AKAP10

Chr 17

A-kinase anchoring protein 10

Also known as: AKAP-10, D-AKAP-2, D-AKAP2, PRKA10

NCBI Gene: 11216ENSG00000108599UniProt: O43572

This gene encodes a member of the A-kinase anchor protein family. A-kinase anchor proteins bind to the regulatory subunits of protein kinase A (PKA) and confine the holoenzyme to discrete locations within the cell. The encoded protein is localized to mitochondria and interacts with both the type I and type II regulatory subunits of PKA. Polymorphisms in this gene may be associated with increased risk of arrhythmias and sudden cardiac death. [provided by RefSeq, May 2012]

207
ClinVar variants
98
Pathogenic / LP
0.11
pLI score
0
Active trials
Clinical Summary— AKAP10
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
98 Pathogenic / Likely Pathogenic· 100 VUS of 207 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.44LOEUF
pLI 0.108
Z-score 4.13
OE 0.25 (0.15–0.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.35Z-score
OE missense 0.79 (0.71–0.88)
263 obs / 332.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.25 (0.15–0.44)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.71–0.88)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.04
0≤1.21.6
LoF obs/exp: 9 / 35.6Missense obs/exp: 263 / 332.3Syn Z: -0.38

ClinVar Variant Classifications

207 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic96
Likely Pathogenic2
VUS100
Likely Benign5
Benign3
Conflicting1
96
Pathogenic
2
Likely Pathogenic
100
VUS
5
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
96
0
96
Likely Pathogenic
0
0
2
0
2
VUS
0
84
16
0
100
Likely Benign
0
0
1
4
5
Benign
0
2
1
0
3
Conflicting
—1
Total0861164207

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

View in ClinVar →

Protein Context — Lollipop Plot

AKAP10 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic association of AKAP10 gene polymorphism with reduced risk of preterm birth.
Langmia IM et al.·J Perinatol
2015
AKAP10 (I646V) functional polymorphism predicts heart rate and heart rate variability in apparently healthy, middle-aged European-Americans.
Neumann SA et al.·Psychophysiology
2009Functional
Association of 1936A > G in AKAP10 (A-kinase anchoring protein 10) and blood pressure in Polish full-term newborns.
Łoniewska B et al.·Blood Press
2013
A-kinase anchoring proteins 10 expression in relation to 2073A/G polymorphism and tumor progression in patients with colorectal cancer.
Wang M et al.·Pathol Oncol Res
2013Cohort
Gene-trapped mouse embryonic stem cell-derived cardiac myocytes and human genetics implicate AKAP10 in heart rhythm regulation.
Tingley WG et al.·Proc Natl Acad Sci U S A
2007Functional
Polymorphism 1936A > G in the AKAP10 gene (encoding A-kinase-anchoring protein 10) is associated with higher cholesterol cord blood concentration in Polish full-term newsborns.
Łoniewska B et al.·J Perinat Med
2013
Identification of genetic association between mitochondrial dysfunction and knee osteoarthritis through integrating multi-omics: a summary data-based Mendelian randomization study.
Xie J et al.·Clin Rheumatol
2024
Identification of clinical characteristics biomarkers for rheumatoid arthritis through targeted DNA methylation sequencing.
Zhao J et al.·Int Immunopharmacol
2024
The functional genetic variant Ile646Val located in the kinase binding domain of the A-kinase anchoring protein 10 is associated with familial breast cancer.
Wirtenberger M et al.·Carcinogenesis
2007Functional
Association of the A1936G (rs203462) of A-kinase anchoring protein 10 polymorphisms with QT interval prolongation during kidney transplantation.
Zukowski M et al.·Transplant Proc
2009
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools