The protein encoded by this gene is a Kazal-type serine protease inhibitor that appears to specifically target kallikrein-related peptidase 5 (KLK5) in the palmo-plantar epidermis. KLK5 is an important initiator of skin desquamation, so the encoded protease inhibitor may regulate skin differentiation in the palms of hands and soles of feet. This cationic protein has also been s... See more...

Aliases for SPINK9 Gene

Aliases for SPINK9 Gene

  • Serine Peptidase Inhibitor Kazal Type 9 2 3 5
  • Lymphoepithelial Kazal-Type-Related Inhibitor 2 3 4
  • Serine Protease Inhibitor Kazal-Type 9 3 4
  • LEKTI2 3 4
  • SPINK9 5

External Ids for SPINK9 Gene

Previous GeneCards Identifiers for SPINK9 Gene

  • GC05P147695
  • GC05P142862

Summaries for SPINK9 Gene

Entrez Gene Summary for SPINK9 Gene

  • The protein encoded by this gene is a Kazal-type serine protease inhibitor that appears to specifically target kallikrein-related peptidase 5 (KLK5) in the palmo-plantar epidermis. KLK5 is an important initiator of skin desquamation, so the encoded protease inhibitor may regulate skin differentiation in the palms of hands and soles of feet. This cationic protein has also been shown to promote keratinocyte migration by activation of the epidermal growth factor receptor (EGFR). [provided by RefSeq, Dec 2015]

GeneCards Summary for SPINK9 Gene

SPINK9 (Serine Peptidase Inhibitor Kazal Type 9) is a Protein Coding gene. Diseases associated with SPINK9 include Pompholyx and Netherton Syndrome. Among its related pathways are Keratinization and Developmental Biology. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase inhibitor activity. An important paralog of this gene is SPINK7.

UniProtKB/Swiss-Prot Summary for SPINK9 Gene

  • Serine protease inhibitor which specifically inhibits KLK5. May contribute to the regulation of the desquamation process in skin by inhibiting KLK5.

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SPINK9 Gene

Genomics for SPINK9 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SPINK9 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH05J148319 Promoter 1.5 EPDnew Ensembl CraniofacialAtlas 250.7 -0.6 -602 1.6 ZNF600 ZBTB10 SIN3A RAD51 FOXA2 BHLHE40 ZBTB48 ZBTB33 GATAD1 GLIS1 SPINK9 SPINK7 ENSG00000251330 LOC102546294
GH05J148335 Promoter 0.3 EPDnew 250.4 +14.3 14337 0.1 SPINK9 ENSG00000283653 FBXO38 LOC102546294
GH05J148342 Enhancer 1 FANTOM5 Ensembl ENCODE 11.7 +22.1 22099 1.9 MAX TAL1 TBP EHMT2 TCF12 NR2F1 NR2F6 TEAD4 ARID1B CBFA2T2 SPINK7 SPINK9 FBXO38 LOC102546294 SPINK14 ENSG00000283653
GH05J148185 Enhancer 0.9 FANTOM5 Ensembl ENCODE 10 -133.9 -133902 4.2 CEBPB EP300 JUND SPI1 NR2F2 CEBPG SPINK6 FBXO38 LOC102546294 SPINK7 SPINK9 HSALNG0045696 piR-40666-004 SPINK14
GH05J148205 Enhancer 0.8 FANTOM5 Ensembl 9.8 -114.0 -114002 5.6 YY1 RXRA ZBTB33 JUND HNF4A FOXA1 REST MAX MAFK SP1 SPINK6 SPINK7 SPINK14 SPINK9 SPINK13 FBXO38 ENSG00000272411 SPINK5 HMGN1P16 MARCOL
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SPINK9 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SPINK9

Top Transcription factor binding sites by QIAGEN in the SPINK9 gene promoter:
  • XBP-1

Genomic Locations for SPINK9 Gene

Latest Assembly
chr5:148,321,203-148,341,974
(GRCh38/hg38)
Size:
20,772 bases
Orientation:
Plus strand

Previous Assembly
chr5:147,715,122-147,719,415
(GRCh37/hg19 by Entrez Gene)
Size:
4,294 bases
Orientation:
Plus strand

chr5:147,700,766-147,719,412
(GRCh37/hg19 by Ensembl)
Size:
18,647 bases
Orientation:
Plus strand

Genomic View for SPINK9 Gene

Genes around SPINK9 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SPINK9 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SPINK9 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SPINK9 Gene

Proteins for SPINK9 Gene

  • Protein details for SPINK9 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q5DT21-ISK9_HUMAN
    Recommended name:
    Serine protease inhibitor Kazal-type 9
    Protein Accession:
    Q5DT21
    Secondary Accessions:
    • B2RPN9

    Protein attributes for SPINK9 Gene

    Size:
    86 amino acids
    Molecular mass:
    9756 Da
    Quaternary structure:
    • Dimer. Interacts with KLK5 and KLK8.

neXtProt entry for SPINK9 Gene

Post-translational modifications for SPINK9 Gene

No Post-translational modifications

Other Protein References for SPINK9 Gene

No data available for DME Specific Peptides for SPINK9 Gene

Domains & Families for SPINK9 Gene

Gene Families for SPINK9 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for SPINK9 Gene

InterPro:
Blocks:
  • Kazal-type serine protease inhibitor signature

Suggested Antigen Peptide Sequences for SPINK9 Gene

GenScript: Design optimal peptide antigens:
  • Lymphoepithelial Kazal-type-related inhibitor 2 (ISK9_HUMAN)
genes like me logo Genes that share domains with SPINK9: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for SPINK9 Gene

Function for SPINK9 Gene

Molecular function for SPINK9 Gene

UniProtKB/Swiss-Prot Function:
Serine protease inhibitor which specifically inhibits KLK5. May contribute to the regulation of the desquamation process in skin by inhibiting KLK5.

Phenotypes From GWAS Catalog for SPINK9 Gene

Gene Ontology (GO) - Molecular Function for SPINK9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004867 serine-type endopeptidase inhibitor activity IDA 19194479
GO:0005515 protein binding IPI 19194479
GO:0030414 peptidase inhibitor activity IEA --
genes like me logo Genes that share ontologies with SPINK9: view
genes like me logo Genes that share phenotypes with SPINK9: view

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SPINK9

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for SPINK9 Gene

Localization for SPINK9 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SPINK9 Gene

Secreted.

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 SPINK9 gene
Compartment Confidence
extracellular 5
plasma membrane 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SPINK9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
genes like me logo Genes that share ontologies with SPINK9: view

Pathways & Interactions for SPINK9 Gene

PathCards logo

SuperPathways for SPINK9 Gene

genes like me logo Genes that share pathways with SPINK9: view

Pathways by source for SPINK9 Gene

Gene Ontology (GO) - Biological Process for SPINK9 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0010466 negative regulation of peptidase activity IEA --
GO:0010951 negative regulation of endopeptidase activity IEA --
GO:0070268 cornification TAS --
genes like me logo Genes that share ontologies with SPINK9: view

No data available for SIGNOR curated interactions for SPINK9 Gene

Drugs & Compounds for SPINK9 Gene

No Compound Related Data Available

Transcripts for SPINK9 Gene

mRNA/cDNA for SPINK9 Gene

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

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SPINK9

Alternative Splicing Database (ASD) splice patterns (SP) for SPINK9 Gene

No ASD Table

Relevant External Links for SPINK9 Gene

GeneLoc Exon Structure for
SPINK9

Expression for SPINK9 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SPINK9 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SPINK9

SOURCE GeneReport for Unigene cluster for SPINK9 Gene:

Hs.631798

mRNA Expression by UniProt/SwissProt for SPINK9 Gene:

Q5DT21-ISK9_HUMAN
Tissue specificity: Skin. Highly expressed at sites of hyperkeratosis. Also detected in thymus, tonsils, testis, pancreas, liver, placenta and brain. Expressed at stratum granulosum and stratum corneum at palmar and plantar sites (at protein level).

Evidence on tissue expression from TISSUES for SPINK9 Gene

  • Skin(4.3)
genes like me logo Genes that share expression patterns with SPINK9: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for SPINK9 Gene

Orthologs for SPINK9 Gene

This gene was present in the common ancestor of mammals.

Orthologs for SPINK9 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia SPINK9 29 30
  • 98.45 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia SPINK9 29 30
  • 82.56 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia SPINK9 29
  • 80.95 (n)
Oppossum
(Monodelphis domestica)
Mammalia -- 30
  • 45 (a)
OneToMany
-- 30
  • 40 (a)
OneToMany
Species where no ortholog for SPINK9 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)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Mouse (Mus musculus)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rat (Rattus norvegicus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • 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)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for SPINK9 Gene

ENSEMBL:
Gene Tree for SPINK9 (if available)
TreeFam:
Gene Tree for SPINK9 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SPINK9: view image
Alliance of Genome Resources:
Additional Orthologs for SPINK9

Paralogs for SPINK9 Gene

Paralogs for SPINK9 Gene

(8) SIMAP similar genes for SPINK9 Gene using alignment to 2 proteins:

  • ISK9_HUMAN
  • D6RJC5_HUMAN
genes like me logo Genes that share paralogs with SPINK9: view

Variants for SPINK9 Gene

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for SPINK9 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for SPINK9 Gene

Variant ID Type Subtype PubMed ID
esv3607102 CNV loss 21293372
esv3607106 CNV loss 21293372
esv3607107 CNV gain 21293372
nsv5058 CNV insertion 18451855
nsv599945 CNV loss 21841781

Variation tolerance for SPINK9 Gene

Residual Variation Intolerance Score: 75.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.64; 65.62% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SPINK9 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
SPINK9
Leiden Open Variation Database (LOVD)
SPINK9

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SPINK9 Gene

Disorders for SPINK9 Gene

MalaCards: The human disease database

(2) MalaCards diseases for SPINK9 Gene - From: COP

Disorder Aliases PubMed IDs
pompholyx
  • cheiropompholyx
netherton syndrome
  • neth
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for SPINK9

genes like me logo Genes that share disorders with SPINK9: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SPINK9 Gene

Publications for SPINK9 Gene

  1. Identification of lympho-epithelial Kazal-type inhibitor 2 in human skin as a kallikrein-related peptidase 5-specific protease inhibitor. (PMID: 19190773) Meyer-Hoffert U … Schröder JM (PloS one 2009) 3 4
  2. SPINK9: a selective, skin-specific Kazal-type serine protease inhibitor. (PMID: 19194479) Brattsand M … Egelrud T (The Journal of investigative dermatology 2009) 3 4
  3. A reference map of the human binary protein interactome. (PMID: 32296183) Luck K … Calderwood MA (Nature 2020) 3
  4. Transmembrane insertases and N-glycosylation critically determine synthesis, trafficking, and activity of the nonselective cation channel TRPC6. (PMID: 31266804) Talbot BE … Schlondorff JS (The Journal of biological chemistry 2019) 3
  5. SPINK9 stimulates metalloprotease/EGFR-dependent keratinocyte migration via purinergic receptor activation. (PMID: 24441102) Sperrhacke M … Reiss K (The Journal of investigative dermatology 2014) 3

Products for SPINK9 Gene

Sources for SPINK9 Gene