SERPINF2

Summary

SERPINF2 (serpin family F member 2, HGNC:9075) is a protein-coding gene on chromosome 17p13.3, encoding Alpha-2-antiplasmin (P08697). Serine protease inhibitor.

This gene encodes a member of the serpin family of serine protease inhibitors. The protein is a major inhibitor of plasmin, which degrades fibrin and various other proteins. Consequently, the proper function of this gene has a major role in regulating the blood clotting pathway. Mutations in this gene result in alpha-2-plasmin inhibitor deficiency, which is characterized by severe hemorrhagic diathesis. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5345 — RefSeq curated summary.

At a glance

• Gene–disease (curated): alpha-2-plasmin inhibitor deficiency (Definitive, ClinGen)
• GWAS associations: 9
• Clinical variants (ClinVar): 112 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 13
• MANE Select transcript: NM_000934

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9075
Approved symbol	SERPINF2
Name	serpin family F member 2
Location	17p13.3
Locus type	gene with protein product
Status	Approved
Aliases	API, ALPHA-2-PI, A2AP, AAP, alpha2AP
Ensembl gene	ENSG00000167711
Ensembl biotype	protein_coding
OMIM	613168
Entrez	5345

Gene structure

Transcript identifiers

Ensembl transcripts: 74 — 74 protein_coding

ENST00000324015, ENST00000382061, ENST00000450523, ENST00000453066, ENST00000453723, ENST00000883591, ENST00000883592, ENST00000883593, ENST00000883594, ENST00000883595, ENST00000883596, ENST00000883597, ENST00000883598, ENST00000883599, ENST00000883600, ENST00000883601, ENST00000883602, ENST00000883603, ENST00000883604, ENST00000883605, ENST00000883606, ENST00000883607, ENST00000883608, ENST00000883609, ENST00000883610, ENST00000883611, ENST00000883612, ENST00000883613, ENST00000883614, ENST00000883615, ENST00000883616, ENST00000883617, ENST00000883618, ENST00000883619, ENST00000883620, ENST00000883621, ENST00000883622, ENST00000883623, ENST00000883624, ENST00000883625, ENST00000883626, ENST00000883627, ENST00000883628, ENST00000883629, ENST00000883630, ENST00000883631, ENST00000883632, ENST00000883633, ENST00000883634, ENST00000883635, ENST00000883636, ENST00000883637, ENST00000883638, ENST00000883639, ENST00000883640, ENST00000883641, ENST00000883642, ENST00000883643, ENST00000883644, ENST00000883645, ENST00000883646, ENST00000883647, ENST00000883648, ENST00000883649, ENST00000883650, ENST00000883651, ENST00000883652, ENST00000883653, ENST00000883654, ENST00000883655, ENST00000960968, ENST00000960969, ENST00000960970, ENST00000960971

RefSeq mRNA: 3 — MANE Select: NM_000934 NM_000934, NM_001165920, NM_001165921

CCDS: CCDS11011, CCDS54064

Canonical transcript exons

ENST00000453066 — 10 exons

Exon	Start	End
ENSE00001116016	1745708	1745909
ENSE00001116017	1745333	1745395
ENSE00001116020	1748598	1748740
ENSE00001116021	1747309	1747512
ENSE00001116023	1747019	1747162
ENSE00001116024	1752586	1752790
ENSE00001245457	1745175	1745213
ENSE00001293547	1754122	1755265
ENSE00001490804	1744992	1745058
ENSE00003902375	1742871	1742908

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 99.71.

FANTOM5 (CAGE): breadth broad, TPM avg 10.0353 / max 3120.9348, expressed in 217 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158748	8.9631	151
158747	0.5973	74
158749	0.3620	69
158750	0.0649	13
158754	0.0481	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	99.71	gold quality
liver	UBERON:0002107	99.56	gold quality
adult mammalian kidney	UBERON:0000082	94.53	gold quality
kidney	UBERON:0002113	89.88	gold quality
left uterine tube	UBERON:0001303	85.63	gold quality
prostate gland	UBERON:0002367	83.78	gold quality
metanephros cortex	UBERON:0010533	83.25	gold quality
upper lobe of left lung	UBERON:0008952	81.27	gold quality
cortex of kidney	UBERON:0001225	81.11	gold quality
right ovary	UBERON:0002118	80.62	gold quality
thoracic mammary gland	UBERON:0005200	79.30	gold quality
right testis	UBERON:0004534	79.19	gold quality
right lobe of thyroid gland	UBERON:0001119	79.11	gold quality
myometrium	UBERON:0001296	78.12	gold quality
omental fat pad	UBERON:0010414	78.02	gold quality
adipose tissue	UBERON:0001013	77.79	gold quality
subcutaneous adipose tissue	UBERON:0002190	77.71	gold quality
popliteal artery	UBERON:0002250	77.64	gold quality
tibial artery	UBERON:0007610	77.62	gold quality
mucosa of stomach	UBERON:0001199	77.36	gold quality
small intestine Peyer’s patch	UBERON:0003454	76.97	gold quality
left coronary artery	UBERON:0001626	76.47	gold quality
body of pancreas	UBERON:0001150	76.42	gold quality
testis	UBERON:0000473	76.33	gold quality
left testis	UBERON:0004533	76.27	gold quality
fallopian tube	UBERON:0003889	76.25	gold quality
left ovary	UBERON:0002119	75.98	gold quality
body of uterus	UBERON:0009853	75.76	gold quality
ovary	UBERON:0000992	75.60	gold quality
endocervix	UBERON:0000458	74.78	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-9	yes	54.64
E-ANND-3	yes	9.56

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, JUN, NR4A1

miRNA regulators (miRDB)

47 targeting SERPINF2, 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-4425	100.00	67.59	1049
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-4999-3P	99.11	65.55	424
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987

Literature-anchored findings (GeneRIF, showing 40)

• Multiple Lys residues within alpha 2-antiplasmin contribute, perhaps in a zipper-like fashion, to its binding to the in-tandem, multikringle array that configures the plasmin heavy chain. (PMID:12549929)
• Alpha2-antiplasmin has an important role in acute pulmonary embolism (PMID:12911586)
• alpha2-antiplasmin induction inhibits E-cadherin processing mediated by the plasminogen activator/plasmin system, leading to suppression of progression of oral squamous cell carcinoma via upregulation of cell-cell adhesion (PMID:17203182)
• the Arg6Trp polymorphism may play a significant role in governing the long-term deposition/removal of intravascular fibrin (PMID:17317851)
• TAFIa, PAI-1 and alpha-antiplasmin: complementary roles in regulating lysis of thrombi and plasma clots (PMID:17388801)
• Fibrinolysis is amplified by converting alpha-antiplasmin from a plasmin inhibitor to a substrate (PMID:17883703)
• Hydroxyethyl starch (HES) dilution enhances fibrinolysis by diminishing alpha2-antiplasmin-plasmin interactions. (PMID:17890952)
• Sequencing analysis revealed the presence of two alpha2-PI gene variations, both in the second half of exon 10: a frameshift mutation and a G to A transition at nucleotide 11337 in codon 407. (PMID:17961166)
• Thrombin activatable fibrinolysis inhibitor and alpha(2)-antiplasmin are not markers for recanalization in patients with ischemic stroke treated with recombinant tissue-type plasminogen activator. (PMID:18048863)
• Identification in human milk of complexes of matriptase with ATIII, A1AT, or A2AP, provides evidence that the proteolytic activity of matriptase, from cells that express no or low levels of HAI-1, may be controlled by secreted serpins. (PMID:18550704)
• Plasmin in nephrotic urine activates the epithelial sodium channel (PMID:19073825)
• deficiency in patients with Philadelphia chromosome-positive haematologic cancer receiving imatinib mesylate (PMID:19492163)
• FXIIIa substrate, A2AP, sequences suggests that the residue located two positions beyond the reactive glutamine is not conserved. this position makes important contributions to effective FXIIIa-A2AP interactions (PMID:19691486)
• OPN is highly susceptible to cleavage near its integrin-binding motifs, and the protein is a novel substrate for plasmin and cathepsin D (PMID:20071328)
• Results describe the functional characterization of the unique plasmin(ogen)-binding region of the human alpha(2)-plasmin inhibitor. (PMID:20112045)
• ADAMTS13 inactivation by plasmin as a potential cause of thrombotic thrombocytopenic purpura (PMID:20553378)
• fibrinolysis is enhanced by inhibiting enzymatic cleavage of precursor alpha2-antiplasmin (PMID:21251197)
• the antifibrinolytic function of FXIII is independent of fibrin-fibrin cross-linking and is expressed exclusively through alphaAP. (PMID:21471521)
• Truncation of monocyte chemoattractant protein 1 by plasmin promotes blood-brain barrier disruption. (PMID:21486949)
• Levels of free full-length alpha2AP were decreased in myocardial infarction (MI); the percentage of C-terminally cleaved alpha2AP was unaltered, and Arg407Lys did not influence alpha2AP levels or MI risk. (PMID:21505192)
• When the C terminus of alpha(2)-antiplasmin was removed, the binding affinity for active site-blocked plasmin remained high, suggesting additional exosite interactions between the serpin core and plasmin. (PMID:21543325)
• Study revealed that plasmin was present in tumor tissue, and that it was responsible for processing progalanin to galanin(1-20) in the extracellular environment. (PMID:21707521)
• Data suggest that decreased amounts of alpha2-plasmin inhibitor in plasma vs serum ex vivo may reflect reduced factor XIII (FXIII) in vivo; thus, plasma vs serum alpha2-plasmin inhibitor may be useful diagnostic marker for severe FXIII deficiency. (PMID:22205503)
• protective mediator during gram-negative (pneumo)sepsis, limiting bacterial growth, inflammation, tissue injury, and coagulation (PMID:23992406)
• increased N-terminal cleavage of alpha2AP may have a role in liver cirrhosis (PMID:24034420)
• Two differentially expressed proteins, alpha-1-antitrypsin (SERPINA1) and alpha-2 antiplasmin (SERPINF2) are associated with purpura fulminans. (PMID:24659849)
• Data suggest serum A2AP (SERPINF2) level can serve as biomarker for diabetic retinopathy; levels of A2AP (but not fibrinogen, plasminogen, or plasminogen activator inhibitor 1) are up-regulated in hyperglycemic type 1 diabetes with retinopathy. (PMID:24818165)
• Possession of the alpha2AP 407Lys allele was negatively associated with AAA, and thus changes in alpha2AP may affect aneurysm growth and development. (PMID:25065555)
• FXIII-A has a functional role through exposure on the activated platelet membrane where it exerts antifibrinolytic function by cross-linking alpha2AP to fibrin (PMID:25331118)
• A significant correlation was found between soluble fibroblast activation protein levels and alpha2-antiplasmin cleavage in coronary thrombosis. (PMID:25464232)
• Changes in plasma A2AP are associated with cardiovascular disease event presentation. (PMID:26088309)
• This review presents recent findings regarding the main aspects of the natural heterogeneity of A2AP with particular focus on the functional and possible clinical implications. [review] (PMID:26626994)
• alpha2AP has a profibrotic effect probably not by the action as a plasmin inhibitor, and the blocking of alpha2AP exerts an antifibrotic effect in humans and mice with systemic sclerosis (PMID:26743600)
• Higher plasma concentrations of a-2-AP and PAI-1 in patients with OSA indicated that these patients had increased prothrombotic activity. OSA increases the risk of cardiovascular complications as it enhances prothrombotic activity. (PMID:27861608)
• Data suggest that protein aggregates interact with tissue-type plasminogen activator and plasminogen to efficiently generate plasmin; this aggregate-bound plasmin is shielded from inhibition by alpha-2-antiplasmin and degrades protein aggregates to release smaller, soluble but relatively hydrophobic peptide fragments; these fragments bind to and are cytotoxic to microglia (by not vascular endothelial cells). (PMID:28710283)
• findings suggest that the alpha2AP Arg407Lys polymorphism could be involved in the pathogenesis of cerebral ischemia and its outcomes (PMID:29306602)
• Studied sex hormone and serpin family F member 2 (SERPINF2) levels in preeclampsia and found a correlation between imbalanced steroid hormone levels and excessive SERPINF2 in early-onset preeclampsia patients. (PMID:30020241)
• Data show that total free alpha-2-plasmin inhibitor (alpha2-PI) in human body fluids can be accurate and fast measured by new sandwich enzyme-linked immunosorbent assay (ELISA) method. (PMID:31129263)
• Abnormal fibrinolysis recognized by thromboelastography in a case of severe bleeding with normal coagulation and platelet function, leads to detection of a novel SERPINF2 variant causing severe alpha-2-antiplasmin deficiency. (PMID:31282989)
• human alpha2-antiplasmin is glycated and acetylated at several sites, with the possible competition between acetylation and glycation at K-182 and K-448; finding suggests possibly relevant alterations to alpha2-antiplasmin function at high glycemia and during aspirin use (PMID:31653347)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	serpinf2b	ENSDARG00000061383
danio_rerio	serpinf2a	ENSDARG00000076448
mus_musculus	Serpinf2	ENSMUSG00000038224
rattus_norvegicus	Serpinf2	ENSRNOG00000003233

Paralogs (36): SERPINB1 (ENSG00000021355), SERPINB3 (ENSG00000057149), SERPIND1 (ENSG00000099937), SERPINA4 (ENSG00000100665), SERPINE1 (ENSG00000106366), SERPINI2 (ENSG00000114204), SERPINC1 (ENSG00000117601), SERPINA7 (ENSG00000123561), SERPINB6 (ENSG00000124570), SERPINF1 (ENSG00000132386), AGT (ENSG00000135744), SERPINE2 (ENSG00000135919), SERPINA10 (ENSG00000140093), SERPING1 (ENSG00000149131), SERPINH1 (ENSG00000149257), SERPINI1 (ENSG00000163536), SERPINA12 (ENSG00000165953), SERPINB7 (ENSG00000166396), SERPINB8 (ENSG00000166401), SERPINB12 (ENSG00000166634), SERPINA9 (ENSG00000170054), SERPINA6 (ENSG00000170099), SERPINB9 (ENSG00000170542), SERPINA11 (ENSG00000186910), SERPINA5 (ENSG00000188488), SERPINA3 (ENSG00000196136), SERPINA1 (ENSG00000197249), SERPINB2 (ENSG00000197632), SERPINB13 (ENSG00000197641), SERPINB11 (ENSG00000206072), SERPINB4 (ENSG00000206073), SERPINB5 (ENSG00000206075), HMSD (ENSG00000221887), SERPINB10 (ENSG00000242550), SERPINE3 (ENSG00000253309), SERPINA2 (ENSG00000258597)

Protein

Protein identifiers

Alpha-2-antiplasmin — P08697 (reviewed: P08697)

Alternative names: Alpha-2-plasmin inhibitor, Serpin F2

All UniProt accessions (3): C9JMH6, C9JPV4, P08697

UniProt curated annotations — full annotation on UniProt →

Function. Serine protease inhibitor. The major targets of this inhibitor are plasmin and trypsin, but it also inactivates matriptase-3/TMPRSS7 and chymotrypsin.

Subunit / interactions. Forms protease inhibiting heterodimer with TMPRSS7.

Subcellular location. Secreted.

Tissue specificity. Expressed by the liver and secreted in plasma.

Post-translational modifications. Proteolytically cleaved at Pro-39 by both the prolyl endopeptidase FAP form and antiplasmin-cleaving enzyme FAP soluble form to generate mature alpha-2-antiplasmin.

Disease relevance. Alpha-2-plasmin inhibitor deficiency (APLID) [MIM:262850] An autosomal recessive disorder resulting in severe hemorrhagic diathesis. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the serpin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P08697-1	1	yes
P08697-2	2

RefSeq proteins (3): NP_000925, NP_001159392, NP_001159393 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000215	Serpin_fam	Family
IPR023795	Serpin_CS	Conserved_site
IPR023796	Serpin_dom	Domain
IPR033833	Alpha2AP_serpin_dom	Domain
IPR036186	Serpin_sf	Homologous_superfamily
IPR042178	Serpin_sf_1	Homologous_superfamily
IPR042185	Serpin_sf_2	Homologous_superfamily

Pfam: PF00079

UniProt features (30 total): sequence variant 8, sequence conflict 5, glycosylation site 4, site 3, splice variant 2, region of interest 2, signal peptide 1, propeptide 1, disulfide bond 1, cross-link 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08697-F1	78.94	0.64

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 (3): 39–40 (cleavage; by prolyl endopeptidase fap, antiplasmin-cleaving enzyme fap soluble form); 403–404 (reactive bond for plasmin); 404–405 (reactive bond for chymotrypsin)

Post-translational modifications (2): 41, 484

Disulfide bonds (1): 70–143

Glycosylation sites (4): 295, 309, 316, 126

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-75205	Dissolution of Fibrin Clot
R-HSA-109582	Hemostasis
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+

MSigDB gene sets: 271 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_COAGULATION, GNF2_GSTM1, GOCC_SECRETORY_GRANULE, GOBP_REGULATION_OF_CELL_CELL_ADHESION_MEDIATED_BY_CADHERIN, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, TTTGTAG_MIR520D, GNF2_HPN, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE

GO Biological Process (17): maintenance of blood vessel diameter homeostasis by renin-angiotensin (GO:0002034), acute-phase response (GO:0006953), negative regulation of plasminogen activation (GO:0010757), collagen fibril organization (GO:0030199), positive regulation of collagen biosynthetic process (GO:0032967), fibrinolysis (GO:0042730), positive regulation of cell differentiation (GO:0045597), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of JNK cascade (GO:0046330), blood vessel morphogenesis (GO:0048514), positive regulation of smooth muscle cell proliferation (GO:0048661), positive regulation of coagulation (GO:0050820), positive regulation of stress fiber assembly (GO:0051496), negative regulation of fibrinolysis (GO:0051918), positive regulation of ERK1 and ERK2 cascade (GO:0070374), positive regulation of transforming growth factor beta production (GO:0071636), positive regulation of cell-cell adhesion mediated by cadherin (GO:2000049)

