UniProtKB/Swiss-Prot P06280: Variant p.Arg301Gln

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 301 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LP/P [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.] 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: From Arginine (R) to Glutamine (Q) at position 301 (R301Q, p.Arg301Gln). 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 (Q) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: 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: In FD; mild; does not significantly affect the enzyme activity but the mutant protein levels are decreased presumably in the ER of the cells. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs104894828 [ dbSNP | Ensembl ]

Sequence information

Variant position: 301 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 429 The length of the canonical sequence.
Location on the sequence: VTQMALWAIMAAPLFMSNDL R HISPQAKALLQDKDVIAINQ 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.
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.

Type	Positions	Description
Chain	32 – 429	Alpha-galactosidase A

Literature citations

Identification of point mutations in the alpha-galactosidase A gene in classical and atypical hemizygotes with Fabry disease.
Sakuraba H.; Oshima A.; Fukuhara Y.; Shimmoto M.; Nagao Y.; Bishop D.F.; Desnick R.J.; Suzuki Y.;
Am. J. Hum. Genet. 47:784-789(1990)
Cited for: VARIANT FD GLN-301; Point mutations in the upstream region of the alpha-galactosidase A gene exon 6 in an atypical variant of Fabry disease.
Ishii S.; Sakuraba H.; Suzuki Y.;
Hum. Genet. 89:29-32(1992)
Cited for: VARIANTS FD GLN-66; CYS-112; GLU-279; GLN-301 AND ARG-328; Galactose stabilizes various missense mutants of alpha-galactosidase in Fabry disease.
Okumiya T.; Ishii S.; Takenaka T.; Kase R.; Kamei S.; Sakuraba H.; Suzuki Y.;
Biochem. Biophys. Res. Commun. 214:1219-1224(1995)
Cited for: VARIANTS FD GLN-66; CYS-112; VAL-156; VAL-166; ALA-260; GLU-279; ILE-296; GLN-301; LYS-320; ARG-328 AND SER-373; Two novel mutations (L32P) and (G85N) among five different missense mutations in six Danish families with Fabry's disease.
Madsen K.M.; Hasholt L.; Soerensen S.A.; Lagerstroem Fermer M.; Dahl N.;
Hum. Mutat. 5:277-278(1995)
Cited for: VARIANTS FD PRO-32; SER-34; ASP-85; THR-156 AND GLN-301; Point mutation in the alpha-galactosidase A gene of atypical Fabry disease with only nephropathy.
Sawada K.; Mizoguchi K.; Hishida A.; Kaneko E.; Koide Y.; Nishimura K.; Kimura M.;
Clin. Nephrol. 45:289-294(1996)
Cited for: VARIANT FD GLN-301; Screening and detection of gene mutations in Japanese patients with Fabry disease by non-radioactive single-stranded conformation polymorphism analysis.
Takata T.; Okumiya T.; Hayashibe H.; Shimmoto M.; Kase R.; Itoh K.; Utsumi K.; Kamei S.; Sakuraba H.;
Brain Dev. 19:111-116(1997)
Cited for: VARIANTS FD PRO-20; SER-40; GLN-66; VAL-72; CYS-112; TYR-142; VAL-156; VAL-166; ASN-242; ALA-260; ASP-261; GLU-279; ILE-296; GLN-301; LYS-320; ARG-328; GLU-358 DEL AND SER-373; Fabry disease: identification of novel alpha-galactosidase A mutations and molecular carrier detection by use of fluorescent chemical cleavage of mismatches.
Germain D.P.; Poenaru L.;
Biochem. Biophys. Res. Commun. 257:708-713(1999)
Cited for: VARIANTS FD TRP-202; GLY-223; ASP-224; GLN-301 AND LYS-327; Characterization of two alpha-galactosidase mutants (Q279E and R301Q) found in an atypical variant of Fabry disease.
Kase R.; Bierfreund U.; Klein A.; Kolter T.; Utsumi K.; Itoh K.; Sandhoff K.; Sakuraba H.;
Biochim. Biophys. Acta 1501:227-235(2000)
Cited for: CHARACTERIZATION OF VARIANTS FD GLU-279 AND GLN-301; FUNCTION; CATALYTIC ACTIVITY; ACTIVITY REGULATION; Fabry disease: twenty-two novel mutations in the alpha-galactosidase A gene and genotype/phenotype correlations in severely and mildly affected hemizygotes and heterozygotes.
Ashton-Prolla P.; Tong B.; Shabbeer J.; Astrin K.H.; Eng C.M.; Desnick R.J.;
J. Invest. Med. 48:227-235(2000)
Cited for: VARIANTS FD LEU-40; SER-95; CYS-112; HIS-112; ASN-148; ARG-172; VAL-187; SER-224; ARG-226; GLN-227; THR-230; HIS-266; GLN-301 AND TYR-320;