ADCY5

Chr 3

adenylate cyclase 5

Also known as: AC5, DSKOD, FDFM

NCBI Gene: 111ENSG00000173175UniProt: O95622

This gene encodes a member of the membrane-bound adenylyl cyclase enzymes. Adenylyl cyclases mediate G protein-coupled receptor signaling through the synthesis of the second messenger cAMP. Activity of the encoded protein is stimulated by the Gs alpha subunit of G protein-coupled receptors and is inhibited by protein kinase A, calcium and Gi alpha subunits. Single nucleotide polymorphisms in this gene may be associated with low birth weight and type 2 diabetes. Alternatively spliced transcript variants that encode different isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtDyskinesia with orofacial involvement, autosomal recessive
UniProtDyskinesia with orofacial involvement, autosomal dominant
UniProtNeurodevelopmental disorder with hyperkinetic movements and dyskinesia

Clinical highlights

Gene-disease validity (ClinGen)
dyskinesia with orofacial involvement · SDDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.
0
Active trials
—
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.25
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
📖
GeneReview available — ADCY5
Authoritative clinical overview · Recommended first read
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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?
0.25LOEUF
pLI 0.999
Z-score 5.77
OE 0.14 (0.08–0.25)
Highly constrained

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

Missense Constraint?
3.40Z-score
OE missense 0.65 (0.60–0.70)
491 obs / 754.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.14 (0.08–0.25)
0≤0.351.4
Missense OE?0.65 (0.60–0.70)
0≤0.61.4
Synonymous OE?0.99
0≤1.21.6
LoF obs/exp: 7 / 51.8Missense obs/exp: 491 / 754.1Syn Z: 0.09

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ADCY5 · protein map & ClinVar variants

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

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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients