ANKRD46

Chr 8

ankyrin repeat domain 46

Also known as: ANK-S, GENX-115279

This gene encodes a protein containing multiple ankyrin repeats that mediate protein-protein interactions in various cellular processes. Mutations cause autosomal recessive intellectual disability with seizures and spastic paraplegia. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.597), consistent with its role in neurodevelopmental disorders.

Summary from RefSeq
Research Assistant →
0
Active trials
2
Pubs (1 yr)
37
P/LP submissions
0%
P/LP missense
0.60
LOEUF
Mechanism
Clinical SummaryANKRD46
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.52) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
37 unique Pathogenic / Likely Pathogenic· 27 VUS of 83 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.60LOEUF
pLI 0.515
Z-score 2.44
OE 0.19 (0.080.60)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.91Z-score
OE missense 0.53 (0.430.64)
67 obs / 127.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.19 (0.080.60)
00.351.4
Missense OE0.53 (0.430.64)
00.61.4
Synonymous OE0.84
01.21.6
LoF obs/exp: 2 / 10.5Missense obs/exp: 67 / 127.6Syn Z: 0.91

ClinVar Variant Classifications

83 submitted variants in ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic1
VUS27
36
Pathogenic
1
Likely Pathogenic
27
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
36
0
36
Likely Pathogenic
0
0
1
0
1
VUS
0
22
5
0
27
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total02242064

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

View in ClinVar →

Protein Context — Lollipop Plot

ANKRD46 · 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
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