UniProtKB/Swiss-Prot P06280: Variant p.Pro40Ser

Alpha-galactosidase A
Gene: GLA
Chromosomal location: Xq22
Variant information

Variant position:  40
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 Proline (P) to Serine (S) at position 40 (P40S, p.Pro40Ser).
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 hydrophobic (P) to small size and polar (S)
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

Involvement in disease:  Fabry disease (FD) [MIM:301500]: Rare X-linked sphingolipidosis disease where glycolipid accumulates in many tissues. The disease consists of an inborn error of glycosphingolipid catabolism. FD patients show systemic accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in the plasma and cellular lysosomes throughout the body. Clinical recognition in males results from characteristic skin lesions (angiokeratomas) over the lower trunk. Patients may show ocular deposits, febrile episodes, and burning pain in the extremities. Death results from renal failure, cardiac or cerebral complications of hypertension or other vascular disease. Heterozygous females may exhibit the disorder in an attenuated form, they are more likely to show corneal opacities. {ECO:0000269|PubMed:10090526, ECO:0000269|PubMed:10208848, ECO:0000269|PubMed:10666480, ECO:0000269|PubMed:10838196, ECO:0000269|PubMed:10916280, ECO:0000269|PubMed:11076046, ECO:0000269|PubMed:11295840, ECO:0000269|PubMed:11668641, ECO:0000269|PubMed:11889412, ECO:0000269|PubMed:12694230, ECO:0000269|PubMed:12786754, ECO:0000269|PubMed:1315715, ECO:0000269|PubMed:15162124, ECO:0000269|PubMed:15712228, ECO:0000269|PubMed:16533976, ECO:0000269|PubMed:1846223, ECO:0000269|PubMed:19621417, ECO:0000269|PubMed:2152885, ECO:0000269|PubMed:2171331, ECO:0000269|PubMed:2539398, ECO:0000269|PubMed:26415523, ECO:0000269|PubMed:27142856, ECO:0000269|PubMed:27211852, ECO:0000269|PubMed:7504405, ECO:0000269|PubMed:7531540, ECO:0000269|PubMed:7575533, ECO:0000269|PubMed:7596372, ECO:0000269|PubMed:7599642, ECO:0000269|PubMed:7759078, ECO:0000269|PubMed:8069316, ECO:0000269|PubMed:8395937, ECO:0000269|PubMed:8738659, ECO:0000269|PubMed:8807334, ECO:0000269|PubMed:8834244, ECO:0000269|PubMed:8863162, ECO:0000269|PubMed:8875188, ECO:0000269|PubMed:8931708, ECO:0000269|PubMed:9100224, ECO:0000269|PubMed:9105656, ECO:0000269|PubMed:9452068, ECO:0000269|PubMed:9452090, ECO:0000269|PubMed:9452111, ECO:0000269|PubMed:9554750}. 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 FD; loss of enzyme activity.
Any additional useful information about the variant.

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

Sequence information

Variant position:  40
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  429
The length of the canonical sequence.

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.

Chain 32 – 429 Alpha-galactosidase A

Literature citations

A case of Fabry's disease in a patient with no alpha-galactosidase A activity caused by a single amino acid substitution of Pro-40 by Ser.
Koide T.; Ishiura M.; Iwai K.; Inoue M.; Kaneda Y.; Okada Y.; Uchida T.;
FEBS Lett. 259:353-356(1990)

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;

Mutation analysis in 11 French patients with Fabry disease.
Guffon N.; Froissart R.; Chevalier-Porst F.; Maire I.;
Hum. Mutat. Suppl. 1:S288-S290(1998)
Cited for: VARIANTS FD SER-40; SER-215; ASP-224; TYR-313 AND TRP-THR-SER-247 INS;

Functional and clinical consequences of novel alpha-galactosidase A mutations in Fabry disease.
Lukas J.; Scalia S.; Eichler S.; Pockrandt A.M.; Dehn N.; Cozma C.; Giese A.K.; Rolfs A.;
Hum. Mutat. 37:43-51(2016)
Cited for: CHARACTERIZATION OF VARIANTS FD ASP-20; PRO-20; PRO-21; GLY-33; GLU-35; TRP-36; SER-40; THR-42; PRO-45; ASP-48; TYR-56; LEU-60; PHE-64; ASP-80; HIS-86; ASN-91; THR-91; SER-94; TYR-94; ILE-113; THR-121; LEU-164; GLY-164; GLN-167; PHE-180; VAL-187; SER-196; THR-198; TYR-202; ARG-204; ARG-213; LEU-214; MET-219; PRO-227; SER-228; VAL-242; PHE-243; PRO-247; LYS-249; THR-253; ALA-254; ARG-259; ARG-262; GLY-269; GLY-276; VAL-309; ASN-315; ALA-316; SER-317; TYR-320; ARG-323; ARG-327; LEU-327; ARG-328; ARG-330; PRO-342; GLY-352; PRO-356; LYS-358; SER-360; ALA-375; SER-392; SER-399 AND ARG-404 DEL; CHARACTERIZATION OF VARIANTS PRO-3; VAL-3; GLY-71; THR-154; VAL-289 AND ASN-313; CATALYTIC ACTIVITY; FUNCTION;

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.