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UniProtKB/Swiss-Prot Q15043: Variant p.Gly383Arg

Zinc transporter ZIP14
Gene: SLC39A14
Variant information

Variant position:  383
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 Glycine (G) to Arginine (R) at position 383 (G383R, p.Gly383Arg).
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 glycine (G) 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:  Hypermanganesemia with dystonia 2 (HMNDYT2) [MIM:617013]: A metabolic autosomal recessive disorder characterized by increased blood manganese levels, neurodegeneration, and rapidly progressive parkinsonism and dystonia. Affected individuals present with loss of developmental milestones, progressive dystonia and bulbar dysfunction in infancy or early childhood. Towards the end of the first decade, they manifest severe generalized pharmacoresistant dystonia, spasticity, limb contractures and scoliosis, and loss of independent ambulation. Cognition may be impaired, but is better preserved than motor function. {ECO:0000269|PubMed:27231142}. 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 HMNDYT2; no effect on protein abundance; no effect on subcellular localization at the plasma membrane and within the cytoplasm; decreased manganese ion transmembrane transporter activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  383
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  492
The length of the canonical sequence.

Location on the sequence:   VFQGISTSVAILCEEFPHEL  G DFVILLNAGMSIQQALFFNF
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                         VFQGISTSVAILCEEFPHELGDFVILLNAGMSIQQALFFNF

Mouse                         VFQGISTSVAILCEEFPHELGDFVILLNAGMSIQQALFFNF

Bovine                        VFQGISTSVAILCEEFPHELGDFVILLNAGMSLQQALFFNF

Xenopus tropicalis            VFQGVSTSIAILCEEFPHELGDFVILLNAGMSIPQALFFNF

Zebrafish                     VFQGISTSVAILCEEFPHELGDFVILLNAGMSIQQALFFNF

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 31 – 492 Zinc transporter ZIP14
Topological domain 246 – 397 Cytoplasmic


Literature citations

Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia.
Tuschl K.; Meyer E.; Valdivia L.E.; Zhao N.; Dadswell C.; Abdul-Sada A.; Hung C.Y.; Simpson M.A.; Chong W.K.; Jacques T.S.; Woltjer R.L.; Eaton S.; Gregory A.; Sanford L.; Kara E.; Houlden H.; Cuno S.M.; Prokisch H.; Valletta L.; Tiranti V.; Younis R.; Maher E.R.; Spencer J.; Straatman-Iwanowska A.; Gissen P.; Selim L.A.; Pintos-Morell G.; Coroleu-Lletget W.; Mohammad S.S.; Yoganathan S.; Dale R.C.; Thomas M.; Rihel J.; Bodamer O.A.; Enns C.A.; Hayflick S.J.; Clayton P.T.; Mills P.B.; Kurian M.A.; Wilson S.W.;
Nat. Commun. 7:11601-11601(2016)
Cited for: FUNCTION; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; INVOLVEMENT IN HMNDYT2; VARIANTS HMNDYT2 VAL-98; ARG-383 AND LYS-469; CHARACTERIZATION OF VARIANTS HMNDYT2 VAL-98; ARG-383 AND LYS-469;

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.