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UniProtKB/Swiss-Prot P02533: Variant p.Arg125Cys

Keratin, type I cytoskeletal 14
Gene: KRT14
Variant information

Variant position:  125
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 Cysteine (C) at position 125 (R125C, p.Arg125Cys).
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 (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  Epidermolysis bullosa simplex, Dowling-Meara type (DM-EBS) [MIM:131760]: A severe form of intraepidermal epidermolysis bullosa characterized by generalized herpetiform blistering, milia formation, dystrophic nails, and mucous membrane involvement. {ECO:0000269|PubMed:10583131, ECO:0000269|PubMed:10730767, ECO:0000269|PubMed:10733662, ECO:0000269|PubMed:10820403, ECO:0000269|PubMed:11710919, ECO:0000269|PubMed:12603865, ECO:0000269|PubMed:12655565, ECO:0000269|PubMed:12707098, ECO:0000269|PubMed:14987259, ECO:0000269|PubMed:16786515, ECO:0000269|PubMed:16882168, ECO:0000269|PubMed:1717157, ECO:0000269|PubMed:7561171, ECO:0000269|PubMed:7688405, ECO:0000269|PubMed:8601736, ECO:0000269|PubMed:9804355, ECO:0000269|PubMed:9989794, ECO:0000269|Ref.32}. Note=The disease is caused by mutations 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 DM-EBS.
Any additional useful information about the variant.

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



Sequence information

Variant position:  125
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  472
The length of the canonical sequence.

Location on the sequence:   AGGDGLLVGSEKVTMQNLND  R LASYLDKVRALEEANADLEV
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                         AG--GDGLLVGSEKVTMQNLNDRLASYLDKVRALEEANADLEV

Mouse                         GGGIGDGLLVGSEKVTMQNLNDRLATYLDKVRALEEANTEL

Rat                           GGGLGDGLLVGSEKVTMQNLNDRLATYLDKVRALEEANSDL

Chicken                       GG--GDGILPAGEKETMQNLNDRLAAYLDKVRALEEANTDL

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 1 – 472 Keratin, type I cytoskeletal 14
Domain 115 – 426 IF rod
Region 115 – 150 Coil 1A


Literature citations

Point mutations in human keratin 14 genes of epidermolysis bullosa simplex patients: genetic and functional analyses.
Coulombe P.A.; Hutton M.E.; Letai A.; Hebert A.; Paller A.S.; Fuchs E.;
Cell 66:1301-1311(1991)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 118-126; VARIANTS DM-EBS PHE-122; CYS-125 AND HIS-125;

Keratin 14 gene mutations in patients with epidermolysis bullosa simplex.
Chen H.; Bonifas J.M.; Matsumura K.; Ikeda S.; Leyden W.A.; Epstein E.H. Jr.;
J. Invest. Dermatol. 105:629-632(1995)
Cited for: VARIANTS WC-EBS ILE-119; ASP-274; ASN-377 AND CYS-388; VARIANTS DM-EBS ARG-120; CYS-125 AND SER-125;

A recurrent keratin 14 mutation in Dowling-Meara epidermolysis bullosa simplex.
Sasaki Y.; Shimizu H.; Akiyama M.; Hiraoka Y.; Takizawa Y.; Yamada S.; Morishima Y.; Yamanishi K.; Aiso S.; Nishikawa T.;
Br. J. Dermatol. 141:747-748(1999)
Cited for: VARIANT DM-EBS CYS-125;

Exempting homologous pseudogene sequences from polymerase chain reaction amplification allows genomic keratin 14 hotspot analysis.
Hut P.H.L.; van der Vlies P.; Jonkman M.F.; Verlind E.; Shimizu H.; Buys C.H.C.M.; Scheffer H.;
J. Invest. Dermatol. 114:616-619(2000)
Cited for: VARIANTS DM-EBS CYS-125; HIS-125 AND GLN-419; VARIANTS K-EBS ASP-247 AND HIS-415; VARIANT WC-EBS LYS-422;

DNA based prenatal testing for the skin blistering disorder epidermolysis bullosa simplex.
Rugg E.L.; Baty D.; Shemanko C.S.; Magee G.; Polak S.; Bergman R.; Kadar T.; Boxer M.; Falik-Zaccai T.; Borochowitz Z.; Lane E.B.;
Prenat. Diagn. 20:371-377(2000)
Cited for: VARIANTS DM-EBS CYS-125 AND HIS-415; VARIANT K-EBS PRO-134;

Epidermolysis bullosa simplex in Japanese and Korean patients: genetic studies in 19 cases.
Yasukawa K.; Sawamura D.; Goto M.; Nakamura H.; Jung S.-Y.; Kim S.-C.; Shimizu H.;
Br. J. Dermatol. 155:313-317(2006)
Cited for: VARIANT WC-EBS VAL-119; VARIANTS DM-EBS HIS-125 AND CYS-125;

Novel and recurrent mutations in keratin KRT5 and KRT14 genes in epidermolysis bullosa simplex: implications for disease phenotype and keratin filament assembly.
Mueller F.B.; Kuester W.; Wodecki K.; Almeida H. Jr.; Bruckner-Tuderman L.; Krieg T.; Korge B.P.; Arin M.J.;
Hum. Mutat. 27:719-720(2006)
Cited for: VARIANTS DM-EBS LYS-123; CYS-125; HIS-125 AND PRO-417; VARIANTS K-EBS LEU-133; THR-272 AND PRO-384; VARIANTS WC-EBS PRO-211 AND GLU-411 DEL;

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.