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UniProtKB/Swiss-Prot Q99895: Variant p.Cys155Tyr

Chymotrypsin-C
Gene: CTRC
Variant information

Variant position:  155
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 Cysteine (C) to Tyrosine (Y) at position 155 (C155Y, p.Cys155Tyr).
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 (C) to large size and aromatic (Y)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:18059268, ECO:0000269|PubMed:18172691, ECO:0000269|PubMed:22580415, ECO:0000269|PubMed:22942235}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Loss-of-function CTRC variants predispose to pancreatitis by diminishing its protective trypsin-degrading activity (PubMed:18059268). They cause loss of function by one or more of three mechanisms: reduced secretion, catalytic defect and increased degradation by trypsin (PubMed:22942235). {ECO:0000269|PubMed:18059268, ECO:0000269|PubMed:22942235}.
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; associated with susceptibility to disease; the mutant is not secreted.
Any additional useful information about the variant.



Sequence information

Variant position:  155
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  268
The length of the canonical sequence.

Location on the sequence:   DTIQVACLPEKDSLLPKDYP  C YVTGWGRLWTNGPIADKLQQ
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                         DTIQVACLPEKDSLLPKDYPCYVTGWGRLWTNGPIADKLQQ

Mouse                         DTIQVACIPEQDSLLPGDYPCYVTGWGRLWTNGPIAEVLQQ

Rat                           NTIQVACIPEEGSLLPQDYPCYVTGWGRLWTNGPIAEVLQQ

Bovine                        DTIQVACLPEEGSLLPQDYPCFVTGWGRLYTNGPIAAELQQ

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 30 – 268 Chymotrypsin-C
Domain 30 – 267 Peptidase S1
Disulfide bond 155 – 222
Beta strand 155 – 160


Literature citations

Association of rare chymotrypsinogen C (CTRC) gene variations in patients with idiopathic chronic pancreatitis.
Masson E.; Chen J.M.; Scotet V.; Le Marechal C.; Ferec C.;
Hum. Genet. 123:83-91(2008)
Cited for: VARIANTS PCTT THR-73; TYR-155; SER-217; ARG-217; ILE-235; 247-LYS--ARG-254 DEL AND TRP-254; VARIANTS HIS-162; GLU-172 AND VAL-200;

Comprehensive functional analysis of chymotrypsin C (CTRC) variants reveals distinct loss-of-function mechanisms associated with pancreatitis risk.
Beer S.; Zhou J.; Szabo A.; Keiles S.; Chandak G.R.; Witt H.; Sahin-Toth M.;
Gut 62:1616-1624(2013)
Cited for: VARIANTS ARG-18; TYR-35 AND SER-227; VARIANTS PCTT ARG-178 AND GLU-250; CHARACTERIZATION OF VARIANTS ARG-18; TYR-35; ARG-48; ARG-61; ARG-220 AND GLN-254; CHARACTERIZATION OF VARIANTS PCTT VAL-32; THR-73; TYR-155; ARG-178; ARG-217; SER-217; ILE-235; 247-LYS--ARG-254 DEL; LEU-249; GLU-250 AND TRP-254;

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.