ANXA13

Chr 8

annexin A13

Also known as: ANX13, ISA

NCBI Gene: 312 ENSG00000104537 UniProt: P27216 OMIM: 602573

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the annexin family. Members of this calcium-dependent phospholipid-binding protein family play a role in the regulation of cellular growth and in signal transduction pathways. The specific function of this gene has not yet been determined; however, it is associated with the plasma membrane of undifferentiated, proliferating endothelial cells and differentiated villus enterocytes. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.08

Clinical Summary— ANXA13

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

64 VUS of 75 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.08LOEUF

pLI 0.000

Z-score 1.26

OE 0.73 (0.50–1.08)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.43Z-score

OE missense 1.08 (0.97–1.21)

231 obs / 213.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.73 (0.50–1.08)

0≤0.351.4

Missense OE?1.08 (0.97–1.21)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 18 / 24.8Missense obs/exp: 231 / 213.3Syn Z: -0.83

This gene — mechanism propensity

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

75 submitted variants in ClinVar

ClinVar

Classification Summary

VUS64

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	64	64
Likely Benign	5	5
Benign	0	0
Total	69	69

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

View in ClinVar →

50 pathogenic / likely-pathogenic (of 54) ClinVar copy-number / structural variants overlap ANXA13 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →