CMKLR2

Chr 2

chemerin chemokine-like receptor 2

Also known as: GPR1

NCBI Gene: 2825 ENSG00000183671 UniProt: P46091 OMIM: 600239

CMKLR2 encodes a G-protein coupled receptor that binds the adipokine chemerin and regulates inflammation and energy homeostasis, and also serves as a receptor for TAFA1 to mediate neuronal stem cell proliferation and differentiation. The gene is not highly constrained against loss-of-function variants and currently no established Mendelian diseases have been definitively linked to CMKLR2 mutations in pediatric patients.

OMIM ResearchSummary from RefSeq, UniProt

Enables adipokinetic hormone binding activity and adipokinetic hormone receptor activity. Predicted to be involved in glucose homeostasis and neuropeptide signaling pathway. Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.48

Clinical Summary— CMKLR2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

54 VUS of 59 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.48LOEUF

pLI 0.000

Z-score 0.44

OE 0.85 (0.51–1.48)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.01Z-score

OE missense 1.00 (0.89–1.13)

182 obs / 181.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.85 (0.51–1.48)

0≤0.351.4

Missense OE?1.00 (0.89–1.13)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 9 / 10.5Missense obs/exp: 182 / 181.5Syn Z: 0.18

This gene — mechanism propensity

0.78top 25%

GOF

0.76top 25%

LOF

0.2189th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

59 submitted variants in ClinVar

ClinVar

Classification Summary

VUS54

Likely Benign1

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	0	54	54
Likely Benign	1	0	1
Benign	0	1	1
Total	1	55	56

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

26 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap CMKLR2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →