UniProtKB/SwissProt variant VAR

Variant information

Variant position:

193

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 Threonine (T) to Alanine (A) at position 193 (T193A, p.Thr193Ala).

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 polar (T) to small size and hydrophobic (A)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

0

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:

Acyl-CoA dehydrogenase medium-chain deficiency (ACADMD) [MIM:201450]: An inborn error of mitochondrial fatty acid beta-oxidation which causes fasting hypoglycemia, hepatic dysfunction and encephalopathy, often resulting in death in infancy. {ECO:0000269|PubMed:10767181, ECO:0000269|PubMed:11349232, ECO:0000269|PubMed:11409868, ECO:0000269|PubMed:11486912, ECO:0000269|PubMed:1363805, ECO:0000269|PubMed:1671131, ECO:0000269|PubMed:1684086, ECO:0000269|PubMed:1902818, ECO:0000269|PubMed:2251268, ECO:0000269|PubMed:2393404, ECO:0000269|PubMed:2394825, ECO:0000269|PubMed:7603790, ECO:0000269|PubMed:7929823, ECO:0000269|PubMed:8198141, ECO:0000269|PubMed:9158144, ECO:0000269|PubMed:9882619}. 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 ACADMD; the thermostability is markedly decreased.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121434279 [ dbSNP | Ensembl ]

Sequence information

Variant position:

193

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

Protein sequence length:

421

The length of the canonical sequence.

Location on the sequence:

KTKAEKKGDEYIINGQKMWI T NGGKANWYFLLARSDPDPKA

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                         KTKAEKKGDEYIINGQKMWITNGGKANWYFLLARSDPDPKA

Chimpanzee                    KTKAEKKGDEYIINGQKMWITNGGKANWYFLLARSDPDPKA

Mouse                         KTKAEKKGDEYVINGQKMWITNGGKANWYFLLARSNPDPKV

Rat                           KTKAEKKGDEYVINGQKMWITNGGKANWYFVLTRSNPDPKV

Pig                           KTKAEKKGDEYIINGQKMWITNGGKANWYFLLARSDPDPKA

Bovine                        KTKAEKKGDEYIINGQKMWITNGGKANWYFLLARSDPDPKA

Caenorhabditis elegans        KTKCEKKGDEYIINGSKAWITGGGHAKWFFVLARSDPNPKT

Drosophila                    KTRAEKKGDEWVINGQKMWITNGGVANWYFVLARTNPDPKC

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	26 – 421	Medium-chain specific acyl-CoA dehydrogenase, mitochondrial
Nucleotide binding	191 – 193	FAD
Modified residue	179 – 179	N6-succinyllysine
Modified residue	212 – 212	N6-acetyllysine; alternate
Modified residue	212 – 212	N6-succinyllysine; alternate
Mutagenesis	191 – 191	W -> A. Loss of electron transfer to ETF.
Mutagenesis	191 – 191	W -> F. Reduces rate of electron transfer to ETF about six-fold.
Beta strand	182 – 193

Literature citations

The molecular basis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in compound heterozygous patients: is there correlation between genotype and phenotype?
Andresen B.S.; Bross P.; Udvari S.; Kirk J.; Gray G.; Kmoch S.; Chamoles N.; Knudsen I.; Winter V.; Wilcken B.; Yokota I.; Hart K.; Packman S.; Harpey J.P.; Saudubray J.-M.; Hale D.E.; Bolund L.; Koelvraa S.; Gregersen N.;
Hum. Mol. Genet. 6:695-707(1997)
Cited for: VARIANTS ACADMD TYR-116; ALA-193 AND CYS-352;

Biochemical characterization of a variant human medium-chain acyl-CoA dehydrogenase with a disease-associated mutation localized in the active site.
Kuchler B.; Abdel-Ghany A.G.; Bross P.; Nandy A.; Rasched I.; Ghisla S.;
Biochem. J. 337:225-230(1999)
Cited for: CHARACTERIZATION OF VARIANT ACADMD ALA-193;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P11310: Variant p.Thr193Ala