ADIPOR2

Chr 12

adiponectin receptor 2

Also known as: ACDCR2, PAQR2

NCBI Gene: 79602 ENSG00000006831 UniProt: Q86V24 OMIM: 607946

ADIPOR2 encodes adiponectin receptor 2, which binds the hormone adiponectin and activates signaling pathways that regulate fatty acid oxidation and glucose uptake. Mutations in this gene cause autosomal recessive diabetes mellitus. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.518), suggesting some intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, UniProt

The adiponectin receptors, ADIPOR1 (MIM 607945) and ADIPOR2, serve as receptors for globular and full-length adiponectin (MIM 605441) and mediate increased AMPK (see MIM 602739) and PPAR-alpha (PPARA; MIM 170998) ligand activities, as well as fatty acid oxidation and glucose uptake by adiponectin (Yamauchi et al., 2003 [PubMed 12802337]).[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.52

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.52LOEUF

pLI 0.362

Z-score 3.01

OE 0.23 (0.11–0.52)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.65Z-score

OE missense 0.49 (0.42–0.58)

105 obs / 214.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.23 (0.11–0.52)

0≤0.351.4

Missense OE?0.49 (0.42–0.58)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 4 / 17.7Missense obs/exp: 105 / 214.3Syn Z: 1.08

Background carrier burden — how many people carry a rare variant somewhere in ADIPOR2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 490

307 rare PASS variants

Rare truncating (LoF)

1 in 6,200

53 rare PASS variants

Rare synonymous (reference)

1 in 270

175 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ADIPOR2. 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 550	1 in 5,300
South Asian	~43k	1 in 440	1 in 7,000
Remaining (unassigned)	~30k	1 in 720	≈ 1 in 15,000
European (Finnish)	~27k	1 in 300	≈ 1 in 13,000
Admixed American	~22k	1 in 280	1 in 1,900
African / African American	~21k	1 in 460	none seen
East Asian	~20k	1 in 240	1 in 1,900
Ashkenazi Jewish	~13k	≈ 1 in 4,400	none seen
Middle Eastern	~2,884	1 in 410	none seen

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 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