TGDS

TDP-glucose 4,6-dehydratase, the group of Short chain dehydrogenase/reductase superfamily

Basic information

Region (hg38): 13:94574054-94596242

Links

ENSG00000088451 ∙ NCBI:23483 ∙ OMIM:616146 ∙ HGNC:20324 ∙ Uniprot:O95455 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Catel-Manzke syndrome (Definitive), mode of inheritance: AR
• Catel-Manzke syndrome (Strong), mode of inheritance: AR
• Catel-Manzke syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Catel-Manzke syndrome	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal	6011685; 9777339; 18501694; 22887726; 25480037

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TGDS gene.

• not_provided (55 variants)
• Inborn_genetic_diseases (33 variants)
• Catel-Manzke_syndrome (17 variants)
• TGDS-related_disorder (5 variants)
• not_specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TGDS gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014305.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	13	2	16
missense	3	5	45	1	2	56
nonsense			1			1
start loss						0
frameshift		1				1
splice donor/acceptor (+/-2bp)		2	1			3
Total	3	8	48	14	4

Highest pathogenic variant AF is 0.00076511194

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TGDS	protein_coding	protein_coding	ENST00000261296	12	22204

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.48e-9	0.467	125698	0	50	125748	0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.300	168	179	0.937	0.00000832	2303
Missense in Polyphen		63	67.097	0.93893		883
Synonymous	1.69	45	61.9	0.727	0.00000302	612
Loss of Function	1.04	16	21.2	0.756	8.92e-7	284

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000675	0.000646
Ashkenazi Jewish	0.000405	0.000397
East Asian	0.000231	0.000217
Finnish	0.0000927	0.0000924
European (Non-Finnish)	0.000164	0.000158
Middle Eastern	0.000231	0.000217
South Asian	0.000352	0.000327
Other	0.000197	0.000163

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Catel-Manzke syndrome (CATMANS) [MIM:616145]: A syndrome characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a large tongue (macroglossia), and a small lower jaw (micrognathia). {ECO:0000269|PubMed:25480037}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.225

Intolerance Scores

• loftool: 0.490
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.75

Haploinsufficiency Scores

• pHI: 0.233
• hipred: N
• hipred_score: 0.350
• ghis: 0.621

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.755

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tgds
• Phenotype: craniofacial phenotype; growth/size/body region phenotype; digestive/alimentary phenotype; skeleton phenotype

Gene ontology

• Molecular function: dTDP-glucose 4,6-dehydratase activity