ADIPOQ

Chr 3AD

adiponectin, C1Q and collagen domain containing

Also known as: ACDC, ACRP30, ADIPQTL1, ADPN, APM-1, APM1, GBP28

NCBI Gene: 9370 ENSG00000181092 UniProt: Q15848 OMIM: 605441

This gene is expressed in adipose tissue exclusively. It encodes a protein with similarity to collagens X and VIII and complement factor C1q. The encoded protein circulates in the plasma and is involved with metabolic and hormonal processes. Mutations in this gene are associated with adiponectin deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Apr 2010]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismADLOEUF 1.911 OMIM phenotype

Clinical Summary— ADIPOQ

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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

2 unique Pathogenic / Likely Pathogenic· 22 VUS of 37 total submissions

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Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

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?

1.91LOEUF

pLI 0.000

Z-score -1.02

OE 1.39 (0.85–1.91)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.13Z-score

OE missense 1.03 (0.90–1.18)

149 obs / 144.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.39 (0.85–1.91)

0≤0.351.4

Missense OE?1.03 (0.90–1.18)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 11 / 7.9Missense obs/exp: 149 / 144.6Syn Z: 0.05

This gene — mechanism propensity

0.7326th %ile

GOF

0.6541th %ile

LOF

0.4038th %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 · 1 literature citation

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.

Literature Evidence

DNA dominant negative ADIPOQ mutation in a diabetic family with renal disease, hypoadiponectinemia, and hyperceramidemia.1

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

References

1.PMID 35869090 ↗

ClinVar Variant Classifications

37 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS22

Likely Benign7

Benign3

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	1	1	0	2
Likely Pathogenic	0	0	0	0
VUS	2	20	0	22
Likely Benign	0	3	4	7
Benign	0	2	1	3
Total	3	26	5	34

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

View in ClinVar →

43 pathogenic / likely-pathogenic (of 49) ClinVar copy-number / structural variants overlap ADIPOQ — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →