AKAP12

Chr 6

A-kinase anchoring protein 12

Also known as: AKAP250, SSeCKS

NCBI Gene: 9590ENSG00000131016UniProt: Q02952

The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. The encoded protein is expressed in endothelial cells, cultured fibroblasts, and osteosarcoma cells. It associates with protein kinases A and C and phosphatase, and serves as a scaffold protein in signal transduction. This protein and RII PKA colocalize at the cell periphery. This protein is a cell growth-related protein. Antibodies to this protein can be produced by patients with myasthenia gravis. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Clinical highlights

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.Based on population constraint only.
1
Active trials
33
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.43
LOEUF
—
Mechanism
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.43LOEUF
pLI 0.036
Z-score 4.61
OE 0.26 (0.17–0.43)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
0.57Z-score
OE missense 0.95 (0.90–1.00)
882 obs / 931.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.26 (0.17–0.43)
0≤0.351.4
Missense OE?0.95 (0.90–1.00)
0≤0.61.4
Synonymous OE?1.01
0≤1.21.6
LoF obs/exp: 12 / 45.6Missense obs/exp: 882 / 931.4Syn Z: -0.13

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

AKAP12 · protein map & ClinVar variants

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

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