UniProtKB/Swiss-Prot Q9H9S5: Variant p.Leu276Ile

Fukutin-related protein
Gene: FKRP
Chromosomal location: 19q13.33
Variant information

Variant position:  276
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Leucine (L) to Isoleucine (I) at position 276 (L276I, p.Leu276Ile).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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 limb-girdle C5 (MDDGC5) [MIM:607155]: An autosomal recessive degenerative myopathy with age of onset ranging from childhood to adult life, and variable severity. Clinical features include proximal muscle weakness, waddling gait, calf hypertrophy, cardiomyopathy and respiratory insufficiency. A reduction of alpha-dystroglycan and laminin alpha-2 expression can be observed on skeletal muscle biopsy from MDDGC5 patients. 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 MDDGC5; reduced secretion to the medium; localizes mainly to the Golgi apparatus.
Any additional useful information about the variant.

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



Sequence information

Variant position:  276
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  495
The length of the canonical sequence.

Location on the sequence:   KAEREGRARRAALLRALGIR  L VSWEGGRLEWFGCNKETTRC
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                         KAEREGRARRAALLRALGIRLVSWEGGRLEWFGCNKETTRC

Mouse                         KAEREGRSRRAALLRSLGIRLVSWEGGRLEWFGCSKESARC

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 – 495 Fukutin-related protein
Topological domain 30 – 495 Lumenal


Literature citations

Fukutin-related protein localizes to the Golgi apparatus and mutations lead to mislocalization in muscle in vivo.
Keramaris-Vrantsis E.; Lu P.J.; Doran T.; Zillmer A.; Ashar J.; Esapa C.T.; Benson M.A.; Blake D.J.; Rosenfeld J.; Lu Q.L.;
Muscle Nerve 36:455-465(2007)
Cited for: SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS ILE-276 AND LEU-448;

Mutations alter secretion of fukutin-related protein.
Lu P.J.; Zillmer A.; Wu X.; Lochmuller H.; Vachris J.; Blake D.; Chan Y.M.; Lu Q.L.;
Biochim. Biophys. Acta 1802:253-258(2010)
Cited for: SUBCELLULAR LOCATION; GLYCOSYLATION; CHARACTERIZATION OF VARIANTS ILE-276 AND LEU-448;

Mutations in the fukutin-related protein gene (FKRP) identify limb girdle muscular dystrophy 2I as a milder allelic variant of congenital muscular dystrophy MDC1C.
Brockington M.; Yuva Y.; Prandini P.; Brown S.C.; Torelli S.; Benson M.A.; Herrmann R.; Anderson L.V.B.; Bashir R.; Burgunder J.-M.; Fallet S.; Romero N.; Fardeau M.; Straub V.; Storey G.; Pollitt C.; Richard I.; Sewry C.A.; Bushby K.; Voit T.; Blake D.J.; Muntoni F.;
Hum. Mol. Genet. 10:2851-2859(2001)
Cited for: VARIANTS MDDGC5 143-ARG--GLU-146 DEL; SER-143; ILE-276; CYS-312; ARG-316 AND LEU-339;

Phenotypic spectrum associated with mutations in the fukutin-related protein gene.
Mercuri E.; Brockington M.; Straub V.; Quijano-Roy S.; Yuva Y.; Herrmann R.; Brown S.C.; Torelli S.; Dubowitz V.; Blake D.J.; Romero N.B.; Estournet B.; Sewry C.A.; Guicheney P.; Voit T.; Muntoni F.;
Ann. Neurol. 53:537-542(2003)
Cited for: VARIANTS MDDGB5 CYS-309; HIS-339 AND LEU-448; VARIANTS MDDGC5 ILE-276; ASN-307; SER-316; ASN-360 AND SER-462;

Asymptomatic carriers for homozygous novel mutations in the FKRP gene: the other end of the spectrum.
de Paula F.; Vieira N.; Starling A.; Yamamoto L.U.; Lima B.; de Cassia Pavanello R.; Vainzof M.; Nigro V.; Zatz M.;
Eur. J. Hum. Genet. 11:923-930(2003)
Cited for: VARIANTS MDDGC5 MET-79; TRP-134; PHE-160; CYS-182; ILE-276; ILE-293; ALA-300; MET-300 AND LEU-358;

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.