ANXA8L1

Chr 10

annexin A8 like 1

Also known as: ANXA8L2, bA145E20.2

NCBI Gene: 728113ENSG00000264230UniProt: Q5VT79

The protein binds calcium and phospholipids and functions as an anticoagulant by indirectly inhibiting the thromboplastin-specific complex. This gene has not been established as a cause of Mendelian disease in humans. The gene shows tolerance to loss-of-function variation (LOEUF 1.84), suggesting that haploinsufficiency may not be pathogenic.

Summary from RefSeq
Research Assistant →
0
Active trials
0
Pubs (1 yr)
47
P/LP submissions
0%
P/LP missense
1.84
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— ANXA8L1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.
📋
ClinVar Variants
47 unique Pathogenic / Likely Pathogenic· 46 VUS of 138 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
1.84LOEUF
pLI 0.334
Z-score 0.65
OE 0.00 (0.00–1.84)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.45Z-score
OE missense 0.64 (0.38–1.16)
8 obs / 12.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–1.84)
0≤0.351.4
Missense OE0.64 (0.38–1.16)
0≤0.61.4
Synonymous OE1.18
0≤1.21.6
LoF obs/exp: 0 / 0.5Missense obs/exp: 8 / 12.5Syn Z: -0.35
DN
0.7229th %ile
GOF
0.80top 10%
LOF
0.2190th %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

138 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic16
VUS46
Likely Benign1
Benign40
31
Pathogenic
16
Likely Pathogenic
46
VUS
1
Likely Benign
40
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
0
16
0
16
VUS
0
17
29
0
46
Likely Benign
0
0
1
0
1
Benign
0
0
39
1
40
Total0171161134

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

View in ClinVar →

Protein Context — Lollipop Plot

ANXA8L1 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
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 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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