ADCY2

Chr 5

adenylate cyclase 2

Also known as: AC2, HBAC2

NCBI Gene: 108ENSG00000078295UniProt: Q08462

This gene encodes a member of the family of adenylate cyclases, which are membrane-associated enzymes that catalyze the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). This enzyme is insensitive to Ca(2+)/calmodulin, and is stimulated by the G protein beta and gamma subunit complex. [provided by RefSeq, Jul 2008]

199
ClinVar variants
104
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— ADCY2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
104 Pathogenic / Likely Pathogenic· 80 VUS of 199 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.26LOEUF
pLI 0.999
Z-score 5.89
OE 0.14 (0.08–0.26)
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.
4.25Z-score
OE missense 0.53 (0.48–0.58)
343 obs / 647.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.14 (0.08–0.26)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.53 (0.48–0.58)
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.0.93
0≤1.21.6
LoF obs/exp: 8 / 55.2Missense obs/exp: 343 / 647.0Syn Z: 0.87

ClinVar Variant Classifications

199 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic103
Likely Pathogenic1
VUS80
Likely Benign9
Benign6
103
Pathogenic
1
Likely Pathogenic
80
VUS
9
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
103
0
103
Likely Pathogenic
0
0
1
0
1
VUS
0
72
7
1
80
Likely Benign
0
3
3
3
9
Benign
0
0
4
2
6
Total0751186199

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

View in ClinVar →

Protein Context — Lollipop Plot

ADCY2 · 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
Identification of fusions with potential clinical significance in melanoma.
Moran JMT et al.·Mod Pathol
2022
A bipolar disorder-associated missense variant alters adenylyl cyclase 2 activity and promotes mania-like behavior.
Sen P et al.·Mol Psychiatry
2025
Role of chromosomal imbalances in the pathogenesis of DSD: A retrospective analysis of 115 prenatal samples.
Mary L et al.·Eur J Med Genet
2023Review
A Multicenter Analysis of Abnormal Chromosomal Microarray Findings in Congenital Heart Disease.
Landis BJ et al.·J Am Heart Assoc
2023
Genome-wide analysis of genetic determinants of circulating factor VII-activating protease (FSAP) activity.
Olsson M et al.·J Thromb Haemost
2018
Investigation of the impact of an ADCY2 polymorphism as a predictive biomarker in bipolar disorder, suicide tendency and response to lithium carbonate therapy: the first report from Iran.
Aghabozorg Afjeh SS et al.·Pharmacogenomics
2020
High-resolution chromosome ideogram representation of recognized genes for bipolar disorder.
Douglas LN et al.·Gene
2016
Identification of novel germline polymorphisms governing capecitabine sensitivity.
O'Donnell PH et al.·Cancer
2012Meta-analysis
Genetic markers of comorbid depression and alcoholism in women.
Procopio DO et al.·Alcohol Clin Exp Res
2013
Resequencing and association analysis of coding regions at twenty candidate genes suggest a role for rare risk variation at AKAP9 and protective variation at NRXN1 in schizophrenia susceptibility.
Suárez-Rama JJ et al.·J Psychiatr Res
2015Meta-analysis
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Germline lung cancer SNPs dysregulate known (LATS1) and novel (ADCY2) oncogenes through distal, spatially-constrained eQTLs.
Khoo A et al.·Cancer Genet
2026
Integrated bioinformatics investigation of adenylyl cyclase family co-expression network in bladder cancer followed by preliminary validation of member 2 (ADCY2) in tumorigenesis and prognosis.
Wang H et al.·Transl Cancer Res
2024🔓 Open Access
circSLC25A13 acts as a ceRNA to regulate AML progression via miR-616-3p/ADCY2 axis.
Wei W et al.·Mol Carcinog
2023
MiR-1224-5p modulates osteogenesis by coordinating osteoblast/osteoclast differentiation via the Rap1 signaling target ADCY2.
Hu L et al.·Exp Mol Med
2022🔓 Open Access
A Novel Lipid Prognostic Signature of ADCY2, LIPE, and OLR1 in Head and Neck Squamous Cell Carcinoma.
Gao X et al.·Front Oncol
2021🔓 Open Access
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