ADCY7

protein-coding

adenylate cyclase 7, the group of MicroRNA protein coding host genes|Adenylate cyclases

Gene summary

This gene encodes a membrane-bound adenylate cyclase that catalyses the formation of cyclic AMP from ATP and is inhibitable by calcium. The product of this gene is a member of the adenylyl cyclase class-4/guanylyl cyclase enzyme family that is characterized by the presence of twelve membrane-spanning domains in its sequences. Several transcript variants have been observed for this gene, but the full-length natures of only two have been determined so far. [provided by RefSeq, Oct 2013]

MANE transcript

NM_001114.5

Inheritance

—

ClinVar variants

U:141B:17

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr16:50,246,137-50,318,135

External References & Databases

Ensembl (ENSG00000121281)

Transcript & Mutation Effects

hg38 • Region Span ~72.0 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 ADCY7 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 138

not providedTotal: 14

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001114.5. 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			4 clinvar	4 clinvar	4 clinvar	12
missense			133 clinvar	8 clinvar	1 clinvar	142
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	141	12	5	158

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 53 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001114.5	RefSeq	NP_001105.1	25	MANE Select
ENST00000673801.1	Ensembl	ENSP00000501053.1	25	MANE Select
NM_001286057.2	RefSeq	NP_001272986.1	18	Standard
ENST00000254235.7	Ensembl	ENSP00000254235.3	25	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
Platelet activation - Homo sapiens (human)
Cortisol synthesis and secretion - Homo sapiens (human)
Relaxin signaling pathway - Homo sapiens (human)
Aldosterone synthesis and secretion - Homo sapiens (human)

Biological Process

regulation of adaptive immune response
renal water homeostasis
cAMP biosynthetic process
G protein-coupled receptor signaling pathway
adenylate cyclase-activating G protein-coupled receptor signaling pathway

Molecular Function

adenylate cyclase activity
ATP binding
metal ion binding

Cellular Component

plasma membrane
integral component of plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000394697
Coding exons: 25
Length: 71999
Individuals with no LoFs: 125630
Homozygous LoFs: 0
Heterozygous LoFs: 118
Defined: 125748
p: 0.000469

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.77	572	705	0.812	0.0000472	6981
Missense (PolyPhen)		188	306.55	0.61327		3022
Synonymous	-1.48	349	316	1.11	0.0000234	2217
Loss of Function	4.17	20	52.7	0.380	0.00000250	585

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00052	0.00052	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00038	0.00038	rare
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00054	0.00054	rare
South Asian	0.00052	0.00052	rare
Other	0.00083	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the formation of cAMP in response to activation of G protein-coupled receptors (Probable). Functions in signaling cascades activated namely by thrombin and sphingosine 1- phosphate and mediates regulation of cAMP synthesis through synergistic action of the stimulatory G alpha protein with GNA13 (PubMed:23229509, PubMed:18541530). Also, during inflammation, mediates zymosan-induced increase intracellular cAMP, leading to protein kinase A pathway activation in order to modulate innate immune responses through heterotrimeric G proteins G(12/13) (By similarity). Functions in signaling cascades activated namely by dopamine and C5 alpha chain and mediates regulation of cAMP synthesis through synergistic action of the stimulatory G protein with G beta:gamma complex (PubMed:23842570, PubMed:23229509). Functions, through cAMP response regulation, to keep inflammation under control during bacterial infection by sensing the presence of serum factors, such as the bioactive lysophospholipid (LPA) that regulate LPS-induced TNF-alpha production. However, it is also required for the optimal functions of B and T cells during adaptive immune responses by regulating cAMP synthesis in both B and T cells (By similarity). {ECO:0000250|UniProtKB:P51829, ECO:0000269|PubMed:18541530, ECO:0000269|PubMed:23229509, ECO:0000269|PubMed:23842570, ECO:0000305|PubMed:18541530, ECO:0000305|PubMed:23229509}.;

Recessive Scores

pRec: 0.203

Intolerance Scores

LoFtool: 0.0788
RVIS EVS: -3.02
RVIS percentile EVS: 0.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.711

Gene Damage Prediction

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