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Mendeliome

Gene: SPINK1

Green List (high evidence)

SPINK1 (serine peptidase inhibitor, Kazal type 1)
EnsemblGeneIds (GRCh38): ENSG00000164266
EnsemblGeneIds (GRCh37): ENSG00000164266
OMIM: 167790, Gene2Phenotype
SPINK1 is in 2 panels

1 review

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Witt et al (2000)(PMID: 10835640) analysed 96 unrelated individuals for mutations in SPINK1 and found mutations in 22 patients. 18 of these had a N34S which was homozygous in 6 of the patients. 4 other variants were found including heterozygous M1T - destroys the initiation codon, heterozygous L14P - results in decreased activity).

Kaneko et al. (2001) (PMID: 11355022) found the N34S mutation in 5 unrelated Japanese patients with chronic pancreatitis with juvenile onset or family history of the disorder. They also found a novel homozygous G-to-A transition in the promoter region of PSTI 215 bp upstream from the translation initiation site in 2 patients (homozygous -215G-A)

Audrezet et al. (2002)(PMID: 11938439) analyzed the entire coding sequence and exon/intron junctions of the SPINK1 gene by denaturing gradient gel electrophoresis (DGGE) and direct sequencing in 39 white French patients with idiopathic chronic pancreatitis. The N34S missense mutation was detected in 4 patients (3 heterozygotes and 1 homozygote), as compared with 3 out of 200 blood donors. In addition, 2 variants were identified in the 5-prime-untranslated region, each identified once in different patients.

Masson et al. (2006) (PMID: 16823394) identified a 1,336-bp deletion encompassing exon 1 in the SPINK1 gene in affected members of a family with chronic pancreatitis.

Kiraly et al. (2007)(PMID: 17274009) reported 2 unrelated families with autosomal dominant chronic pancreatitis and a variant leading to L14R. First family had 2 affected members, second had 3. Functional studies showed decreased SPINK1 activity.

Lek et al. (2016)(PMID: 27535533) noted that the N34S variant has a high allele frequency (0.0219) in the South Asian population in the ExAC database, suggesting that it is not pathogenic.

However, even excluding the N34S which is now classified as a VUS, there are still 3 variants in unrelated families that are plausibily disease causing.
Created: 6 Apr 2022, 8:23 a.m. | Last Modified: 6 Apr 2022, 8:23 a.m.
Panel Version: 0.12612

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Tropical calcific pancreatitis, MIM# 608189; Pancreatitis, hereditary, MIM# 167800

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • Tropical calcific pancreatitis, MIM# 608189
  • Pancreatitis, hereditary, MIM# 167800
OMIM
167790
Clinvar variants
Variants in SPINK1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

6 Apr 2022, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: spink1 has been classified as Green List (High Evidence).

6 Apr 2022, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: SPINK1 were changed from to Tropical calcific pancreatitis, MIM# 608189; Pancreatitis, hereditary, MIM# 167800

6 Apr 2022, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: SPINK1 were set to

6 Apr 2022, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: SPINK1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

17 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: SPINK1 was added gene: SPINK1 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: SPINK1 was set to Unknown