UniProtKB/SwissProt variant VAR

UDP-D-glucose 4,6-dehydratase
Gene: TGDS
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Variant information Variant position:

100 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LP/P [Disclaimer] 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 Alanine (A) to Serine (S) at position 100 (A100S, p.Ala100Ser). 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 small size and hydrophobic (A) 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
Variant description:

In CATMANS; decreased UDP-D-glucose 4,6-dehydratase activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs140430952 [ dbSNP | Ensembl ]

Sequence information Variant position:

100 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

350 The length of the canonical sequence.
Location on the sequence:

SHFVKLLFETEKIDIVLHFA A QTHVDLSFVRAFEFTYVNVY 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                         SHFVKLLFETEKIDIVLHFAAQTHVDLSFVRAFEFTYVNVY

Mouse                         SHFVKLLFEVEKIDIVLHFAAQTHVDLSFVRAFEFTYVNVY

Bovine                        SHFVKLLFETEKIDIVLHFAAQTHVDLSFVRAFEFTYVNVY

Slime mold                    SELLENIFEKEKIDIVIHLAAYTHVDNSFKQSIKFTENNIL

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 – 350	UDP-D-glucose 4,6-dehydratase
Binding site	98 – 98
Binding site	102 – 102

Literature citations
A missing enzyme-rescue metabolite as cause of a rare skeletal dysplasia.
Jacobs J.; Lyubenova H.; Potelle S.; Kopp J.; Gerin I.; Chan W.L.; Rodriguez de Los Santos M.; Huelsemann W.; Mensah M.A.; Cormier-Daire V.; Joosten M.; Bruggenwirth H.T.; Stuurman K.E.; Miranda V.; Campeau P.M.; Wittler L.; Graff J.; Mundlos S.; Ibrahim D.M.; Van Schaftingen E.; Fischer-Zirnsak B.; Kornak U.; Ehmke N.; Bommer G.T.;
Nature 0:0-0(2025)
Cited for: FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; SUBCELLULAR LOCATION; VARIANTS CATMANS GLY-90; SER-100; ILE-102; VAL-239 DEL AND LYS-322;
Homozygous and compound-heterozygous mutations in TGDS cause Catel-Manzke syndrome.
Ehmke N.; Caliebe A.; Koenig R.; Kant S.G.; Stark Z.; Cormier-Daire V.; Wieczorek D.; Gillessen-Kaesbach G.; Hoff K.; Kawalia A.; Thiele H.; Altmueller J.; Fischer-Zirnsak B.; Knaus A.; Zhu N.; Heinrich V.; Huber C.; Harabula I.; Spielmann M.; Horn D.; Kornak U.; Hecht J.; Krawitz P.M.; Nuernberg P.; Siebert R.; Manzke H.; Mundlos S.;
Am. J. Hum. Genet. 95:763-770(2014)
Cited for: VARIANTS CATMANS GLY-90; LEU-98; SER-100; HIS-234 AND ASP-298;
Catel-Manzke Syndrome: Further Delineation of the Phenotype Associated with Pathogenic Variants in TGDS.
Pferdehirt R.; Jain M.; Blazo M.A.; Lee B.; Burrage L.C.;
Mol. Genet. Metab. Rep. 4:89-91(2015)
Cited for: VARIANT CATMANS SER-100;
Mutations in TGDS associated with additional malformations of the middle fingers and halluces: Atypical Catel-Manzke syndrome in a fetus.
Schoner K.; Bald R.; Horn D.; Rehder H.; Kornak U.; Ehmke N.;
Am. J. Med. Genet. A 173:1694-1697(2017)
Cited for: VARIANTS CATMANS SER-100 AND ASN-299;
TGDS pathogenic variants cause Catel-Manzke syndrome without hyperphalangy.
Boschann F.; Stuurman K.E.; de Bruin C.; van Slegtenhorst M.; van Duyvenvoorde H.A.; Kant S.G.; Ehmke N.;
Am. J. Med. Genet. A 182:431-436(2020)
Cited for: VARIANTS CATMANS SER-100 AND HIS-234;
Catel-Manzke syndrome without Manzke dysostosis.
Miller D.E.; Chow P.; Gallagher E.R.; Perkins J.A.; Wenger T.L.;
Am. J. Med. Genet. A 182:437-440(2020)
Cited for: VARIANTS CATMANS SER-100 AND ARG-103;

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.

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O95455: Variant p.Ala100Ser