Intolerance Scores

LoFtool: 0.513
RVIS EVS: -0.52
RVIS percentile EVS: 21.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.279

Gene Damage Prediction

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