TKT

Summary

TKT (transketolase, HGNC:11834) is a protein-coding gene on chromosome 3p21.1, encoding Transketolase (P29401). 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. It is a selective cancer dependency (DepMap: 38.2% of cell lines).

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.

Source: NCBI Gene 7086 — RefSeq curated summary.

At a glance

• Gene–disease (curated): transketolase deficiency (Strong, GenCC)
• GWAS associations: 20
• Clinical variants (ClinVar): 136 total — 2 pathogenic, 2 likely-pathogenic
• GTEx eGene: eQTL in 31 tissues, sQTL in 19 (q < 0.05)
• Phenotypes (HPO): 32
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 38.2% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.92 (unconstrained)
• MANE Select transcript: NM_001064
• Interaction hub: 2,835 STRING partners (top 3% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11834
Approved symbol	TKT
Name	transketolase
Location	3p21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163931
Ensembl biotype	protein_coding
OMIM	606781
Entrez	7086

Gene structure

Transcript identifiers

Ensembl transcripts: 58 — 31 nonsense_mediated_decay, 20 protein_coding, 6 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000462138

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 9, TSL 5: 1

ENST00000462138, ENST00000423516, ENST00000423525, ENST00000450814, ENST00000460243, ENST00000460343, ENST00000461139, ENST00000466765, ENST00000469678, ENST00000472528, ENST00000483706, ENST00000487660, ENST00000494523, ENST00000869610, ENST00000869611, ENST00000869612, ENST00000869613, ENST00000935658, ENST00000935659, ENST00000935660, ENST00000935661, ENST00000935662, ENST00000935663, ENST00000935664, ENST00000935665, ENST00000971004, ENST00000971005, ENST00001001994, ENST00001001995, ENST00001048348, ENST00001048350, ENST00001048353, ENST00001048355, ENST00001048356, ENST00001048357, ENST00001048358, ENST00001048360, ENST00001048361, ENST00001048362, ENST00001048363, ENST00001048364, ENST00001048365, ENST00001048366, ENST00001048367, ENST00001048368, ENST00001048373, ENST00001048374, ENST00001048376, ENST00001048377, ENST00001048378, ENST00001048379, ENST00001048381, ENST00001048382, ENST00001048383, ENST00001088353, ENST00001088364, ENST00001088366, ENST00001144836

RefSeq mRNA: 3 — MANE Select: NM_001064 NM_001064, NM_001135055, NM_001258028

CCDS: CCDS2871, CCDS58834

Canonical transcript exons

ENST00000462138 — 14 exons

Exon	Start	End
ENSE00001863311	53224712	53225931
ENSE00002276357	53255836	53256022
ENSE00003481595	53241132	53241245
ENSE00003488544	53229007	53229137
ENSE00003489724	53228276	53228359
ENSE00003491015	53226756	53226878
ENSE00003537400	53228056	53228149
ENSE00003558006	53230457	53230621
ENSE00003563912	53234983	53235174
ENSE00003567663	53229280	53229436
ENSE00003578799	53242125	53242242
ENSE00003579380	53233156	53233274
ENSE00003586584	53231357	53231550
ENSE00003614831	53240251	53240348

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 535.1975 / max 3614.5788, expressed in 1828 samples.

Highest expression (Bgee): monocyte, mononuclear cell, leukocyte, granulocyte, blood.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TKT is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 31 tissues and its splicing (sQTL) in 19 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 50 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	1.2e-28	-0.18	3:53252916:C:T
Cells EBV-transformed lymphocytes	eqtl	4.3e-18	-0.41	3:53252916:C:T
Whole Blood	sqtl	6.3e-14	-0.47	3:53237660:T:C
Nerve Tibial	eqtl	1.0e-12	+0.27	3:53226082:G:GT
Cells Cultured fibroblasts	sqtl	2.2e-12	-0.28	3:53223033:G:A
Esophagus Muscularis	sqtl	2.5e-12	-0.70	3:53243530:G:C
Artery Aorta	eqtl	4.0e-12	+0.33	3:53221293:A:G
Muscle Skeletal	eqtl	1.3e-11	+0.17	3:53255511:T:G
Brain Spinal cord cervical c-1	eqtl	2.3e-11	-0.41	3:53290885:G:A
Nerve Tibial	sqtl	3.7e-10	-0.41	3:53221293:A:G
Esophagus Mucosa	eqtl	1.9e-09	-0.15	3:53264588:A:C
Thyroid	sqtl	2.5e-09	-0.37	3:53237660:T:C
Cells Cultured fibroblasts	eqtl	6.8e-09	-0.12	3:53225980:G:A
Brain Cerebellar Hemisphere	eqtl	8.8e-08	+0.22	3:53232515:C:T
Brain Caudate basal ganglia	eqtl	8.9e-08	+0.32	3:53230995:T:C
Brain Nucleus accumbens basal ganglia	eqtl	9.9e-08	+0.31	3:53221293:A:G
Colon Sigmoid	sqtl	1.4e-07	-0.60	3:53243795:C:T
Artery Tibial	eqtl	1.5e-07	+0.19	3:53237024:A:C
Brain Putamen basal ganglia	eqtl	3.6e-07	+0.36	3:53238051:G:A
Skin Sun Exposed Lower leg	eqtl	3.9e-07	+0.16	3:53226887:G:C

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
42511	511.9851	1828
42510	21.1277	1799
42507	1.1098	648
42509	0.9749	566

