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SERPINC1 serpin family C member 1 [ Homo sapiens (human) ]

Gene ID: 462, updated on 23-Mar-2024

Summary

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Official Symbol
SERPINC1provided by HGNC
Official Full Name
serpin family C member 1provided by HGNC
Primary source
HGNC:HGNC:775
See related
Ensembl:ENSG00000117601 MIM:107300; AllianceGenome:HGNC:775
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
AT3; AT3D; ATIII; THPH7; ATIII-R2; ATIII-T1; ATIII-T2
Summary
The protein encoded by this gene, antithrombin III, is a plasma protease inhibitor and a member of the serpin superfamily. This protein inhibits thrombin as well as other activated serine proteases of the coagulation system, and it regulates the blood coagulation cascade. The protein includes two functional domains: the heparin binding-domain at the N-terminus of the mature protein, and the reactive site domain at the C-terminus. The inhibitory activity is enhanced by the presence of heparin. Numerous mutations have been identified for this gene, many of which are known to cause antithrombin-III deficiency which constitutes a strong risk factor for thrombosis. A reduction in the serum level of this protein is associated with severe cases of Coronavirus Disease 19 (COVID-19). [provided by RefSeq, Sep 2020]
Annotation information
Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in cytokine storm inflammatory response.
Expression
Restricted expression toward liver (RPKM 926.4) See more
Orthologs
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Genomic context

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Location:
1q25.1
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (173903800..173917327, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (173261916..173275453, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (173872938..173886465, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr1:173837597-173838796 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2118 Neighboring gene small nucleolar RNA, C/D box 74 Neighboring gene zinc finger and BTB domain containing 37 Neighboring gene growth arrest specific 5 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr1:173863193-173864392 Neighboring gene uncharacterized LOC124904457 Neighboring gene RNA, 5S ribosomal pseudogene 67 Neighboring gene ring finger and CCCH-type domains 1 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr1:173915901-173917100 Neighboring gene RNA, 5S ribosomal pseudogene 68

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Antithrombin Deficiency: Frequency in Patients with Thrombosis and Thrombophilic Families. Pejková MA, et al. Acta Medica (Hradec Kralove), 2023. PMID 37384805
  2. [Case report of pulmonary embolism after balloon pulmonary angioplasty triggered by decreased antithrombin Ⅲ activity in a patient with chronic thromboembolic disease]. Guo WL, et al. Zhonghua Xin Xue Guan Bing Za Zhi, 2023 Jan 24. PMID 36655246
  3. Identification and functional analysis of three novel genetic variants resulting in premature termination codons in three unrelated patients with hereditary antithrombin deficiency. Imai Y, et al. Int J Hematol, 2023 Apr. PMID 36526880
  4. Two SERPINC1 variants affecting N-glycosylation of Asn224 cause severe thrombophilia not detected by functional assays. de la Morena-Barrio ME, et al. Blood, 2022 Jul 14. PMID 35486842, Free PMC Article
  5. New SERPINC1 gene mutations in patients with antithrombin deficiency: antithrombin Lodz I, II, III, and IV. Nowak W, et al. Pol Arch Intern Med, 2022 Jan 28. PMID 34851072

See all (287) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Functional, biochemical, molecular and clinical characterization of antithrombin c.1157T>C (p.Ile386Thr), a recurrent Polish variant with a founder effect.
    Title: Functional, biochemical, molecular and clinical characterization of antithrombin c.1157T>C (p.Ile386Thr), a recurrent Polish variant with a founder effect.
  2. A novel mutation p.Met1Val in SERPINC1 gene causes hereditary antithrombin deficiency in a Chinese family with thrombotic disease.
    Title: A novel mutation p.Met1Val in SERPINC1 gene causes hereditary antithrombin deficiency in a Chinese family with thrombotic disease.
  3. [Phenotypic and genetic analysis of a Chinese pedigree affected with Hereditary antithrombin deficiency due to a novel variant of SERPINC1 gene].
    Title: [Phenotypic and genetic analysis of a Chinese pedigree affected with Hereditary antithrombin deficiency due to a novel variant of SERPINC1 gene].
  4. Clinical and functional characterization of rare compound heterozygous mutations in the SERPINC1 gene causing severe thrombophilia.
    Title: Clinical and functional characterization of rare compound heterozygous mutations in the SERPINC1 gene causing severe thrombophilia.
  5. Antithrombin Deficiency Is Associated with Prothrombotic Plasma Fibrin Clot Phenotype.
    Title: Antithrombin Deficiency Is Associated with Prothrombotic Plasma Fibrin Clot Phenotype.
  6. Antithrombin Deficiency: Frequency in Patients with Thrombosis and Thrombophilic Families.
    Title: Antithrombin Deficiency: Frequency in Patients with Thrombosis and Thrombophilic Families.
  7. Identification and functional analysis of three novel genetic variants resulting in premature termination codons in three unrelated patients with hereditary antithrombin deficiency.
    Title: Identification and functional analysis of three novel genetic variants resulting in premature termination codons in three unrelated patients with hereditary antithrombin deficiency.
  8. Native and activated antithrombin inhibits TMPRSS2 activity and SARS-CoV-2 infection.
    Title: Native and activated antithrombin inhibits TMPRSS2 activity and SARS-CoV-2 infection.
  9. [Case report of pulmonary embolism after balloon pulmonary angioplasty triggered by decreased antithrombin activity in a patient with chronic thromboembolic disease].
    Title: [Case report of pulmonary embolism after balloon pulmonary angioplasty triggered by decreased antithrombin Ⅲ activity in a patient with chronic thromboembolic disease].
  10. Two SERPINC1 variants affecting N-glycosylation of Asn224 cause severe thrombophilia not detected by functional assays.
    Title: Two SERPINC1 variants affecting N-glycosylation of Asn224 cause severe thrombophilia not detected by functional assays.
Submit: New GeneRIF Correction See all GeneRIFs (156)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Hereditary antithrombin deficiency
MedGen: C0272375 OMIM: 613118 GeneReviews: Not available
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env Activated granulocytes and macrophages producing hypochlorite/hypochlorous acid-altered isolated proteins antithrombin III and human serum albumin bind to gp120 and inhibit viral proliferation PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC22579

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables heparin binding IEA
Inferred from Electronic Annotation
more info
  
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protease binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables serine-type endopeptidase inhibitor activity NAS
Non-traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in blood coagulation IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of blood coagulation IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in blood microparticle HDA PubMed 
located_in collagen-containing extracellular matrix HDA PubMed 
located_in endoplasmic reticulum lumen TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
located_in extracellular region NAS
Non-traceable Author Statement
more info
 PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
located_in extracellular space HDA PubMed 
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in extracellular space IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
antithrombin-III
Names
serine (or cysteine) proteinase inhibitor, clade C (antithrombin), member 1
serpin peptidase inhibitor clade C member 1
serpin peptidase inhibitor, clade C (antithrombin), member 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_012462.1 RefSeqGene

    Range
    5001..18575
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_577

mRNA and Protein(s)

  1. NM_000488.4 → NP_000479.1  antithrombin-III isoform 1 precursor

    See identical proteins and their annotated locations for NP_000479.1

    Status: REVIEWED

    Source sequence(s)
    AL136170
    Consensus CDS
    CCDS1313.1
    UniProtKB/Swiss-Prot
    B2R6P0, P01008, P78439, P78447, Q13815, Q5TC78, Q7KZ43, Q7KZ97, Q9UC78
    UniProtKB/TrEMBL
    A0A0K0Q2Z1
    Related
    ENSP00000356671.3, ENST00000367698.4
    Conserved Domains (1) summary
    cd02045
    Location:79 → 458
    antithrombin-III_like; Antithrombin is a serine proteinase inhibitor (serpin) which controls the process of coagulation. It is the most important anticoagulant molecule in mammalian circulation systems, controlled by its interaction with the co-factor, heparin, which ...

  2. NM_001365052.2 → NP_001351981.1  antithrombin-III isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1.
    Source sequence(s)
    AL136170
    UniProtKB/TrEMBL
    A0A0K0Q2Z1
    Conserved Domains (1) summary
    cl00137
    Location:31 → 410
    SERPIN; SERine Proteinase INhibitors (serpins) exhibit conformational polymorphism shifting from native to cleaved, latent, delta, or polymorphic forms. Many serpins, such as antitrypsin and antichymotrypsin, function as serine protease inhibitors which regulate ...

  3. NM_001386302.1 → NP_001373231.1  antithrombin-III isoform 3 precursor

    Status: REVIEWED

    Source sequence(s)
    AL136170
    UniProtKB/TrEMBL
    A0A0K0Q2Z1, A0A2S0BDD1
    Conserved Domains (1) summary
    cd02045
    Location:70 → 504
    serpinC1_AT3; serpin family C member 1, antithrombin III

  4. NM_001386303.1 → NP_001373232.1  antithrombin-III isoform 4

    Status: REVIEWED

    Source sequence(s)
    AL136170
    UniProtKB/TrEMBL
    A0A0K0Q2Z1
    Conserved Domains (1) summary
    cd02045
    Location:97 → 490
    serpinC1_AT3; serpin family C member 1, antithrombin III

  5. NM_001386304.1 → NP_001373233.1  antithrombin-III isoform 5 precursor

    Status: REVIEWED

    Source sequence(s)
    AL136170
    UniProtKB/TrEMBL
    A0A0K0Q2Z1
    Conserved Domains (1) summary
    cd02045
    Location:70 → 456
    serpinC1_AT3; serpin family C member 1, antithrombin III

  6. NM_001386305.1 → NP_001373234.1  antithrombin-III isoform 6 precursor

    Status: REVIEWED

    Source sequence(s)
    AL136170
    UniProtKB/TrEMBL
    A0A0K0Q2Z1
    Conserved Domains (1) summary
    cd02045
    Location:70 → 444
    serpinC1_AT3; serpin family C member 1, antithrombin III

  7. NM_001386306.1 → NP_001373235.1  antithrombin-III isoform 7 precursor

    Status: REVIEWED

    Source sequence(s)
    AL136170
    UniProtKB/TrEMBL
    A0A0K0Q2Z1
    Conserved Domains (1) summary
    cl38926
    Location:70 → 391
    serpin; SERine Proteinase INhibitors (serpin) family

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    173903800..173917327 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    173261916..173275453 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P01008.1 GenPept UniProtKB/Swiss-Prot:P01008

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