ADCY9

Chr 16

adenylate cyclase 9

Also known as: AC9, ACIX

NCBI Gene: 115ENSG00000162104UniProt: O60503

Adenylate cyclase is a membrane bound enzyme that catalyses the formation of cyclic AMP from ATP. It is regulated by a family of G protein-coupled receptors, protein kinases, and calcium. The type 9 adenylyl cyclase is a widely distributed adenylyl cyclase, and it is stimulated by beta-adrenergic receptor activation but is insensitive to forskolin, calcium, and somatostatin. [provided by RefSeq, Jul 2008]

246
ClinVar variants
44
Pathogenic / LP
0.98
pLI score· haploinsufficient
0
Active trials
Clinical Summary— ADCY9
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
44 Pathogenic / Likely Pathogenic· 170 VUS of 246 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.31LOEUF
pLI 0.979
Z-score 5.28
OE 0.17 (0.10–0.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.25Z-score
OE missense 0.88 (0.83–0.93)
730 obs / 831.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.17 (0.10–0.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.83–0.93)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.19
0≤1.21.6
LoF obs/exp: 8 / 47.2Missense obs/exp: 730 / 831.1Syn Z: -2.93

ClinVar Variant Classifications

246 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic41
Likely Pathogenic3
VUS170
Likely Benign21
Benign11
41
Pathogenic
3
Likely Pathogenic
170
VUS
21
Likely Benign
11
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
41
0
41
Likely Pathogenic
0
0
3
0
3
VUS
0
160
10
0
170
Likely Benign
0
10
4
7
21
Benign
0
1
0
10
11
Total01715817246

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

View in ClinVar →

Protein Context — Lollipop Plot

ADCY9 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The rs2601796 variant in ADCY9 gene is associated with severe asthma and less bronchodilator response.
Teixeira HMP et al.·Gene
2023
Advancing Beyond Failed High-density Lipoprotein Clinical Trials to Pharmacogenetic Studies of ADCY9 and Cholesterol Ester Transfer Protein Inhibition.
Black DM et al.·J Cardiovasc Pharmacol
2021Review
An Ile to Met polymorphism in ADCY9 promotes airway obstruction and remodeling in asthma.
Liang LM et al.·Biochim Biophys Acta Mol Basis Dis
2025Functional
A sex-specific evolutionary interaction between ADCY9 and CETP.
Gamache I et al.·Elife
2021
Pharmacogenomic approaches to lipid-regulating trials.
Bertrand MJ et al.·Curr Opin Lipidol
2016Review
Role of the ADCY9 gene in cardiac abnormalities of the Rubinstein-Taybi syndrome.
Wu Y et al.·Orphanet J Rare Dis
2020Case report
ADCY9 Genetic Variants and Cardiovascular Outcomes With Evacetrapib in Patients With High-Risk Vascular Disease: A Nested Case-Control Study.
Nissen SE et al.·JAMA Cardiol
2018Cohort
Combined pharmacogenetic effect of ADCY9 and ADRB2 gene polymorphisms on the bronchodilator response to inhaled combination therapy.
Kim SH et al.·J Clin Pharm Ther
2011Clinical trial
Pharmacogenomic determinants of the cardiovascular effects of dalcetrapib.
Tardif JC et al.·Circ Cardiovasc Genet
2015Clinical trial
Pharmacogenetics of inhaled long-acting beta2-agonists in asthma: A systematic review.
Slob EMA et al.·Pediatr Allergy Immunol
2018Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools