F13B

Summary

F13B (coagulation factor XIII B chain, HGNC:3534) is a protein-coding gene on chromosome 1q31.3, encoding Coagulation factor XIII B chain (P05160). 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.

This gene encodes coagulation factor XIII B subunit. Coagulation factor XIII is the last zymogen to become activated in the blood coagulation cascade. Plasma factor XIII is a heterotetramer composed of 2 A subunits and 2 B subunits. The A subunits have catalytic function, and the B subunits do not have enzymatic activity and may serve as a plasma carrier molecules. Platelet factor XIII is comprised only of 2 A subunits, which are identical to those of plasma origin. Upon activation by the cleavage of the activation peptide by thrombin and in the presence of calcium ion, the plasma factor XIII dissociates its B subunits and yields the same active enzyme, factor XIIIa, as platelet factor XIII. This enzyme acts as a transglutaminase to catalyze the formation of gamma-glutamyl-epsilon-lysine crosslinking between fibrin molecules, thus stabilizing the fibrin clot. Factor XIII deficiency is classified into two categories: type I deficiency, characterized by the lack of both the A and B subunits; and type II deficiency, characterized by the lack of the A subunit alone. These defects can result in a lifelong bleeding tendency, defective wound healing, and habitual abortion.

Source: NCBI Gene 2165 — RefSeq curated summary.

At a glance

• Gene–disease (curated): factor XIII, b subunit, deficiency of (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 172 total — 11 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 30
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001994

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3534
Approved symbol	F13B
Name	coagulation factor XIII B chain
Location	1q31.3
Locus type	gene with protein product
Status	Approved
Aliases	FXIIIB
Ensembl gene	ENSG00000143278
Ensembl biotype	protein_coding
OMIM	134580
Entrez	2165

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000367412, ENST00000490002, ENST00000649282, ENST00000895399, ENST00000895400, ENST00000895401, ENST00000895402, ENST00000895403, ENST00000895404

RefSeq mRNA: 1 — MANE Select: NM_001994 NM_001994

CCDS: CCDS1388

Canonical transcript exons

ENST00000367412 — 12 exons

Exon	Start	End
ENSE00000959010	197062857	197063057
ENSE00000959011	197061784	197061969
ENSE00000959012	197060899	197061075
ENSE00000959013	197060366	197060542
ENSE00000959014	197057286	197057465
ENSE00000959015	197057013	197057198
ENSE00000959016	197055715	197055897
ENSE00000959017	197052634	197052834
ENSE00000959018	197050697	197050879
ENSE00001444453	197067160	197067260
ENSE00003470340	197040522	197040735
ENSE00003901727	197038741	197039411

Expression profiles

Bgee: expression breadth broad, 36 present calls, max score 95.55.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3805 / max 144.7995, expressed in 19 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16486	0.3526	19
16487	0.0279	6

Top tissues by expression

251 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	95.55	gold quality
liver	UBERON:0002107	93.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.46	gold quality
jejunal mucosa	UBERON:0000399	63.04	gold quality
duodenum	UBERON:0002114	56.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	53.57	gold quality
jejunum	UBERON:0002115	52.74	gold quality
pancreatic ductal cell	CL:0002079	50.95	silver quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
quadriceps femoris	UBERON:0001377	49.92	gold quality
epithelial cell of pancreas	CL:0000083	49.63	gold quality
gall bladder	UBERON:0002110	49.55	gold quality
tibialis anterior	UBERON:0001385	49.42	silver quality
colonic epithelium	UBERON:0000397	49.40	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
vastus lateralis	UBERON:0001379	49.17	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.23

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF4A

miRNA regulators (miRDB)

18 targeting F13B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-3171	99.49	69.06	776
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-376A-5P	97.70	65.61	863

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 28)

• role of FXIIIB in modifying catalytic activity of FXIIIA2 during factor XIII mediated crosslinking of fibrinogen (PMID:11816711)
• the associations of factor XIIIA and XIIIB polymorphisms and their interactions with estrogen therapy on risk of nonfatal myocardial infarction (PMID:12456499)
• F13 B subunit antigen may have a role in susceptibility to stroke based on this study of family members of patients in South Asia (PMID:15634282)
• FXIII A2 is released from activated or injured alveolar macrophages into the bronchoalveolar lining fluid; in bronchoalveolar inflammatory diseases, FXIII A2B2 also leaks out from the capillaries (PMID:15892856)
• FXIII-gene variants, in particular the non-wild-type alleles Leu34 and Leu564, were associated with a smaller venous ulcer surface and might have favorable effects on reparative processes. (PMID:16945500)
• Genetic variants of factor XIIIb were evaluated on the effects of survival in myocardial infarction. (PMID:17515963)
• Activations of FXIII by IIa and by Ca2+ as well as FXIIIa inhibition by the K9 DON peptide and iodoacetamide were further examined. New for FXIIIaIIa included alkylation of C238 and C327, acetylation of K68, and increased proteolysis of 207-214. (PMID:17691819)
• at least 3 out of the 10 Sushi domains of FXIII-B have the distinct function of forming a homodimer and a heterotetramer, which should be ascribed to the differences in their amino acid sequences (PMID:18652485)
• A specific colorimetric assay for measuring FXIIIB activity is reported. (PMID:19646949)
• FXIIIb subunit is found to be within normal range in eight Tunisian famillies with congenital factor XIII deficiency caused by two mutations, while expression of the FXIIIA subunit gene is decreased or undetectable. (PMID:19937244)
• Develop ELISA/chemoluminescence assay demonstrating that FXIII-A and FXIII-B are low concentration components of tear proteome. (PMID:20079358)
• A review analyzes and present an exhaustive amount of F13B mutational data from the past three decades. (PMID:21640452)
• Letter: suggest that recurrent pregnancy loss in the general population is not associated with reduced FXIII plasma levels. (PMID:22329719)
• Factor XIII levels are decreased in Crohn’s disease patients, but did not correlate with the time course of disease evolution, CRP, serum fibrin levels, platelet count, disease distribution within the bowel, or the presence of a fistulising form. (PMID:22398040)
• Case Report: congenital FXIII-B deficiency in which alloantibodies developed to exogenous FXIII-B. (PMID:23407795)
• Data suggest that Factor XIII (composed of subunits F13A and F13B) increases rigidity/strength of fibrin clot, protects fibrin clot against shear stress in circulation, and protects fibrin from prompt elimination by fibrinolytic system. [REVIEW] (PMID:24476525)
• Here, we update the knowledge about the pathophysiology of factor XIII deficiency and its therapeutic options. [review] (PMID:24503678)
• The FXIII-B intron K nt29756 G allele was associated with significant protection against CAS and MI in patients with a fibrinogen level in the upper tertile. (PMID:25569091)
• Changes in plasma levels of FXIIIB are associated with cognitive decline in the elderly. (PMID:26088309)
• Genetic markers associated with low FXIIIB levels increase risk of ischemic stroke cardioembolic subtype. (PMID:26159793)
• The Val34Leu polymorphism of FXIII was not found in Korean people, and compared with Caucasians, a noticeably low incidence of deep vein thrombosis was shown. (PMID:26802299)
• These findings provide insight into assembly of the fibrinogen/FXIII-A2B2 complex in both physiologic and therapeutic situations. (PMID:27561317)
• The results suggest that plasma FXIII levels are subjected to multifactorial regulation with age, fibrinogen level and FXIII-B intron K polymorphism being the major determinants. Their effect on FXIII levels might influence the risk of thrombotic diseases. (PMID:27821352)
• In VTE patients the changes of FXIII level and their effect on the risk of VTE show considerable sex-specific differences. Intron K polymorphism results in decreased FXIII levels, but does not influence the risk of VTE. (PMID:28865246)
• Effect of factor XIII levels and polymorphisms on the risk of myocardial infarction in young patients (PMID:29484525)
• investigations show no effect of FXIII-B subunit on the rate of complement activation (PMID:30915671)
• Role, Laboratory Assessment and Clinical Relevance of Fibrin, Factor XIII and Endogenous Fibrinolysis in Arterial and Venous Thrombosis. (PMID:33540604)
• Reciprocal stabilization of coagulation factor XIII-A and -B subunits is a determinant of plasma FXIII concentration. (PMID:37883802)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	cfh	ENSDARG00000100442
danio_rerio	cfhl4	ENSDARG00000102456
danio_rerio	cfhl2	ENSDARG00000103760
danio_rerio	cfhl3	ENSDARG00000104205
danio_rerio	cfhl5	ENSDARG00000105052
danio_rerio	cfhl1	ENSDARG00000105212
mus_musculus	F13b	ENSMUSG00000026368
rattus_norvegicus	F13b	ENSRNOG00000012613

Paralogs (39): CFH (ENSG00000000971), SELE (ENSG00000007908), C8B (ENSG00000021852), C6 (ENSG00000039537), SEZ6 (ENSG00000063015), CFHR2 (ENSG00000080910), APOH (ENSG00000091583), SEZ6L (ENSG00000100095), SUSD6 (ENSG00000100647), SRPX (ENSG00000101955), SRPX2 (ENSG00000102359), C7 (ENSG00000112936), C9 (ENSG00000113600), PAPPA2 (ENSG00000116183), CFHR3 (ENSG00000116785), CR2 (ENSG00000117322), CD46 (ENSG00000117335), CSMD2 (ENSG00000121904), C4BPA (ENSG00000123838), C4BPB (ENSG00000123843), CFHR4 (ENSG00000134365), CFHR5 (ENSG00000134389), SUSD4 (ENSG00000143502), C8A (ENSG00000157131), SUSD3 (ENSG00000157303), CSMD3 (ENSG00000164796), SVEP1 (ENSG00000165124), C2 (ENSG00000166278), SELP (ENSG00000174175), SEZ6L2 (ENSG00000174938), PRF1 (ENSG00000180644), PAPPA (ENSG00000182752), CSMD1 (ENSG00000183117), SELL (ENSG00000188404), CD55 (ENSG00000196352), CR1L (ENSG00000197721), CR1 (ENSG00000203710), CFB (ENSG00000243649), CFHR1 (ENSG00000244414)

Protein

Protein identifiers

Coagulation factor XIII B chain — P05160 (reviewed: P05160)

Alternative names: Fibrin-stabilizing factor B subunit, Protein-glutamine gamma-glutamyltransferase B chain, Transglutaminase B chain

All UniProt accessions (2): P05160, A0A3B3IS66

UniProt curated annotations — full annotation on UniProt →

Function. 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.

Subunit / interactions. Tetramer of two A chains (F13A1) and two B (F13B) chains.

Subcellular location. Secreted.

Disease relevance. Factor XIII subunit B deficiency (FA13BD) [MIM:613235] An autosomal recessive hematologic disorder characterized by a life-long bleeding tendency, impaired wound healing and spontaneous abortion in affected women. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_001985* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000436	Sushi_SCR_CCP_dom	Domain
IPR035976	Sushi/SCR/CCP_sf	Homologous_superfamily
IPR051503	ComplSys_Reg/VirEntry_Med	Family

Pfam: PF00084

UniProt features (82 total): strand 29, disulfide bond 20, sequence variant 16, domain 10, glycosylation site 2, helix 2, signal peptide 1, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8CMU	ELECTRON MICROSCOPY	2.41
8CMT	ELECTRON MICROSCOPY	3.04

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P05160-F1	80.55	0.15

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (20): 25–76, 59–87, 91–135, 118–146, 153–197, 180–208, 213–255, 241–267, 274–316, 302–327, 336–378, 364–389, 396–439, 425–450, 454–505, 486–515, 524–567, 553–578, 582–636, 616–646

Glycosylation sites (2): 162, 545

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9769733	Fibrin formation
R-HSA-140875

MSigDB gene sets: 143 (showing top): GOBP_PROTEIN_ACTIVATION_CASCADE, HNF1_Q6, GOBP_WOUND_HEALING, GOBP_PROTEIN_MATURATION, RGTTAMWNATT_HNF1_01, HSIAO_LIVER_SPECIFIC_GENES, HNF4_01, GOBP_HEMOSTASIS, ACEVEDO_LIVER_CANCER_UP, GOBP_REGULATION_OF_BODY_FLUID_LEVELS, KEGG_COMPLEMENT_AND_COAGULATION_CASCADES, GOCC_TRANSFERASE_COMPLEX, REACTOME_COMMON_PATHWAY_OF_FIBRIN_CLOT_FORMATION, BOCHKIS_FOXA2_TARGETS, HMGIY_Q6

GO Biological Process (3): blood coagulation (GO:0007596), blood coagulation, fibrin clot formation (GO:0072378), hemostasis (GO:0007599)

GO Molecular Function (0):

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), transferase complex (GO:1990234)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Coagulation pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
hemostasis	1
wound healing	1
coagulation	1
blood coagulation	1
protein activation cascade	1
regulation of body fluid levels	1
cellular anatomical structure	1
catalytic complex	1

Protein interactions and networks

STRING

988 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
F13B	F13A1	P00488	945
F13B	CNDP2	Q96KP4	713
F13B	PGC	P20142	690
F13B	SERPINF2	P08697	675
F13B	FGG	P02679	643
F13B	FGA	P02671	637
F13B	FGB	P02675	629
F13B	CFB	P00751	622
F13B	PROC	P04070	616
F13B	VWF	P04275	610
F13B	PDC	P20941	595
F13B	SERPIND1	P05546	578
F13B	PROZ	P22891	537
F13B	C3	P01024	535
F13B	PGM1	P36871	534

IntAct

3 interactions, top by confidence:

A	B	Type	Score
F13B	A2M	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): F13B (Co-purification), F13B (Co-fractionation), F13B (Reconstituted Complex), FGG (Co-purification)

ESM2 similar proteins: O02839, O08569, O19124, O62685, O62837, O88174, P02749, P04003, P05160, P08607, P14151, P15529, P16109, P17690, P19070, P20023, P26644, P27113, P30836, P42201, P49457, P70105, P79138, P98107, P98109, P98131, Q01102, Q03472, Q07968, Q28065, Q28768, Q2VPA4, Q5R4D0, Q60401, Q60736, Q61475, Q61476, Q63135, Q63514, Q64735

Diamond homologs: A0JNA2, A2AVA0, O02839, O08569, O19124, O62685, O62837, O88174, P02749, P04003, P05160, P06681, P06909, P08174, P08607, P10643, P15529, P16581, P17927, P19070, P20023, P49457, P68638, P68639, P70105, P79138, Q01016, Q01339, Q22328, Q28065, Q28085, Q29RN8, Q2HRD4, Q2VPA4, Q4LDE5, Q4V9Z5, Q501P1, Q53EL9, Q5R4D0, Q5RAD0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

172 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	6
Uncertain significance	118
Likely benign	8
Benign	17

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
1069026	NM_001994.3(F13B):c.162dup (p.Leu55fs)	Pathogenic
1098468	NM_001994.3(F13B):c.565G>T (p.Gly189Ter)	Pathogenic
1322006	NM_001994.3(F13B):c.1505C>G (p.Ser502Cys)	Pathogenic
16518	NM_001994.3(F13B):c.65-2del	Pathogenic
16519	NM_001994.3(F13B):c.1349G>T (p.Cys450Phe)	Pathogenic
16522	NM_001994.3(F13B):c.1498del (p.Glu500fs)	Pathogenic
1698968	NM_001994.3(F13B):c.1152_1155dup (p.Pro386fs)	Pathogenic
1808698	GRCh37/hg19 1q31.2-32.1(chr1:193011753-199882947)x1	Pathogenic
3573006	NM_001994.3(F13B):c.1731_1735del (p.Leu577fs)	Pathogenic
4687426	NM_001994.3(F13B):c.10A>T (p.Lys4Ter)	Pathogenic
627055	NM_001994.3(F13B):c.299_300insAAC (p.Tyr100Ter)	Pathogenic
1324365	NM_001994.3(F13B):c.805+1G>A	Likely pathogenic
2636960	NM_001994.3(F13B):c.1053dup (p.Lys352Ter)	Likely pathogenic
3256928	NM_001994.3(F13B):c.91G>T (p.Glu31Ter)	Likely pathogenic
3576261	NM_001994.3(F13B):c.647T>A (p.Leu216Ter)	Likely pathogenic
3899383	NM_001994.3(F13B):c.1317C>A (p.Cys439Ter)	Likely pathogenic
4542132	NM_001994.3(F13B):c.302T>A (p.Ile101Asn)	Likely pathogenic

SpliceAI

2127 predictions. Top by Δscore:

Variant	Effect	Δscore
1:197040378:G:GC	acceptor_gain	1.0000
1:197052766:T:A	donor_gain	1.0000
1:197055894:TTTT:T	acceptor_gain	1.0000
1:197055898:C:CC	acceptor_gain	1.0000
1:197057009:ATAC:A	donor_loss	1.0000
1:197057010:TA:T	donor_loss	1.0000
1:197057012:CCAA:C	donor_gain	1.0000
1:197057467:T:C	acceptor_gain	1.0000
1:197057469:A:C	acceptor_gain	1.0000
1:197060538:TAATT:T	acceptor_gain	1.0000
1:197060541:TT:T	acceptor_gain	1.0000
1:197060543:C:A	acceptor_loss	1.0000
1:197060543:C:CC	acceptor_gain	1.0000
1:197060544:T:G	acceptor_loss	1.0000
1:197060897:A:AC	donor_gain	1.0000
1:197060898:C:CC	donor_gain	1.0000
1:197060946:T:TA	donor_gain	1.0000
1:197061793:T:A	donor_gain	1.0000
1:197062938:C:CT	acceptor_gain	1.0000
1:197062939:A:T	acceptor_gain	1.0000
1:197040378:G:C	acceptor_gain	0.9900
1:197046060:A:AC	donor_gain	0.9900
1:197046061:C:CC	donor_gain	0.9900
1:197049629:T:C	acceptor_gain	0.9900
1:197050692:CATA:C	donor_loss	0.9900
1:197050693:ATACC:A	donor_loss	0.9900
1:197050694:TACC:T	donor_loss	0.9900
1:197050695:A:AG	donor_loss	0.9900
1:197050696:C:G	donor_loss	0.9900
1:197052835:C:CC	acceptor_gain	0.9900

AlphaMissense

4323 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:197057035:C:A	W383C	0.999
1:197057035:C:G	W383C	0.999
1:197055737:C:A	W444C	0.998
1:197055737:C:G	W444C	0.998
1:197057308:C:A	W321C	0.998
1:197057308:C:G	W321C	0.998
1:197057037:A:G	W383R	0.997
1:197057037:A:T	W383R	0.997
1:197057310:A:G	W321R	0.997
1:197057310:A:T	W321R	0.997
1:197052675:C:G	C505S	0.996
1:197052676:A:T	C505S	0.996
1:197055739:A:G	W444R	0.996
1:197055739:A:T	W444R	0.996
1:197050702:C:G	C578S	0.994
1:197050703:A:T	C578S	0.994
1:197055795:C:G	C425S	0.994
1:197055796:A:T	C425S	0.994
1:197057324:C:G	C316S	0.994
1:197057325:A:T	C316S	0.994
1:197060391:C:A	W260C	0.994
1:197060391:C:G	W260C	0.994
1:197040567:C:G	C636S	0.993
1:197040568:A:T	C636S	0.993
1:197050719:C:A	W572C	0.993
1:197050719:C:G	W572C	0.993
1:197055753:C:G	C439S	0.993
1:197055754:A:T	C439S	0.993
1:197055721:A:G	C450R	0.992
1:197060393:A:G	W260R	0.992

dbSNP variants (sampled 300 via entrez): RS1000016618 (1:197045949 C>A,T), RS1000085183 (1:197039108 T>A,C), RS1000184822 (1:197052301 G>A), RS1000235761 (1:197052060 G>A), RS1000570217 (1:197066130 A>T), RS1000589721 (1:197039115 A>G), RS1000748308 (1:197058594 T>C), RS1000802210 (1:197068207 G>A), RS1001033041 (1:197041077 A>C,G), RS1001077377 (1:197046947 G>A), RS1001086712 (1:197040838 T>A), RS1001160820 (1:197056463 C>T), RS1001256377 (1:197038974 C>G), RS1001288468 (1:197044329 T>C), RS1001308638 (1:197038748 G>A)

Disease associations

OMIM: gene MIM:134580 | disease phenotypes: MIM:613235

GenCC curated gene-disease

Disease	Classification	Inheritance
factor XIII, b subunit, deficiency of	Strong	Autosomal recessive
congenital factor XIII deficiency	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
factor XIII, b subunit, deficiency of	Definitive	AR

Mondo (4): factor XIII, b subunit, deficiency of (MONDO:0013190), cholesteatoma (MONDO:0006530), factor XIII deficiency (MONDO:0002241), congenital factor XIII deficiency (MONDO:0018029)

Orphanet (1): Congenital factor XIII deficiency (Orphanet:331)

HPO phenotypes

30 total (30 of 30 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000132	Menorrhagia
HP:0000225	Gingival bleeding
HP:0000421	Epistaxis
HP:0000978	Bruising susceptibility
HP:0001058	Poor wound healing
HP:0001342	Cerebral hemorrhage
HP:0001399	Hepatic failure
HP:0001892	Abnormal bleeding
HP:0001933	Subcutaneous hemorrhage
HP:0001934	Persistent bleeding after trauma
HP:0002037	Inflammation of the large intestine
HP:0003577	Congenital onset
HP:0004846	Prolonged bleeding after surgery
HP:0005261	Joint hemorrhage
HP:0006298	Prolonged bleeding after dental extraction
HP:0007420	Spontaneous hematomas
HP:0008357	Reduced factor XIII activity
HP:0011884	Abnormal umbilical stump bleeding
HP:0011889	Bleeding with minor or no trauma
HP:0011891	Post-partum hemorrhage
HP:0012233	Intramuscular hematoma
HP:0012324	Myeloid leukemia
HP:0030137	Prolonged bleeding following circumcision
HP:0030140	Oral cavity bleeding
HP:0030657	Umbilical cord hematoma
HP:0031364	Ecchymosis
HP:0040232	Delayed onset bleeding
HP:0040234	Factor XIII subunit B deficiency
HP:0200067	Recurrent spontaneous abortion

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001572_5	Erectile dysfunction in type 1 diabetes	6.000000e-06
GCST001899_1	Age-related macular degeneration	1.000000e-16
GCST002479_5	Lupus nephritis in systemic lupus erythematosus	5.000000e-06

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D002781	Cholesteatoma	C17.800.428.260
D005177	Factor XIII Deficiency	C15.378.100.100.335; C15.378.100.141.335; C15.378.463.335; C16.320.099.335
C567688	Factor XIII, B Subunit, Deficiency Of (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3351193 (SINGLE PROTEIN), CHEMBL6066544 (PROTEIN COMPLEX)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.40	IC50	4	nM	CHEMBL5803781
8.00	IC50	10	nM	CHEMBL5803781

CTD chemical–gene interactions

41 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	4
Aflatoxin B1	affects expression, decreases expression, decreases methylation	3
sodium arsenite	decreases expression, increases expression	2
perfluorooctane sulfonic acid	decreases expression	2
Benzo(a)pyrene	decreases expression, increases mutagenesis	2
2,4,6-tribromophenol	increases expression	1
propionaldehyde	decreases expression	1
bisphenol A	decreases methylation	1
decabromobiphenyl ether	decreases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	increases expression	1
perfluorooctanoic acid	decreases expression	1
pentanal	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Acetaminophen	decreases expression	1
Ethanol	decreases expression	1
Aldehydes	decreases expression	1
Arbutin	decreases expression	1
Calcitriol	increases expression	1
Chenodeoxycholic Acid	decreases expression, affects cotreatment	1
Citrulline	increases expression	1
Deoxycholic Acid	affects cotreatment, decreases expression	1
Estradiol	decreases expression	1
Glycochenodeoxycholic Acid	affects cotreatment, decreases expression	1
Glycocholic Acid	decreases expression, affects cotreatment	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3388948	Binding	Binding affinity to nonactivated recombinant F13B subunit (unknown origin) by microscale thermophoresis method	Novel insights into structure and function of factor XIIIa-inhibitor tridegin. — J Med Chem

Clinical trials (associated diseases)

24 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00885742	PHASE3	COMPLETED	A Study of Factor XIII Concentrate in Subjects With Congenital Factor XIII Deficiency
NCT00945906	PHASE3	COMPLETED	An Open Enrollment Study of Factor XIII Concentrate in Subjects With Congenital Factor XIII Deficiency
NCT01638052	PHASE2	COMPLETED	Great Auricular Nerve Block for Children Undergoing Tympanomastoid Surgery
NCT00883090	PHASE2	COMPLETED	A Study of the Use of Factor XIII Concentrate in Patients With Inherited FXIII Deficiency
NCT00270660	Not specified	UNKNOWN	A Study of the Clinicopathologic Behaviour of the Different Types of Unsafe Chronic Otitis Media
NCT00682409	Not specified	COMPLETED	Magnetic Resonance (MR) Imaging in the Post Operative Follow-up of Cholesteatoma in Children
NCT01855425	Not specified	COMPLETED	Cone Beam CT for Diagnosis of Select Otorhinolaryngology (ENT) Indications at Lower Dose
NCT02019888	Not specified	COMPLETED	Wide Frequency Band Test of Hearing in Veterans
NCT02903550	Not specified	UNKNOWN	Usefulness of Non EPI-DWI-MRI / CT 3D Static Co-registration Prior to Surgery of Cholesteatomas
NCT03294421	Not specified	UNKNOWN	Combined Access Closed Tympanomastoidectomy: Microsurgery Allied to Endoscopy
NCT03305796	Not specified	UNKNOWN	Detection of Cholesteatoma Using Diffusion Magnetic Resonance Imaging
NCT03915392	Not specified	UNKNOWN	Diffusion Weighted MRI Accuracy in Cholesteatoma Localization
NCT03954288	Not specified	UNKNOWN	The Serum Sclerostin Levels in Cholesteatoma Patients
NCT04959539	Not specified	COMPLETED	Endoscopic Transcanal Tympanoplasty With Attico-antrostomy Versus Endoscopic-assisted Canal Wall up Mastoidectomy in Management of Localized Cholesteatoma: A Randomized Clinical Trial
NCT05921643	Not specified	RECRUITING	Short- and Medium-term Evaluation of Mastoid Filling Using Bioactive Glass
NCT06016335	Not specified	COMPLETED	MRI-based Synthetic CT Images of the Head and Neck
NCT06268938	Not specified	ACTIVE_NOT_RECRUITING	Outcomes of Mastoid Obliteration Canal Wall Down Tympanomastoidectomy in Cholesteatoma Surgery
NCT06424704	Not specified	NOT_YET_RECRUITING	Chronic Suppurative Otitis Media Microbiology
NCT06738927	Not specified	NOT_YET_RECRUITING	Otological Study of Facial Cleft Patients Over 10 Years of Age (Excluding Isolated Cleft Lip) (EFEOF)
NCT00640289	Not specified	COMPLETED	Clinical Trial of Factor XIII (FXIII) Concentrate
NCT00735579	Not specified	COMPLETED	Wound Healing Abnormalities in Major Abdominal Surgery
NCT01106937	Not specified	UNKNOWN	Factor XIII and Pulmonary Embolism in Neurosurgical Patients
NCT03188913	Not specified	UNKNOWN	Factor XIII in Major Burns Coagulation
NCT03523624	Not specified	COMPLETED	Factor XIII and Other Biomarkers in ST Segment Elevation Myocardial Infarction