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Aliases for SPINT2 Gene

Aliases for SPINT2 Gene

  • Serine Peptidase Inhibitor, Kunitz Type 2 2 3 5
  • Hepatocyte Growth Factor Activator Inhibitor Type 2 3 4
  • Serine Protease Inhibitor, Kunitz Type, 2 2 3
  • Placental Bikunin 2 4
  • HAI-2 3 4
  • HAI2 3 4
  • Kop 3 4
  • Kunitz-Type Protease Inhibitor 2 3
  • Testicular Tissue Protein Li 183 3
  • DIAR3 3
  • PB 3

External Ids for SPINT2 Gene

Previous GeneCards Identifiers for SPINT2 Gene

  • GC19P039369
  • GC19P039146
  • GC19P043431
  • GC19P043447
  • GC19P038755
  • GC19P035203
  • GC19P038734

Summaries for SPINT2 Gene

Entrez Gene Summary for SPINT2 Gene

  • 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]

GeneCards Summary for SPINT2 Gene

SPINT2 (Serine Peptidase Inhibitor, Kunitz Type 2) is a Protein Coding gene. Diseases associated with SPINT2 include Diarrhea 3, Secretory Sodium, Congenital, Syndromic and Diarrhea. Among its related pathways are CFTR-dependent regulation of ion channels in Airway Epithelium (norm and CF) and MET promotes cell motility. GO annotations related to this gene include serine-type endopeptidase inhibitor activity and endopeptidase inhibitor activity. An important paralog of this gene is TFPI.

UniProtKB/Swiss-Prot for SPINT2 Gene

  • Inhibitor of HGF activator. Also inhibits plasmin, plasma and tissue kallikrein, and factor XIa.

Gene Wiki entry for SPINT2 Gene

Additional gene information for SPINT2 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SPINT2 Gene

Genomics for SPINT2 Gene

Regulatory Elements for SPINT2 Gene

Enhancers for SPINT2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH19H038312 2 FANTOM5 Ensembl ENCODE dbSUPER 16.4 +73.6 73586 9.9 HDGF PKNOX1 ARNT ARID4B SIN3A DMAP1 ZNF2 YY1 ZNF766 CBX5 C19orf33 HNRNPL CATSPERG ZNF573 ENSG00000266963 ZNF527 PAK4 ENSG00000268756 SPINT2 ZNF571
GH19H038249 1.5 Ensembl ENCODE dbSUPER 12.1 +8.2 8189 5.1 FOXA2 MLX YY1 ZNF121 GLIS2 ZNF548 REST PPARG NFIL3 GLIS1 CATSPERG ENSG00000266963 PPP1R14A HNRNPL ENSG00000269445 ENSG00000267375 ENSG00000269172 ZNF793 ZNF527 SPINT2
GH19H038262 1.3 ENCODE dbSUPER 13.3 +21.8 21831 6.7 HDGF PKNOX1 SIN3A ZNF2 ZNF143 FOS SP3 ZC3H11A REST ZNF592 ZNF527 HNRNPL CATSPERG ZFP30 C19orf33 ZNF571 HKR1 ENSG00000267682 ENSG00000266963 ZNF573
GH19H038276 1.3 Ensembl ENCODE dbSUPER 12.3 +33.9 33860 2.6 PKNOX1 JUN SIN3A CEBPG CTBP1 ZNF316 GATA3 POLR2A SCRT2 FOS C19orf33 ZFP30 ZNF540 ZNF793 ZNF781 ENSG00000267152 ZNF527 ZNF607 PPP1R14A SPINT2
GH19H038279 0.8 ENCODE dbSUPER 19.2 +36.6 36614 1.4 ZFHX2 RBAK ZNF169 PRDM2 C19orf33 SPINT2 ENSG00000267682 ZNF527 PPP1R14A YIF1B KCNK6 CATSPERG ZFP30 HKR1
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around SPINT2 on UCSC Golden Path with GeneCards custom track

Promoters for SPINT2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

Genomic Locations for SPINT2 Gene

Genomic Locations for SPINT2 Gene
48,580 bases
Plus strand

Genomic View for SPINT2 Gene

Genes around SPINT2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SPINT2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SPINT2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SPINT2 Gene

Proteins for SPINT2 Gene

  • Protein details for SPINT2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Kunitz-type protease inhibitor 2
    Protein Accession:
    Secondary Accessions:
    • A8K667
    • B4DLU1
    • O00271
    • O14895
    • Q5TZQ3
    • Q969E0

    Protein attributes for SPINT2 Gene

    252 amino acids
    Molecular mass:
    28228 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for SPINT2 Gene

    Alternative splice isoforms for SPINT2 Gene


neXtProt entry for SPINT2 Gene

Post-translational modifications for SPINT2 Gene

  • Ubiquitination at Lys247
  • Glycosylation at Asn57, posLast=9494, posLast=101101, posLast=102102, Ser108, Ser109, and posLast=112112
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for SPINT2 Gene

Domains & Families for SPINT2 Gene

Gene Families for SPINT2 Gene

Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted membrane proteins
  • Predicted secreted proteins

Protein Domains for SPINT2 Gene

Suggested Antigen Peptide Sequences for SPINT2 Gene

Graphical View of Domain Structure for InterPro Entry



  • This inhibitor contains two inhibitory domains.
  • This inhibitor contains two inhibitory domains.
genes like me logo Genes that share domains with SPINT2: view

Function for SPINT2 Gene

Molecular function for SPINT2 Gene

GENATLAS Biochemistry:
serine protease inhibitor,Kunitz-type 2,expressed at high level in placenta and brain and at lower levels in brain,lung,kidney with an endogenous soluble form called placental likumin,inhibiting trypsin,plasma kallikrein and plasmin,overexpressed in pancreatic cancer
UniProtKB/Swiss-Prot Function:
Inhibitor of HGF activator. Also inhibits plasmin, plasma and tissue kallikrein, and factor XIa.

Phenotypes From GWAS Catalog for SPINT2 Gene

Gene Ontology (GO) - Molecular Function for SPINT2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004866 endopeptidase inhibitor activity TAS 9115294
GO:0004867 serine-type endopeptidase inhibitor activity IDA,IEA 19185281
GO:0005515 protein binding IPI 16140784
GO:0030414 peptidase inhibitor activity IEA --
genes like me logo Genes that share ontologies with SPINT2: view
genes like me logo Genes that share phenotypes with SPINT2: view

Human Phenotype Ontology for SPINT2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

miRNA for SPINT2 Gene

Clone Products

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for SPINT2 Gene

Localization for SPINT2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SPINT2 Gene

Membrane; Single-pass type I membrane protein.

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SPINT2 gene
Compartment Confidence
extracellular 5
plasma membrane 3

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (1)
  • Intermediate filaments (1)
  • Plasma membrane (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SPINT2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS 9346890
GO:0005737 cytoplasm IDA 11606055
GO:0005886 plasma membrane IEA --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with SPINT2: view

Pathways & Interactions for SPINT2 Gene

genes like me logo Genes that share pathways with SPINT2: view

Pathways by source for SPINT2 Gene

Gene Ontology (GO) - Biological Process for SPINT2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001843 neural tube closure IEA --
GO:0006928 movement of cell or subcellular component TAS 9434156
GO:0007163 establishment or maintenance of cell polarity IEA --
GO:0010466 negative regulation of peptidase activity IEA --
GO:0010951 negative regulation of endopeptidase activity IEA --
genes like me logo Genes that share ontologies with SPINT2: view

No data available for SIGNOR curated interactions for SPINT2 Gene

Drugs & Compounds for SPINT2 Gene

(1) Drugs for SPINT2 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(1) Additional Compounds for SPINT2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with SPINT2: view

Transcripts for SPINT2 Gene

Unigene Clusters for SPINT2 Gene

Serine peptidase inhibitor, Kunitz type, 2:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for SPINT2 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2a · 2b ^ 3 ^ 4a · 4b ^ 5a · 5b · 5c ^ 6a · 6b · 6c ^ 7a · 7b ^ 8a · 8b · 8c
SP1: - - - -
SP2: - - - - -
SP3: - - - - - -
SP4: - - - - - -
SP5: - - - - -
SP6: -
SP7: -

Relevant External Links for SPINT2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for SPINT2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SPINT2 Gene

mRNA differential expression in normal tissues according to GTEx for SPINT2 Gene

This gene is overexpressed in Pituitary (x4.0).

Protein differential expression in normal tissues from HIPED for SPINT2 Gene

This gene is overexpressed in Breast (20.7), Amniocyte (18.3), and Urine (7.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for SPINT2 Gene

NURSA nuclear receptor signaling pathways regulating expression of SPINT2 Gene:


SOURCE GeneReport for Unigene cluster for SPINT2 Gene:


mRNA Expression by UniProt/SwissProt for SPINT2 Gene:

Tissue specificity: Expressed in placenta, kidney, pancreas, prostate, testis, thymus, and trachea.

Evidence on tissue expression from TISSUES for SPINT2 Gene

  • Intestine(4.9)
  • Pancreas(4.4)
  • Nervous system(4.2)
  • Lung(3.6)
  • Stomach(3.3)
  • Kidney(2.3)
  • Thyroid gland(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SPINT2 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • digestive
  • nervous
  • reproductive
  • respiratory
Head and neck:
  • eye
  • head
  • mouth
  • nose
  • pharynx
  • intestine
  • large intestine
  • small intestine
  • placenta
  • uterus
genes like me logo Genes that share expression patterns with SPINT2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Protein tissue co-expression partners for SPINT2 Gene

Orthologs for SPINT2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for SPINT2 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia SPINT2 34
  • 99 (a)
(Canis familiaris)
Mammalia SPINT2 33 34
  • 84.07 (n)
(Bos Taurus)
Mammalia SPINT2 33 34
  • 82 (n)
(Mus musculus)
Mammalia Spint2 33 16 34
  • 77.51 (n)
(Rattus norvegicus)
Mammalia Spint2 33
  • 76.8 (n)
(Monodelphis domestica)
Mammalia SPINT2 34
  • 57 (a)
(Ornithorhynchus anatinus)
Mammalia SPINT2 34
  • 43 (a)
(Anolis carolinensis)
Reptilia SPINT2 34
  • 36 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia spint2 33
  • 51.22 (n)
(Danio rerio)
Actinopterygii spint2 33
  • 52.8 (n)
lrp11 34
  • 8 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3864 34
  • 7 (a)
Species where no ortholog for SPINT2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for SPINT2 Gene

Gene Tree for SPINT2 (if available)
Gene Tree for SPINT2 (if available)

Paralogs for SPINT2 Gene

Paralogs for SPINT2 Gene

(6) SIMAP similar genes for SPINT2 Gene using alignment to 8 proteins:

genes like me logo Genes that share paralogs with SPINT2: view

Variants for SPINT2 Gene

Sequence variations from dbSNP and Humsavar for SPINT2 Gene

SNP ID Clin Chr 19 pos Sequence Context AA Info Type
rs121908403 Pathogenic, Diarrhea 3, secretory sodium, congenital, with or without other congenital anomalies (DIAR3) [MIM:270420] 38,290,215(+) CATCT(A/G)TGGAG reference, missense
rs112576957 Pathogenic 38,290,282(+) TTCCG(A/C/T)AAGTC splice-donor-variant
rs121908404 Pathogenic 38,264,893(+) TGGCC(A/T)TGGCG reference, missense
rs606231154 Pathogenic 38,291,839(+) CCTCA(A/G)TGGTG splice-acceptor-variant
rs606231155 Pathogenic 38,287,937(+) AGTGG(C/T)AGGTT splice-donor-variant

Structural Variations from Database of Genomic Variants (DGV) for SPINT2 Gene

Variant ID Type Subtype PubMed ID
nsv833822 CNV loss 17160897
nsv833821 CNV loss 17160897
nsv1129623 CNV tandem duplication 24896259
nsv1119471 CNV insertion 24896259

Variation tolerance for SPINT2 Gene

Residual Variation Intolerance Score: 73.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.38; 42.25% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for SPINT2 Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SPINT2 Gene

Disorders for SPINT2 Gene

MalaCards: The human disease database

(6) MalaCards diseases for SPINT2 Gene - From: HGMD, OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
diarrhea 3, secretory sodium, congenital, syndromic
  • congenital secretory sodium diarrhea 3
  • diarrhea of presumed infectious origin
secretory diarrhea
diarrhea 5, with tufting enteropathy, congenital
  • congenital diarrhea 5 with tufting enteropathy
c1 inhibitor deficiency
  • quincke edema
- elite association - COSMIC cancer census association via MalaCards


  • Diarrhea 3, secretory sodium, congenital, with or without other congenital anomalies (DIAR3) [MIM:270420]: A disease characterized by life-threatening secretory diarrhea, severe metabolic acidosis and hyponatremia. Hyponatremia is secondary to extraordinarily high fecal sodium loss, with low or normal excretion of urinary sodium, in the absence of infectious, autoimmune and endocrine causes. {ECO:0000269 PubMed:19185281}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for SPINT2

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with SPINT2: view

No data available for Genatlas for SPINT2 Gene

Publications for SPINT2 Gene

  1. Identification and cloning of human placental bikunin, a novel serine protease inhibitor containing two Kunitz domains. (PMID: 9115294) Marlor CW … Tamburini PP (The Journal of biological chemistry 1997) 2 3 4 22 60
  2. Purification and cloning of hepatocyte growth factor activator inhibitor type 2, a Kunitz-type serine protease inhibitor. (PMID: 9346890) Kawaguchi T … Kitamura N (The Journal of biological chemistry 1997) 2 3 4 22 60
  3. Cloning of a new Kunitz-type protease inhibitor with a putative transmembrane domain overexpressed in pancreatic cancer. (PMID: 9434156) Müller-Pillasch F … Gress TM (Biochimica et biophysica acta 1998) 3 4 22 60
  4. Hepatocyte growth factor activator inhibitor-2 (HAI-2) is a favorable prognosis marker and inhibits cell growth through the apoptotic pathway in cervical cancer. (PMID: 18689863) Nakamura K … Hiramatsu Y (Annals of oncology : official journal of the European Society for Medical Oncology 2009) 3 22 60
  5. HAI-2 is epigenetically downregulated in human hepatocellular carcinoma, and its Kunitz domain type 1 is critical for anti-invasive functions. (PMID: 19107935) Tung EK … Ng IO (International journal of cancer 2009) 3 22 60

Products for SPINT2 Gene

Sources for SPINT2 Gene

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