Ankyrin-3 is a membrane-cytoskeleton linker protein that localizes ion channels and cell adhesion molecules at axonal initial segments and nodes of Ranvier in neurons. Mutations cause autosomal recessive intellectual developmental disorder. This gene is highly constrained against loss-of-function variants (pLI=1, LOEUF=0.089), indicating that complete loss of ankyrin-3 function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.091 OMIM phenotype
Clinical SummaryANK3
🧬
Gene-Disease Validity (ClinGen)
intellectual disability · ARModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.09LOEUF
pLI 1.000
Z-score 11.22
OE 0.05 (0.030.09)
Highly constrained

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

Missense Constraint
2.79Z-score
OE missense 0.84 (0.810.87)
1928 obs / 2305.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.05 (0.030.09)
00.351.4
Missense OE0.84 (0.810.87)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 8 / 162.2Missense obs/exp: 1928 / 2305.5Syn Z: -0.66
DN
0.3991th %ile
GOF
0.5071th %ile
LOF
0.77top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.09

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in 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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →