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UniProtKB/Swiss-Prot Q8WZA1: Variant p.Cys269Tyr

Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1
Gene: POMGNT1
Variant information

Variant position:  269
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 Cysteine (C) to Tyrosine (Y) at position 269 (C269Y, p.Cys269Tyr).
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 polar (C) to large size and aromatic (Y)
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:  Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A3 (MDDGA3) [MIM:253280]: An autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities, cobblestone lissencephaly, and cerebellar and pontine hypoplasia. Patients present severe congenital myopia, congenital glaucoma, pallor of the optic disks, retinal hypoplasia, mental retardation, hydrocephalus, abnormal electroencephalograms, generalized muscle weakness and myoclonic jerks. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease. {ECO:0000269|PubMed:11709191, ECO:0000269|PubMed:12588800, ECO:0000269|PubMed:12788071, ECO:0000269|PubMed:15207699, ECO:0000269|PubMed:15236414, ECO:0000269|PubMed:15466003, ECO:0000269|PubMed:17030669, ECO:0000269|PubMed:19067344}. 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 MDDGA3; specific activity abolished of the membrane bound form but not the soluble form.
Any additional useful information about the variant.

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



Sequence information

Variant position:  269
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  660
The length of the canonical sequence.

Location on the sequence:   AEEAECHWADTELNRRRRRF  C SKVEGYGSVCSCKDPTPIEF
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                         AEEAECHWADTELNRRRRRFCSKVEGYGSVCSCKDPTPIEF

Mouse                         AEEAECHWADTELNRRRRRFCSKVEGYGSVCSCKDPTPIEF

Rat                           AEEAECHWADTELNRRRRRFCSKVEGYGSVCSCKDPTPIEF

Bovine                        AEEAECHWADTELNRRRRRFCSKVEGYGSVCSCKDPTPIEF

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 1 – 660 Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1
Topological domain 59 – 660 Lumenal
Region 92 – 288 Carbohydrate-binding stem domain
Disulfide bond 254 – 281
Disulfide bond 269 – 279
Helix 261 – 269


Literature citations

Worldwide distribution and broader clinical spectrum of muscle-eye-brain disease.
Taniguchi K.; Kobayashi K.; Saito K.; Yamanouchi H.; Ohnuma A.; Hayashi Y.K.; Manya H.; Jin D.K.; Lee M.; Parano E.; Falsaperla R.; Pavone P.; Coster R.V.; Talim B.; Steinbrecher A.; Straub V.; Nishino I.; Topaloglu H.; Voit T.; Endo T.; Toda T.;
Hum. Mol. Genet. 12:527-534(2003)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANTS MDDGA3 LYS-223 AND TYR-269; VARIANT VAL-623;

Loss-of-function of an N-acetylglucosaminyltransferase, POMGnT1, in muscle-eye-brain disease.
Manya H.; Sakai K.; Kobayashi K.; Taniguchi K.; Kawakita M.; Toda T.; Endo T.;
Biochem. Biophys. Res. Commun. 306:93-97(2003)
Cited for: CHARACTERIZATION OF VARIANTS MDDGA3 LYS-223; TYR-269 AND ARG-493; CATALYTIC ACTIVITY; COFACTOR;

Structure-function analysis of human protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase 1, POMGnT1.
Akasaka-Manya K.; Manya H.; Kobayashi K.; Toda T.; Endo T.;
Biochem. Biophys. Res. Commun. 320:39-44(2004)
Cited for: IDENTIFICATION OF CATALYTIC DOMAIN; CHARACTERIZATION OF VARIANTS MDDGA3 LYS-223 AND TYR-269;

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.