TKT

transketolase

Basic information

Region (hg38): 3:53224712-53256052

Links

ENSG00000163931 ∙ NCBI:7086 ∙ OMIM:606781 ∙ HGNC:11834 ∙ Uniprot:P29401 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• transketolase deficiency (Strong), mode of inheritance: AR
• transketolase deficiency (Strong), mode of inheritance: AR
• transketolase deficiency (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Short stature, developmental delay, and congenital heart defects	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Musculoskeletal; Neurologic	27259054

ClinVar

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

• not_specified (77 variants)
• not_provided (35 variants)
• Transketolase_deficiency (13 variants)
• TKT-related_disorder (10 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TKT gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001064.4. 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			2	19	4	25
missense	1		86	7	2	96
nonsense	1	1				2
start loss						0
frameshift			1			1
splice donor/acceptor (+/-2bp)		1	2			3
Total	2	2	91	26	6

Highest pathogenic variant AF is 0.00006815661

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TKT	protein_coding	protein_coding	ENST00000423516	15	31346

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125710	0	38	125748	0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.66	306	399	0.766	0.0000250	4152
Missense in Polyphen		126	188.46	0.66858		1904
Synonymous	-0.427	174	167	1.04	0.0000115	1237
Loss of Function	3.31	9	27.9	0.323	0.00000128	344

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000304	0.000304
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000435	0.000435
Finnish	0.00	0.00
European (Non-Finnish)	0.000186	0.000185
Middle Eastern	0.000435	0.000435
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate. {ECO:0000269|PubMed:27259054}.
• Disease: DISEASE: Short stature, developmental delay, and congenital heart defects (SDDHD) [MIM:617044]: An autosomal recessive syndrome characterized by short stature, developmental delay, intellectual disability and congenital heart defects including ventricular septal defect, atrial septal defect and patent foramen ovale. Cataract and uveitis are observed in some patients. {ECO:0000269|PubMed:27259054}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Pentose phosphate pathway - Homo sapiens (human);Warburg Effect;Pentose Phosphate Pathway;Glucose-6-phosphate dehydrogenase deficiency;Ribose-5-phosphate isomerase deficiency;Transaldolase deficiency;Pentose Phosphate Pathway;Pentose phosphate pathway (hexose monophosphate shunt);Metabolism of carbohydrates;Insulin effects increased synthesis of Xylulose-5-Phosphate;Metabolism;Pentose phosphate cycle;pentose phosphate pathway (non-oxidative branch);pentose phosphate pathway;EGFR1;Integration of energy metabolism (Consensus)

Recessive Scores

• pRec: 0.459

Intolerance Scores

• loftool: 0.172
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.7

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.885

Gene Damage Prediction

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

Gene ontology

• Biological process: xylulose biosynthetic process;pentose-phosphate shunt;pentose-phosphate shunt, non-oxidative branch;regulation of growth;glyceraldehyde-3-phosphate biosynthetic process
• Cellular component: nucleoplasm;peroxisome;cytosol;nuclear body;nuclear speck;vesicle;myelin sheath;extracellular exosome
• Molecular function: transketolase activity;protein binding;protein homodimerization activity;metal ion binding;cofactor binding