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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9Y5P6: Variant p.Ile219Thr

Mannose-1-phosphate guanylyltransferase catalytic subunit beta
Gene: GMPPB
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Variant information Variant position: help 219 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Isoleucine (I) to Threonine (T) at position 219 (I219T, p.Ile219Thr). 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: help Change from medium size and hydrophobic (I) to medium size and polar (T) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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
Variant description: help In MDDGC14; reduces catalytic activity. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 219 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 360 The length of the canonical sequence.
Location on the sequence: help PIMAKEGQLYAMELQGFWMD I GQPKDFLTGMCLFLQSLRQK 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         PIMAKEGQLYAMELQGFWMDIGQPKDFLTGMCLFLQSLRQK

Mouse                         PVMAKEGQLYAMELQGFWMDIGQPKDFLTGMCLFLQSLRQK

Pig                           PVMAKEGQLYAMELQGFWMDIGQPKDFLTGMCLFLQSLRQK

Bovine                        PVMAKEGQLYAMELQGFWMDIGQPKDFLTGMCLFLKSLRQK

Xenopus tropicalis            PAMAQEGQLFAMELQGFWMDIGQPKDFLTGMCMYLQSVRQK

Zebrafish                     PVMAEEGQLYAMELQGFWMDIGQPKDFLTGMCMYLQSVRQQ

Caenorhabditis elegans        PEMAFSGNLYAFVLPGFWMDVGQPKDFLKGMSLFLNHCHTT

Drosophila                    PEMTQQQELYAMDLTGFWMDIGQPKDFLTGMCLYLSSLRQK

Slime mold                    PAMAADSQLYCMQLEGFWMDVGQPKDFLSGMGLYLNSLKSK
Sequence annotation in neighborhood: help 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 1 – 360 Mannose-1-phosphate guanylyltransferase catalytic subunit beta
Region 2 – 222 Substrate-binding domain
Binding site 218 – 218
Binding site 218 – 218
Mutagenesis 218 – 218 D -> A. Reduces GDP-alpha-D-mannose binding affinity and inhibits catalytic activity but does not affect assembly of GMPPA-GMPPB complex. Does not rescue the knockdown phenotype in a zebrafish disease model.
Mutagenesis 218 – 218 D -> Q. Abrogates enzyme activity.



Literature citations
Cryo-EM structures of human GMPPA-GMPPB complex reveal how cells maintain GDP-mannose homeostasis.
Zheng L.; Liu Z.; Wang Y.; Yang F.; Wang J.; Huang W.; Qin J.; Tian M.; Cai X.; Liu X.; Mo X.; Gao N.; Jia D.;
Nat. Struct. Mol. Biol. 28:1-12(2021)
Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.0 ANGSTROMS) OF 1-420 IN COMPLEXES WITH GMPPB; MG2+; GTP AND GDP-MANNOSE; FUNCTION; CATALYTIC ACTIVITY; COFACTOR MG; ACTIVITY REGULATION; BIOPHYSICOCHEMICAL PROPERTIES; PATHWAY; SUBUNIT; DOMAIN; ACTIVE SITE; CHARACTERIZATION OF VARIANT MDDGA14 ASN-334; CHARACTERIZATION OF VARIANT MDDGB14 LEU-32; CHARACTERIZATION OF VARIANT MDDGC14 SER-22; HIS-27; THR-219; TRP-293 AND HIS-357; MUTAGENESIS OF ILE-193; ASP-218; CYS-266; ARG-287; LEU-303; GLU-335; 344-LEU--LYS-347 AND 358-ILE--MET-360; GMPPB-associated dystroglycanopathy: Emerging common variants with phenotype correlation.
Jensen B.S.; Willer T.; Saade D.N.; Cox M.O.; Mozaffar T.; Scavina M.; Stefans V.A.; Winder T.L.; Campbell K.P.; Moore S.A.; Mathews K.D.;
Hum. Mutat. 36:1159-1163(2015)
Cited for: VARIANTS MDDGC14 HIS-27; SER-32; CYS-132; THR-219; SER-241; MET-254; GLN-287; TRP-287; ALA-318 AND ILE-330;
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.