ADCY3

Chr 2AR

adenylate cyclase 3

Also known as: AC-III, AC3, BMIQ19

Adenylyl cyclase 3 catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling and is specifically activated by G alpha protein GNAL in olfactory epithelium, playing roles in olfaction, insulin regulation, and body fat accumulation. Autosomal recessive mutations cause obesity susceptibility. This gene is not highly constrained against loss-of-function variants.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

{Obesity, susceptibility to, BMIQ19}MIM #617885
AR
1
Active trials
27
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.68
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryADCY3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.68LOEUF
pLI 0.000
Z-score 3.47
OE 0.49 (0.360.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.57Z-score
OE missense 0.73 (0.680.79)
541 obs / 737.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.49 (0.360.68)
00.351.4
Missense OE0.73 (0.680.79)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 27 / 54.7Missense obs/exp: 541 / 737.6Syn Z: -0.94
DN
0.7034th %ile
GOF
0.76top 25%
LOF
0.3164th %ile

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

GOFprediction above median
DNprediction 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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ADCY3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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