SPINK1
serine peptidase inhibitor Kazal type 1, the group of Serine peptidase inhibitors, Kazal type
Basic information
Region (hg38): 5:147824572-147831671
Links
Phenotypes
GenCC
Source:
- hereditary chronic pancreatitis (No Known Disease Relationship), mode of inheritance: Unknown
- tropical pancreatitis (Strong), mode of inheritance: AD
- hereditary chronic pancreatitis (Strong), mode of inheritance: AD
- hereditary chronic pancreatitis (Supportive), mode of inheritance: AD
- hereditary chronic pancreatitis (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Pancreatitis, hereditary; Tropical calcific pancreatitis | AD/AR | Gastrointestinal; Endocrine; Oncologic | Dietary measures (eg, low-fat diet with frequent feeding), hydration, and antioxidants, with avoidance of precipitants such as alcohol and tobacco, can beneficial in order to ameliorate episodes of pancreatitis; Individuals may be at increased risk of insulin-dependent, ketosis-resistant diabetes mellitus, and awareness may enable early diagnosis and management; Individuals may be at high risk of pancreatic cancer, and awareness may allow early diagnosis and treatment | Endocrine; Gastrointestinal; Oncologic | 2813331; 10691414; 10835640; 11938439; 12011155; 16492714; 17274009; 18184119; 18755888; 20543535; 20664488; 21610753; 20676769; 21415673; 21375584; 20977904; 22228370; 24624459 |
ClinVar
This is a list of variants' phenotypes submitted to
- Hereditary_pancreatitis (190 variants)
- not_provided (38 variants)
- not_specified (35 variants)
- Tropical_pancreatitis (13 variants)
- SPINK1-related_disorder (6 variants)
- Pancreatitis,_chronic,_susceptibility_to (2 variants)
- Diabetes_mellitus (1 variants)
- Chronic_pancreatitis (1 variants)
- Pancreatitis (1 variants)
- Finnish_congenital_nephrotic_syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPINK1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001379610.1. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 49 | 50 | ||||
| missense | 82 | 17 | 101 | |||
| nonsense | 3 | |||||
| start loss | 1 | 1 | 1 | 3 | ||
| frameshift | 4 | |||||
| splice donor/acceptor (+/-2bp) | 6 | |||||
| Total | 6 | 7 | 86 | 66 | 2 |
Highest pathogenic variant AF is 0.000113728
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SPINK1 | protein_coding | protein_coding | ENST00000296695 | 4 | 7219 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.315 | 0.621 | 125456 | 0 | 82 | 125538 | 0.000327 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.123 | 45 | 42.7 | 1.05 | 0.00000216 | 501 |
| Missense in Polyphen | 13 | 14.521 | 0.89527 | 164 | ||
| Synonymous | -0.773 | 18 | 14.3 | 1.26 | 6.11e-7 | 146 |
| Loss of Function | 1.43 | 1 | 4.14 | 0.241 | 1.73e-7 | 54 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000870 | 0.0000870 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00335 | 0.00334 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000124 | 0.000123 |
| Middle Eastern | 0.00335 | 0.00334 |
| South Asian | 0.0000660 | 0.0000653 |
| Other | 0.000329 | 0.000327 |
dbNSFP
Source:
- Function
- FUNCTION: Serine protease inhibitor which exhibits anti-trypsin activity (PubMed:7142173). In the pancreas, protects against trypsin-catalyzed premature activation of zymogens (By similarity). {ECO:0000250|UniProtKB:P09036, ECO:0000269|PubMed:7142173}.;
- Disease
- DISEASE: Pancreatitis, hereditary (PCTT) [MIM:167800]: A disease characterized by pancreas inflammation, permanent destruction of the pancreatic parenchyma, maldigestion, and severe abdominal pain attacks. {ECO:0000269|PubMed:10691414, ECO:0000269|PubMed:10835640, ECO:0000269|PubMed:12974284, ECO:0000269|PubMed:18617776, ECO:0000269|PubMed:19888199}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Tropical calcific pancreatitis (TCP) [MIM:608189]: Idiopathic, juvenile, nonalcoholic form of chronic pancreatitis widely prevalent in several tropical countries. It can be associated with fibrocalculous pancreatic diabetes (FCPD) depending on both environmental and genetic factors. TCP differs from alcoholic pancreatitis by a much younger age of onset, pancreatic calcification, a high incidence of insulin dependent but ketosis resistant diabetes mellitus, and an exceptionally high incidence of pancreatic cancer. {ECO:0000269|PubMed:12011155, ECO:0000269|PubMed:12187509}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
- Pathway
- Androgen Receptor Network in Prostate Cancer
(Consensus)
Recessive Scores
- pRec
- 0.179
Intolerance Scores
- loftool
- 0.542
- rvis_EVS
- 0.81
- rvis_percentile_EVS
- 87.82
Haploinsufficiency Scores
- pHI
- 0.384
- hipred
- N
- hipred_score
- 0.146
- ghis
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.547
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Spink1
- Phenotype
- homeostasis/metabolism phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; immune system phenotype; digestive/alimentary phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);
Gene ontology
- Biological process
- negative regulation of nitric oxide mediated signal transduction;sperm capacitation;negative regulation of peptidyl-tyrosine phosphorylation;regulation of acrosome reaction;negative regulation of calcium ion import;negative regulation of serine-type endopeptidase activity;regulation of store-operated calcium entry
- Cellular component
- extracellular exosome
- Molecular function
- endopeptidase inhibitor activity;serine-type endopeptidase inhibitor activity;protein binding