F13A1

Summary

F13A1 (coagulation factor XIII A chain, HGNC:3531) is a protein-coding gene on chromosome 6p25.1, encoding Coagulation factor XIII A chain (P00488). 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.

This gene encodes the coagulation factor XIII A 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 plasma carrier molecules. Platelet factor XIII is comprised only of 2 A subunits, which are identical to those of plasma origin. Upon 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. It also crosslinks alpha-2-plasmin inhibitor, or fibronectin, to the alpha chains of fibrin. 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 2162 — RefSeq curated summary.

At a glance

• Gene–disease (curated): factor XIII, A subunit, deficiency of (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 16
• Clinical variants (ClinVar): 320 total — 31 pathogenic, 21 likely-pathogenic
• Phenotypes (HPO): 39
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000129

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3531
Approved symbol	F13A1
Name	coagulation factor XIII A chain
Location	6p25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000124491
Ensembl biotype	protein_coding
OMIM	134570
Entrez	2162

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 retained_intron

ENST00000264870, ENST00000414279, ENST00000431222, ENST00000445223, ENST00000451619, ENST00000479211, ENST00000878383, ENST00000950946, ENST00000950947

RefSeq mRNA: 1 — MANE Select: NM_000129 NM_000129

CCDS: CCDS4496

Canonical transcript exons

ENST00000264870 — 15 exons

Exon	Start	End
ENSE00001603521	6144084	6145772
ENSE00001855494	6320587	6320662
ENSE00001959052	6222033	6222171
ENSE00001967644	6248312	6248419
ENSE00001969635	6250811	6250929
ENSE00001971321	6197223	6197326
ENSE00001972641	6305351	6305539
ENSE00001973719	6151813	6151949
ENSE00001981205	6195797	6195885
ENSE00001984164	6174580	6174867
ENSE00001984690	6224686	6224860
ENSE00001989225	6167458	6167618
ENSE00001990320	6181988	6182141
ENSE00003647127	6318535	6318682
ENSE00003692064	6266558	6266809

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 99.05.

FANTOM5 (CAGE): breadth broad, TPM avg 14.3485 / max 3815.6906, expressed in 458 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71565	14.2443	457
71564	0.0726	35
71559	0.0170	6
71560	0.0146	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.05	gold quality
mononuclear cell	CL:0000842	98.97	gold quality
pericardium	UBERON:0002407	98.73	gold quality
leukocyte	CL:0000738	98.72	gold quality
placenta	UBERON:0001987	98.45	gold quality
decidua	UBERON:0002450	97.94	gold quality
synovial joint	UBERON:0002217	97.19	gold quality
right coronary artery	UBERON:0001625	96.99	gold quality
upper leg skin	UBERON:0004262	96.69	gold quality
skin of hip	UBERON:0001554	96.55	gold quality
mucosa of stomach	UBERON:0001199	96.40	gold quality
gall bladder	UBERON:0002110	95.99	gold quality
apex of heart	UBERON:0002098	95.76	gold quality
heart right ventricle	UBERON:0002080	95.03	gold quality
tibia	UBERON:0000979	94.50	gold quality
upper arm skin	UBERON:0004263	94.42	gold quality
granulocyte	CL:0000094	94.29	gold quality
vermiform appendix	UBERON:0001154	94.24	gold quality
layer of synovial tissue	UBERON:0007616	94.15	gold quality
omental fat pad	UBERON:0010414	93.98	gold quality
peritoneum	UBERON:0002358	93.93	gold quality
calcaneal tendon	UBERON:0003701	93.93	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.85	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.66	gold quality
adipose tissue	UBERON:0001013	93.29	gold quality
rectum	UBERON:0001052	92.84	gold quality
mucosa of urinary bladder	UBERON:0001259	92.79	gold quality
connective tissue	UBERON:0002384	92.61	gold quality
left ventricle myocardium	UBERON:0006566	92.47	gold quality
blood	UBERON:0000178	92.35	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	6223.30
E-HCAD-24	yes	1661.53
E-MTAB-6701	yes	1427.12
E-MTAB-7407	yes	1348.54
E-GEOD-84465	yes	1170.44
E-MTAB-8322	yes	997.71
E-GEOD-100618	yes	654.43
E-ANND-5	yes	549.52
E-GEOD-135922	yes	47.11
E-HCAD-4	yes	29.19
E-CURD-122	yes	23.78
E-MTAB-9221	yes	22.80
E-HCAD-1	yes	7.16
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, ETS1, GATA1, NR3C2, SP1, TCF3

miRNA regulators (miRDB)

133 targeting F13A1, 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-4776-3P	100.00	68.73	1340
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• Polymorphisms of coagulation factor XIII subunit A and risk of hemorrhagic stroke in young white women. (PMID:11692020)
• The results suggest that the Leu 34 allele of the A-chain factor XIII gene has a minor role in the development of non-traumatic primary intracerebral haemorrhage. (PMID:11920201)
• A common polymorphism in the gene for factor XIII A subunit (F13A1 V34L) has been associated with a decreased risk for coronary artery disease, cerebrovascular disease, and deep venous thrombosis. (PMID:11941274)
• Numbers of epidermal and dermal CD1a(+) cells and factor XIIIa(+) cells were significantly greater than in normal control skin, while in psoriasis only factor XIIIa(+) cells were significantly increased in number. (PMID:12373334)
• the associations of factor XIIIA and XIIIB polymorphisms and their interactions with estrogen therapy on risk of nonfatal myocardial infarction (PMID:12456499)
• Interaction between the FII 20210A and FXIII-A Leu34 alleles forms a synergistic coeffect that strongly predisposes for MI, placing combined carriers at high risk for MI. (PMID:12480694)
• activation caused by a specific mutation of neighboring thrombin cleavage site(s) in the activation peptide of FXIII-A like V34L resulted in the real-time amount of the activated factor XIII-A (PMID:12526104)
• Valproate induces reversible factor XIII deficiency with risk of perioperative bleeding. (PMID:12859294)
• Factor XIII subunit A as an intracellular transglutaminase. Review. (PMID:12861374)
• Gene profiling identified F13A from peripheral blood cells in coronary artery disease. (PMID:12878486)
• direct relation of FXIII A-subunit to fibrinogen levels argues for significant consumption of these coagulation factors in pulmonary embolism. (PMID:12958612)
• investigate the hypothesisis that TAFI -438 G/A and factor XIIIA Val34Leu polymorphisms might influence the formation and fate of emboli and accordingly the risk of pulmonary embolism in a case control study (PMID:12958613)
• 3 novel F13A gene mutations were identified; cytoplasm FXIII mRNA level was normal suggesting that the mutations may lead to formation of mutant FXIII that is very unstable and rapidly degraded in cytoplasm (PMID:14604285)
• Kinetic and nuclear magnetic resonance studies reveal that the N-terminal portions of FXIII activation peptide AP (28-37) (Val34 and Val34Leu) are not necessary for effective interaction with the thrombin active site surface. (PMID:15065858)
• platelet FXIII and calpain have roles in regulating integrin alpha(IIb)beta3 adhesive function (PMID:15131115)
• F13A plays a role in the fcgamma and complement receptor-mediated phagocytic activities of monocytes/maacrophages. (PMID:15219459)
• Factor XIII V34L polymorphism modulates the risk of chronic venous leg ulcer progression and extension. Skin lesion size was inversely related to the number of polymorphic L34 alleles, regardless of FXIII levels. (PMID:15453833)
• computer modeling of the new missense mutations predicted that Gly210Arg will cause protein misfolding, Ala318Val and Thr398Asn will interfere with the catalytic process or protein stability, Arg260Leu will impair dimerization. (PMID:15456491)
• The proangiogenic effect of FXIIIa is mediated by enhancement of crosslinked alpha(v)beta3/VEGFR-2 complex formation; tyrosine phosphorylation of VEGFR-2; upregulation of c-Jun and Egr-1; and downregulation of TSP-1 induced by c-Jun through WT-1. (PMID:15618543)
• the thrombo-protective effect of Leu34 allele prevails only in certain genetic and/or environmental constellations (PMID:15692256)
• 3 new factor XIII deficiency mutations were found: 2 new nonsense mutations, and 1 new deletion of a single nucleotide. (PMID:16330458)
• analysis of the expression, localization and activity of TG2 and FXIIIA in mineralizing tissues [review] (PMID:16368540)
• a novel mutation in factor XIIIA gene that caused severe congenital factor XIII deficiency (PMID:16456856)
• Factor XIII may have a role in disseminated intravascular coagulation (PMID:16642548)
• V34L is the main functional polymorphism influencing FXIII activation. (Factor XIII A) (PMID:16763156)
• Results suggests the importance of individual FXIIIa subsites that are controlled by chemical environment and sterics. (PMID:16820332)
• a significant gene-covariate interaction exists between the FXIII Val34Leu variant and fibrinogen levels (PMID:16881935)
• Results suggest that Factor XIIIA declines during the active phase of Crohn’s disease because it might be consumed in the repair of injured tissue. (PMID:16911684)
• in whole plasma the onset of FXIII-A activation is determined by fibrin formation, while the rate of activation is modulated by Val34Leu polymorphism (PMID:16920044)
• 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)
• FXIII-V34L and P564L are positively associated with shorter mean healing times after superficial venous surgery in patients with chronic venous insufficiency. A role of FXIII gene variants is suggested in healing and tissue regeneration of skin lesions. (PMID:16950433)
• Our results do not support an independent association of the FXIII Val34Leu polymorphism with idiopathic venous thromboembolism in our Caucasian Canadian study population. (PMID:16988547)
• Some differences were observed among cases and controls in the prevalence of FXIII val34leu (increase in double mutant allele carriership in CD), these did not explain an excess risk of thrombosis. (PMID:17156138)
• investigated FXIII levels in three consecutive patients presenting with acute myocardial rupture following myocardial infarction. FXIII levels in these patients were only 5768% of normal (PMID:17183677)
• Results support the protective effect of FXIII Val34Leu polymorphism in venous thrombosis. (PMID:17195962)
• Fibrinogen concentration modulates the effect of Leu34 allele on the risk of MI; its protective effect emerges at increasing fibrinogen concentration (PMID:17250879)
• This study shows for the first time an association between FXIII Val34Leu polymorphism and AD. (PMID:17288735)
• factor XIII may have a role in development of myocardial infarction in women (PMID:17296595)
• Factor-XIIIa-mediated vimentin dimerization produces a novel unifying pathway by which vasodilatory and remodeling responses may be regulated. (PMID:17476115)
• Genetic variants of factor XIIIa were evaluated on the effects of survival in myocardial infarction. (PMID:17515963)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	f13a1b	ENSDARG00000036893
danio_rerio	f13a1a.1	ENSDARG00000045453
danio_rerio	F13A1	ENSDARG00000094832
mus_musculus	F13a1	ENSMUSG00000039109
rattus_norvegicus	F13a1	ENSRNOG00000015957
drosophila_melanogaster	Tg	FBGN0031975

Paralogs (8): TGM1 (ENSG00000092295), TGM5 (ENSG00000104055), TGM3 (ENSG00000125780), TGM7 (ENSG00000159495), TGM4 (ENSG00000163810), EPB42 (ENSG00000166947), TGM6 (ENSG00000166948), TGM2 (ENSG00000198959)

Protein

Protein identifiers

Coagulation factor XIII A chain — P00488 (reviewed: P00488)

Alternative names: Protein-glutamine gamma-glutamyltransferase A chain, Transglutaminase A chain

All UniProt accessions (5): A6PVK5, P00488, H0Y4W5, H0Y796, Q9NQP5

UniProt curated annotations — full annotation on UniProt →

Function. 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.

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

Subcellular location. Cytoplasm. Secreted.

Post-translational modifications. The activation peptide is released by thrombin.

Disease relevance. Factor XIII subunit A deficiency (FA13AD) [MIM:613225] 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.

Cofactor. Binds 1 Ca(2+) ion per subunit.

Polymorphism. There are four main allelic forms of this protein; F13A1A, F13A1B, F13A2A and F13A2B. In addition two other intermediate forms (F13A*(2)A and F13A*(2)B) seem to exist. The sequence shown is that of F13A*1B.

Similarity. Belongs to the transglutaminase superfamily. Transglutaminase family.

RefSeq proteins (1): NP_000120* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001102	Transglutaminase_N	Domain
IPR002931	Transglutaminase-like	Domain
IPR008958	Transglutaminase_C	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR013808	Transglutaminase_AS	Active_site
IPR014756	Ig_E-set	Homologous_superfamily
IPR023608	Transglutaminase_animal	Family
IPR036238	Transglutaminase_C_sf	Homologous_superfamily
IPR036985	Transglutaminase-like_sf	Homologous_superfamily
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR050779	Transglutaminase	Family

Pfam: PF00868, PF00927, PF01841

Enzyme classification (BRENDA):

• EC 2.3.2.13 — protein-glutamine gamma-glutamyltransferase (BRENDA: 68 organisms, 476 substrates, 772 inhibitors, 122 Km, 49 kcat entries)

Substrate kinetics (BRENDA)

60 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PUTRESCINE	0.035–9.63	13
L-LYSINE	2.9–15.8	6
N-CBZ-GLN-GLY	12.83–59.5	5
HYDROXYLAMINE	1.37–61.9	4
NALPHA-BENZYLOXYCARBONYL-L-GLN-GLY	11.2–30	4
CASEIN	0.006–0.012	3
CBZ-GLN-GLY	0.0169–5.9	3
CBZ-GLN-GLY-OH	3.53–8.55	3
METHYLAMINE	0.024–0.061	3
MONODANSYLCADAVERINE	0.01–0.034	3
N-CARBOXYBENZOYL-L-GLUTAMINYL-GLYCINE	0.0547–69.4	3
PENTYLAMINE	0.0029–0.0203	3
Z-GLN-GLY	1.8–11.6	3
ACETYL-ALPHAS1-CASEIN	0.0029–0.0032	2
GTP	0.0044–0.01	2

Catalyzed reactions (Rhea), 1 shown:

• L-glutaminyl-[protein] + L-lysyl-[protein] = [protein]-L-lysyl-N(6)-5-L-glutamyl-[protein] + NH4(+) (RHEA:54816)

UniProt features (118 total): strand 48, sequence variant 29, helix 19, turn 6, binding site 4, active site 3, sequence conflict 2, initiator methionine 1, propeptide 1, site 1, modified residue 1, glycosylation site 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
4KTY	X-RAY DIFFRACTION	1.98
1EX0	X-RAY DIFFRACTION	2
1EVU	X-RAY DIFFRACTION	2.01
1F13	X-RAY DIFFRACTION	2.1
1GGU	X-RAY DIFFRACTION	2.1
5MHM	X-RAY DIFFRACTION	2.12
5MHL	X-RAY DIFFRACTION	2.4
8CMU	ELECTRON MICROSCOPY	2.41
5MHN	X-RAY DIFFRACTION	2.48
1FIE	X-RAY DIFFRACTION	2.5
1GGY	X-RAY DIFFRACTION	2.5
1QRK	X-RAY DIFFRACTION	2.5
1GGT	X-RAY DIFFRACTION	2.65
5MHO	X-RAY DIFFRACTION	2.92
8CMT	ELECTRON MICROSCOPY	3.04

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00488-F1	91.15	0.70

Functional residue map

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

Catalytic / active sites (4): 38–39 (cleavage; by thrombin; to produce active factor xiii-a); 315; 374; 397

Ligand- & substrate-binding residues (4): 491; 437; 439; 486

Post-translational modifications (1): 2

Glycosylation sites (1): 614

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-9769733	Fibrin formation
R-HSA-140875

MSigDB gene sets: 330 (showing top): GOBP_PROTEIN_ACTIVATION_CASCADE, MCLACHLAN_DENTAL_CARIES_UP, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, MODULE_45, GOBP_PEPTIDE_CROSS_LINKING, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, KONG_E2F3_TARGETS, STOSSI_RESPONSE_TO_ESTRADIOL, BOHN_PRIMARY_IMMUNODEFICIENCY_SYNDROM_DN, PID_INTEGRIN_A9B1_PATHWAY, PATIL_LIVER_CANCER, GOBP_WOUND_HEALING, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN

GO Biological Process (4): blood coagulation (GO:0007596), peptide cross-linking (GO:0018149), blood coagulation, fibrin clot formation (GO:0072378), hemostasis (GO:0007599)

GO Molecular Function (5): protein-glutamine gamma-glutamyltransferase activity (GO:0003810), metal ion binding (GO:0046872), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)

GO Cellular Component (7): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012), platelet alpha granule lumen (GO:0031093), blood microparticle (GO:0072562), transferase complex (GO:1990234), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Signaling by Interleukins	1
Coagulation pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
hemostasis	1
wound healing	1
coagulation	1
protein modification process	1
blood coagulation	1
protein activation cascade	1
regulation of body fluid levels	1
aminoacyltransferase activity	1
catalytic activity, acting on a protein	1
cation binding	1
binding	1
catalytic activity	1
transferase activity	1
external encapsulating structure	1
platelet alpha granule	1
secretory granule lumen	1
extracellular region	1
catalytic complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2214 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
F13A1	F13B	P05160	945
F13A1	APLNR	P35414	777
F13A1	FGA	P02671	726
F13A1	F12	P00748	701
F13A1	FGB	P02675	701
F13A1	FGG	P02679	681
F13A1	ME2	P23368	669
F13A1	GLO1	P78375	668
F13A1	SERPINF2	P08697	659
F13A1	APLN	Q9ULZ1	641
F13A1	VWF	P04275	632
F13A1	SERPINB1	P30740	601
F13A1	PPBP	P02775	582
F13A1	P3H1	Q32P28	564
F13A1	F2	P00734	561

IntAct

108 interactions, top by confidence:

A	B	Type	Score
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
PLEK	CAVIN2	psi-mi:“MI:0914”(association)	0.560
F13A1	IL16	psi-mi:“MI:0915”(physical association)	0.560
POLR2E	F13A1	psi-mi:“MI:0915”(physical association)	0.560
TCAP	F13A1	psi-mi:“MI:0915”(physical association)	0.560
TSPAN2	F13A1	psi-mi:“MI:0915”(physical association)	0.560
TIMM17B	F13A1	psi-mi:“MI:0915”(physical association)	0.560
	F13A1	psi-mi:“MI:0915”(physical association)	0.560
F13A1	KLHL20	psi-mi:“MI:0915”(physical association)	0.560
F13A1	WWOX	psi-mi:“MI:0915”(physical association)	0.560
ESRP1	F13A1	psi-mi:“MI:0915”(physical association)	0.560
F13A1	CDCA4	psi-mi:“MI:0915”(physical association)	0.560
ASB13	F13A1	psi-mi:“MI:0915”(physical association)	0.560
F13A1	EGFL8	psi-mi:“MI:0915”(physical association)	0.560
TMTC1	F13A1	psi-mi:“MI:0915”(physical association)	0.560
ZHX1-C8orf76	F13A1	psi-mi:“MI:0915”(physical association)	0.560
RFFL	F13A1	psi-mi:“MI:0915”(physical association)	0.560
CMTM3	F13A1	psi-mi:“MI:0915”(physical association)	0.560
SGSM1	F13A1	psi-mi:“MI:0915”(physical association)	0.560
PPP1R21	F13A1	psi-mi:“MI:0915”(physical association)	0.560
FAM163A	F13A1	psi-mi:“MI:0915”(physical association)	0.560
PABIR3	F13A1	psi-mi:“MI:0915”(physical association)	0.560
LGALS9C	F13A1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (24): F13A1 (Co-purification), F13A1 (Co-fractionation), F13B (Co-purification), F13B (Co-fractionation), F13B (Reconstituted Complex), FN1 (Reconstituted Complex), FGA (Co-crystal Structure), HSPB1 (Co-localization), F13A1 (Affinity Capture-MS), F13A1 (Affinity Capture-MS), F13A1 (Proximity Label-MS), F13A1 (Two-hybrid), F13A1 (Affinity Capture-MS), F13A1 (Two-hybrid), F13A1 (Proximity Label-MS)

ESM2 similar proteins: A0A0Q3IBS1, I1H0V9, O08619, O18733, O54732, O82088, O88917, O94910, O97831, P00488, P08587, P13696, P14780, P22735, P22758, P23606, P30086, P31044, P41245, P41246, P51176, P51511, P52176, P52181, P52183, P54185, P93003, Q3YIX4, Q41261, Q5R4R0, Q656A5, Q80TR1, Q8MK67, Q8VIN1, Q8VWH2, Q93WI9, Q95220, Q9ASJ1, Q9D9G2, Q9FIT4

Diamond homologs: A6QP57, D4A5U3, O08619, O43548, O46510, O95932, P00488, P08587, P16452, P21980, P21981, P22735, P22758, P23606, P49221, P51176, P52181, P52183, Q01841, Q05187, Q08188, Q08189, Q8BH61, Q8BZH1, Q96PF1, Q99041, Q9D7I9, Q9GLK0, Q9JLF6, Q9WVJ6, P49222, P12260

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	31
Likely pathogenic	21
Uncertain significance	157
Likely benign	36
Benign	47

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1322859	NM_000129.4(F13A1):c.1405_1408del (p.Gln469fs)	Pathogenic
1526251	NM_000129.4(F13A1):c.460_461insGC (p.Ile154fs)	Pathogenic
16523	NM_000129.4(F13A1):c.131_132del	Pathogenic
16524	NM_000129.4(F13A1):c.2045G>A (p.Arg682His)	Pathogenic
16525	NM_000129.4(F13A1):c.514C>T (p.Arg172Ter)	Pathogenic
16526	NM_000129.4(F13A1):c.1326C>A (p.Tyr442Ter)	Pathogenic
16527	NM_000129.4(F13A1):c.183C>A (p.Asn61Lys)	Pathogenic
16529	NM_000129.4(F13A1):c.1687G>A (p.Gly563Arg)	Pathogenic
16530	NM_000129.4(F13A1):c.1243G>T (p.Val415Phe)	Pathogenic
16531	NM_000129.4(F13A1):c.782G>A (p.Arg261His)	Pathogenic
16534	NM_000129.4(F13A1):c.949G>T (p.Val317Phe)	Pathogenic
16535	NM_000129.4(F13A1):c.851A>G (p.Tyr284Cys)	Pathogenic
16536	NM_000129.4(F13A1):c.1201dup (p.Gln401fs)	Pathogenic
16539	NM_000129.4(F13A1):c.1984C>T (p.Arg662Ter)	Pathogenic
16540	NM_000129.4(F13A1):c.728T>C (p.Met243Thr)	Pathogenic
1705952	NM_000129.4(F13A1):c.1503C>A (p.Tyr501Ter)	Pathogenic
1809752	NM_000129.4(F13A1):c.27del (p.Phe9fs)	Pathogenic
2425612	NC_000006.11:g.(?5109657)(6320826_?)del	Pathogenic
2637102	NM_000129.4(F13A1):c.1305+1G>A	Pathogenic
2683978	NM_000129.4(F13A1):c.232C>T (p.Arg78Cys)	Pathogenic
29694	NM_000129.4(F13A1):c.603_606del (p.Arg202fs)	Pathogenic
29695	NM_000129.4(F13A1):c.-19+12=	Pathogenic
3032801	NM_000129.4(F13A1):c.521del (p.Ser174fs)	Pathogenic
3336542	NC_000006.11:g.(6146006_6152045)_(6182375_6196029)del	Pathogenic
3381001	NM_000129.4(F13A1):c.631G>A (p.Gly211Arg)	Pathogenic
3594056	NM_000129.4(F13A1):c.523C>T (p.Arg175Ter)	Pathogenic
4279121	GRCh37/hg19 6p25.1(chr6:6152630-6181197)x1	Pathogenic
4279369	GRCh37/hg19 6p25.1(chr6:6074094-6153379)x1	Pathogenic
617620	NM_000129.4(F13A1):c.1817del (p.His606fs)	Pathogenic
634901	NM_000129.4(F13A1):c.563G>T (p.Trp188Leu)	Pathogenic

SpliceAI

2328 predictions. Top by Δscore:

Variant	Effect	Δscore
6:6167453:CTGA:C	donor_loss	1.0000
6:6167454:TGACC:T	donor_loss	1.0000
6:6167455:GACCT:G	donor_loss	1.0000
6:6167456:ACC:A	donor_loss	1.0000
6:6167457:C:A	donor_loss	1.0000
6:6167614:CTTGA:C	acceptor_gain	1.0000
6:6167616:TGA:T	acceptor_gain	1.0000
6:6167616:TGACT:T	acceptor_loss	1.0000
6:6167619:C:CA	acceptor_loss	1.0000
6:6167619:C:CC	acceptor_gain	1.0000
6:6174578:A:AC	donor_gain	1.0000
6:6174579:C:CC	donor_gain	1.0000
6:6174579:CAGGA:C	donor_gain	1.0000
6:6181983:ATTAC:A	donor_loss	1.0000
6:6181984:TTAC:T	donor_loss	1.0000
6:6181985:TA:T	donor_loss	1.0000
6:6181987:CC:C	donor_loss	1.0000
6:6181987:CCTT:C	donor_gain	1.0000
6:6222032:CCA:C	donor_gain	1.0000
6:6222032:CCACA:C	donor_gain	1.0000
6:6222115:C:CT	acceptor_gain	1.0000
6:6222172:C:CC	acceptor_gain	1.0000
6:6224680:ACTT:A	donor_loss	1.0000
6:6224682:T:TC	donor_loss	1.0000
6:6224683:T:TC	donor_loss	1.0000
6:6224684:A:AC	donor_gain	1.0000
6:6224684:A:AT	donor_loss	1.0000
6:6224685:C:CT	donor_gain	1.0000
6:6224685:CA:C	donor_gain	1.0000
6:6224685:CAT:C	donor_gain	1.0000

AlphaMissense

4847 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:6224771:G:C	S296R	1.000
6:6224771:G:T	S296R	1.000
6:6224773:T:G	S296R	1.000
6:6197313:A:G	W376R	0.999
6:6197313:A:T	W376R	0.999
6:6222034:A:G	W371R	0.999
6:6222034:A:T	W371R	0.999
6:6195840:C:T	G421D	0.998
6:6195870:C:T	G411D	0.998
6:6197236:C:A	Q401H	0.998
6:6197236:C:G	Q401H	0.998
6:6197262:A:G	W393R	0.998
6:6197262:A:T	W393R	0.998
6:6197282:A:G	L386P	0.998
6:6197291:C:A	R383M	0.998
6:6197291:C:G	R383T	0.998
6:6197319:G:C	H374D	0.998
6:6197326:C:A	W371C	0.998
6:6197326:C:G	W371C	0.998
6:6224819:C:A	W280C	0.998
6:6224819:C:G	W280C	0.998
6:6224821:A:G	W280R	0.998
6:6224821:A:T	W280R	0.998
6:6266738:A:G	W131R	0.998
6:6266738:A:T	W131R	0.998
6:6174834:G:T	A498D	0.997
6:6182063:C:A	G462W	0.997
6:6195809:A:C	F431L	0.997
6:6195809:A:T	F431L	0.997
6:6195811:A:G	F431L	0.997

dbSNP variants (sampled 300 via entrez): RS1000016413 (6:6161835 C>T), RS1000022102 (6:6204831 T>C), RS1000056351 (6:6158117 A>G), RS1000071329 (6:6284862 A>G), RS1000082016 (6:6320011 G>A,C), RS1000088809 (6:6237614 T>G), RS1000089120 (6:6197969 G>A,C), RS1000117646 (6:6180993 G>A), RS1000127040 (6:6277842 T>G), RS1000128157 (6:6237248 G>C), RS1000132972 (6:6156018 T>C), RS1000225025 (6:6210043 T>C), RS1000252275 (6:6230471 C>T), RS1000268561 (6:6284560 C>A), RS1000284074 (6:6163367 A>G)

Disease associations

OMIM: gene MIM:134570 | disease phenotypes: MIM:613225, MIM:614946, MIM:188050, MIM:608446

GenCC curated gene-disease

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

Mondo (6): factor XIII, A subunit, deficiency of (MONDO:0013187), combined oxidative phosphorylation defect type 14 (MONDO:0013986), congenital factor XIII deficiency (MONDO:0018029), thrombophilia due to thrombin defect (MONDO:0008559), myocardial infarction, susceptibility to (MONDO:0012039), thrombocytopenia (MONDO:0002049)

Orphanet (2): Congenital factor XIII deficiency (Orphanet:331), Combined oxidative phosphorylation defect type 14 (Orphanet:319519)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
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:0001907	Thromboembolism
HP:0001933	Subcutaneous hemorrhage
HP:0001934	Persistent bleeding after trauma
HP:0002037	Inflammation of the large intestine
HP:0002170	Intracranial hemorrhage
HP:0002204	Pulmonary embolism
HP:0002625	Deep venous thrombosis
HP:0003577	Congenital onset
HP:0003623	Neonatal onset
HP:0004419	Recurrent thrombophlebitis
HP:0004846	Prolonged bleeding after surgery
HP:0005261	Joint hemorrhage
HP:0005305	Cerebral venous thrombosis
HP:0006298	Prolonged bleeding after dental extraction
HP:0007420	Spontaneous hematomas
HP:0008357	Reduced factor XIII activity
HP:0011463	Childhood onset
HP:0011884	Abnormal umbilical stump bleeding
HP:0011889	Bleeding with minor or no trauma
HP:0011891	Post-partum hemorrhage

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST000899_1	Entorhinal cortical volume	3.000000e-07
GCST001798_10	End-stage coagulation	1.000000e-17
GCST001798_12	End-stage coagulation	4.000000e-17
GCST001798_17	End-stage coagulation	3.000000e-186
GCST001798_18	End-stage coagulation	8.000000e-142
GCST001798_9	End-stage coagulation	5.000000e-18
GCST003542_46	Night sleep phenotypes	7.000000e-06
GCST004125_3	Type 2 diabetes (age of onset)	4.000000e-06
GCST005166_6	GIP levels in response to oral glucose tolerance test (120 minutes)	4.000000e-08
GCST005956_65	Waist-to-hip ratio adjusted for BMI	9.000000e-15
GCST005957_8	Waist-to-hip ratio adjusted for BMI (age <50)	3.000000e-06
GCST005958_12	Waist-to-hip ratio adjusted for BMI (age >50)	2.000000e-09
GCST005962_23	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	4.000000e-14
GCST006102_3	Interleukin-10 levels	7.000000e-08
GCST009441_3	Age-related cognitive decline (memory) (slope of z-scores)	4.000000e-06
GCST010292_4	Response to lamotrigine and valproic acid in genetic generalized epilepsy	2.000000e-06

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0005092	entorhinal cortical volume
EFO:0004307	glucose tolerance test
EFO:0008464	glucose-dependent insulinotropic peptide measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004750	interleukin 10 measurement
EFO:0007710	cognitive decline measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C567691	Factor Xiii, A Subunit, Deficiency Of (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4530 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 63,007 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL19612	SPERMIDINE	3	63,007

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs5985	Efficacy	3	aspirin
rs5985	Efficacy	3	Photodynamic therapy	Choroidal Neovascularization

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs5985	F13A1	3	2.75	2	aspirin;Photodynamic therapy

Binding affinities (BindingDB)

13 measured of 28 human assays (28 total across all organisms); most potent 13 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[2-[4-(adamantane-1-carbonyl)piperazin-1-yl]-2-oxo-ethyl]-2-bromo-acetamide (6e)	IC50	3.9 nM
(2S)-1-[(2S)-3-(1H-indol-3-yl)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(E,2S)-7-methoxy-7-oxo-2-[[(2S)-4-oxopyrrolidine-2-carbonyl]amino]hept-5-enoyl]amino]hexanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]pyrrolidine-2-carboxylic acid	IC50	56 nM	US-11472838: Inhibitors of blood coagulation factor XIII
(2S)-1-[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(E,2S)-2-[[(2R)-2-acetamido-3-carboxypropanoyl]amino]-7-methoxy-7-oxohept-5-enoyl]amino]hexanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]pyrrolidine-2-carboxylic acid	IC50	110 nM	US-11472838: Inhibitors of blood coagulation factor XIII
N-[2-[4-(adamantane-1-carbonyl)piperazin-1-yl]-2-oxo-ethyl]prop-2-enamide (3e)	IC50	125 nM
(2S)-3-(1H-indol-3-yl)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(E,2S)-7-methoxy-7-oxo-2-[[(2S)-4-oxopyrrolidine-2-carbonyl]amino]hept-5-enoyl]amino]hexanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]propanoic acid	IC50	226 nM	US-11472838: Inhibitors of blood coagulation factor XIII
(3R)-3-acetamido-4-[[(E,2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(1S)-1-carboxy-2-(1H-indol-3-yl)ethyl]carbamoyl]pyrrolidin-1-yl]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-7-methoxy-1,7-dioxohept-5-en-2-yl]amino]-4-oxobutanoic acid	IC50	465 nM	US-11472838: Inhibitors of blood coagulation factor XIII
[2-[[2-[4-(1-Adamantylmethoxycarbonyl)piperazin-1-yl]-2-oxo-ethyl]amino]-2-oxoethyl]-dimethyl-sulfonium bromide (1f)	IC50	775 nM
[2-[[2-[4-(Adamantane-1-carbonyl)piperazin-1-yl]-2-oxo-ethyl]amino]-2-oxo-ethyl]-dimethyl-sulfonium bromide (1e)	IC50	889 nM
1-Adamantylmethyl 4-[2-(prop-2-enoylamino)acetyl]piperazine-1-carboxylate (3f)	IC50	1620 nM
2-[[(E,2S)-1-[[(2S)-1-[(2S)-2-[[1-[2-[[(2S)-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]-2-oxo-3-pyridinyl]carbamoyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-7-methoxy-1,7-dioxohept-5-en-2-yl]carbamoyl]-5-nitrobenzoic acid	IC50	2140 nM	US-11472838: Inhibitors of blood coagulation factor XIII
CHEMBL2086541	IC50	2200 nM
CHEMBL2086544	IC50	2500 nM
CHEMBL5273326	IC50	118000 nM

ChEMBL bioactivities

173 potent at pChembl≥5 of 189 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.40	IC50	4	nM	CHEMBL3423198
8.40	IC50	4	nM	CHEMBL3423195
8.00	IC50	10	nM	CHEMBL5912424
7.96	IC50	11	nM	CHEMBL5872808
7.92	IC50	12	nM	CHEMBL5932274
7.89	IC50	13	nM	CHEMBL6009354
7.82	IC50	15	nM	CHEMBL6019101
7.80	IC50	16	nM	CHEMBL5803781
7.80	IC50	16	nM	CHEMBL5958971
7.77	IC50	17	nM	CHEMBL5842415
7.75	IC50	18	nM	CHEMBL5905380
7.70	IC50	20	nM	CHEMBL6029478
7.70	IC50	20	nM	CHEMBL5856535
7.68	IC50	21	nM	CHEMBL5941565
7.68	IC50	21	nM	CHEMBL5946903
7.62	IC50	24	nM	CHEMBL5803781
7.62	IC50	24	nM	CHEMBL5932274
7.58	IC50	26	nM	CHEMBL5281897
7.58	IC50	26	nM	CHEMBL5920169
7.57	IC50	27	nM	CHEMBL5912424
7.54	IC50	29	nM	CHEMBL5269766
7.46	IC50	35	nM	CHEMBL5972329
7.44	IC50	36	nM	CHEMBL5778990
7.41	IC50	39	nM	CHEMBL2086505
7.41	IC50	39	nM	CHEMBL6059760
7.39	IC50	41	nM	CHEMBL5812001
7.39	IC50	41	nM	CHEMBL6046024
7.38	IC50	42	nM	CHEMBL6018716
7.38	IC50	42	nM	CHEMBL5944421
7.37	IC50	43	nM	CHEMBL5739631
7.33	IC50	47	nM	CHEMBL5787046
7.32	IC50	48	nM	CHEMBL3423194
7.29	IC50	51	nM	CHEMBL2086890
7.29	IC50	51	nM	CHEMBL6061666
7.26	IC50	55	nM	CHEMBL3423193
7.25	IC50	56	nM	CHEMBL6003831
7.25	IC50	56	nM	CHEMBL6058715
7.23	IC50	59	nM	CHEMBL5971276
7.18	IC50	66	nM	CHEMBL2086891
7.16	IC50	70	nM	CHEMBL6033334
7.16	IC50	69	nM	CHEMBL5890665
7.16	IC50	69	nM	CHEMBL6040875
7.09	IC50	81	nM	CHEMBL5978266
7.07	IC50	86	nM	CHEMBL3423202
7.07	IC50	86	nM	CHEMBL5768237
7.05	IC50	90	nM	CHEMBL3423200
7.04	IC50	91	nM	CHEMBL5964005
7.02	IC50	96	nM	CHEMBL5970871
7.00	IC50	100	nM	CHEMBL193220
7.00	IC50	100	nM	CHEMBL3423203

