UniProtKB/Swiss-Prot P07902: Variant p.Gln188Arg

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 188 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 Glutamine (Q) to Arginine (R) at position 188 (Q188R, p.Gln188Arg). 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 (Q) to large size and basic (R) 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 GALAC1; most common mutation; 10% of normal galactose uridylyltransferase activity; impairs protein folding. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs75391579 [ dbSNP | Ensembl ]

Sequence information

Variant position: 188 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 379 The length of the canonical sequence.
Location on the sequence: VQIFENKGAMMGCSNPHPHC Q VWASSFLPDIAQREERSQQA 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	1 – 379	Galactose-1-phosphate uridylyltransferase
Active site	186 – 186	Tele-UMP-histidine intermediate
Binding site	173 – 173
Binding site	184 – 184
Binding site	188 – 188	in other chain
Binding site	202 – 202
Beta strand	184 – 194

Literature citations

The human galactose-1-phosphate uridyltransferase gene.
Leslie N.D.; Immerman E.B.; Flach J.E.; Florez M.; Fridovich-Keil J.L.; Elsas L.J.;
Genomics 14:474-480(1992)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS GALAC1 THR-81 AND ARG-188; INVOLVEMENT IN GALAC1; Correlation assessment among clinical phenotypes, expression analysis and molecular modeling of 14 novel variations in the human galactose-1-phosphate uridylyltransferase gene.
Tang M.; Facchiano A.; Rachamadugu R.; Calderon F.; Mao R.; Milanesi L.; Marabotti A.; Lai K.;
Hum. Mutat. 33:1107-1115(2012)
Cited for: FUNCTION; PATHWAY; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; VARIANTS GALAC1 ASN-34; GLN-132; LEU-168; THR-170; PRO-227; GLN-259; VAL-291 AND PRO-327; CHARACTERIZATION OF VARIANTS GALAC1 ASN-34; GLN-132; LEU-135; LEU-168; THR-170; HIS-185; ARG-188; CYS-201; LYS-220; SER-223; PRO-227; GLN-259; ASN-278; PHE-289; VAL-291 AND PRO-327; Molecular basis of classic galactosemia from the structure of human galactose 1-phosphate uridylyltransferase.
McCorvie T.J.; Kopec J.; Pey A.L.; Fitzpatrick F.; Patel D.; Chalk R.; Shrestha L.; Yue W.W.;
Hum. Mol. Genet. 25:2234-2244(2016)
Cited for: X-RAY CRYSTALLOGRAPHY (1.73 ANGSTROMS) IN COMPLEX WITH GLUCOSE-1-PHOSPHATE; UMP AND ZINC IONS; FUNCTION; PATHWAY; CATALYTIC ACTIVITY; COFACTOR; SUBUNIT; ACTIVE SITE; CHARACTERIZATION OF VARIANT GALAC1 ARG-188 AND ASN-285; Molecular characterization of two galactosemia mutations: correlation of mutations with highly conserved domains in galactose-1-phosphate uridyl transferase.
Reichardt J.K.V.; Packman S.; Woo S.L.C.;
Am. J. Hum. Genet. 49:860-867(1991)
Cited for: VARIANTS GALAC1 ARG-188 AND TRP-333; Identification and functional analysis of three distinct mutations in the human galactose-1-phosphate uridyltransferase gene associated with galactosemia in a single family.
Fridovich-Keil J.L.; Langley S.D.; Mazur L.A.; Lennon J.C.; Dembure P.P.; Elsas L.J. II;
Am. J. Hum. Genet. 56:640-646(1995)
Cited for: VARIANTS GALAC1 LEU-135; ALA-151 AND ARG-188; Three new mutations (P183T, V150L, 528insG) and eleven sequence polymorphisms in Italian patients with galactose-1-phosphate uridyltransferase (GALT) deficiency.
Maceratesi P.; Sangiuolo F.; Novelli G.; Ninfali P.; Magnani M.; Reichardt J.K.V.; Dallapiccola B.;
Hum. Mutat. 8:369-372(1996)
Cited for: VARIANTS GALAC1 LEU-150; THR-183; ARG-188 AND GLN-319; Molecular analysis in newborns from Texas affected with galactosemia.
Yang Y.P.; Corley N.; Garcia-Heras J.;
Hum. Mutat. 19:82-83(2002)
Cited for: VARIANTS GALAC1 ALA-23; LEU-135; MET-138; GLN-184; ARG-188; PRO-195; SER-251; ASN-285; LYS-344 AND ASP-345; VARIANT ASP-314; Low allelic heterogeneity in a sample of Mexican patients with classical galactosaemia.
Velazquez-Aragon J.; Alcantara-Ortigoza M.A.; Vela-Amieva M.; Monroy S.; Martinez-Cruz V.; Todd-Quinones C.; Gonzalez-del Angel A.;
J. Inherit. Metab. Dis. 31:S333-S337(2008)
Cited for: VARIANTS GALAC1 ARG-112 AND ARG-188; VARIANT ASP-314; Biochemical and molecular characterization of GALT gene from Indian galactosemia patients: Identification of 10 novel mutations and their structural and functional implications.
Singh R.; Thapa B.R.; Kaur G.; Prasad R.;
Clin. Chim. Acta 414:191-196(2012)
Cited for: VARIANTS GALAC1 HIS-89; ARG-103; ALA-166; SER-171; PHE-181; LEU-185; ARG-188; ARG-285; GLN-319 AND LEU-333; VARIANT ASP-314; Functional and structural impact of the most prevalent missense mutations in classic galactosemia.
Coelho A.I.; Trabuco M.; Ramos R.; Silva M.J.; Tavares de Almeida I.; Leandro P.; Rivera I.; Vicente J.B.;
Mol. Genet. Genomic Med. 2:484-496(2014)
Cited for: VARIANTS GALAC1 LEU-135; GLN-148; ASP-175; SER-185; ARG-188; CYS-231; HIS-231; ASN-285 AND ASP-314; CHARACTERIZATION OF VARIANTS GALAC1 LEU-135; ASP-175 AND ARG-188; Clinical and molecular spectra in galactosemic patients from neonatal screening in northeastern Italy: Structural and functional characterization of new variations in the galactose-1-phosphate uridyltransferase (GALT) gene.
Viggiano E.; Marabotti A.; Burlina A.P.; Cazzorla C.; D'Apice M.R.; Giordano L.; Fasan I.; Novelli G.; Facchiano A.; Burlina A.B.;
Gene 559:112-118(2015)
Cited for: VARIANTS GALAC1 PRO-33; ASN-34; VAL-83; THR-142; ARG-188; SER-244; ARG-267; VAL-267; ASP-271; ASN-285; ASP-314 AND TRP-333;