congenital factor XIII deficiency

Summary

congenital factor XIII deficiency (MONDO:0018029) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 3
• Phenotypes (HPO): 26

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000	0.05	Europe	Validated
Annual incidence	<1 / 1 000 000	0.04	Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

26 HPO clinical features (Orphanet curated; top 26 by frequency):

HPO ID	Term	Frequency
HP:0008357	Reduced factor XIII activity	Very frequent (80-99%)
HP:0011884	Abnormal umbilical stump bleeding	Very frequent (80-99%)
HP:0030657	Umbilical cord hematoma	Very frequent (80-99%)
HP:0000978	Bruising susceptibility	Frequent (30-79%)
HP:0001342	Cerebral hemorrhage	Frequent (30-79%)
HP:0001933	Subcutaneous hemorrhage	Frequent (30-79%)
HP:0005261	Joint hemorrhage	Frequent (30-79%)
HP:0007420	Spontaneous hematomas	Frequent (30-79%)
HP:0012233	Intramuscular hematoma	Frequent (30-79%)
HP:0030140	Oral cavity bleeding	Frequent (30-79%)
HP:0000132	Menorrhagia	Occasional (5-29%)
HP:0000225	Gingival bleeding	Occasional (5-29%)
HP:0000421	Epistaxis	Occasional (5-29%)
HP:0001058	Poor wound healing	Occasional (5-29%)
HP:0001934	Persistent bleeding after trauma	Occasional (5-29%)
HP:0004846	Prolonged bleeding after surgery	Occasional (5-29%)
HP:0006298	Prolonged bleeding after dental extraction	Occasional (5-29%)
HP:0011889	Bleeding with minor or no trauma	Occasional (5-29%)
HP:0011891	Post-partum hemorrhage	Occasional (5-29%)
HP:0030137	Prolonged bleeding following circumcision	Occasional (5-29%)
HP:0031364	Ecchymosis	Occasional (5-29%)
HP:0040232	Delayed onset bleeding	Occasional (5-29%)
HP:0200067	Recurrent spontaneous abortion	Occasional (5-29%)
HP:0001399	Hepatic failure	Very rare (<1-4%)
HP:0002037	Inflammation of the large intestine	Very rare (<1-4%)
HP:0012324	Myeloid leukemia	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital factor XIII deficiency
Mondo ID	MONDO:0018029
Orphanet	331
DOID	DOID:2211
NCIT	C131633
SNOMED CT	50189006
UMLS	C0015530
MedGen	4639
GARD	0010766
Is cancer (heuristic)	no

Also known as: fibrin stabilising factor deficiency · fibrin stabilizing factor deficiency · fibrin-stabilizing factor deficiency

Data availability: 3 ClinVar variants · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood coagulation disease › coagulation protein disease › factor XIII deficiency › congenital factor XIII deficiency

Related subtypes (1): acquired factor XIII deficiency

Subtypes (2): factor XIII, A subunit, deficiency of, factor XIII, b subunit, deficiency of

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

2 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
634901	NM_000129.4(F13A1):c.563G>T (p.Trp188Leu)	F13A1	Pathogenic	no assertion criteria provided
255183	NM_000129.4(F13A1):c.1694C>T (p.Pro565Leu)	F13A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
294576	NM_001994.3(F13B):c.1163A>T (p.Glu388Val)	F13B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
F13A1	Definitive	Autosomal recessive	factor XIII, A subunit, deficiency of	4
F13B	Strong	Autosomal recessive	factor XIII, b subunit, deficiency of	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
F13A1	Orphanet:331	Congenital factor XIII deficiency
F13B	Orphanet:331	Congenital factor XIII deficiency

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
F13A1	HGNC:3531	ENSG00000124491	P00488	Coagulation factor XIII A chain	gencc,clinvar
F13B	HGNC:3534	ENSG00000143278	P05160	Coagulation factor XIII B chain	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
F13A1	Coagulation factor XIII A chain	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.
F13B	Coagulation factor XIII B chain	The B chain of factor XIII is not catalytically active, but is thought to stabilize the A subunits and regulate the rate of transglutaminase formation by thrombin.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Complement	1	134.0×	0.015
Antibody/Immunoglobulin	1	14.6×	0.067

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
F13A1	Antibody/Immunoglobulin	yes	2.3.2.13	Transglutaminase_N, Transglutaminase-like, Transglutaminase_C
F13B	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, ComplSys_Reg/VirEntry_Med

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
monocyte	1
mononuclear cell	1
pericardium	1
liver	1
male germ line stem cell (sensu Vertebrata) in testis	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
F13A1	261	broad	marker	monocyte, mononuclear cell, pericardium
F13B	36	tissue_specific	marker	right lobe of liver, liver, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
F13A1	2,346
F13B	995

Intra-cohort edges

A	B	Sources
F13A1	F13B	biogrid_interaction, string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
F13A1	P00488	15
F13B	P05160	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Fibrin formation	2	878.5×	4e-06	F13A1, F13B
Interleukin-4 and Interleukin-13 signaling	1	51.4×	0.023	F13A1
Platelet degranulation	1	43.9×	0.023	F13A1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
blood coagulation, fibrin clot formation	2	1685.2×	1e-06	F13A1, F13B
blood coagulation	2	173.7×	5e-05	F13A1, F13B
peptide cross-linking	1	702.2×	0.001	F13A1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
F13A1	1	3
F13B	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
SPERMIDINE	3	F13A1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
F13A1	42	Binding:42
F13B	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
F13A1	2.3.2.13	protein-glutamine gamma-glutamyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
SPERMIDINE	3	F13A1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	F13A1
C	Druggable family + PDB, no drug	1	F13B
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
F13B	3	F13A1

Clinical trials & evidence

Clinical trials

Clinical trials: 0.