F13A1

Chr 6ADAR

coagulation factor XIII A chain

ENSG00000124491 UniProt: P00488 OMIM: 134570

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.

OMIM ResearchSummary from RefSeq, UniProt

Factor XIII is activated by thrombin and calcium ion to a transglutaminase that catalyzes the formation of gamma-glutamyl-epsilon-lysine cross-links between fibrin chains, thus stabilizing the fibrin clot. Also cross-link alpha-2-plasmin inhibitor, or fibronectin, to the alpha chains of fibrin

OMIM ResearchGenerating clinical summary…

DNmechanismAD/ARLOEUF 0.743 OMIM phenotypes

Clinical Summary— F13A1

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Gene-Disease Validity (ClinGen)

factor XIII, A subunit, deficiency of · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

28 unique Pathogenic / Likely Pathogenic· 105 VUS of 196 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.74LOEUF

pLI 0.000

Z-score 2.79

OE 0.50 (0.34–0.74)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.05Z-score

OE missense 0.86 (0.78–0.93)

356 obs / 416.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.50 (0.34–0.74)

0≤0.351.4

Missense OE?0.86 (0.78–0.93)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 18 / 36.1Missense obs/exp: 356 / 416.2Syn Z: -0.77

This gene — mechanism propensity

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

196 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11

Likely Pathogenic17

VUS105

Likely Benign24

Benign30

Pathogenic

Likely Pathogenic

105

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	7	2	2	0	11
Likely Pathogenic	11	6	0	0	17
VUS	0	102	3	0	105
Likely Benign	0	6	3	15	24
Benign	0	0	30	0	30
Total	18	116	38	15	187

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

View in ClinVar →

4 pathogenic / likely-pathogenic (of 4) ClinVar copy-number / structural variants overlap F13A1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →