ANXA13

Chr 8

annexin A13

Also known as: ANX13, ISA

The protein binds to membranes containing phosphatidylserine or phosphatidylglycerol in a calcium-dependent manner and is associated with endothelial cell and enterocyte plasma membranes. ANXA13 mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by seizures, developmental delay, and neurological regression. The gene shows low constraint against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
50
P/LP submissions
0%
P/LP missense
1.08
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryANXA13
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
50 unique Pathogenic / Likely Pathogenic· 67 VUS of 128 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.08LOEUF
pLI 0.000
Z-score 1.26
OE 0.73 (0.501.08)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.43Z-score
OE missense 1.08 (0.971.21)
231 obs / 213.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.73 (0.501.08)
00.351.4
Missense OE1.08 (0.971.21)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 18 / 24.8Missense obs/exp: 231 / 213.3Syn Z: -0.83
DN
0.78top 25%
GOF
0.79top 25%
LOF
0.1399th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

128 submitted variants in ClinVar

Classification Summary

Pathogenic50
VUS67
Likely Benign5
50
Pathogenic
67
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
50
0
50
Likely Pathogenic
0
0
0
0
0
VUS
0
63
4
0
67
Likely Benign
0
5
0
0
5
Benign
0
0
0
0
0
Total068540122

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

View in ClinVar →

Protein Context — Lollipop Plot

ANXA13 · 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
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC