TGDS

Chr 13AR

TDP-glucose 4,6-dehydratase

Also known as: CATMANS, SDR2E1, TDPGD

The protein is UTP-glucose 4,6-dehydratase, which converts UDP-glucose into UDP-4-keto-6-deoxyglucose and is required for glycosaminoglycan biosynthesis and skeletal development. Mutations cause Catel-Manzke syndrome, characterized by Pierre Robin sequence (undersized jaw, backwards tongue displacement causing airway obstruction, and often cleft palate) and radial deviation of the index finger due to an accessory bone. This condition follows autosomal recessive inheritance.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.151 OMIM phenotype
Clinical SummaryTGDS
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Gene-Disease Validity (ClinGen)
Catel-Manzke syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
90 unique Pathogenic / Likely Pathogenic· 65 VUS of 231 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.15LOEUF
pLI 0.000
Z-score 1.04
OE 0.76 (0.511.15)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.30Z-score
OE missense 0.94 (0.831.06)
168 obs / 179.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.76 (0.511.15)
00.351.4
Missense OE0.94 (0.831.06)
00.61.4
Synonymous OE0.73
01.21.6
LoF obs/exp: 16 / 21.2Missense obs/exp: 168 / 179.3Syn Z: 1.69
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveTGDS-related Catel-Manzke syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6841th %ile
GOF
0.4480th %ile
LOF
0.3746th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

231 submitted variants in ClinVar

Classification Summary

Pathogenic83
Likely Pathogenic7
VUS65
Likely Benign31
Benign26
Conflicting2
83
Pathogenic
7
Likely Pathogenic
65
VUS
31
Likely Benign
26
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
80
0
83
Likely Pathogenic
2
5
0
0
7
VUS
2
51
11
1
65
Likely Benign
0
1
13
17
31
Benign
0
2
23
1
26
Conflicting
2
Total46212719214

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TGDS · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