ANXA5

Chr 4AD

annexin A5

Also known as: ANX5, CPB-I, ENX2, HEL-S-7, PP4, RPRGL3, VAC-alph

NCBI Gene: 308ENSG00000164111UniProt: P08758

Annexin 5 is a calcium-dependent phospholipid binding protein that functions as an anticoagulant by indirectly inhibiting the thromboplastin-specific complex in the blood coagulation cascade. Mutations cause autosomal dominant susceptibility to recurrent pregnancy loss. The gene shows very low constraint against loss-of-function variants (pLI near zero), suggesting that complete loss of function may be tolerated.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

{Pregnancy loss, recurrent, susceptibility to, 3}MIM #614391
AD
3
Active trials
63
Pubs (1 yr)
21
P/LP submissions
0%
P/LP missense
1.45
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— ANXA5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
21 unique Pathogenic / Likely Pathogenic· 50 VUS of 103 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
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
1.45LOEUF
pLI 0.000
Z-score -0.06
OE 1.01 (0.72–1.45)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.55Z-score
OE missense 0.88 (0.77–1.01)
149 obs / 169.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.01 (0.72–1.45)
0≤0.351.4
Missense OE0.88 (0.77–1.01)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 22 / 21.7Missense obs/exp: 149 / 169.2Syn Z: 0.26
DN
0.7131th %ile
GOF
0.83top 10%
LOF
0.1796th %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

103 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic1
VUS50
Likely Benign3
Benign2
20
Pathogenic
1
Likely Pathogenic
50
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
1
0
1
VUS
0
43
7
0
50
Likely Benign
0
2
0
1
3
Benign
0
0
1
1
2
Total04529276

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

View in ClinVar →

Protein Context — Lollipop Plot

ANXA5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
COL10A1 transcriptional regulation of ANXA5-mediated ferroptosis is involved in malignant progression of head and neck squamous cell carcinoma.
Mou T et al.·Transl Cancer Res
2026Open Access
Conformation of CD40LG and ANXA5 as Key Events of 2,7-Dibromocarbazole-Induced Cardiotoxicity Using in Vivo and in Vitro Models.
Ji C et al.·Environ Sci Technol
2026Functional
Remdesivir alleviates inflammation and tissue damage in experimental colitis via AnxA5 Signaling.
Li H et al.·Int Immunopharmacol
2026
Single nucleotide variations in the ANXA5 promoter regulated piglet weight in the Min pig.
Han M et al.·Front Vet Sci
2025Open Access
Identification of functional SNP associated with sperm quality in porcine ANXA5 that contributes to the growth of immature Sertoli cell.
Han M et al.·Front Vet Sci
2025Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

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