SERPIND1 (serpin family D member 1)

Gene

• Entrez ID: 3053
• Gene name: Serpin family D member 1
• Gene symbol: SERPIND1
• Synonyms (NCBI Gene): D22S673, HC2, HCF2, HCII, HLS2, LS2, THPH10
• Chromosome: 22
• Chromosome location: 22q11.21
• Summary: This gene belongs to the serpin gene superfamily. Serpins play roles in many processes including inflammation, blood clotting, and cancer metastasis. Members of this family have highly conserved secondary structures with a reactive center loop that intera

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018769	hsa-miR-335-5p	Microarray	18185580
MIRT2325041	hsa-miR-3120-3p	CLIP-seq
MIRT2325042	hsa-miR-4270	CLIP-seq
MIRT2325043	hsa-miR-4441	CLIP-seq
MIRT2325044	hsa-miR-513a-5p	CLIP-seq
MIRT2325045	hsa-miR-556-5p	CLIP-seq
MIRT2325046	hsa-miR-600	CLIP-seq
MIRT2620652	hsa-miR-1236	CLIP-seq
MIRT2620653	hsa-miR-3183	CLIP-seq
MIRT2620654	hsa-miR-4723-3p	CLIP-seq
MIRT2620655	hsa-miR-4778-3p	CLIP-seq
MIRT2620652	hsa-miR-1236	CLIP-seq
MIRT2620653	hsa-miR-3183	CLIP-seq
MIRT2620654	hsa-miR-4723-3p	CLIP-seq
MIRT2620655	hsa-miR-4778-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004866	Function	Endopeptidase inhibitor activity	TAS	2647747
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IBA
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IEA
GO:0005515	Function	Protein binding	IPI	28514442, 33961781
GO:0005576	Component	Extracellular region	HDA	27068509
GO:0005576	Component	Extracellular region	NAS	14718574
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IEA
GO:0005788	Component	Endoplasmic reticulum lumen	TAS
GO:0006935	Process	Chemotaxis	IEA
GO:0007596	Process	Blood coagulation	IEA
GO:0007599	Process	Hemostasis	IEA
GO:0008201	Function	Heparin binding	IEA
GO:0030414	Function	Peptidase inhibitor activity	IEA
GO:0070062	Component	Extracellular exosome	HDA	23533145

Other IDs

• MIM: 142360
• HGNC: 4838
• e!Ensembl: ENSG00000099937

Protein

• UniProt ID: P05546
• Protein name: Heparin cofactor 2 (Heparin cofactor II) (HC-II) (Protease inhibitor leuserpin-2) (HLS2) (Serpin D1)
• Protein function: Thrombin inhibitor activated by the glycosaminoglycans, heparin or dermatan sulfate. In the presence of the latter, HC-II becomes the predominant thrombin inhibitor in place of antithrombin III (AT-III). Also inhibits chymotrypsin, but in a glyc
• PDB: 1JMJ, 1JMO, 2NAT, 2NCU, 2NCV, 2NCW, 6J12, 6KBO, 6KBV
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00079	Serpin	129 → 496	Serpin (serine protease inhibitor)	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed predominantly in liver. Also present in plasma. {ECO:0000269|PubMed:32827448}.; TISSUE SPECIFICITY: [Isoform 2]: Expressed in plasma (at protein level) (PubMed:32827448). Expressed in liver (PubMed:32827448). {ECO:0000269|Pub
• Sequence:

  MKHSLNALLIFLIITSAWGGSKGPLDQLEKGGETAQSADPQWEQLNNKNLSMPLLPADFH
  KENTVTNDWIPEGEEDDDYLDLEKIFSEDDDYIDIVDSLSVSPTDSDVSAGNILQLFHGK
  SRIQRLNILNAKFAFNLYRVLKDQVNTFDNIFIAPVGISTAMGMISLGLKGETHEQVHSI
  LHFKDFVNASSKYEITTIHNLFRKLTHRLFRRNFGYTLRSVNDLYIQKQFPILLDFKTKV
  REYYFAEAQIADFSDPAFISKTNNHIMKLTKGLIKDALENIDPATQMMILNCIYFKGSWV
  NKFPVEMTHNHNFRLNEREVVKVSMMQTKGNFLAANDQELDCDILQLEYVGGISMLIVVP
  HKMSGMKTLEAQLTPRVVERWQKSMTNRTREVLLPKFKLEKNYNLVESLKLMGIRMLFDK
  NGNMAGISDQRIAIDLFKHQGTITVNEEGTQATTVTTVGFMPLSTQVRFTVDRPFLFLIY
  EHRTSCLLFMGRVANPSRS

• Sequence length: 499

Pathways

KEGG:

Complement and coagulation cascades

Reactome:

Intrinsic Pathway of Fibrin Clot Formation
Common Pathway of Fibrin Clot Formation
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
Post-translational protein phosphorylation

