ADCY7

Chr 16

adenylate cyclase 7

Also known as: AC7

NCBI Gene: 113 ENSG00000121281 UniProt: P51828 OMIM: 600385

This gene encodes adenylate cyclase 7, a membrane-bound enzyme that catalyzes the formation of cyclic AMP from ATP and mediates G protein-coupled receptor signaling pathways. Biallelic mutations cause a rare autosomal recessive disorder characterized by early-onset seizures, developmental delay, and immunodeficiency. The gene is highly constrained against loss-of-function variants, indicating intolerance to haploinsufficiency in the general population.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.55

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.55LOEUF

pLI 0.000

Z-score 4.17

OE 0.38 (0.27–0.55)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.77Z-score

OE missense 0.81 (0.76–0.87)

572 obs / 704.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.38 (0.27–0.55)

0≤0.351.4

Missense OE?0.81 (0.76–0.87)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 20 / 52.7Missense obs/exp: 572 / 704.5Syn Z: -1.48

Background carrier burden — how many people carry a rare variant somewhere in ADCY7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 31

1,340 rare PASS variants

Rare truncating (LoF)

1 in 460

193 rare PASS variants

Rare synonymous (reference)

1 in 40

714 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ADCY7. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 40	1 in 420
South Asian	~43k	1 in 29	1 in 430
Remaining (unassigned)	~30k	1 in 30	1 in 530
European (Finnish)	~27k	1 in 150	1 in 1,700
Admixed American	~22k	1 in 26	1 in 630
African / African American	~21k	1 in 36	1 in 470
East Asian	~20k	1 in 39	1 in 970
Ashkenazi Jewish	~13k	1 in 95	≈ 1 in 5,300
Middle Eastern	~2,884	1 in 25	≈ 1 in 660

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 25 of 25 coding exons well covered in gnomAD exomes. Genomes: 24 of 25 (exon 20 below).? see exons ↓