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    SPINT2 serine peptidase inhibitor, Kunitz type 2 [ Homo sapiens (human) ]

    Gene ID: 10653, updated on 28-Oct-2024

    Summary

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    Official Symbol
    SPINT2provided by HGNC
    Official Full Name
    serine peptidase inhibitor, Kunitz type 2provided by HGNC
    Primary source
    HGNC:HGNC:11247
    See related
    Ensembl:ENSG00000167642 MIM:605124; AllianceGenome:HGNC:11247
    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
    PB; Kop; HAI2; DIAR3; HAI-2
    Summary
    This gene encodes a transmembrane protein with two extracellular Kunitz domains that inhibits a variety of serine proteases. The protein inhibits HGF activator which prevents the formation of active hepatocyte growth factor. This gene is a putative tumor suppressor, and mutations in this gene result in congenital sodium diarrhea. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
    Expression
    Broad expression in colon (RPKM 172.2), thyroid (RPKM 135.2) and 22 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SPINT2 in Genome Data Viewer
    Location:
    19q13.2
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (38264573..38292615)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (41066744..41094785)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (38755213..38783255)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr19:38707788-38708987 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:38709595-38710094 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10563 Neighboring gene double PHD fingers 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:38718119-38718889 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10564 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14569 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:38729145-38729644 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:38734884-38735760 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:38746806-38746993 Neighboring gene protein phosphatase 1 regulatory inhibitor subunit 14A Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:38751829-38752766 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:38752767-38753703 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:38753844-38754761 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10565 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:38785153-38785654 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:38788840-38789473 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:38791160-38791852 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:38792217-38792464 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:38794013-38794750 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:38794751-38795488 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:38795489-38796226 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:38798184-38798353 Neighboring gene chromosome 19 open reading frame 33 Neighboring gene Yip1 interacting factor homolog B, membrane trafficking protein Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10566 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:38810313-38810936 Neighboring gene potassium two pore domain channel subfamily K member 6

    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 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. SPINT2 Deregulation in Prostate Carcinoma. Pereira MS, et al. J Histochem Cytochem, 2016 Jan. PMID 26442953, Free PMC Article
    2. SPINT2 (HAI-2) missense variants identified in congenital sodium diarrhea/tufting enteropathy affect the ability of HAI-2 to inhibit prostasin but not matriptase. Holt-Danborg L, et al. Hum Mol Genet, 2019 Mar 1. PMID 30445423
    3. Study on the methylation status of SPINT2 gene and its expression in cervical carcinoma. Wang N, et al. Cancer Biomark, 2018. PMID 29843210
    4. Congenital sodium diarrhea and chorioretinal coloboma with optic disc coloboma in a patient with biallelic SPINT2 mutations, including p.(Tyr163Cys). Hirabayashi KE, et al. Am J Med Genet A, 2018 Apr. PMID 29575628, Free PMC Article
    5. Isolated choanal and gut atresias: pathogenetic role of serine protease inhibitor type 2 (SPINT2) gene mutations unlikely. Niederwanger C, et al. Eur J Med Res, 2018 Mar 2. PMID 29499739, Free PMC Article

    See all (104) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. SPINT2 mutations in the Kunitz domain 2 found in SCSD patients inactivate HAI-2 as prostasin inhibitor via abnormal protein folding and N-glycosylation.
      Title: SPINT2 mutations in the Kunitz domain 2 found in SCSD patients inactivate HAI-2 as prostasin inhibitor via abnormal protein folding and N-glycosylation.
    2. Targeted HAI-2 deletion causes excessive proteolysis with prolonged active prostasin and depletion of HAI-1 monomer in intestinal but not epidermal epithelial cells.
      Title: Targeted HAI-2 deletion causes excessive proteolysis with prolonged active prostasin and depletion of HAI-1 monomer in intestinal but not epidermal epithelial cells.
    3. Loss of USP28 and SPINT2 expression promotes cancer cell survival after whole genome doubling.
      Title: Loss of USP28 and SPINT2 expression promotes cancer cell survival after whole genome doubling.
    4. Comprehensive Analysis of the Expression and Prognostic Value of SPINT1/2 in Breast Carcinoma.
      Title: Comprehensive Analysis of the Expression and Prognostic Value of SPINT1/2 in Breast Carcinoma.
    5. Expansion of the ophthalmic phenotype of SPINT2-related syndromic congenital sodium diarrhea.
      Title: Expansion of the ophthalmic phenotype of SPINT2-related syndromic congenital sodium diarrhea.
    6. Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction.
      Title: Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction.
    7. The endogenous cellular protease inhibitor SPINT2 controls SARS-CoV-2 viral infection and is associated to disease severity.
      Title: The endogenous cellular protease inhibitor SPINT2 controls SARS-CoV-2 viral infection and is associated to disease severity.
    8. The Physiological TMPRSS2 Inhibitor HAI-2 Alleviates SARS-CoV-2 Infection.
      Title: The Physiological TMPRSS2 Inhibitor HAI-2 Alleviates SARS-CoV-2 Infection.
    9. Loss of SPINT2 expression frequently occurs in glioma, leading to increased growth and invasion via MMP2.
      Title: Loss of SPINT2 expression frequently occurs in glioma, leading to increased growth and invasion via MMP2.
    10. SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses.
      Title: SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses.
    Submit: New GeneRIF Correction See all GeneRIFs (63)

    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
    Congenital secretory sodium diarrhea 3
    MedGen: C5441927 OMIM: 270420 GeneReviews: Not available
    		Compare labs

    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

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ45571

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables endopeptidase inhibitor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables serine-type endopeptidase inhibitor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables serine-type endopeptidase inhibitor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in basement membrane organization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to BMP stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in epithelial cell morphogenesis involved in placental branching IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in establishment or maintenance of cell polarity IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within negative regulation of cell motility IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within negative regulation of cell-cell adhesion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of neural precursor cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of peptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in neural tube closure IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    kunitz-type protease inhibitor 2
    Names
    HGF activator inhibitor 2
    Kunitz domain containing protein overexpressed in pancreatic cancer
    hepatocyte growth factor activator inhibitor type 2
    hepatocyte growth factor activator inhibitor-2
    serine protease inhibitor, Kunitz type, 2
    testicular tissue protein Li 183

    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_013372.1 RefSeqGene

      Range
      5116..33158
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001166103.2 → NP_001159575.1  kunitz-type protease inhibitor 2 isoform b precursor

      See identical proteins and their annotated locations for NP_001159575.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (b) lacks an alternate in-frame exon in the 5' coding region, compared to variant a. The resulting isoform (b) lacks an internal segment near the N-terminus, compared to isoform a.
      Source sequence(s)
      AC011479, AI199013, AK297154, AW275313
      Consensus CDS
      CCDS54261.1
      UniProtKB/TrEMBL
      A0A140VJV6, K7EM91
      Related
      ENSP00000389788.2, ENST00000454580.7
      Conserved Domains (1) summary
      pfam00014
      Location:75 → 126
      Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain

    2. NM_021102.4 → NP_066925.1  kunitz-type protease inhibitor 2 isoform a precursor

      See identical proteins and their annotated locations for NP_066925.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (a) represents the longer transcript and encodes the longer isoform (a).
      Source sequence(s)
      AC011479, AW275313, BC001668
      Consensus CDS
      CCDS12510.1
      UniProtKB/Swiss-Prot
      A8K667, B4DLU1, O00271, O14895, O43291, Q5TZQ3, Q969E0
      UniProtKB/TrEMBL
      Q6LEU8
      Related
      ENSP00000301244.5, ENST00000301244.12
      Conserved Domains (1) summary
      pfam00014
      Location:37 → 88
      Kunitz_BPTI; Kunitz/Bovine pancreatic trypsin inhibitor domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      38264573..38292615
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      41066744..41094785
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O43291.2 GenPept UniProtKB/Swiss-Prot:O43291

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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