SERPINF2 (serpin family F member 2)

Gene

• Entrez ID: 5345
• Gene name: Serpin family F member 2
• Gene symbol: SERPINF2
• Synonyms (NCBI Gene): A2AP, AAP, ALPHA-2-PI, API, PLI, alpha2AP
• Chromosome: 17
• Chromosome location: 17p13.3
• Summary: 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121965061	AGA>-	Pathogenic	Coding sequence variant, inframe deletion
rs121965062	G>A	Pathogenic	Coding sequence variant, missense variant
rs148395057	C>G,T	Conflicting-interpretations-of-pathogenicity, likely-benign	Synonymous variant, coding sequence variant
rs1597325785	GGCAA>-	Pathogenic	Frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT437913	hsa-miR-224-5p	qRT-PCR, Western blot	24785373
MIRT662475	hsa-miR-4687-5p	HITS-CLIP	23824327
MIRT662474	hsa-miR-6887-3p	HITS-CLIP	23824327
MIRT662473	hsa-miR-6892-3p	HITS-CLIP	23824327
MIRT662472	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT662471	hsa-miR-4287	HITS-CLIP	23824327
MIRT662470	hsa-miR-4685-3p	HITS-CLIP	23824327
MIRT662469	hsa-miR-204-5p	HITS-CLIP	23824327
MIRT662468	hsa-miR-211-5p	HITS-CLIP	23824327
MIRT662467	hsa-miR-3191-5p	HITS-CLIP	23824327
MIRT662466	hsa-miR-4768-5p	HITS-CLIP	23824327
MIRT662465	hsa-miR-6833-3p	HITS-CLIP	23824327
MIRT662464	hsa-miR-6809-3p	HITS-CLIP	23824327
MIRT662475	hsa-miR-4687-5p	HITS-CLIP	23824327
MIRT662474	hsa-miR-6887-3p	HITS-CLIP	23824327
MIRT662473	hsa-miR-6892-3p	HITS-CLIP	23824327
MIRT662472	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT662471	hsa-miR-4287	HITS-CLIP	23824327
MIRT662470	hsa-miR-4685-3p	HITS-CLIP	23824327
MIRT662469	hsa-miR-204-5p	HITS-CLIP	23824327
MIRT662468	hsa-miR-211-5p	HITS-CLIP	23824327
MIRT662467	hsa-miR-3191-5p	HITS-CLIP	23824327
MIRT662466	hsa-miR-4768-5p	HITS-CLIP	23824327
MIRT662465	hsa-miR-6833-3p	HITS-CLIP	23824327
MIRT662464	hsa-miR-6809-3p	HITS-CLIP	23824327
MIRT1338900	hsa-miR-124	CLIP-seq
MIRT1338901	hsa-miR-1976	CLIP-seq
MIRT1338902	hsa-miR-4421	CLIP-seq
MIRT1338903	hsa-miR-4504	CLIP-seq
MIRT1338904	hsa-miR-506	CLIP-seq
MIRT1338905	hsa-miR-3147	CLIP-seq
MIRT1338906	hsa-miR-3202	CLIP-seq
MIRT1338907	hsa-miR-34a	CLIP-seq
MIRT1338908	hsa-miR-34c-5p	CLIP-seq
MIRT1338909	hsa-miR-4425	CLIP-seq
MIRT1338910	hsa-miR-4476	CLIP-seq
MIRT1338911	hsa-miR-449a	CLIP-seq
MIRT1338912	hsa-miR-449b	CLIP-seq
MIRT1338913	hsa-miR-450b-3p	CLIP-seq
MIRT1338914	hsa-miR-4713-3p	CLIP-seq
MIRT1338915	hsa-miR-638	CLIP-seq
MIRT1338916	hsa-miR-769-3p	CLIP-seq
MIRT1338905	hsa-miR-3147	CLIP-seq
MIRT1338907	hsa-miR-34a	CLIP-seq
MIRT1338908	hsa-miR-34c-5p	CLIP-seq
MIRT1338909	hsa-miR-4425	CLIP-seq
MIRT1338911	hsa-miR-449a	CLIP-seq
MIRT1338912	hsa-miR-449b	CLIP-seq
MIRT1338913	hsa-miR-450b-3p	CLIP-seq
MIRT1338914	hsa-miR-4713-3p	CLIP-seq
MIRT2325047	hsa-miR-516a-5p	CLIP-seq
MIRT1338915	hsa-miR-638	CLIP-seq
MIRT1338916	hsa-miR-769-3p	CLIP-seq
MIRT2394236	hsa-miR-125a-3p	CLIP-seq
MIRT2394237	hsa-miR-1298	CLIP-seq
MIRT2394238	hsa-miR-3934	CLIP-seq
MIRT2394239	hsa-miR-664	CLIP-seq
MIRT2394240	hsa-miR-764	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002020	Function	Protease binding	IPI	134998, 6980881, 7679575, 15853774, 17317851
GO:0002034	Process	Maintenance of blood vessel diameter homeostasis by renin-angiotensin	IEA
GO:0002034	Process	Maintenance of blood vessel diameter homeostasis by renin-angiotensin	ISS
GO:0004866	Function	Endopeptidase inhibitor activity	IDA	7679575
GO:0004866	Function	Endopeptidase inhibitor activity	TAS	2830248
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IBA
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IDA	134998
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IEA
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	NAS	12878203
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	TAS	2433286
GO:0005515	Function	Protein binding	IPI	12878203, 14687906
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	NAS	14718574
GO:0005576	Component	Extracellular region	TAS
GO:0005577	Component	Fibrinogen complex	IDA	17317851
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IDA	6980881
GO:0005615	Component	Extracellular space	IEA
GO:0006953	Process	Acute-phase response	IEA
GO:0009986	Component	Cell surface	IDA	17958745
GO:0010757	Process	Negative regulation of plasminogen activation	IDA	134998
GO:0030199	Process	Collagen fibril organization	IEA
GO:0030199	Process	Collagen fibril organization	ISS	17958745
GO:0030414	Function	Peptidase inhibitor activity	IEA
GO:0031012	Component	Extracellular matrix	HDA	28675934
GO:0031093	Component	Platelet alpha granule lumen	TAS
GO:0032967	Process	Positive regulation of collagen biosynthetic process	IDA	17958745
GO:0032967	Process	Positive regulation of collagen biosynthetic process	IEA
GO:0042730	Process	Fibrinolysis	TAS
GO:0042803	Function	Protein homodimerization activity	IPI	134998
GO:0045597	Process	Positive regulation of cell differentiation	IDA	20008146
GO:0045597	Process	Positive regulation of cell differentiation	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	17958745
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0046330	Process	Positive regulation of JNK cascade	IDA	20008146
GO:0048514	Process	Blood vessel morphogenesis	IEA
GO:0048514	Process	Blood vessel morphogenesis	ISS
GO:0048661	Process	Positive regulation of smooth muscle cell proliferation	IEA
GO:0048661	Process	Positive regulation of smooth muscle cell proliferation	ISS
GO:0050820	Process	Positive regulation of coagulation	IBA
GO:0051496	Process	Positive regulation of stress fiber assembly	IDA	20008146
GO:0051918	Process	Negative regulation of fibrinolysis	IDA	134998
GO:0051918	Process	Negative regulation of fibrinolysis	IEA
GO:0070062	Component	Extracellular exosome	HDA	23533145
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	IDA	20008146
GO:0071636	Process	Positive regulation of transforming growth factor beta production	IDA	17958745, 20008146
GO:0071636	Process	Positive regulation of transforming growth factor beta production	IEA
GO:0072562	Component	Blood microparticle	HDA	22516433
GO:2000049	Process	Positive regulation of cell-cell adhesion mediated by cadherin	TAS	17203182

