ADCYAP1

protein-coding

adenylate cyclase activating polypeptide 1, the group of Neuropeptides

Gene summary

This gene encodes a secreted proprotein that is further processed into multiple mature peptides. These peptides stimulate adenylate cyclase and increase cyclic adenosine monophosphate (cAMP) levels, resulting in the transcriptional activation of target genes. The products of this gene are key mediators of neuroendocrine stress responses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2013]

MANE transcript

NM_001099733.2

Inheritance

—

ClinVar variants

U:23B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr18:904,871-912,172

External References & Databases

Ensembl (ENSG00000141433)

Transcript & Mutation Effects

hg38 • Region Span ~7.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ADCYAP1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 25

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001099733.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			23 clinvar	1 clinvar		24
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	23	2	0	25

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001099733.2	RefSeq	NP_001093203.1	4	MANE Select
ENST00000450565.8	Ensembl	ENSP00000411658.3	4	MANE Select
NM_001117.5	RefSeq	NP_001108.2	4	Standard
ENST00000579794.1	Ensembl	ENSP00000462647.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
adcyap1b	Danio rerio	Structure: forebrain Quality: deformed abnormal

Gene / Model

Organism

Observed Phenotype

adcyap1b

Danio rerio

Structure: forebrain

Quality: deformed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Renin secretion - Homo sapiens (human)
Insulin secretion - Homo sapiens (human)
Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways
Signaling by GPCR
Activation of TRKA receptors

Biological Process

G protein-coupled receptor signaling pathway
adenylate cyclase-activating G protein-coupled receptor signaling pathway
activation of adenylate cyclase activity
positive regulation of cytosolic calcium ion concentration
neuropeptide signaling pathway

Molecular Function

signaling receptor binding
neuropeptide hormone activity
protein binding
pituitary adenylate cyclase activating polypeptide activity
peptide hormone receptor binding

Cellular Component

extracellular region
neuron projection
perikaryon

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000579794
Coding exons: 4
Length: 7230
Individuals with no LoFs: 125726
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125731
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.433	112	99.8	1.12	0.00000449	1086
Missense (PolyPhen)		16	31.006	0.51602		352
Synonymous	-2.77	70	46.1	1.52	0.00000217	362
Loss of Function	1.96	1	6.30	0.159	2.66e-7	84

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binding to its receptor activates G proteins and stimulates adenylate cyclase in pituitary cells. Promotes neuron projection development through the RAPGEF2/Rap1/B-Raf/ERK pathway. In chromaffin cells, induces long-lasting increase of intracellular calcium concentrations and neuroendocrine secretion (By similarity). Involved in the control of glucose homeostasis, induces insulin secretion by pancreatic beta cells (By similarity). {ECO:0000250|UniProtKB:O70176, ECO:0000250|UniProtKB:P13589, ECO:0000269|PubMed:11175907, ECO:0000269|PubMed:23800469}.;

Recessive Scores

pRec: 0.311

Intolerance Scores

LoFtool: 0.484
RVIS EVS: -0.19
RVIS percentile EVS: 39.68

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.574

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium