SPINT1
protein-codingserine peptidase inhibitor, Kunitz type 1
Gene summary
The protein encoded by this gene is a member of the Kunitz family of serine protease inhibitors. The protein is a potent inhibitor specific for HGF activator and is thought to be involved in the regulation of the proteolytic activation of HGF in injured tissues. Alternative splicing results in multiple variants encoding different isoforms. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.2 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 SPINT1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003710.4. 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 | 89 | 6 | 3 | 98 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 7 | 7 | ||||
| Total | 0 | 0 | 97 | 6 | 3 | 106 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003701.1 | 10 | MANE Select | |
| Ensembl | ENSP00000457076.1 | 10 | MANE Select | |
| RefSeq | NP_001027539.1 | 10 | Standard | |
| RefSeq | NP_001373802.1 | 10 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| spint1a | Danio rerio | Structure: neutrophil Quality: mislocalised abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Prostate cancer - Homo sapiens (human)
- Transcriptional misregulation in cancer - Homo sapiens (human)
- Signal Transduction
- MET Receptor Activation
- Signaling by MET
Biological Process
- neural tube closure
- negative regulation of endopeptidase activity
- extracellular matrix organization
- positive regulation of glial cell differentiation
- branching involved in labyrinthine layer morphogenesis
Molecular Function
- serine-type endopeptidase inhibitor activity
Cellular Component
- extracellular region
- extracellular space
- plasma membrane
- membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000344051
- Coding exons
- 10
- Length
- 14190
- Individuals with no LoFs
- 125629
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 119
- Defined
- 125748
- p
- 0.000473
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0731 | 322 | 326 | 0.989 | 0.0000186 | 3445 |
| Missense (PolyPhen) | 81 | 92.185 | 0.87866 | 1065 | ||
| Synonymous | 0.749 | 125 | 136 | 0.918 | 0.00000801 | 1065 |
| Loss of Function | 2.24 | 12 | 23.8 | 0.505 | 0.00000102 | 271 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.0022 | 0.0022 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00026 | 0.00025 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Inhibitor of HGF activator. Also acts as an inhibitor of matriptase (ST14).;
Recessive Scores
- pRec
- 0.169
Intolerance Scores
- LoFtool
- 0.148
- RVIS EVS
- 0.27
- RVIS percentile EVS
- 70.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.908
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |