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UniProtKB/Swiss-Prot P11310: Variant p.Thr121Ile

Medium-chain specific acyl-CoA dehydrogenase, mitochondrial
Gene: ACADM
Variant information

Variant position:  121
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 Isoleucine (I) at position 121 (T121I, p.Thr121Ile).
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 medium size and hydrophobic (I)
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:  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.
Any additional useful information about the variant.

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



Sequence information

Variant position:  121
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:   GTFDACLISEELAYGCTGVQ  T AIEGNSLGQMPIIIAGNDQQ
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                         GTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGNDQQ

Chimpanzee                    GTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGNDQQ

Mouse                         GTFDACLITEELAYGCTGVQTAIEANSLGQMPVILAGNDQQ

Rat                           GTFDACLITEELAYGCTGVQTAIEANSLGQMPVIIAGNDQQ

Pig                           GIIDSCLITEELAYGCTGVQTAIEANTLGQVPLIIGGNYQQ

Bovine                        GTFDSCLISEELAYGCTGVQTAIEANSLGQMPVIIAGNDQQ

Caenorhabditis elegans        TTLETALIVEALSYGCTGIQLGIMGPSLAIAPVYISGNEEQ

Drosophila                    DVFTTCLSAEELAYGCTGIMTALEASGLGQTPVILSGNKEQ

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 26 – 421 Medium-chain specific acyl-CoA dehydrogenase, mitochondrial
Mutagenesis 108 – 108 I -> M. Strongly reduced rate of electron transfer to ETF.
Helix 117 – 136


Literature citations

Medium-chain acyl-CoA dehydrogenase (MCAD) mutations identified by MS/MS-based prospective screening of newborns differ from those observed in patients with clinical symptoms: identification and characterization of a new, prevalent mutation that results in mild MCAD deficiency.
Andresen B.S.; Dobrowolski S.F.; O'Reilly L.; Muenzer J.; McCandless S.E.; Frazier D.M.; Udvari S.; Bross P.; Knudsen I.; Banas R.; Chace D.H.; Engel P.C.; Naylor E.W.; Gregersen N.;
Am. J. Hum. Genet. 68:1408-1418(2001)
Cited for: VARIANTS ACADMD HIS-67; THR-78; ILE-121 AND ARG-310;

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.