ADCYAP1R1

Chr 7

ADCYAP receptor type I

Also known as: PAC1, PAC1R, PACAPR, PACAPRI

NCBI Gene: 117ENSG00000078549UniProt: P41586

This gene encodes type I adenylate cyclase activating polypeptide receptor, which is a membrane-associated protein and shares significant homology with members of the glucagon/secretin receptor family. This receptor mediates diverse biological actions of adenylate cyclase activating polypeptide 1 and is positively coupled to adenylate cyclase. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Dec 2010]

0
Active trials
24
Pathogenic / LP
82
ClinVar variants
10
Pubs (1 yr)
1.4
Missense Z
0.87
LOEUF
Clinical Summary— ADCYAP1R1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 52 VUS of 82 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.87LOEUF
pLI 0.000
Z-score 2.17
OE 0.60 (0.42–0.87)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.39Z-score
OE missense 0.77 (0.69–0.86)
219 obs / 285.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.60 (0.42–0.87)
0≤0.351.4
Missense OE0.77 (0.69–0.86)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 20 / 33.5Missense obs/exp: 219 / 285.1Syn Z: -0.13
DNGOF
DN
0.86top 5%
GOF
0.84top 5%
LOF
0.1895th %ile

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

DNprediction above median
GOFprediction 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

82 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic5
VUS52
Likely Benign4
Benign2
19
Pathogenic
5
Likely Pathogenic
52
VUS
4
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
5
0
5
VUS
0
45
7
0
52
Likely Benign
0
3
1
0
4
Benign
0
0
1
1
2
Total04833182

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

View in ClinVar →

ADCYAP1R1 · 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 →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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