ANK3

Chr 10

ankyrin 3

Also known as: ANKYRIN-G, MRT37

NCBI Gene: 288ENSG00000151150UniProt: Q12955

Ankyrins are a family of proteins that are believed to link the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities such as cell motility, activation, proliferation, contact, and the maintenance of specialized membrane domains. Multiple isoforms of ankyrin with different affinities for various target proteins are expressed in a tissue-specific, developmentally regulated manner. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. Ankyrin 3 is an immunologically distinct gene product from ankyrins 1 and 2, and was originally found at the axonal initial segment and nodes of Ranvier of neurons in the central and peripheral nervous systems. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder, autosomal recessive 37

Clinical highlights

Gene-disease validity (ClinGen)
intellectual disability · ARModerateconsider for supplementary testing
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.
2
Active trials
43
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.09
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?
0.09LOEUF
pLI 1.000
Z-score 11.22
OE 0.05 (0.03–0.09)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
2.79Z-score
OE missense 0.84 (0.81–0.87)
1928 obs / 2305.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.05 (0.03–0.09)
0≤0.351.4
Missense OE?0.84 (0.81–0.87)
0≤0.61.4
Synonymous OE?1.03
0≤1.21.6
LoF obs/exp: 8 / 162.2Missense obs/exp: 1928 / 2305.5Syn Z: -0.66

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ANK3 · 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