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UniProtKB/Swiss-Prot P41229: Variant p.Pro480Leu

Lysine-specific demethylase 5C
Gene: KDM5C
Variant information

Variant position:  480
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 Proline (P) to Leucine (L) at position 480 (P480L, p.Pro480Leu).
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

Involvement in disease:  Mental retardation, X-linked, syndromic, Claes-Jensen type (MRXSCJ) [MIM:300534]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSCJ patients manifest mental retardation associated with variable features such as slowly progressive spastic paraplegia, seizures, facial dysmorphism. {ECO:0000269|PubMed:15586325, ECO:0000269|PubMed:16538222, ECO:0000269|PubMed:16541399, ECO:0000269|PubMed:17320160, ECO:0000269|PubMed:17468742, ECO:0000269|PubMed:23356856, ECO:0000269|PubMed:25666439}. 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 MRXSCJ; patient fibroblasts show decreased enzymatic activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  480
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1560
The length of the canonical sequence.

Location on the sequence:   RHLTPEEEEYATSGWNLNVM  P VLEQSVLCHINADISGMKVP
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                         RHLTPEEEEYATSGWNLNVMPVLEQSVLCHINADISGMKVP

                              RHLTPEEEEYATSGWNLNVMPVLEQSVLCHINADISGMKVP

Mouse                         RHLTPEEEEYATSGWNLNVMPVLEQSVLCHINADISGMKVP

Pig                           RHLTPEEEEYATSGWNLNVMPVLEQSVLCHINADISGMKVP

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 – 1560 Lysine-specific demethylase 5C
Domain 468 – 634 JmjC
Helix 479 – 481


Literature citations

Multilocus loss of DNA methylation in individuals with mutations in the histone H3 lysine 4 demethylase KDM5C.
Grafodatskaya D.; Chung B.H.; Butcher D.T.; Turinsky A.L.; Goodman S.J.; Choufani S.; Chen Y.A.; Lou Y.; Zhao C.; Rajendram R.; Abidi F.E.; Skinner C.; Stavropoulos J.; Bondy C.A.; Hamilton J.; Wodak S.; Scherer S.W.; Schwartz C.E.; Weksberg R.;
BMC Med. Genomics 6:1-1(2013)
Cited for: VARIANT MRXSCJ LEU-480;

Mutations in the intellectual disability gene KDM5C reduce protein stability and demethylase activity.
Brookes E.; Laurent B.; Ounap K.; Carroll R.; Moeschler J.B.; Field M.; Schwartz C.E.; Gecz J.; Shi Y.;
Hum. Mol. Genet. 24:2861-2872(2015)
Cited for: CHARACTERIZATION OF VARIANTS MRXSCJ TYR-402 AND LEU-480;

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.