GO Molecular Function (6): protease binding (GO:0002020), endopeptidase inhibitor activity (GO:0004866), serine-type endopeptidase inhibitor activity (GO:0004867), protein homodimerization activity (GO:0042803), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (8): extracellular region (GO:0005576), fibrinogen complex (GO:0005577), obsolete extracellular space (GO:0005615), cell surface (GO:0009986), extracellular matrix (GO:0031012), platelet alpha granule lumen (GO:0031093), extracellular exosome (GO:0070062), blood microparticle (GO:0072562)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Hemostasis	2
Response to elevated platelet cytosolic Ca2+	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
positive regulation of MAPK cascade	2
regulation of systemic arterial blood pressure by renin-angiotensin	1
blood vessel diameter maintenance	1
acute inflammatory response	1
regulation of plasminogen activation	1
negative regulation of protein processing	1
plasminogen activation	1
extracellular matrix organization	1
positive regulation of biosynthetic process	1
positive regulation of collagen metabolic process	1
collagen biosynthetic process	1
regulation of collagen biosynthetic process	1
negative regulation of blood coagulation	1
cell differentiation	1
regulation of cell differentiation	1
positive regulation of cellular process	1
positive regulation of developmental process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
JNK cascade	1
regulation of JNK cascade	1
blood vessel development	1
tube morphogenesis	1
positive regulation of cell population proliferation	1
smooth muscle cell proliferation	1
regulation of smooth muscle cell proliferation	1
coagulation	1
regulation of coagulation	1
positive regulation of multicellular organismal process	1
positive regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
positive regulation of blood coagulation	1
positive regulation of response to external stimulus	1
fibrinolysis	1
negative regulation of biological process	1
regulation of fibrinolysis	1
ERK1 and ERK2 cascade	1

Protein interactions and networks

STRING

1356 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERPINF2	PLG	P00747	999
SERPINF2	A2M	P01023	964
SERPINF2	PLAT	P00750	886
SERPINF2	CPB2	Q96IY4	862
SERPINF2	F2	P00734	852
SERPINF2	VTN	P01141	847
SERPINF2	FN1	P02751	832
SERPINF2	KLKB1	P03952	804
SERPINF2	F3	P13726	764
SERPINF2	ALB	P02768	738
SERPINF2	SERPINA1	P01009	732
SERPINF2	PLAU	P00749	718
SERPINF2	F13B	P05160	675
SERPINF2	FGA	P02671	667
SERPINF2	VWF	P04275	660

IntAct

15 interactions, top by confidence:

A	B	Type	Score
SSR1	SERPINF2	psi-mi:“MI:0915”(physical association)	0.370
BCAP31	SERPINF2	psi-mi:“MI:0915”(physical association)	0.370
SLC22A4	RTL8C	psi-mi:“MI:0914”(association)	0.350
ANKRD9	TIMM8A	psi-mi:“MI:0914”(association)	0.350
HIBADH	RNASEH1	psi-mi:“MI:0914”(association)	0.350
SERPINF2	RNASEH1	psi-mi:“MI:0914”(association)	0.350
STIM1	SERPINF2	psi-mi:“MI:0914”(association)	0.350
CES2	SERPINF2	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
AGPAT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
UBE2U	IGLL5	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
ATF1	ESYT2	psi-mi:“MI:0914”(association)	0.350
PPARA	SCD	psi-mi:“MI:0914”(association)	0.350

BioGRID (26): SERPINF2 (Reconstituted Complex), SERPINF2 (Biochemical Activity), SERPINF2 (Reconstituted Complex), SERPINF2 (Reconstituted Complex), PLAT (Affinity Capture-MS), DAPP1 (Affinity Capture-MS), SERPINF2 (Affinity Capture-MS), SERPINF2 (Affinity Capture-MS), RNASEH1 (Affinity Capture-MS), SERPINF2 (Affinity Capture-MS), SERPINF2 (Affinity Capture-MS), SERPINF2 (Affinity Capture-MS), POMGNT2 (Affinity Capture-MS), SERPINF2 (Biochemical Activity), SERPINF2 (Biochemical Activity)

ESM2 similar proteins: A2I7N3, A6QPQ2, A6QQ92, A8MV23, B0UYL8, B2D1U1, E1BF81, P01017, P01019, P05154, P05155, P05545, P07758, P07759, P08185, P08697, P09006, P20757, P22323, P23035, P23775, P26595, P28800, P29621, P29622, P36955, P49920, P50448, P50451, P97298, Q00896, Q00898, Q03734, Q09055, Q5I2A0, Q5R9E3, Q5RDA8, Q60396, Q61247, Q63556

