AKAP11

Chr 13

A-kinase anchoring protein 11

Also known as: AKAP-11, AKAP220, PPP1R44, PRKA11

NCBI Gene: 11215 ENSG00000023516 UniProt: Q9UKA4

The protein anchors and targets protein kinase A regulatory subunits to specific cellular locations and is highly expressed during spermatogenesis. AKAP11 is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.3), suggesting mutations may cause significant clinical effects. Specific disease associations and inheritance patterns for AKAP11 mutations have not been established in the provided data.

ResearchSummary from RefSeq, UniProt

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 at high levels throughout spermatogenesis and in mature sperm. It binds the RI and RII subunits of PKA in testis. It may serve a function in cell cycle control of both somatic cells and germ cells in addition to its putative role in spermatogenesis and sperm function. [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.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.30

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.979

Z-score 6.07

OE 0.19 (0.12–0.30)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

0.31Z-score

OE missense 0.97 (0.92–1.03)

920 obs / 947.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.19 (0.12–0.30)

0≤0.351.4

Missense OE?0.97 (0.92–1.03)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 12 / 64.7Missense obs/exp: 920 / 947.1Syn Z: -0.39

Background carrier burden — how many people carry a rare variant somewhere in AKAP11?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 24

2,346 rare PASS variants

Rare truncating (LoF)

1 in 3,800

114 rare PASS variants

Rare synonymous (reference)

1 in 74

832 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for AKAP11. 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 44	1 in 4,100
South Asian	~43k	1 in 27	1 in 3,500
Remaining (unassigned)	~30k	1 in 20	≈ 1 in 7,300
European (Finnish)	~27k	1 in 68	1 in 1,800
Admixed American	~22k	1 in 24	1 in 4,000
African / African American	~21k	1 in 24	1 in 3,600
East Asian	~20k	1 in 33	1 in 4,000
Ashkenazi Jewish	~13k	1 in 87	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 23	none seen

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): 8 of 11 coding exons well covered in gnomAD exomes; exons 3, 4, 6 marginal. Genomes: all 11.? see exons ↓