Other IDs

• MIM: 613168
• HGNC: 9075
• e!Ensembl: ENSG00000167711

Protein

• UniProt ID: P08697
• Protein name: Alpha-2-antiplasmin (Alpha-2-AP) (Alpha-2-plasmin inhibitor) (Alpha-2-PI) (Serpin F2)
• Protein function: Serine protease inhibitor. The major targets of this inhibitor are plasmin and trypsin, but it also inactivates matriptase-3/TMPRSS7 and chymotrypsin.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00079	Serpin	84 → 436	Serpin (serine protease inhibitor)	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma.
• Sequence:

  MALLWGLLVLSWSCLQGPCSVFSPVSAMEPLGRQLTSGPNQEQVSPLTLLKLGNQEPGGQ
  TALKSPPGVCSRDPTPEQTHRLARAMMAFTADLFSLVAQTSTCPNLILSPLSVALALSHL
  ALGAQNHTLQRLQQVLHAGSGPCLPHLLSRLCQDLGPGAFRLAARMYLQKGFPIKEDFLE
  QSEQLFGAKPVSLTGKQEDDLANINQWVKEATEGKIQEFLSGLPEDTVLLLLNAIHFQGF
  WRNKFDPSLTQRDSFHLDEQFTVPVEMMQARTYPLRWFLLEQPEIQVAHFPFKNNMSFVV
  LVPTHFEWNVSQVLANLSWDTLHPPLVWERPTKVRLPKLYLKHQMDLVATLSQLGLQELF
  QAPDLRGISEQSLVVSGVQHQSTLELSEVGVEAAAATSIAMSRMSLSSFSVNRPFLFFIF
  EDTTGLPLFVGSVRNPNPSAPRELKEQQDSPGNKDFLQSLKGFPRGDKLFGPDLKLVPPM
  EEDYPQFGSPK

• Sequence length: 491

Pathways

KEGG:

Complement and coagulation cascades

Reactome:

Platelet degranulation
Dissolution of Fibrin Clot

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abnormal bleeding	Pathogenic	rs1597325785	RCV000851601	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Alpha-2-plasmin inhibitor deficiency	Pathogenic	rs2543443583, rs121965061, rs121965062	RCV000000298 RCV000000299 RCV000000300	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANTI-PLASMIN DEFICIENCY, CONGENITAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL ALPHA-2-ANTIPLASMIN DEFICIENCY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL ALPHA2-ANTIPLASMIN DEFICIENCY	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GOUT	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	-	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HODGKINS LYMPHOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOGONADISM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SERPINF2-related disorder	Likely benign; Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Relationship Type	References	Evidence Score
Alzheimer Disease	Associate	25129075	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Anti plasmin deficiency congenital	Associate	1689597	★☆☆☆☆ Found in Text Mining only
Apnea	Associate	27861608	★☆☆☆☆ Found in Text Mining only
Arterial Occlusive Diseases	Stimulate	25069814	★☆☆☆☆ Found in Text Mining only
Axial Spondyloarthritis	Associate	33317138	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Associate	16980951, 36316888, 37195148	★☆☆☆☆ Found in Text Mining only
Carcinoma Non Small Cell Lung	Associate	40211143	★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Associate	27861608	★☆☆☆☆ Found in Text Mining only
Corneal Perforation	Associate	23190581	★☆☆☆☆ Found in Text Mining only
Corneal Ulcer	Associate	23190581	★☆☆☆☆ Found in Text Mining only
COVID 19	Associate	33571675	★☆☆☆☆ Found in Text Mining only
Escherichia coli Infections	Associate	17093030	★☆☆☆☆ Found in Text Mining only
Fibrosis	Inhibit	24034420	★☆☆☆☆ Found in Text Mining only
Glaucoma Open Angle	Associate	29847670	★☆☆☆☆ Found in Text Mining only
Hemolysis	Associate	22421605	★☆☆☆☆ Found in Text Mining only
Hemorrhagic Disorders	Associate	2445779	★☆☆☆☆ Found in Text Mining only
Inflammation	Associate	23190581	★☆☆☆☆ Found in Text Mining only
Intracranial Hemorrhages	Associate	33669007	★☆☆☆☆ Found in Text Mining only
Liver Cirrhosis	Associate	24034420	★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Associate	21505192	★☆☆☆☆ Found in Text Mining only
Neoplasms	Inhibit	16980951	★☆☆☆☆ Found in Text Mining only
Non alcoholic Fatty Liver Disease	Associate	36260611	★☆☆☆☆ Found in Text Mining only
Otosclerosis	Inhibit	27056980	★☆☆☆☆ Found in Text Mining only
Post Acute COVID 19 Syndrome	Associate	36131342	★☆☆☆☆ Found in Text Mining only
Purpura Fulminans	Associate	24659849	★☆☆☆☆ Found in Text Mining only
Schizophrenia	Stimulate	29249827	★☆☆☆☆ Found in Text Mining only
Sleep Apnea Obstructive	Stimulate	27861608	★☆☆☆☆ Found in Text Mining only
Thrombocythemia Essential	Associate	25989112	★☆☆☆☆ Found in Text Mining only
Thrombosis	Inhibit	11122093	★☆☆☆☆ Found in Text Mining only
Tomaculous neuropathy	Associate	156196, 2445779	★☆☆☆☆ Found in Text Mining only