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UniProtKB/Swiss-Prot P07237: Variant p.Tyr393Cys

Protein disulfide-isomerase
Gene: P4HB
Variant information

Variant position:  393
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Tyrosine (Y) to Cysteine (C) at position 393 (Y393C, p.Tyr393Cys).
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 aromatic (Y) to medium size and polar (C)
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

Variant description:  In CLCRP1; impairs ability to act as a disulfide isomerase enzyme.
Any additional useful information about the variant.

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



Sequence information

Variant position:  393
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  508
The length of the canonical sequence.

Location on the sequence:   VGKNFEDVAFDEKKNVFVEF  Y APWCGHCKQLAPIWDKLGET
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                         VGKNFEDVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGET

Mouse                         VGANFEEVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGET

Rat                           VGKNFEEVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGET

Bovine                        VGKNFEEVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGET

Rabbit                        VGKNFEEVAFDEKKNVFVEFYAPWCGHCKQLAPIWDKLGET

Chicken                       VGKNFEEVAFDENKNVFVEFYAPWCGHCKQLAPIWDKLGET

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 18 – 508 Protein disulfide-isomerase
Domain 349 – 475 Thioredoxin 2
Active site 397 – 397 Nucleophile
Active site 400 – 400 Nucleophile
Site 398 – 398 Contributes to redox potential value
Site 399 – 399 Contributes to redox potential value
Beta strand 387 – 393


Literature citations

Cole-Carpenter syndrome is caused by a heterozygous missense mutation in P4HB.
Rauch F.; Fahiminiya S.; Majewski J.; Carrot-Zhang J.; Boudko S.; Glorieux F.; Mort J.S.; Baechinger H.P.; Moffatt P.;
Am. J. Hum. Genet. 96:425-431(2015)
Cited for: INVOLVEMENT IN CLCRP1; VARIANT CLCRP1 CYS-393; CHARACTERIZATION OF VARIANT CLCRP1 CYS-393;

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.