UniProtKB/Swiss-Prot Q8N0X4 : Variant p.Asp28Tyr
Citramalyl-CoA lyase, mitochondrial
Gene: CLYBL
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Variant information
Variant position:
28
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:
LB/B
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 Aspartate (D) to Tyrosine (Y) at position 28 (D28Y, p.Asp28Tyr).
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 (D) to large size and aromatic (Y)
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
Polymorphism:
The protein is absent in 2.7% of the human population due to a loss-of-function polymorphism (rs41281112) that changes Arg-259 to a premature stop codon, leading to loss of the protein product (PubMed:23754956 , PubMed:24334609 ). This polymorphism is associated with reduction of circulating vitamin B12 (PubMed:23754956 , PubMed:24334609 ). The reduction of circulating vitamin B12 is caused by accumulation of citramalyl-CoA, an intermediate in the C5-dicarboxylate metabolic pathway that includes itaconate (PubMed:29056341 ). Itaconate acting as a vitamin B12-poisoning metabolite that inactivates the mitochondrial methylglutaconyl-CoA hydratase (AUH) enzyme (PubMed:29056341 ).
Additional information on the polymorphism described.
Other resources:
Links to websites of interest for the variant.
Sequence information
Variant position:
28
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:
340
The length of the canonical sequence.
Location on the sequence:
RAARGAAAAALLRLKASLAA
D IPRLGYSSSSHHKYIPRRAV
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 RAARGAAAAALLRLKASLAAD IPRLGYSSSSHHKYIPRRAV
Mouse NTVRGAA--ALPRLKASHVVS VYKPRYSSLSNHKYVPRRAV
Rat NAVRGAA--ALPRLKASLVAS VCRPGYSSLSNHKYVPRRAV
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.
Type Positions Description
Chain
23 – 340
Citramalyl-CoA lyase, mitochondrial
Literature citations
No reference for the current variant in UniProtKB/Swiss-Prot.
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.