PubChem BioAssay actives

111 with measured affinity, of 240 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2R,3S)-2-N-(3-phenoxyphenyl)oxirane-2,3-dicarboxamide	1204592: Inhibition of thrombin-activated F13-A (unknown origin) in plasma assessed as inhibition of fibrin clot formation after 7 mins by biotin incorporation assay	ic50	0.0040	uM
(2S,3R)-2-N-(4-bromo-3-chlorophenyl)oxirane-2,3-dicarboxamide	1204592: Inhibition of thrombin-activated F13-A (unknown origin) in plasma assessed as inhibition of fibrin clot formation after 7 mins by biotin incorporation assay	ic50	0.0040	uM
8-(3-oxocyclopropen-1-yl)-N-(2-phenylethyl)octanamide	1931553: Inhibition of human plasma coagulation factor XIIIa by fluorescence spectrophotometeric assay	ic50	0.0260	uM
ethyl 4-[[(E,2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-7-methoxy-1,7-dioxohept-5-en-2-yl]carbamoyl]-1,3-thiazole-2-carboxylate	1931557: Inhibition of human recombinant coagulation factor XIIIa	ic50	0.0290	uM
benzyl 4-[4-(prop-2-enoylamino)-2-(trifluoromethyl)phenyl]sulfonylpiperazine-1-carboxylate	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.0390	uM
(2R,3S)-2-N-(3-chlorophenyl)oxirane-2,3-dicarboxamide	1204592: Inhibition of thrombin-activated F13-A (unknown origin) in plasma assessed as inhibition of fibrin clot formation after 7 mins by biotin incorporation assay	ic50	0.0480	uM
tert-butyl 4-[2-fluoro-4-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.0510	uM
(2R,3S)-2-N-(4-phenoxyphenyl)oxirane-2,3-dicarboxamide	1204592: Inhibition of thrombin-activated F13-A (unknown origin) in plasma assessed as inhibition of fibrin clot formation after 7 mins by biotin incorporation assay	ic50	0.0550	uM
tert-butyl 4-[2-chloro-4-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.0660	uM
(2S,3R)-2-N-[4-(4-aminophenoxy)phenyl]oxirane-2,3-dicarboxamide	1204592: Inhibition of thrombin-activated F13-A (unknown origin) in plasma assessed as inhibition of fibrin clot formation after 7 mins by biotin incorporation assay	ic50	0.0860	uM
(2S,3R)-2-N-[4-[2-[(2-nitrophenyl)sulfonylamino]ethyl]phenyl]oxirane-2,3-dicarboxamide	1204592: Inhibition of thrombin-activated F13-A (unknown origin) in plasma assessed as inhibition of fibrin clot formation after 7 mins by biotin incorporation assay	ic50	0.0900	uM
(4S)-5-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[2-[[(2S,3S)-1-[(2S)-2-[[(2S)-4-amino-1-[(2S)-2-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2R)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[(2S)-2-[[(2S)-5-amino-1-[[(1R)-1-carboxy-2-sulfanylethyl]amino]-1,5-dioxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1,4-dioxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-[[(2S)-6-amino-2-[[(2R)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[2-(3-hydroxy-6-oxoxanthen-9-yl)benzoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-3-sulfanylpropanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid	1171554: Binding affinity to recombinant F13A (unknown origin) by microscale thermophoresis method	kd	0.1000	uM
(2S,3R)-2-N-[4-[4-[(4-fluorobenzoyl)amino]phenoxy]phenyl]oxirane-2,3-dicarboxamide	1204592: Inhibition of thrombin-activated F13-A (unknown origin) in plasma assessed as inhibition of fibrin clot formation after 7 mins by biotin incorporation assay	ic50	0.1000	uM
1-[(5-methyl-[1,3]thiazolo[2,3-b][1,3,4]thiadiazol-4-ium-2-yl)sulfanyl]propan-2-one perchlorate	240700: In vitro inhibitory concentration of compound against factor XIIIa	ic50	0.1000	uM
1-[(5-methyl-[1,3]thiazolo[2,3-b][1,3,4]thiadiazol-4-ium-2-yl)sulfanyl]propan-2-one	1931545: Inhibition of human plasma coagulation factor XIIIa	ic50	0.1000	uM
methyl (E,6S)-6-(1H-benzimidazole-2-carbonylamino)-7-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-7-oxohept-2-enoate	1931557: Inhibition of human recombinant coagulation factor XIIIa	ic50	0.1020	uM
N-[6-[imidazo[1,2-d][1,2,4]thiadiazol-3-yl(methyl)amino]hexyl]-2-nitrobenzenesulfonamide	240700: In vitro inhibitory concentration of compound against factor XIIIa	ic50	0.1100	uM
(2S,3R)-2-N-(3,4-dimethylphenyl)oxirane-2,3-dicarboxamide	1204592: Inhibition of thrombin-activated F13-A (unknown origin) in plasma assessed as inhibition of fibrin clot formation after 7 mins by biotin incorporation assay	ic50	0.1100	uM
(2S)-1-[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(E,2S)-2-[[(2R)-2-acetamido-3-carboxypropanoyl]amino]-7-methoxy-7-oxohept-5-enoyl]amino]hexanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]pyrrolidine-2-carboxylic acid	1931557: Inhibition of human recombinant coagulation factor XIIIa	ic50	0.1100	uM
N-[6-(imidazo[1,2-d][1,2,4]thiadiazol-3-ylamino)hexyl]-2-nitrobenzenesulfonamide	240700: In vitro inhibitory concentration of compound against factor XIIIa	ic50	0.1300	uM
(2S,3R)-2-N-(4-bromophenyl)oxirane-2,3-dicarboxamide	1204592: Inhibition of thrombin-activated F13-A (unknown origin) in plasma assessed as inhibition of fibrin clot formation after 7 mins by biotin incorporation assay	ic50	0.1300	uM
methyl (E,6S)-7-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-6-[(2-methyl-1,3-thiazole-4-carbonyl)amino]-7-oxohept-2-enoate	1931557: Inhibition of human recombinant coagulation factor XIIIa	ic50	0.1390	uM
N-[4-[4-(adamantane-1-carbonyl)piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.1800	uM
ethyl 4-[4-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.1800	uM
N-[2-(4-hydroxyphenyl)ethyl]acetamide	1931556: Inhibition of human coagulation factor XIIIa	ic50	0.2000	uM
N-[4-[4-[(1S,2S)-2-phenylcyclopropanecarbonyl]piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.2000	uM
tert-butyl 4-[2-methyl-4-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.2100	uM
(2R,3S)-2-N-(4-butylphenyl)oxirane-2,3-dicarboxamide	1204592: Inhibition of thrombin-activated F13-A (unknown origin) in plasma assessed as inhibition of fibrin clot formation after 7 mins by biotin incorporation assay	ic50	0.2200	uM
N-[4-[4-(6-methyl-2-pyridinyl)piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.2200	uM
(2-methylphenyl)methyl 4-[4-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.2300	uM
cyclopentyl 4-[4-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.2400	uM
(2-chlorophenyl)methyl 4-[4-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.2500	uM
N-[4-[4-[3-(trifluoromethyl)-2-pyridinyl]piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.2500	uM
N-[4-[4-(cyclopentanecarbonyl)piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.2800	uM
N-[4-[4-(3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinoline-2-carbonyl)piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.2800	uM
N-[4-[4-(piperidine-1-carbonyl)piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.3000	uM
11-(3-oxocyclopropen-1-yl)undecanoic acid	1931553: Inhibition of human plasma coagulation factor XIIIa by fluorescence spectrophotometeric assay	ic50	0.3100	uM
N-[4-[4-(cyclopropanecarbonyl)piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.3100	uM
N-[4-[4-(4,4-difluoropiperidine-1-carbonyl)piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.3100	uM
benzyl N-[1-[4-(prop-2-enoylamino)phenyl]sulfonylpiperidin-4-yl]carbamate	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.3100	uM
methyl 4-[4-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.3100	uM
(2,3-difluorophenyl)methyl 4-[4-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.3200	uM
(4-fluorophenyl)methyl 4-[4-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.3300	uM
N-[4-[4-(3,4,4a,5,6,7,8,8a-octahydro-2H-quinoline-1-carbonyl)piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.3300	uM
[2-(trifluoromethyl)phenyl]methyl 4-[4-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.3400	uM
N-[4-[4-(3-methyl-2-pyridinyl)piperazin-1-yl]sulfonylphenyl]prop-2-enamide	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.3400	uM
1-(1,3-dimethyl-4,5-diphenylimidazol-1-ium-2-yl)sulfanylpropan-2-one	1931545: Inhibition of human plasma coagulation factor XIIIa	ic50	0.3500	uM
benzyl 4-[3-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.3500	uM
N-[4-(4-phenylpiperazin-1-yl)sulfonylphenyl]prop-2-enamide	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.3700	uM
naphthalen-1-ylmethyl 4-[4-(prop-2-enoylamino)phenyl]sulfonylpiperazine-1-carboxylate	683887: Inhibition of thrombin activated human F13a by fluorescent transamidation assay	ic50	0.3800	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects expression, affects cotreatment, decreases expression	3
Valproic Acid	affects expression, decreases expression, increases expression	3
nickel sulfate	decreases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Progesterone	affects cotreatment, decreases expression	2
triphenyl phosphate	affects expression	1
lead acetate	increases expression	1
sulforaphane	decreases expression	1
tebuconazole	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
belinostat	increases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
incobotulinumtoxinA	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	increases expression	1
Benzene	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Calcitriol	decreases expression	1
Copper	affects cotreatment, increases expression	1
Succimer	affects cotreatment, decreases expression	1
Dinitrochlorobenzene	decreases expression	1
Doxorubicin	decreases expression	1
Eugenol	decreases expression	1
Iodoacetamide	decreases activity	1
Iron	decreases expression	1

ChEMBL screening assays

42 unique, capped per target: 42 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2091160	Binding	Inhibition of thrombin activated human F13a by fluorescent transamidation assay	Discovery and structure-activity relationship of potent and selective covalent inhibitors of transglutaminase 2 for Huntington’s disease. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00077753	PHASE4	COMPLETED	EXCLAIM:Extended Prophylaxis for Venous ThromboEmbolism (VTE) in Acutely Ill Medical Patients With Prolonged Immobilization
NCT00196118	PHASE4	COMPLETED	Study of IVC Filter Retrieval With the Günther Tulip Vena Cava Filter
NCT00437697	PHASE4	TERMINATED	Thromboprophylaxis in Critically Ill Patients
NCT00445328	PHASE4	TERMINATED	Dalteparin vs Unfractionated Heparin For The Prevention Of Venous Thromboembolism (VTE) In Hospitalized Acutely Ill Medical Patients
NCT00689520	PHASE4	COMPLETED	Long-Term Low-Molecular-Weight Heparin Versus Oral Anticoagulants in Deep Venous Thrombosis
NCT00851864	PHASE4	COMPLETED	Safety and Efficacy of Therapeutic Anticoagulation With Tinzaparin During Pregnancy Via Weight-based Dosing
NCT00966277	PHASE4	COMPLETED	Dalteparin for Primary Venous Thromboembolism (VTE) Prophylaxis in Pancreatic Cancer Patients
NCT00967304	PHASE4	COMPLETED	Clinical Decision Rule Validation Study to Predict Low Recurrent Risk in Patients With Unprovoked Venous Thromboembolism
NCT01119261	PHASE4	COMPLETED	EUropean Pharmacogenetics of AntiCoagulant Therapy - Acenocoumarol
NCT01119274	PHASE4	COMPLETED	EUropean Pharmacogenetics of AntiCoagulant Therapy - Phenprocoumon
NCT01119300	PHASE4	COMPLETED	EUropean Pharmacogenetics of AntiCoagulant Therapy - Warfarin
NCT01210755	PHASE4	COMPLETED	Study in Healthy Volunteers of the Reversion by Haemostatic Drugs of the Anticoagulant Effect of New Anti-thrombotics
NCT01304108	PHASE4	COMPLETED	Improving Venous Thromboembolism Prophylaxis
NCT01467583	PHASE4	COMPLETED	Fondaparinux in Critically Ill Patients With Renal Failure
NCT01916707	PHASE4	UNKNOWN	Weight Based Enoxaparin in Trauma Patients
NCT02095509	PHASE4	COMPLETED	Pharmacokinetics of Enoxaparin in Intensive Care Patients
NCT02396732	PHASE4	TERMINATED	Aspirin and Enoxaparin for VTE in Trauma
NCT02412982	PHASE4	COMPLETED	Evaluation of Venous Thromboembolism Prevention in High-Risk Trauma Patients
NCT02464969	PHASE4	COMPLETED	Apixaban for the Acute Treatment of Venous Thromboembolism in Children
NCT02474212	PHASE4	COMPLETED	: Pharmacokinetics of Enoxaparin After Coronary Artery Bypass Graft Surgery
NCT02559856	PHASE4	COMPLETED	Comparison of Bleeding Risk Between Rivaroxaban and Apixaban: The Pilot Study
NCT02856295	PHASE4	COMPLETED	anti10a Levels in Women Treated With LMWH in the Postpartum Period
NCT02945280	PHASE4	TERMINATED	Apixaban for Routine Management of Upper Extremity Deep Venous Thrombosis
NCT02958969	PHASE4	COMPLETED	Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
NCT03006562	PHASE4	TERMINATED	PREvention of VENous ThromboEmbolism Following Radical Prostatectomy
NCT03158792	PHASE4	COMPLETED	Enoxaparin 20mg Versus 30mg Subcutaneously Once Daily in Elderly Patients With Impaired Renal Function
NCT03196349	PHASE4	TERMINATED	Comparison of Oral Anticoagulants for Extended VEnous Thromboembolism
NCT03244020	PHASE4	ENROLLING_BY_INVITATION	LMWH vs Aspirin for VTE Prophylaxis in Orthopaedic Oncology
NCT03266783	PHASE4	COMPLETED	Comparison of Bleeding Risk Between Rivaroxaban and Apixaban for the Treatment of Acute Venous Thromboembolism
NCT03426982	PHASE4	UNKNOWN	Comparision Between Activated Partial Thromboplastin Time Versus Anti-Xa Activity in Heparin Monitoring
NCT03678506	PHASE4	TERMINATED	Apixaban for Extended Anticoagulation (APIDULCIS)
NCT03988101	PHASE4	COMPLETED	Role of Statin in Venous Dysfunction in Patients With Venous Thromboembolism Event
NCT03988231	PHASE4	WITHDRAWN	Enoxaparin Versus Placebo for Venous Thromboembolism Prevention in Low Risk Cancer Patients After Surgical Procedures: a Randomized, Double Blind, Placebo Controlled Clinical Trial Pilot Study
NCT04128254	PHASE4	UNKNOWN	A Prospective Study in Chinese Patients With Lower Extremity Ankle Fracture of Oral Anticoagulants to Prevent Venous Thromboembolism (VTE)
NCT04157881	PHASE4	COMPLETED	A Study on the Impact of Rabeprazole-induced Elevated Stomach pH on APO-Dabigatran Exposure in Healthy Volunteers
NCT04168203	PHASE4	COMPLETED	Extended-Duration Low-Intensity Apixaban to Prevent Recurrence in High-Risk Patients With Provoked Venous Thromboembolism
NCT04169269	PHASE4	UNKNOWN	Deep Vein Thrombosis Prophylaxis Adherence: Enoxaparin vs Rivaroxaban
NCT04263038	PHASE4	RECRUITING	Clinical Surveillance vs. Anticoagulation for Low-risk Patients With Isolated Subsegmental Pulmonary Embolism
NCT04352439	PHASE4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
NCT04409834	PHASE4	COMPLETED	Prevention of Arteriovenous Thrombotic Events in Critically-Ill COVID-19 Patients Trial