• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
SPINK1 (HGNC:11244) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
serine peptidase inhibitor Kazal type 1
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
Spink3, PCTT, PSTI, TATI
%HI
90(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.31(Read more about gnomAD pLI score)
LOEUF
1.13(Read more about gnomAD LOEUF score)
Cytoband
5q32
Genomic Coordinates
GRCh37/hg19: chr5:147204145-147218759 NCBI Ensembl UCSC
GRCh38/hg38: chr5:147824582-147839196 NCBI Ensembl UCSC
MANE Select Transcript
NM_001379610.1 ENST00000296695.10 (Read more about MANE Select)
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}. In the male reproductive tract, binds to sperm heads where it modulates sperm capacitance by inhibiting calcium uptake and nitrogen oxide (NO) production. {ECO:0000250|UniProtKB:P09036}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-36990
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Assoc. with Reduced Penetrance:
Yes
Individuals with variants in SPINK1 associated with an increased risk for pancreatitis may only develop the disease in the presence of additional risk factors (PMID:24624459).
Last Evaluated:
10/25/2021

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • hereditary chronic pancreatitis Monarch
HI Evidence:
  • PUBMED: 17681820
    Masson et al. (2007) identified a 30,588-bp deletion encompassing the entire SPINK1 gene in a 47 year old female with chronic pancreatitis and her affected father and paternal uncle.
  • PUBMED: 22427236
    Rosendahl et al. (2013) used PCR and gene sequencing on 660 unrelated individuals with hereditary chronic pancreatitis (HP) or Idiopathic chronic pancreatitis (ICP) and a control group of 1758 individuals. 12 variants were detected in SPINK1, 10 variants were missense, a variant found in one individual was frameshift (p.V60YfsX35), and a variant found in one individual was a deletion (c.27delC). Inheritance for all variants identified is unknown.
  • PUBMED: 10835640
    Using intron-spanning long range PCR, Witt et al. (2020) identified 18 SPINK1 pathogenic variants in 22 individuals out of 96 unrelated children and adolescents living in Germany or Austria with hereditary or idiopathic chronic pancreatitis. Twelve intronic variants, five missense variants, and one variant affecting the 5' UTR region were detected. The authors attribute loss of or aberrant function of the SPINK1 protein product causes inappropriate intrapancreatic activation of zymogens by trypsin and leads to enzymatic autodigestion and pancreatitis.
  • PUBMED: 16823394
    Previously, a heterozygous 1,336-bp deletion encompassing exon 1 of the SPINK1 gene was detected in an individual and her two brothers, both with chronic pancreatitis, by HPLC. Parental samples were unavailable.
  • PUBMED: 27578509
    Cho, et al. (2016) used PCR on 116 Korean participants with idiopathic chronic pancreatitis. “A novel pathogenic splicing variation, c.194+1G>A, was found in a 41 yr old man diagnosed with pancreatic duct stones and CP. This variant affects an intron splice donor site by altering the highly conserved GT dinucleotide.”
  • PUBMED: 14722925
    Marechal, et al. (2003) used denaturing high performance liquid chromatography (DHPLC) and PCR on 46 families with pancreatitis. Two families were identified to have a microdeletion in SPINK1 (c.27delC). In Family 1, three individuals were identified to have this variant, two affected family members and one unaffected family member. In Family 2, 7 individuals had this variant, 2 affected and 5 unaffected.
HI Evidence Comments:
Overview of pancreatitis in GeneReviews reports heterozygous pathogenic variants in SPINK1 are a cause of chronic pancreatitis (PMID: 24624459). Pathogenic variants in SPINK1 are responsible for 28% of all chronic pancreatitis cases in children and in 7% of adult cases (PMID: 30897605). Several common variants are associated with mild to moderate risk, and reduced penetrance in families has also been described. Chronic pancreatitis can be caused by a variant in the cationic trypsinogen gene (PRSS1) and the SPINK1 gene (OMIM: 167800; PMID: 24624459, 30897605). SPINK1 is associated with 28% of pediatric chronic pancreatitis and 15% of adult onset disease (PMID: 24624459). Missense mutations account for approximately 40% (24/60) of pathogenic variants in SPINK1 associated with chronic pancreatitis. Splicing and regulatory variants (26/60 or 43%), and intragenic deletions and duplications (5/60 or 8%) have also been reported (NM_003122.5, HGMD, http://www.pancreasgenetics.org/index.php). SPINK1 has also been implicated in both autosomal dominant and autosomal recessive tropical calcific pancreatitis (OMIM: 608189); affected individuals have been reported with heterozygous and biallelic missense variants. Reduced penetrance and varying phenotypic severity has been observed in families with variants in SPINK1.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000005.9) (NC_000005.10)