SPINK9
protein-codingserine peptidase inhibitor Kazal type 9, the group of Serine peptidase inhibitors, Kazal type
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~18.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SPINK9 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001040433.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 13 | 13 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 13 | 0 | 0 | 13 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001035523.1 | 4 | MANE Select | |
| Ensembl | ENSP00000367139.1 | 4 | MANE Select | |
| Ensembl | ENSP00000427240.2 | 4 | Standard | |
| Ensembl | ENSP00000427240.2 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Keratinization
- Developmental Biology
- Formation of the cornified envelope
Biological Process
- negative regulation of endopeptidase activity
- cornification
Molecular Function
- serine-type endopeptidase inhibitor activity
- protein binding
Cellular Component
- extracellular region
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000377906
- Coding exons
- 4
- Length
- 18647
- Individuals with no LoFs
- 121710
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 22
- Defined
- 121732
- p
- 0.0000904
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.260 | 40 | 44.9 | 0.891 | 0.00000209 | 574 |
| Missense (PolyPhen) | 7 | 11.74 | 0.59624 | 165 | ||
| Synonymous | 0.297 | 13 | 14.4 | 0.900 | 7.83e-7 | 143 |
| Loss of Function | 0.677 | 3 | 4.56 | 0.658 | 1.92e-7 | 59 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00012 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000065 | 0.000063 | rare |
| South Asian | 0.00044 | 0.00039 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine protease inhibitor which specifically inhibits KLK5. May contribute to the regulation of the desquamation process in skin by inhibiting KLK5. {ECO:0000269|PubMed:19190773, ECO:0000269|PubMed:19194479}.;
Recessive Scores
- pRec
- 0.0940
Intolerance Scores
- LoFtool
- 0.694
- RVIS EVS
- 0.04
- RVIS percentile EVS
- 56.25
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.221
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |