To improve security and privacy, we are moving our web pages and services from HTTP to HTTPS.
To give users of web services time to transition to HTTPS, we will support separate HTTP and HTTPS services until the end of 2017.
From January 2018 most HTTP traffic will be automatically redirected to HTTPS. [more...]
View this page in https

UniProtKB/Swiss-Prot A4D126: Variant p.Arg126His

D-ribitol-5-phosphate cytidylyltransferase
Gene: ISPD
Chromosomal location: 7p21.1
Variant information

Variant position:  126
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 Arginine (R) to Histidine (H) at position 126 (R126H, p.Arg126His).
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 large size and basic (R) to medium size and polar (H)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  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

Involvement in disease:  Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A7 (MDDGA7) [MIM:614643]: An autosomal recessive disorder characterized by congenital muscular dystrophy associated with cobblestone lissencephaly and other brain anomalies, eye malformations, profound mental retardation, and death usually in the first years of life. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease. {ECO:0000269|PubMed:22522420, ECO:0000269|PubMed:22522421, ECO:0000269|PubMed:23217329, ECO:0000269|PubMed:23288328, ECO:0000269|PubMed:24120487}. 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 MDDGA7; also found in a patient with an atypical phenotype presenting with limb-girdle muscular dystrophy, ocular features and cerebellar involvement.
Any additional useful information about the variant.

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



Sequence information

Variant position:  126
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  451
The length of the canonical sequence.

Location on the sequence:   KSIIQKYQHKRISLVEAGVT  R HRSIFNGLKALAEDQINSKL
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                         KSIIQKYQHKRISLVEAGVTRHRSIFNGLKALAEDQI-NSKL

Mouse                         RSIIQRYGHKRISLAEAGATRHRSIFNGLKALAEDQP-DCK

Rat                           RSIIQRYGHKRISLAEAGATRHRSIFNGLKALAEDQP-GCE

Bovine                        KGIIQRYQHKRISLVEAGVTRHRSIFNGLKALAEDQP-NCR

Xenopus tropicalis            KAIIHKYGHQRVTLVKGGETRHRSIFNGLKVFSENHSDDTA

Zebrafish                     LNIVRKFNHTKVKVVHGGTTRHRSIYNGLQAFSDST--DSS

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 – 451 D-ribitol-5-phosphate cytidylyltransferase
Helix 126 – 137


Literature citations

Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of alpha-dystroglycan.
Roscioli T.; Kamsteeg E.J.; Buysse K.; Maystadt I.; van Reeuwijk J.; van den Elzen C.; van Beusekom E.; Riemersma M.; Pfundt R.; Vissers L.E.; Schraders M.; Altunoglu U.; Buckley M.F.; Brunner H.G.; Grisart B.; Zhou H.; Veltman J.A.; Gilissen C.; Mancini G.M.; Delree P.; Willemsen M.A.; Ramadza D.P.; Chitayat D.; Bennett C.; Sheridan E.; Peeters E.A.; Tan-Sindhunata G.M.; de Die-Smulders C.E.; Devriendt K.; Kayserili H.; El-Hashash O.A.; Stemple D.L.; Lefeber D.J.; Lin Y.Y.; van Bokhoven H.;
Nat. Genet. 44:581-585(2012)
Cited for: VARIANTS MDDGA7 PRO-122; HIS-126 AND ASP-216; FUNCTION;

ISPD gene mutations are a common cause of congenital and limb-girdle muscular dystrophies.
Cirak S.; Foley A.R.; Herrmann R.; Willer T.; Yau S.; Stevens E.; Torelli S.; Brodd L.; Kamynina A.; Vondracek P.; Roper H.; Longman C.; Korinthenberg R.; Marrosu G.; Nuernberg P.; Michele D.E.; Plagnol V.; Hurles M.; Moore S.A.; Sewry C.A.; Campbell K.P.; Voit T.; Muntoni F.;
Brain 136:269-281(2013)
Cited for: VARIANTS MDDGC7 THR-53; LEU-149; 215-GLN--ALA-451 DEL; CYS-226; VAL-372 DEL AND 395-ARG--ALA-451 DEL; VARIANT MDDGA7 HIS-126;

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.