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UniProtKB/Swiss-Prot P36021: Variant p.Leu217Arg

Monocarboxylate transporter 8
Gene: SLC16A2
Variant information

Variant position:  217
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 Leucine (L) to Arginine (R) at position 217 (L217R, p.Leu217Arg).
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 hydrophobic (L) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:  Monocarboxylate transporter 8 deficiency (MCT8 deficiency) [MIM:300523]: Consists of a severe form of X-linked psychomotor retardation combined with abnormal thyroid hormone (TH) levels. Thyroid hormone deficiency can be caused by defects of hormone synthesis and action, but it has also been linked to a defect in cellular hormone transport. Affected patients are males with abnormal relative concentrations of three circulating iodothyronines, as well as severe neurological abnormalities, including global developmental delay, central hypotonia, spastic quadriplegia, dystonic movements, rotary nystagmus, and impaired gaze and hearing. Heterozygous females had a milder thyroid phenotype and no neurological defects. {ECO:0000269|PubMed:14661163, ECO:0000269|PubMed:15488219, ECO:0000269|PubMed:15889350, ECO:0000269|PubMed:18636565, ECO:0000269|PubMed:23550058, ECO:0000269|PubMed:25380603, ECO:0000269|PubMed:25527620, ECO:0000269|PubMed:26426690, ECO:0000269|PubMed:27805744, ECO:0000269|Ref.8}. 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 MCT8 deficiency; atypical form; characterized by developmental delay hypotonia and delayed myelination.
Any additional useful information about the variant.



Sequence information

Variant position:  217
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  539
The length of the canonical sequence.

Location on the sequence:   RYFTYGILFGCGCSFAFQPS  L VILGHYFQRRLGLANGVVSA
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                         RYFTYGILFGCGCSFAFQPSLVILGHYFQRRLGLANGVVSA

Mouse                         RYFTYGILFGCGCSFAFQPSLVILGHYFQRRLGLANGVVSA

Rat                           RYFTYGILFGCGCSFAFQPSLVILDHYFQRRLGLANGVVSA

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 2 – 539 Monocarboxylate transporter 8
Transmembrane 201 – 221 Helical
Mutagenesis 216 – 216 S -> A. No effect on thyroid hormone transport. No effect on protein abundance. No effect on protein localization to the plasma membrane.


Literature citations

Myelination delay and Allan-Herndon-Dudley syndrome caused by a novel mutation in the SLC16A2 gene.
La Piana R.; Vanasse M.; Brais B.; Bernard G.;
J. Child Neurol. 30:1371-1374(2015)
Cited for: INVOLVEMENT IN MCT8 DEFICIENCY; VARIANT MCT8 DEFICIENCY ARG-217;

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.