ADCY1

Chr 7

adenylate cyclase 1

Also known as: AC1, DFNB44

NCBI Gene: 107ENSG00000164742UniProt: Q08828

This gene encodes a member of the of adenylate cyclase gene family that is primarily expressed in the brain. This protein is regulated by calcium/calmodulin concentration and may be involved in brain development. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

Primary Disease Associations & Inheritance

UniProtDeafness, autosomal recessive, 44
415
ClinVar variants
23
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— ADCY1
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Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
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.
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ClinVar Variants
23 Pathogenic / Likely Pathogenic· 160 VUS of 415 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
0.27LOEUF
pLI 0.997
Z-score 5.51
OE 0.14 (0.08–0.27)
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.
4.38Z-score
OE missense 0.52 (0.48–0.57)
347 obs / 664.8 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 (0.08–0.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.52 (0.48–0.57)
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.0.99
0≤1.21.6
LoF obs/exp: 7 / 48.4Missense obs/exp: 347 / 664.8Syn Z: 0.19

ClinVar Variant Classifications

415 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic1
VUS160
Likely Benign184
Benign46
Conflicting2
22
Pathogenic
1
Likely Pathogenic
160
VUS
184
Likely Benign
46
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
1
0
1
VUS
1
145
12
2
160
Likely Benign
0
5
78
101
184
Benign
0
2
39
5
46
Conflicting
—2
Total1152152108415

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

View in ClinVar →

Protein Context — Lollipop Plot

ADCY1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Circ-LTBP1 is involved in doxorubicin-induced intracellular toxicity in cardiomyocytes via miR-107/ADCY1 signal.
Li C et al.·Mol Cell Biochem
2022
Adenylate cyclase 1 (ADCY1) mutations cause recessive hearing impairment in humans and defects in hair cell function and hearing in zebrafish.
Santos-Cortez RL et al.·Hum Mol Genet
2014Functional
MicroRNA-23a-3p Inhibits Mucosal Melanoma Growth and Progression through Targeting Adenylate Cyclase 1 and Attenuating cAMP and MAPK Pathways.
Ma M et al.·Theranostics
2019
Methylated DNA in Pancreatic Juice Distinguishes Patients With Pancreatic Cancer From Controls.
Majumder S et al.·Clin Gastroenterol Hepatol
2020Cohort
Forskolin alleviates cholestatic liver disease by inhibiting the Hippo/YAP-mediated ductular reaction and fibrosis progression.
El-Maadawy WH et al.·Eur J Pharmacol
2025
High-resolution chromosome ideogram representation of recognized genes for bipolar disorder.
Douglas LN et al.·Gene
2016
Cognitive predictors of mental health trajectories are mediated by inferior frontal and occipital development during adolescence.
Li Q et al.·Mol Psychiatry
2025
Genetic analyses of the endocannabinoid pathway in association with affective phenotypic variants.
Lazary J et al.·Neurosci Lett
2021
Identification of Vascular Genes Differentially Expressed in the Brain of Patients with Alzheimer's Disease.
Jara-Medina K et al.·Curr Vasc Pharmacol
2024Cohort
Genetic markers of comorbid depression and alcoholism in women.
Procopio DO et al.·Alcohol Clin Exp Res
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
The ADCY1-mediated cAMP signaling pathway mediates functional effects of montelukast treatment in brain organoids.
Xu Z et al.·Cell Mol Life Sci
2025🔓 Open AccessFunctional
Ginsenoside Rg1 alleviates cognitive impairment in vascular dementia by modulating Adcy1/Kdr-mediated cholinergic synapse and PI3K-AKT pathway.
Wang Y et al.·Phytomedicine
2025
The Role of ADCY1 in Regulating the Sensitivity of Platinum-Based Chemotherapy in NSCLC.
Zou T et al.·Pharmaceuticals (Basel)
2024🔓 Open Access
Ca2+-stimulated ADCY1 and ADCY8 regulate distinct aspects of synaptic and cognitive flexibility.
Zhang M et al.·Front Cell Neurosci
2023🔓 Open Access
Downregulated INHBB in endometrial tissue of recurrent implantation failure patients impeded decidualization through the ADCY1/cAMP signalling pathway.
Zhang H et al.·J Assist Reprod Genet
2023🔓 Open AccessCohort
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