AKAP3

Chr 12AR

A-kinase anchoring protein 3

Also known as: AKAP 110, AKAP110, CT82, FSP95, HEL159, PRKA3, SOB1, SPGF82

This gene encodes a member of A-kinase anchoring proteins (AKAPs), a family of functionally related proteins that target protein kinase A to discrete locations within the cell. The encoded protein is reported to participate in protein-protein interactions with the R-subunit of the protein kinase A as well as sperm-associated proteins. This protein is expressed in spermatozoa and localized to the acrosomal region of the sperm head as well as the length of the principal piece. It may function as a regulator of motility, capacitation, and the acrosome reaction. [provided by RefSeq, May 2013]

Primary Disease Associations & Inheritance

Spermatogenic failure 82MIM #620353
AR
0
Active trials
10
Pubs (1 yr)
59
P/LP submissions
2%
P/LP missense
0.53
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryAKAP3
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.28) despite low pLI — interpret in context.
📋
ClinVar Variants
59 unique Pathogenic / Likely Pathogenic· 119 VUS of 205 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.53LOEUF
pLI 0.056
Z-score 3.32
OE 0.28 (0.160.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.47Z-score
OE missense 0.94 (0.871.02)
441 obs / 469.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.28 (0.160.53)
00.351.4
Missense OE0.94 (0.871.02)
00.61.4
Synonymous OE0.87
01.21.6
LoF obs/exp: 7 / 24.9Missense obs/exp: 441 / 469.5Syn Z: 1.42
DN
0.6840th %ile
GOF
0.78top 25%
LOF
0.3355th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

205 submitted variants in ClinVar

Classification Summary

Pathogenic54
Likely Pathogenic5
VUS119
Likely Benign11
Benign3
54
Pathogenic
5
Likely Pathogenic
119
VUS
11
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
52
0
54
Likely Pathogenic
0
0
5
0
5
VUS
0
111
8
0
119
Likely Benign
0
10
0
1
11
Benign
0
0
1
2
3
Total1122663192

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

View in ClinVar →

Protein Context — Lollipop Plot

AKAP3 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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