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UniProtKB/Swiss-Prot P35914: Variant p.Arg41Gln

Hydroxymethylglutaryl-CoA lyase, mitochondrial
Gene: HMGCL
Variant information

Variant position:  41
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 Arginine (R) to Glutamine (Q) at position 41 (R41Q, p.Arg41Gln).
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 (Q)
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

Variant description:  In HMGCLD; loss of activity and of proton exchange.
Any additional useful information about the variant.

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



Sequence information

Variant position:  41
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  325
The length of the canonical sequence.

Location on the sequence:   VSTSSMGTLPKRVKIVEVGP  R DGLQNEKNIVSTPVKIKLID
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                         VSTSSMGTLPKRVKIVEVGPRDGLQNEKNIVSTPVKIKLID

Mouse                         VSTSSMGTLPKQVKIVEVGPRDGLQNEKSIVPTPVKIRLID

Rat                           ASTSSMGTLPKRVKIVEVGPRDGLQNEKSIVPTPVKIKLID

Bovine                        VSTSSVGTFPKQVKIVEVGPRDGLQNEKNIVPTPVKIKLID

Chicken                       -------AFPQRVKVVEVGPRDGLQNEKSVVPTPVKIRLID

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 28 – 325 Hydroxymethylglutaryl-CoA lyase, mitochondrial
Domain 33 – 300 Pyruvate carboxyltransferase
Metal binding 42 – 42 Divalent metal cation
Binding site 41 – 41 Substrate
Modified residue 48 – 48 N6-acetyllysine; alternate
Modified residue 48 – 48 N6-succinyllysine; alternate
Mutagenesis 37 – 37 E -> D. Normal activity.
Mutagenesis 41 – 41 R -> M. Reduced activity, and loss of proton exchange.
Mutagenesis 42 – 42 D -> AN. Loss of activity, and reduced proton exchange rate.
Turn 39 – 41


Literature citations

HMG CoA lyase deficiency: identification of five causal point mutations in codons 41 and 42, including a frequent Saudi Arabian mutation, R41Q.
Mitchell G.A.; Ozand P.T.; Robert M.-F.; Ashmarina L.; Roberts J.; Gibson K.M.; Wanders R.J.; Wang S.; Chevalier I.; Ploechl E.; Miziorko H.;
Am. J. Hum. Genet. 62:295-300(1998)
Cited for: VARIANTS HMGCLD GLN-41; GLU-42; GLY-42 AND HIS-42;

Mutations underlying 3-hydroxy-3-methylglutaryl CoA lyase deficiency in the Saudi population.
Al-Sayed M.; Imtiaz F.; Alsmadi O.A.; Rashed M.S.; Meyer B.F.;
BMC Med. Genet. 7:86-86(2006)
Cited for: VARIANT HMGCLD GLN-41;

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.