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UniProtKB/Swiss-Prot Q99456: Variant p.Leu132Pro

Keratin, type I cytoskeletal 12
Gene: KRT12
Variant information

Variant position:  132
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 Leucine (L) to Proline (P) at position 132 (L132P, p.Leu132Pro).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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

Variant description:  In MECD1; increased expression of keratins KRT5, KRT6, KRT14 and KRT16 and decreased expression of KRT12 in the corneal epithelium; increased expression of DDIT3/CHOP and CASP12 in the corneal epithelium indicative of up-regulation of the unfolded protein response..
Any additional useful information about the variant.

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



Sequence information

Variant position:  132
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  494
The length of the canonical sequence.

Location on the sequence:   ILSGNDGGLLSGSEKETMQN  L NDRLASYLDKVRALEEANTE
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                         ILSGNDGGLLSGSEKETMQNLNDRLASYLDKVRALEEANTE

Mouse                         IFSGNDGGLLSGSEKETMQNLNDRLASYLGKVRSLEEANAE

Rat                           IFSGNDGGLLSGSEKETMQNLNDRLASYLGKVRALEEANAE

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 – 494 Keratin, type I cytoskeletal 12
Domain 125 – 440 IF rod
Region 125 – 160 Coil 1A


Literature citations

Keratin 12 missense mutation induces the unfolded protein response and apoptosis in Meesmann epithelial corneal dystrophy.
Allen E.H.; Courtney D.G.; Atkinson S.D.; Moore J.E.; Mairs L.; Poulsen E.T.; Schiroli D.; Maurizi E.; Cole C.; Hickerson R.P.; James J.; Murgatroyd H.; Smith F.J.; MacEwen C.; Enghild J.J.; Nesbit M.A.; Leslie Pedrioli D.M.; McLean W.H.; Moore C.B.;
Hum. Mol. Genet. 25:1176-1191(2016)
Cited for: FUNCTION; TISSUE SPECIFICITY; CHARACTERIZATION OF VARIANT MECD1 PRO-132;

Severe Meesmann's epithelial corneal dystrophy phenotype due to a missense mutation in the helix-initiation motif of keratin 12.
Hassan H.; Thaung C.; Ebenezer N.D.; Larkin G.; Hardcastle A.J.; Tuft S.J.;
Eye 27:367-373(2013)
Cited for: VARIANT MECD1 PRO-132;

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.