F13A1

Chr 6ADAR

coagulation factor XIII A chain

Also known as: F13A

The F13A1 gene encodes the catalytic A subunit of coagulation factor XIII, a transglutaminase that stabilizes fibrin clots by forming cross-links between fibrin chains and cross-linking plasmin inhibitors and fibronectin to fibrin. Mutations cause factor XIII A subunit deficiency, an autosomal recessive bleeding disorder characterized by lifelong bleeding tendency, poor wound healing, and recurrent pregnancy loss. This gene is extremely constrained against loss-of-function variants (pLI near 1.0), indicating that haploinsufficiency is likely not tolerated in the general population.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismAD/ARLOEUF 0.743 OMIM phenotypes
Clinical SummaryF13A1
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Gene-Disease Validity (ClinGen)
factor XIII, A subunit, deficiency of · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.74LOEUF
pLI 0.000
Z-score 2.79
OE 0.50 (0.340.74)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.05Z-score
OE missense 0.86 (0.780.93)
356 obs / 416.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.50 (0.340.74)
00.351.4
Missense OE0.86 (0.780.93)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 18 / 36.1Missense obs/exp: 356 / 416.2Syn Z: -0.77
DN
0.6746th %ile
GOF
0.5856th %ile
LOF
0.2483th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

F13A1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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