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UniProtKB/Swiss-Prot Q9C0K1: Variant p.Gly38Arg

Metal cation symporter ZIP8
Gene: SLC39A8
Variant information

Variant position:  38
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 Glycine (G) to Arginine (R) at position 38 (G38R, p.Gly38Arg).
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

Variant description:  In CDG2N; loss of manganese ion transmembrane transport; loss of localization to the plasma membrane; retained in the endoplasmic reticulum; no effect on protein abundance.
Any additional useful information about the variant.

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



Sequence information

Variant position:  38
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  460
The length of the canonical sequence.

Location on the sequence:   LGGVAEGPGLAFSEDVLSVF  G ANLSLSAAQLQHLLEQMGAA
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                         LGGVAEGPGLAFSEDVLSVFGANLSLSAAQLQHLLEQMGAA

Mouse                         LGHPSEGPELAFSEDVLSVFGANRSLSAAQLGRLLERLGAA

Rat                           LGRPSEGPELAFTEDVLRVFGANQSLSAAQLGRLLERLGAA

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 23 – 460 Metal cation symporter ZIP8
Topological domain 23 – 132 Extracellular
Glycosylation 40 – 40 N-linked (GlcNAc...) asparagine
Alternative sequence 1 – 67 Missing. In isoform 2.


Literature citations

Autosomal-recessive intellectual disability with cerebellar atrophy syndrome caused by mutation of the manganese and zinc transporter gene SLC39A8.
Boycott K.M.; Beaulieu C.L.; Kernohan K.D.; Gebril O.H.; Mhanni A.; Chudley A.E.; Redl D.; Qin W.; Hampson S.; Kuery S.; Tetreault M.; Puffenberger E.G.; Scott J.N.; Bezieau S.; Reis A.; Uebe S.; Schumacher J.; Hegele R.A.; McLeod D.R.; Galvez-Peralta M.; Majewski J.; Ramaekers V.T.; Nebert D.W.; Innes A.M.; Parboosingh J.S.; Abou Jamra R.;
Am. J. Hum. Genet. 97:886-893(2015)
Cited for: VARIANT CDG2N ARG-38; FUNCTION; CATALYTIC ACTIVITY; CHARACTERIZATION OF VARIANT CDG2N ARG-38;

SLC39A8 deficiency: a disorder of manganese transport and glycosylation.
Park J.H.; Hogrebe M.; Grueneberg M.; DuChesne I.; von der Heiden A.L.; Reunert J.; Schlingmann K.P.; Boycott K.M.; Beaulieu C.L.; Mhanni A.A.; Innes A.M.; Hoertnagel K.; Biskup S.; Gleixner E.M.; Kurlemann G.; Fiedler B.; Omran H.; Rutsch F.; Wada Y.; Tsiakas K.; Santer R.; Nebert D.W.; Rust S.; Marquardt T.;
Am. J. Hum. Genet. 97:894-903(2015)
Cited for: VARIANTS CDG2N MET-33; ARG-38; CYS-204; THR-335 AND ASN-340;

Functional analysis of SLC39A8 mutations and their implications for manganese deficiency and mitochondrial disorders.
Choi E.K.; Nguyen T.T.; Gupta N.; Iwase S.; Seo Y.A.;
Sci. Rep. 8:3163-3163(2018)
Cited for: CHARACTERIZATION OF VARIANT CDG2N ARG-38; CHARACTERIZATION OF VARIANT SER-113; FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; INDUCTION;

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.