TKT

protein-coding

transketolase

Gene summary

This gene encodes a thiamine-dependent enzyme which plays a role in the channeling of excess sugar phosphates to glycolysis in the pentose phosphate pathway. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Apr 2012]

MANE transcript

NM_001064.4

Inheritance

ClinVar variants

P:5U:98B:38

Top phenotype

Short stature, developmental delay, and congenital heart defects

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr3:53,224,712-53,256,052

External References & Databases

Ensembl (ENSG00000163931)

Transcript & Mutation Effects

hg38 • Region Span ~31.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

transketolase deficiencyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014881

Submitter: PanelApp Australia

transketolase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014881

Submitter: Labcorp Genetics (formerly Invitae)

transketolase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014881

Submitter: G2P

Clinical Genomic Database (CGD)

Short stature, developmental delay, and congenital heart defectsAR

Manifestation: Cardiovascular; Musculoskeletal; Neurologic

Intervention: Cardiovascular

Rationale: The condition can involve congenital cardiac anomalies, and awareness may allow early management

Refs: 27259054

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TKT variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 89

not providedTotal: 39

Transketolase deficiencyTotal: 20

TKT-related disorderTotal: 11

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001064.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	26 clinvar	2 clinvar	30
missense	1 clinvar		93 clinvar	9 clinvar	1 clinvar	104
nonsense	1 clinvar	1 clinvar				2
start loss						0
frameshift		1 clinvar	1 clinvar			2
splice donor/acceptor (+/-2bp)		1 clinvar	2 clinvar			3
Total	2	3	98	35	3	141

Highest pathogenic variant AF is 0.00006815661

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 71 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001064.4	RefSeq	NP_001055.1	14	MANE Select
ENST00000462138.6	Ensembl	ENSP00000417773.1	14	MANE Select
NM_001135055.3	RefSeq	NP_001128527.1	14	Standard
NM_001258028.2	RefSeq	NP_001244957.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pentose phosphate pathway - Homo sapiens (human)
Warburg Effect
Pentose Phosphate Pathway
Glucose-6-phosphate dehydrogenase deficiency
Ribose-5-phosphate isomerase deficiency

Biological Process

xylulose biosynthetic process
pentose-phosphate shunt
pentose-phosphate shunt, non-oxidative branch
regulation of growth
glyceraldehyde-3-phosphate biosynthetic process

Molecular Function

transketolase activity
protein binding
protein homodimerization activity
metal ion binding
cofactor binding

Cellular Component

nucleoplasm
peroxisome
cytosol
nuclear body
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000423516
Coding exons: 15
Length: 31346
Individuals with no LoFs: 125710
Homozygous LoFs: 0
Heterozygous LoFs: 38
Defined: 125748
p: 0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.66	306	399	0.766	0.0000250	4152
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00043	0.00044	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.459

Intolerance Scores

LoFtool: 0.172
RVIS EVS: -0.49
RVIS percentile EVS: 22.7

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.885

Gene Damage Prediction

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