AHNAK

Chr 11

AHNAK nucleoprotein

ENSG00000124942 UniProt: Q09666 OMIM: 103390

AHNAK encodes a large 700 kDa structural scaffold protein that may be required for neuronal cell differentiation and is involved in blood-brain barrier formation, cell structure and migration, and cardiac calcium channel regulation. Mutations in this gene cause neurodevelopmental disorders with autosomal dominant inheritance. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

May be required for neuronal cell differentiation

OMIM 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)

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P/LP submissions

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P/LP missense

0.31

LOEUF· LoF intol.

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Mechanism

Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.31LOEUF

pLI 0.898

Z-score 6.84

OE 0.21 (0.14–0.31)

Highly constrained

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

Missense Constraint?

-2.97Z-score

OE missense 1.15 (1.12–1.18)

3534 obs / 3071.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.21 (0.14–0.31)

0≤0.351.4

Missense OE?1.15 (1.12–1.18)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 18 / 86.7Missense obs/exp: 3534 / 3071.2Syn Z: -1.33

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 6

8,014 rare PASS variants

Rare truncating (LoF)

1 in 710

251 rare PASS variants

Rare synonymous (reference)

1 in 15

2,724 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for AHNAK. 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 9	1 in 810
South Asian	~43k	1 in 7	1 in 450
Remaining (unassigned)	~30k	1 in 6	1 in 470
European (Finnish)	~27k	1 in 28	1 in 3,000
Admixed American	~22k	1 in 7	1 in 310
African / African American	~21k	1 in 7	1 in 920
East Asian	~20k	1 in 8	1 in 770
Ashkenazi Jewish	~13k	1 in 22	1 in 1,100
Middle Eastern	~2,884	1 in 6	≈ 1 in 960

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): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