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 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
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	Relationship Type	References	Evidence Score
Autism Spectrum Disorder	Associate	37031449	★☆☆☆☆ Found in Text Mining only
Blood Coagulation Disorders	Associate	34248840	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Associate	34469466	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Associate	32596344	★☆☆☆☆ Found in Text Mining only
COVID 19	Associate	34248840	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Associate	34248840	★☆☆☆☆ Found in Text Mining only
Glioma	Associate	35093128	★☆☆☆☆ Found in Text Mining only
Ischemic Attack Transient	Associate	29385837	★☆☆☆☆ Found in Text Mining only