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

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.

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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				13	6	19
missense			39	4	2	45
nonsense		1				1
start loss						0
frameshift			1			1
inframe indel		1				1
splice donor/acceptor (+/-2bp)			1			1
splice region				1		1
non coding				2	6	8
Total	0	2	41	19	14

Variants in TKT

This is a list of pathogenic ClinVar variants found in the TKT region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-53225769-A-T		not specified	Uncertain significance (Apr 18, 2024)
3-53225833-C-G		not specified	Uncertain significance (Aug 23, 2021)
3-53225835-G-T		See cases	Uncertain significance (Mar 21, 2022)
3-53225838-T-C			Benign (Dec 31, 2019)
3-53225846-T-C			Benign (Dec 31, 2019)
3-53225857-G-A		not specified	Uncertain significance (Nov 10, 2023)
3-53225869-G-T		not specified	Uncertain significance (Jul 05, 2023)
3-53225883-A-G		not specified	Uncertain significance (Jan 30, 2024)
3-53225911-A-T		not specified	Uncertain significance (Jun 06, 2023)
3-53225980-G-A		Transketolase deficiency	Benign (Sep 10, 2021)
3-53226761-T-C		not specified	Uncertain significance (Apr 22, 2022)
3-53226803-C-T		not specified	Uncertain significance (Apr 07, 2022)
3-53226848-A-T		Transketolase deficiency	Uncertain significance (Jan 06, 2021)
3-53228076-G-A		not specified	Uncertain significance (Oct 19, 2021)
3-53228089-C-T		Transketolase deficiency	Uncertain significance (Jun 01, 2018)
3-53228090-G-C		TKT-related disorder	Likely benign (Mar 31, 2018)
3-53228109-C-A		not specified	Uncertain significance (Apr 25, 2022)
3-53228116-C-T		not specified	Uncertain significance (Dec 17, 2021)
3-53228149-C-T		not specified	Uncertain significance (Nov 07, 2022)
3-53228287-C-T			Uncertain significance (Apr 03, 2019)
3-53228343-C-T		not specified	Uncertain significance (May 10, 2022)
3-53229018-C-T		not specified	Uncertain significance (May 15, 2024)
3-53229019-G-C			Likely benign (Nov 18, 2017)
3-53229049-G-A			Likely benign (May 31, 2018)
3-53229096-T-C			Benign (Dec 31, 2019)

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
0.00675	0.993	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

Haploinsufficiency Scores

• pHI: 0.705
• hipred: Y
• hipred_score: 0.756
• ghis: 0.548

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

Mouse Genome Informatics

• Gene name: Tkt
• Phenotype: liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; renal/urinary system phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

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