UniProtKB/SwissProt variant VAR

Variant information

Variant position:

42

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 Aspartate (D) to Glycine (G) at position 42 (D42G, p.Asp42Gly).

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 glycine (G)

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.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs1467902610 [ dbSNP | Ensembl ]

Sequence information

Variant position:

42

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:

STSSMGTLPKRVKIVEVGPR D GLQNEKNIVSTPVKIKLIDM

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                         STSSMGTLPKRVKIVEVGPRDGLQNEKNIVSTPVKIKLIDM

Mouse                         STSSMGTLPKQVKIVEVGPRDGLQNEKSIVPTPVKIRLIDM

Rat                           STSSMGTLPKRVKIVEVGPRDGLQNEKSIVPTPVKIKLIDM

Bovine                        STSSVGTFPKQVKIVEVGPRDGLQNEKNIVPTPVKIKLIDM

Chicken                       ------AFPQRVKVVEVGPRDGLQNEKSVVPTPVKIRLIDM

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	28 – 325	Hydroxymethylglutaryl-CoA lyase, mitochondrial
Domain	33 – 300	Pyruvate carboxyltransferase
Binding site	41 – 41
Binding site	42 – 42
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.
Helix	42 – 45

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;

Ten novel HMGCL mutations in 24 patients of different origin with 3-hydroxy-3-methyl-glutaric aciduria.
Menao S.; Lopez-Vinas E.; Mir C.; Puisac B.; Gratacos E.; Arnedo M.; Carrasco P.; Moreno S.; Ramos M.; Gil M.C.; Pie A.; Ribes A.; Perez-Cerda C.; Ugarte M.; Clayton P.T.; Korman S.H.; Serra D.; Asins G.; Ramos F.J.; Gomez-Puertas P.; Hegardt F.G.; Casals N.; Pie J.;
Hum. Mutat. 30:E520-E529(2009)
Cited for: VARIANTS HMGCLD LYS-37; GLY-42; PHE-142; TYR-174; SER-192; PHE-200 AND ARG-233; CHARACTERIZATION OF VARIANTS HMGCLD LYS-37; PHE-142; TYR-174; SER-192 AND PHE-200;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P35914: Variant p.Asp42Gly