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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q96IJ6: Variant p.Asn401Thr

Mannose-1-phosphate guanylyltransferase regulatory subunit alpha
Gene: GMPPA
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Variant information Variant position: help 401 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 Asparagine (N) to Threonine (T) at position 401 (N401T, p.Asn401Thr). 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 Similar physico-chemical property. Both residues are medium size and polar. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 0 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 AAMR; drastically reduced protein expression; reduces allosteric inhibition of GMPPB; fails to rescue phenotype when expressed in a zebrafish disease model. Any additional useful information about the variant.


Sequence information Variant position: help 401 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 420 The length of the canonical sequence.
Location on the sequence: help LPAITILGCRVRIPAEVLIL N SIVLPHKELSRSFTNQIIL 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                         LPAITILGCRVRIPAEVLILNSIVLPHKELSRSFTNQIIL

Mouse                         LPAITILGCRVRIPAEVLILNSIVLPHKELSRSFTNQIIL

Rat                           LPAITILGCRVRIPAEVLILNSIVLPHKELSRSFTNQIIL

Pig                           LPAITILGCRVRIPAEVLILNSIVLPHKELSRSFTNQIIL

Xenopus tropicalis            TPSITILGCNVSIPAEVVILNSIVLPHKELSRSFKNQIIL

Slime mold                    RRGVTIFGAGAQANGEIIVSNCIVMPHKQLDRNYNNEIIL
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 – 420 Mannose-1-phosphate guanylyltransferase regulatory subunit alpha
Region 273 – 420 Hexapeptide repeat domain
Mutagenesis 396 – 396 E -> R. Disrupts the interaction with other GMPPA molecules but not with GMPPB.
Mutagenesis 408 – 408 K -> E. Does not disrupt the interaction with GMPPB or other GMPPA molecules.
Beta strand 398 – 401



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; PATHWAY; SUBUNIT; DOMAIN; CHARACTERIZATION OF VARIANTS AAMR PRO-334 AND THR-401; MUTAGENESIS OF GLU-85; ARG-99; ASP-100; GLN-247; ARG-318; TRP-350; ARG-352; 362-PRO--PRO-365; GLU-372; GLU-396 AND LYS-408; Mutations in GMPPA cause a glycosylation disorder characterized by intellectual disability and autonomic dysfunction.
Koehler K.; Malik M.; Mahmood S.; Giesselmann S.; Beetz C.; Hennings J.C.; Huebner A.K.; Grahn A.; Reunert J.; Nurnberg G.; Thiele H.; Altmuller J.; Nurnberg P.; Mumtaz R.; Babovic-Vuksanovic D.; Basel-Vanagaite L.; Borck G.; Bramswig J.; Muhlenberg R.; Sarda P.; Sikiric A.; Anyane-Yeboa K.; Zeharia A.; Ahmad A.; Coubes C.; Wada Y.; Marquardt T.; Vanderschaeghe D.; Van Schaftingen E.; Kurth I.; Huebner A.; Hubner C.A.;
Am. J. Hum. Genet. 93:727-734(2013)
Cited for: VARIANTS AAMR ASP-182; MET-334; PRO-334; PRO-390 AND THR-401; FUNCTION; SUBCELLULAR LOCATION; TISSUE SPECIFICITY;
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.