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UniProtKB/Swiss-Prot P00995: Variant p.Asn34Ser

Serine protease inhibitor Kazal-type 1
Gene: SPINK1
Chromosomal location: 5q31-q35
Variant information

Variant position:  34
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Asparagine (N) to Serine (S) at position 34 (N34S, p.Asn34Ser).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from medium size and polar (N) to small size and polar (S)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in 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.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Involvement in 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.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In PCTT and TCP; associated with disease susceptibility; risk factor also for acute pancreatitis; may confer susceptibility to fibrocalculous pancreatic diabetes.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  34
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  79
The length of the canonical sequence.

Location on the sequence:   LLSLSGNTGADSLGREAKCY  N ELNGCTKIYDPVCGTDGNTY
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         LLSLSGNT-GADSLGREAKCYNELNGCTKIYDPVCGTDGNTY

                              ----------NNMLQRQANCNLKVNGCNKIYNPICGSDGIT

Mouse                         LLSLAGNTFSAKVTGKEASCHDAVAGCPRIYDPVCGTDGIT

Rat                           LLSLAGNP-PAEVNGKTPNCPKQIMGCPRIYDPVCGTNGIT

Pig                           -----------TSPQREATCTSEVSGCPKIYNPVCGTDGIT

Bovine                        LMSLSGNS-GANILGREAKCTNEVNGCPRIYNPVCGTDGVT

Sheep                         -----------NILGREAKCTNEVNGCPRIYNPVCGTDGVT

Horse                         -----------DSLGREAKCNNNAGGCTKIYNPVCGTDGNT

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 24 – 79 Serine protease inhibitor Kazal-type 1
Domain 26 – 79 Kazal-like
Disulfide bond 32 – 61


Literature citations

Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis.
Witt H.; Luck W.; Hennies H.C.; Classen M.; Kage A.; Lass U.; Landt O.; Becker M.;
Nat. Genet. 25:213-216(2000)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS PCTT PRO-14 AND SER-34; VARIANT SER-55;

Mutational analysis of the human pancreatic secretory trypsin inhibitor (PSTI) gene in hereditary and sporadic chronic pancreatitis.
Chen J.-M.; Mercier B.; Audrezet M.-P.; Ferec C.;
J. Med. Genet. 37:67-69(2000)
Cited for: VARIANT PCTT SER-34; VARIANT SER-55;

SPINK1 is a susceptibility gene for fibrocalculous pancreatic diabetes in subjects from the Indian subcontinent.
Hassan Z.; Mohan V.; Ali L.; Allotey R.; Barakat K.; Faruque M.O.; Deepa R.; McDermott M.F.; Jackson A.E.; Cassell P.; Curtis D.; Gelding S.V.; Vijayaravaghan S.; Gyr N.; Whitcomb D.C.; Azad Khan A.K.; Hitman G.A.;
Am. J. Hum. Genet. 71:964-968(2002)
Cited for: VARIANT TCP SER-34; INVOLVEMENT IN FIBROCALCULOUS PANCREATIC DIABETES;

Mutations in the pancreatic secretory trypsin inhibitor gene (PSTI/SPINK1) rather than the cationic trypsinogen gene (PRSS1) are significantly associated with tropical calcific pancreatitis.
Chandak G.R.; Idris M.M.; Reddy D.N.; Bhaskar S.; Sriram P.V.J.; Singh L.;
J. Med. Genet. 39:347-351(2002)
Cited for: VARIANT TCP SER-34; VARIANT SER-55;

The SPINK1 N34S variant is associated with acute pancreatitis.
O'Reilly D.A.; Witt H.; Rahman S.H.; Schulz H.U.; Sargen K.; Kage A.; Cartmell M.T.; Landt O.; Larvin M.; Demaine A.G.; McMahon M.J.; Becker M.; Kingsnorth A.N.;
Eur. J. Gastroenterol. Hepatol. 20:726-731(2008)
Cited for: VARIANT PCTT SER-34; VARIANT SER-55;

SPINK1 N34S is strongly associated with recurrent acute pancreatitis but is not a risk factor for the first or sentinel acute pancreatitis event.
Aoun E.; Muddana V.; Papachristou G.I.; Whitcomb D.C.;
Am. J. Gastroenterol. 105:446-451(2010)
Cited for: VARIANT PCTT SER-34;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.