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UniProtKB/Swiss-Prot P35520: Variant p.Glu302Lys

Cystathionine beta-synthase
Gene: CBS
Variant information

Variant position:  302
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 Glutamate (E) to Lysine (K) at position 302 (E302K, p.Glu302Lys).
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 acidic (E) to large size and basic (K)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
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:  Cystathionine beta-synthase deficiency (CBSD) [MIM:236200]: An enzymatic deficiency resulting in altered sulfur metabolism and homocystinuria. The clinical features of untreated homocystinuria due to CBS deficiency include myopia, ectopia lentis, mental retardation, skeletal anomalies resembling Marfan syndrome, and thromboembolic events. Light skin and hair can also be present. Biochemical features include increased urinary homocystine and methionine. {ECO:0000269|PubMed:10215408, ECO:0000269|PubMed:10408774, ECO:0000269|PubMed:10462600, ECO:0000269|PubMed:11013450, ECO:0000269|PubMed:11359213, ECO:0000269|PubMed:11553052, ECO:0000269|PubMed:12007221, ECO:0000269|PubMed:12124992, ECO:0000269|PubMed:12815602, ECO:0000269|PubMed:1301198, ECO:0000269|PubMed:14635102, ECO:0000269|PubMed:15146473, ECO:0000269|PubMed:15365998, ECO:0000269|PubMed:15993874, ECO:0000269|PubMed:16205833, ECO:0000269|PubMed:16429402, ECO:0000269|PubMed:20506325, ECO:0000269|PubMed:21240075, ECO:0000269|PubMed:21520339, ECO:0000269|PubMed:22738154, ECO:0000269|PubMed:23974653, ECO:0000269|PubMed:23981774, ECO:0000269|PubMed:25044645, ECO:0000269|PubMed:7506602, ECO:0000269|PubMed:7564249, ECO:0000269|PubMed:7611293, ECO:0000269|PubMed:7635485, ECO:0000269|PubMed:7762555, ECO:0000269|PubMed:7849717, ECO:0000269|PubMed:7967489, ECO:0000269|PubMed:7981678, ECO:0000269|PubMed:8353501, ECO:0000269|PubMed:8528202, ECO:0000269|PubMed:8755636, ECO:0000269|PubMed:8803779, ECO:0000269|PubMed:8990018, ECO:0000269|PubMed:9156316, ECO:0000269|PubMed:9266356, ECO:0000269|PubMed:9361025, ECO:0000269|PubMed:9889017}. 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 CBSD; no effect on cystathionine beta-synthase activity; inhibited by AdoHcy and impaired activation by AdoMet; no effect on homotetramer formation.
Any additional useful information about the variant.

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

Sequence information

Variant position:  302
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  551
The length of the canonical sequence.

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.







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.

Chain 1 – 551 Cystathionine beta-synthase

Literature citations

Cystathionine beta-synthase mutations: effect of mutation topology on folding and activity.
Kozich V.; Sokolova J.; Klatovska V.; Krijt J.; Janosik M.; Jelinek K.; Kraus J.P.;
Hum. Mutat. 31:809-819(2010)
Cited for: CHARACTERIZATION OF VARIANTS CBSD LEU-49; ARG-65; ARG-78; ASN-102; VAL-114; GLN-125; LYS-144; ARG-148; TYR-165; LYS-176; ALA-180; MET-191; LYS-228; ARG-262; LYS-266; THR-278; LYS-302; ARG-305; SER-307; CYS-369; LEU-422; THR-435; GLN-439; ASN-444; LEU-466 AND SER-539; FUNCTION; CATALYTIC ACTIVITY; PATHWAY; ACTIVITY REGULATION; SUBUNIT;

Four novel mutations in the cystathionine beta-synthase gene: effect of a second linked mutation on the severity of the homocystinuric phenotype.
de Franchis R.; Kraus E.; Kozich V.; Sebastio G.; Kraus J.P.;
Hum. Mutat. 13:453-457(1999)
Cited for: VARIANTS CBSD TRP-58; VAL-126; LYS-302 AND CYS-336;

The molecular basis of cystathionine beta-synthase deficiency in Australian patients: genotype-phenotype correlations and response to treatment.
Gaustadnes M.; Wilcken B.; Oliveriusova J.; McGill J.; Fletcher J.; Kraus J.P.; Wilcken D.E.;
Hum. Mutat. 20:117-126(2002)
Cited for: VARIANTS CBSD LEU-49; PRO-101; ARG-109; GLN-125; LYS-144; TYR-165; LYS-228; THR-278; LYS-302; SER-307; GLU-331; CYS-336; SER-347; MET-353; CYS-369; MET-371 AND GLN-439; CHARACTERIZATION OF VARIANTS CBSD PRO-101; ARG-109; LYS-228 AND SER-347;

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.