OXGR1

Chr 13AD

oxoglutarate receptor 1

Also known as: CAON2, GPR80, GPR99, P2RY15, P2Y15, aKGR

NCBI Gene: 27199 ENSG00000165621 UniProt: Q96P68 OMIM: 606922

The protein functions as a G protein-coupled receptor that binds dicarboxylates including alpha-ketoglutarate, itaconate, and leukotriene E4, regulating renal salt reabsorption, respiratory mucociliary clearance, and mucin release in response to allergens. Mutations cause autosomal dominant nephrolithiasis with calcium oxalate stones and nephrocalcinosis. The gene shows low constraint to loss-of-function variation (pLI 0.00005, LOEUF 1.588), suggesting tolerance to protein-truncating variants.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Nephrolithiasis, calcium oxalate, 2, with nephrocalcinosisMIM #620374

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Nephrolithiasis, calcium oxalate, 2, with nephrocalcinosis; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.59

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.59LOEUF

pLI 0.000

Z-score 0.35

OE 0.87 (0.49–1.59)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.09Z-score

OE missense 0.98 (0.87–1.11)

182 obs / 185.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.87 (0.49–1.59)

0≤0.351.4

Missense OE?0.98 (0.87–1.11)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 7 / 8.1Missense obs/exp: 182 / 185.4Syn Z: 0.39

Background carrier burden — how many people carry a rare variant somewhere in OXGR1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

432 rare PASS variants

Rare truncating (LoF)

1 in 750

54 rare PASS variants

Rare synonymous (reference)

1 in 290

201 rare PASS variants

Rare missense and truncating variants are carried at similar rates in OXGR1; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 200	1 in 350
South Asian	~43k	1 in 140	1 in 1,200
Remaining (unassigned)	~30k	1 in 99	1 in 1,000
European (Finnish)	~27k	1 in 330	none seen
Admixed American	~22k	1 in 110	1 in 3,800
African / African American	~21k	1 in 150	1 in 730
East Asian	~20k	1 in 110	1 in 1,800
Ashkenazi Jewish	~13k	1 in 1,000	1 in 1,600
Middle Eastern	~2,884	1 in 100	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