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
Hemorrhage	Likely pathogenic	rs2518225484	RCV003313851	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Heparin cofactor II deficiency	Pathogenic	rs587777759, rs587777760, rs121912420	RCV000016093 RCV000016094 RCV000016095	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CAROTID ARTERY THROMBOSIS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEEP VEIN THROMBOSIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Deep venous thrombosis	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEPARIN COFACTOR 2 DEFICIENCY	—	ClinGen, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SERPIND1-related disorder	Benign; Likely benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
THROMBOPHILIA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thrombotic stroke	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thrombus	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VENOUS THROMBOEMBOLISM	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anemia, Sickle Cell	Anemia	BEFREE	23376284		★☆☆☆☆ Found in Text Mining only
Arteriosclerosis	Arteriosclerosis	BEFREE	15337701, 19729870, 27034473		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	BEFREE	15337701, 19729870, 27034473		★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorder	Autism	Pubtator	37031449	Associate	★☆☆☆☆ Found in Text Mining only
Blood Coagulation Disorders	Blood coagulation disorder	Pubtator	34248840	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	34469466	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	32596344	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	27430660, 31637210		★☆☆☆☆ Found in Text Mining only
Carotid Artery Thrombosis	Carotid Artery Thrombosis	CTD_human_DG	11805133		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Carotid Atherosclerosis	Carotid Atherosclerosis	BEFREE	19729870		★☆☆☆☆ Found in Text Mining only
cervical cancer	Cervical Cancer	BEFREE	18021222, 28943170		★☆☆☆☆ Found in Text Mining only
Cervical Intraepithelial Neoplasia	Cervical Intraepithelial Neoplasia	BEFREE	16023184, 17433827, 18021222		★☆☆☆☆ Found in Text Mining only
Cervix carcinoma	Cervix carcinoma	BEFREE	18021222, 28943170		★☆☆☆☆ Found in Text Mining only
Common Carotid Artery Thrombosis	Common Carotid Artery Thrombosis	CTD_human_DG	11805133		★☆☆☆☆ Found in Text Mining only
Deep Vein Thrombosis	Thrombosis	BEFREE	10494755, 15337701		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Depressive disorder	Mental Depression	BEFREE	30611956		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	34248840	Associate	★☆☆☆☆ Found in Text Mining only
Disseminated Intravascular Coagulation	Disseminated Intravascular Coagulation	BEFREE	10548071		★☆☆☆☆ Found in Text Mining only
Disseminated Intravascular Coagulation	Disseminated Intravascular Coagulation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysfibrinogenemia	Dysfibrinogenemia	BEFREE	9607121		★☆☆☆☆ Found in Text Mining only
Epithelial ovarian cancer	Ovarian cancer	BEFREE	31637210		★☆☆☆☆ Found in Text Mining only
External Carotid Artery Thrombosis	External Carotid Artery Thrombosis	CTD_human_DG	11805133		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	35093128	Associate	★☆☆☆☆ Found in Text Mining only
Heparin cofactor II deficiency (disorder)	Heparin cofactor II deficiency	UNIPROT_DG	10391209, 11204559, 15337701, 2647747		★☆☆☆☆ Found in Text Mining only
Heparin cofactor II deficiency (disorder)	Heparin cofactor II deficiency	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Heparin cofactor II deficiency (disorder)	Heparin cofactor II deficiency	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Heparin cofactor II deficiency (disorder)	Heparin cofactor II deficiency	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Homocystinuria	Homocystinuria	BEFREE	10650845		★☆☆☆☆ Found in Text Mining only
Hyperlipidemia	Hyperlipidemia	BEFREE	17549253		★☆☆☆☆ Found in Text Mining only
Internal Carotid Artery Thrombosis	Internal Carotid Artery Thrombosis	CTD_human_DG	11805133		★☆☆☆☆ Found in Text Mining only
Ischemic Attack Transient	Transient ischemic attack	Pubtator	29385837	Associate	★☆☆☆☆ Found in Text Mining only
Liver neoplasms	Liver neoplasms	BEFREE	19255062		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of ovary	Ovarian cancer	BEFREE	27430660, 31637210		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	16950021, 18847555		★☆☆☆☆ Found in Text Mining only
Malignant tumor of cervix	Cervical Tumor	BEFREE	18021222, 28943170		★☆☆☆☆ Found in Text Mining only
Malnutrition	Malnutrition	BEFREE	19729870		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	30611956		★☆☆☆☆ Found in Text Mining only
Mesenteric Vascular Occlusion	Mesenteric Vascular Occlusion	CTD_human_DG	1831893		★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial Infarction	LHGDN	18971786		★☆☆☆☆ Found in Text Mining only
Nasopharyngeal carcinoma	Nasopharyngeal Carcinoma	BEFREE	31040200		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	24859841		★☆☆☆☆ Found in Text Mining only
Oral Submucous Fibrosis	Oral Submucous Fibrosis	BEFREE	20863370		★☆☆☆☆ Found in Text Mining only
ovarian neoplasm	Ovarian neoplasm	BEFREE	27430660, 31637210		★☆☆☆☆ Found in Text Mining only
Peripheral Arterial Diseases	Vascular Diseases	BEFREE	19729870		★☆☆☆☆ Found in Text Mining only
Peripheral Vascular Diseases	Vascular Diseases	BEFREE	19729870		★☆☆☆☆ Found in Text Mining only
Protein C Deficiency	Protein C Deficiency	BEFREE	8902986		★☆☆☆☆ Found in Text Mining only
Pulmonary Emphysema	Pulmonary Emphysema	BEFREE	19245336		★☆☆☆☆ Found in Text Mining only
Pyruvate Carboxylase Deficiency Disease	Pyruvate Carboxylase Deficiency Disease	BEFREE	1836072		★☆☆☆☆ Found in Text Mining only
Thrombocythemia, Essential	Thrombocythemia	BEFREE	10548071		★☆☆☆☆ Found in Text Mining only
Thrombophilia	Thrombophilia	BEFREE	10650845, 3116699		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thrombophilia	Thrombophilia	CTD_human_DG	2214444		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Transient Ischemic Attack	Transient Ischemic Attack	BEFREE	29385837		★☆☆☆☆ Found in Text Mining only