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UniProtKB/Swiss-Prot P07477: Variant p.Arg122His

Trypsin-1
Gene: PRSS1
Variant information

Variant position:  122
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 Arginine (R) to Histidine (H) at position 122 (R122H, p.Arg122His).
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 large size and basic (R) to medium size and polar (H)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  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:10204851, ECO:0000269|PubMed:10381903, ECO:0000269|PubMed:10930381, ECO:0000269|PubMed:11073545, ECO:0000269|PubMed:11788572, ECO:0000269|PubMed:11866271, ECO:0000269|PubMed:14695529, ECO:0000269|PubMed:15776435, ECO:0000269|PubMed:8841182, ECO:0000269|PubMed:9322498, ECO:0000269|PubMed:9633818}. 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; suppresses an autocleavage site which is probably part of a fail-safe mechanism by which trypsin, which is activated within the pancreas, may be inactivated; loss of this cleavage site would permit autodigestion resulting in pancreatitis.
Any additional useful information about the variant.

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



Sequence information

Variant position:  122
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  247
The length of the canonical sequence.

Location on the sequence:   KTLNNDIMLIKLSSRAVINA  R VSTISLPTAPPATGTKCLIS
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                         KTLNNDIMLIKLSSRAVINARVSTISLPTAPPATGTKCLIS

                              NTIDNDIMLIKLSSPATLNSRVSAIALPKSCPAAGTQCLIS

Rat                           WTLNNDIMLIKLSSPVKLNARVAPVALPSACAPAGTQCLIS

Bovine                        NTLNNDIMLIKLKSAASLNSRVASISLPTSCASAGTQCLIS

Chicken                       NTLNNDIMLIKLSKAATLNSYVNTVPLPTSCVTAGTTCLIS

Xenopus laevis                YTLDNDIMLIKLSSPASLNAAVNTVPLPSGCSAAGTSCLIS

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 – 247 Trypsin-1
Chain 24 – 122 Alpha-trypsin chain 1
Domain 24 – 244 Peptidase S1
Active site 107 – 107 Charge relay system
Disulfide bond 30 – 160
Beta strand 120 – 122


Literature citations

Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene.
Whitcomb D.C.; Gorry M.C.; Preston R.A.; Furey W.; Sossenheimer M.J.; Ulrich C.D.; Martin S.P.; Gates L.K. Jr.; Amann S.T.; Toskes P.P.; Liddle R.; McGrath K.; Uomo G.; Post J.C.; Ehrlich G.D.;
Nat. Genet. 14:141-145(1996)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 68-151; VARIANT PCTT HIS-122;

Mutational screening of patients with nonalcoholic chronic pancreatitis: identification of further trypsinogen variants.
Teich N.; Bauer N.; Mossner J.; Keim V.;
Am. J. Gastroenterol. 97:341-346(2002)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 68-151; VARIANTS PCTT ILE-29; PRO-104; CYS-116; HIS-122 AND PHE-139;

Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis.
Gorry M.C.; Gabbaizedeh D.; Furey W.; Gates L.K. Jr.; Preston R.A.; Aston C.E.; Zhang Y.; Ulrich C.; Ehrlich G.D.; Whitcomb D.C.;
Gastroenterology 113:1063-1068(1997)
Cited for: VARIANTS PCTT ILE-29 AND HIS-122;

A signal peptide cleavage site mutation in the cationic trypsinogen gene is strongly associated with chronic pancreatitis.
Witt H.; Luck W.; Becker M.;
Gastroenterology 117:7-10(1999)
Cited for: VARIANTS PCTT VAL-16 AND HIS-122;

A CGC>CAT gene conversion-like event resulting in the R122H mutation in the cationic trypsinogen gene and its implication in the genotyping of pancreatitis.
Chen J.-M.; Raguenes O.; Ferec C.; Deprez P.H.; Verellen-Dumoulin C.;
J. Med. Genet. 37:E36-E36(2000)
Cited for: VARIANT PCTT HIS-122;

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.