Diamond homologs: A0A090BX51, A0A0K8RJ89, A0A0K8RJV9, A2I7M9, A2I7N0, A2I7N1, O54757, O54758, O54759, O54760, P05545, P05619, P06293, P07759, P08697, P09005, P14369, P22323, P23035, P26595, P28800, P30740, P32759, P36955, P50448, P80229, P97298, Q03734, Q1JPB0, Q3ZEJ6, Q40066, Q4G075, Q52L45, Q5I0S8, Q5I2A0, Q5R536, Q5SV42, Q60396, Q61247, Q63556

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	60
Likely benign	22
Benign	11

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
274	NM_000934.4(SERPINF2):c.1437dup (p.Met480fs)	Pathogenic
275	NM_000934.4(SERPINF2):c.525AGA[1] (p.Glu176del)	Pathogenic
276	NM_000934.4(SERPINF2):c.1231G>A (p.Val411Met)	Pathogenic
626930	NM_000934.4(SERPINF2):c.561_565del (p.Lys189fs)	Pathogenic
2050407	NM_000934.4(SERPINF2):c.103-2A>G	Likely pathogenic

SpliceAI

2021 predictions. Top by Δscore:

Variant	Effect	Δscore
17:1745903:GCAC:G	donor_gain	1.0000
17:1747158:GAAAG:G	donor_gain	1.0000
17:1747439:G:GT	donor_gain	1.0000
17:1747449:G:GT	donor_gain	1.0000
17:1747450:A:T	donor_gain	1.0000
17:1747470:G:GT	donor_gain	1.0000
17:1747511:GG:G	donor_gain	1.0000
17:1747512:G:GT	donor_gain	1.0000
17:1752581:TGTA:T	acceptor_loss	1.0000
17:1752582:GTAG:G	acceptor_loss	1.0000
17:1752583:TA:T	acceptor_loss	1.0000
17:1752584:A:AC	acceptor_loss	1.0000
17:1752585:G:GT	acceptor_loss	1.0000
17:1752786:GCTGG:G	donor_gain	1.0000
17:1745173:A:AG	acceptor_gain	0.9900
17:1745174:G:GG	acceptor_gain	0.9900
17:1745873:C:CG	donor_gain	0.9900
17:1745873:C:G	donor_gain	0.9900
17:1745958:GAAC:G	donor_gain	0.9900
17:1747014:TCCA:T	acceptor_loss	0.9900
17:1747016:CAG:C	acceptor_loss	0.9900
17:1747017:A:C	acceptor_loss	0.9900
17:1747018:G:GC	acceptor_loss	0.9900
17:1747018:GGT:G	acceptor_gain	0.9900
17:1747146:G:GT	donor_gain	0.9900
17:1747161:AGGTA:A	donor_loss	0.9900
17:1747306:CAGG:C	acceptor_loss	0.9900
17:1747307:A:AG	acceptor_gain	0.9900
17:1747307:A:AT	acceptor_loss	0.9900
17:1747307:AG:A	acceptor_gain	0.9900

AlphaMissense

1640 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:1748603:T:A	W241R	0.993
17:1748603:T:C	W241R	0.993
17:1745876:A:C	S112R	0.991
17:1745878:T:A	S112R	0.991
17:1745878:T:G	S112R	0.991
17:1748605:G:C	W241C	0.991
17:1748605:G:T	W241C	0.991
17:1748615:T:C	F245L	0.991
17:1748617:T:A	F245L	0.991
17:1748617:T:G	F245L	0.991
17:1748616:T:G	F245C	0.990
17:1747418:G:C	W207C	0.986
17:1747418:G:T	W207C	0.986
17:1748616:T:C	F245S	0.986
17:1747329:T:C	F178L	0.983
17:1747331:C:A	F178L	0.983
17:1747331:C:G	F178L	0.983
17:1747497:G:C	A234P	0.982
17:1747416:T:A	W207R	0.981
17:1747416:T:C	W207R	0.981
17:1747330:T:G	F178C	0.980
17:1745820:T:C	L93P	0.977
17:1747022:C:A	A124D	0.973
17:1747021:G:C	A124P	0.972
17:1747330:T:C	F178S	0.972
17:1748604:G:C	W241S	0.972
17:1747428:G:C	A211P	0.970
17:1747019:G:A	G123D	0.969
17:1747046:T:C	L132P	0.968
17:1747342:C:T	S182F	0.968

dbSNP variants (sampled 300 via entrez): RS1000023247 (17:1751266 T>C,G), RS1000225522 (17:1751326 G>A), RS1000454970 (17:1740552 C>A,G,T), RS1000541801 (17:1754929 G>A), RS1000760268 (17:1744088 T>TG), RS1000891787 (17:1754082 C>A,G), RS1000961383 (17:1743794 G>A), RS1001646140 (17:1749234 T>C), RS1001696609 (17:1750361 A>C), RS1001781786 (17:1748971 T>C), RS1001812537 (17:1745633 G>T), RS1001848750 (17:1744815 G>T), RS1001927049 (17:1744356 G>A), RS1002079156 (17:1749166 G>A,T), RS1002087596 (17:1744540 C>T)

Disease associations

OMIM: gene MIM:613168 | disease phenotypes: MIM:262850

GenCC curated gene-disease

Disease	Classification	Inheritance
alpha-2-plasmin inhibitor deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
alpha-2-plasmin inhibitor deficiency	Definitive	AR

Mondo (1): alpha-2-plasmin inhibitor deficiency (MONDO:0009883)

Orphanet (1): Congenital alpha2-antiplasmin deficiency (Orphanet:79)

HPO phenotypes

13 total (13 of 13 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000225	Gingival bleeding
HP:0000790	Hematuria
HP:0000978	Bruising susceptibility
HP:0001892	Abnormal bleeding
HP:0001934	Persistent bleeding after trauma
HP:0002170	Intracranial hemorrhage
HP:0002653	Bone pain
HP:0005261	Joint hemorrhage
HP:0011884	Abnormal umbilical stump bleeding
HP:0012151	Hemothorax
HP:0012233	Intramuscular hematoma
HP:0040247	Reduced euglobulin clot lysis time

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000769_6	Calcium levels	7.000000e-07
GCST001699_15	Serum albumin levels	7.000000e-13
GCST001699_6	Serum albumin levels	1.000000e-14
GCST002201_12	Calcium levels	2.000000e-06
GCST005988_15	Serum albumin levels	2.000000e-11
GCST008971_123	Urate levels	4.000000e-07
GCST008972_26	Urate levels	2.000000e-08
GCST012335_27	Hodgkin’s lymphoma	5.000000e-11
GCST90026413_13	Severe insulin-deficient type 2 diabetes	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004838	calcium measurement
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537777	Anti-plasmin deficiency, congenital (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, increases expression, decreases reaction, increases abundance	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Cyclosporine	decreases expression, affects cotreatment, affects expression	3
sodium arsenite	decreases expression	2
Air Pollutants	affects methylation, increases abundance, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
Asian ginseng	decreases expression, decreases reaction	1
ginger extract	decreases reaction, increases abundance, increases expression	1
methyleugenol	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
periodate-oxidized adenosine	affects expression	1
ferrous chloride	increases expression	1
benazol P	affects expression	1
perfluorodecanoic acid	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
perfluorododecanoic acid	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Zoledronic Acid	decreases expression	1
Arsenic Trioxide	increases expression	1
Troglitazone	decreases expression	1
Acetaminophen	decreases expression	1
Allergens	increases expression	1
Arsenates	affects cotreatment, increases expression	1
Atrazine	increases expression, affects cotreatment	1
Cholic Acids	affects expression, affects cotreatment	1

Clinical trials (associated diseases)

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