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 ... See more...

Aliases for SPINT2 Gene

Aliases for SPINT2 Gene

  • Serine Peptidase Inhibitor, Kunitz Type 2 2 3 5
  • HAI-2 2 3 4
  • Hepatocyte Growth Factor Activator Inhibitor Type 2 3 4
  • Serine Protease Inhibitor, Kunitz Type, 2 2 3
  • Kunitz-Type Protease Inhibitor 2 3 4
  • Placental Bikunin 2 4
  • HAI2 3 4
  • Kop 2 3
  • Testicular Tissue Protein Li 183 3
  • SPINT2 5
  • DIAR3 3
  • KOP 4
  • 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, With Or Without Other Congenital Anomalies and Syndromic Congenital Sodium Diarrhea. Among its related pathways are Signaling by GPCR and MET promotes cell motility. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase inhibitor activity and endopeptidase inhibitor activity. An important paralog of this gene is SPINT1.

UniProtKB/Swiss-Prot Summary for SPINT2 Gene

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

Gene Wiki entry for SPINT2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SPINT2 Gene

Genomics for SPINT2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SPINT2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SPINT2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SPINT2

Top Transcription factor binding sites by QIAGEN in the SPINT2 gene promoter:
  • AP-1
  • ATF-2
  • c-Fos
  • c-Jun
  • CREB
  • deltaCREB

Genomic Locations for SPINT2 Gene

Genomic Locations for SPINT2 Gene
chr19:38,244,035-38,292,615
(GRCh38/hg38)
Size:
48,581 bases
Orientation:
Plus strand
chr19:38,734,675-38,783,254
(GRCh37/hg19)
Size:
48,580 bases
Orientation:
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:
    O43291-SPIT2_HUMAN
    Recommended name:
    Kunitz-type protease inhibitor 2
    Protein Accession:
    O43291
    Secondary Accessions:
    • A8K667
    • B4DLU1
    • O00271
    • O14895
    • Q5TZQ3
    • Q969E0

    Protein attributes for SPINT2 Gene

    Size:
    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

    UniProtKB/Swiss-Prot:

neXtProt entry for SPINT2 Gene

Post-translational modifications for SPINT2 Gene

  • Glycosylation at Asn94, Ser108, Ser109, Ser112, Asn57, Thr101, and Ser102
  • Ubiquitination at Lys242 and Lys247
  • 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

Protein Domains for SPINT2 Gene

InterPro:
Blocks:
  • Pancreatic trypsin inhibitor (Kunitz)
ProtoNet:

Suggested Antigen Peptide Sequences for SPINT2 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ52992, highly similar to Kunitz-type protease inhibitor 2 (B4DLU1_HUMAN)
  • SPINT2 protein (Q6LEU8_HUMAN)
  • Placental bikunin (SPIT2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O43291

UniProtKB/Swiss-Prot:

SPIT2_HUMAN :
  • This inhibitor contains two inhibitory domains.
Domain:
  • 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

UniProtKB/Swiss-Prot Function:
Inhibitor of HGF activator. Also inhibits plasmin, plasma and tissue kallikrein, and factor XIa.
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

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 IEA,IDA 19185281
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

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SPINT2

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

COMPARTMENTS
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
nucleus 2
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1

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,IBA 21873635
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

PathCards logo

SuperPathways for SPINT2 Gene

SuperPathway Contained pathways
1 MET promotes cell motility
2 Signaling by GPCR
3 Signaling by MST1
4 CFTR-dependent regulation of ion channels in Airway Epithelium (norm and CF)
-
genes like me logo Genes that share pathways with SPINT2: view

Pathways by source for SPINT2 Gene

1 GeneGo (Thomson Reuters) pathway for SPINT2 Gene
  • CFTR-dependent regulation of ion channels in Airway Epithelium (norm and CF)

Gene Ontology (GO) - Biological Process for SPINT2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001843 neural tube closure IEA --
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 --
GO:0022408 negative regulation of cell-cell adhesion IDA 19592578
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

mRNA/cDNA for SPINT2 Gene

2 REFSEQ mRNAs :
21 NCBI additional mRNA sequence :
11 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SPINT2

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: -
SP8:
SP9:
SP10:

Relevant External Links for SPINT2 Gene

GeneLoc Exon Structure for
SPINT2

Expression for SPINT2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and 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, MaxQB, and MOPED for SPINT2 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SPINT2

SOURCE GeneReport for Unigene cluster for SPINT2 Gene:

Hs.31439

mRNA Expression by UniProt/SwissProt for SPINT2 Gene:

O43291-SPIT2_HUMAN
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(4.6)
  • Nervous system(4.3)
  • Lung(3.8)
  • Stomach(3.6)
  • Kidney(2.9)
  • Skin(2.7)
  • Eye(2.6)
  • Blood(2.5)
  • Thyroid gland(2.4)
  • Spleen(2.2)

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

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
  • nervous
  • reproductive
  • respiratory
Regions:
Head and neck:
  • eye
  • head
  • mouth
  • nose
  • pharynx
Abdomen:
  • intestine
  • large intestine
  • small intestine
Pelvis:
  • 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
Chimpanzee
(Pan troglodytes)
Mammalia SPINT2 31
  • 99 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia SPINT2 30 31
  • 84.07 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia SPINT2 30 31
  • 82 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Spint2 30 17 31
  • 77.51 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Spint2 30
  • 76.8 (n)
Oppossum
(Monodelphis domestica)
Mammalia SPINT2 31
  • 57 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia SPINT2 31
  • 43 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia SPINT2 31
  • 36 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia spint2 30
  • 51.22 (n)
Zebrafish
(Danio rerio)
Actinopterygii spint2 30
  • 52.8 (n)
lrp11 31
  • 8 (a)
ManyToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.3864 31
  • 7 (a)
OneToMany
Species where no ortholog for SPINT2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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 Vase (Ciona intestinalis)
  • 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

ENSEMBL:
Gene Tree for SPINT2 (if available)
TreeFam:
Gene Tree for SPINT2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SPINT2: view image

Paralogs for SPINT2 Gene

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

  • SPIT2_HUMAN
  • K7EJS4_HUMAN
  • K7EKC8_HUMAN
  • K7EKQ0_HUMAN
  • K7EM91_HUMAN
  • K7ES27_HUMAN
  • K7ESI5_HUMAN
  • Q6LEU8_HUMAN
genes like me logo Genes that share paralogs with SPINT2: view

Variants for SPINT2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SPINT2 Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
635284 Pathogenic: Diarrhea 3, secretory sodium, congenital, syndromic 38,290,174(+) G/A NONSENSE
753749 Likely Benign: not provided 38,291,831(+) C/T INTRON_VARIANT
768987 Benign: not provided 38,283,804(+) T/C INTRON_VARIANT
774527 Benign: not provided 38,290,578(+) A/G INTRON_VARIANT
rs112576957 Pathogenic: Diarrhea 3, secretory sodium, congenital, syndromic 38,290,282(+) T/A SPLICE_DONOR_VARIANT

Additional dbSNP identifiers (rs#s) for SPINT2 Gene

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

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

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)

Additional Variant Information for SPINT2 Gene

Human Gene Mutation Database (HGMD)
SPINT2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SPINT2

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

Disorders for SPINT2 Gene

MalaCards: The human disease database

(12) MalaCards diseases for SPINT2 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, Orphanet, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

SPIT2_HUMAN
  • 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.
genes like me logo Genes that share disorders with SPINT2: view

No data available for Genatlas for SPINT2 Gene

Publications for SPINT2 Gene

  1. 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 23
  2. 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 23
  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 23
  4. Mutations in SPINT2 cause a syndromic form of congenital sodium diarrhea. (PMID: 19185281) Heinz-Erian P … Janecke AR (American journal of human genetics 2009) 3 4
  5. Expression of hepatocyte growth factor activator inhibitors (HAI-1 and HAI-2) in ovarian cancer. (PMID: 19148468) Nakamura K … Hiramatsu Y (International journal of oncology 2009) 3 23

Products for SPINT2 Gene

Sources for SPINT2 Gene