Top tissues by expression

showing 100 of 302 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.54	gold quality
mononuclear cell	CL:0000842	99.49	gold quality
leukocyte	CL:0000738	99.47	gold quality
granulocyte	CL:0000094	99.30	gold quality
blood	UBERON:0000178	99.19	gold quality
right lobe of thyroid gland	UBERON:0001119	99.03	gold quality
body of pancreas	UBERON:0001150	98.96	gold quality
bone marrow	UBERON:0002371	98.89	gold quality
left lobe of thyroid gland	UBERON:0001120	98.74	gold quality
left adrenal gland	UBERON:0001234	98.61	gold quality
right adrenal gland cortex	UBERON:0035827	98.57	gold quality
esophagus mucosa	UBERON:0002469	98.54	gold quality
left adrenal gland cortex	UBERON:0035825	98.52	gold quality
right adrenal gland	UBERON:0001233	98.50	gold quality
stromal cell of endometrium	CL:0002255	98.43	gold quality
right lung	UBERON:0002167	98.43	gold quality
thyroid gland	UBERON:0002046	98.40	gold quality
adrenal cortex	UBERON:0001235	98.38	gold quality
upper lobe of lung	UBERON:0008948	98.35	gold quality
upper lobe of left lung	UBERON:0008952	98.35	gold quality
lower esophagus mucosa	UBERON:0035834	98.35	gold quality
esophagus	UBERON:0001043	98.33	gold quality
bone marrow cell	CL:0002092	98.31	gold quality
spleen	UBERON:0002106	98.30	gold quality
gall bladder	UBERON:0002110	98.26	gold quality
cortical plate	UBERON:0005343	98.24	gold quality
embryo	UBERON:0000922	98.22	gold quality
lower esophagus	UBERON:0013473	98.14	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.13	gold quality
bone element	UBERON:0001474	98.08	gold quality
adrenal gland	UBERON:0002369	98.07	gold quality
pharyngeal mucosa	UBERON:0000355	98.06	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.99	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.99	gold quality
ganglionic eminence	UBERON:0004023	97.98	gold quality
adipose tissue	UBERON:0001013	97.97	gold quality
right ovary	UBERON:0002118	97.96	gold quality
islet of Langerhans	UBERON:0000006	97.94	gold quality
trabecular bone tissue	UBERON:0002483	97.94	gold quality
endometrium epithelium	UBERON:0004811	97.94	gold quality
omental fat pad	UBERON:0010414	97.92	gold quality
peritoneum	UBERON:0002358	97.91	gold quality
lower lobe of lung	UBERON:0008949	97.91	gold quality
left ovary	UBERON:0002119	97.87	gold quality
body of stomach	UBERON:0001161	97.84	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.80	gold quality
mucosa of transverse colon	UBERON:0004991	97.77	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.71	gold quality
transverse colon	UBERON:0001157	97.68	gold quality
connective tissue	UBERON:0002384	97.67	gold quality
dorsal root ganglion	UBERON:0000044	97.51	gold quality
substantia nigra pars compacta	UBERON:0001965	97.50	gold quality
spinal cord	UBERON:0002240	97.50	gold quality
descending thoracic aorta	UBERON:0002345	97.48	gold quality
pancreas	UBERON:0001264	97.45	gold quality
ectocervix	UBERON:0012249	97.45	gold quality
mammalian vulva	UBERON:0000997	97.43	gold quality
urinary bladder	UBERON:0001255	97.35	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.30	gold quality
caudate nucleus	UBERON:0001873	97.28	gold quality
ventricular zone	UBERON:0003053	97.26	gold quality
right coronary artery	UBERON:0001625	97.25	gold quality
trigeminal ganglion	UBERON:0001675	97.24	gold quality
left coronary artery	UBERON:0001626	97.23	gold quality
thoracic aorta	UBERON:0001515	97.19	gold quality
ascending aorta	UBERON:0001496	97.17	gold quality
right frontal lobe	UBERON:0002810	97.16	gold quality
prefrontal cortex	UBERON:0000451	97.13	gold quality
coronary artery	UBERON:0001621	97.13	gold quality
superior vestibular nucleus	UBERON:0007227	97.12	gold quality
mucosa of stomach	UBERON:0001199	97.05	gold quality
nucleus accumbens	UBERON:0001882	97.05	gold quality
penis	UBERON:0000989	97.03	gold quality
cranial nerve II	UBERON:0000941	97.01	gold quality
putamen	UBERON:0001874	96.99	gold quality
cingulate cortex	UBERON:0003027	96.99	gold quality
anterior cingulate cortex	UBERON:0009835	96.98	gold quality
type B pancreatic cell	CL:0000169	96.96	gold quality
left uterine tube	UBERON:0001303	96.95	gold quality
sigmoid colon	UBERON:0001159	96.93	gold quality
stomach	UBERON:0000945	96.92	gold quality
endocervix	UBERON:0000458	96.88	gold quality
colon	UBERON:0001155	96.87	gold quality
hypothalamus	UBERON:0001898	96.86	gold quality
pericardium	UBERON:0002407	96.86	gold quality
aorta	UBERON:0000947	96.84	gold quality
lung	UBERON:0002048	96.81	gold quality
nipple	UBERON:0002030	96.80	gold quality
tibial nerve	UBERON:0001323	96.77	gold quality
duodenum	UBERON:0002114	96.77	gold quality
fundus of stomach	UBERON:0001160	96.74	gold quality
minor salivary gland	UBERON:0001830	96.74	gold quality
amygdala	UBERON:0001876	96.74	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.72	gold quality
pons	UBERON:0000988	96.70	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.70	gold quality
large intestine	UBERON:0000059	96.69	gold quality
adenohypophysis	UBERON:0002196	96.67	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.65	gold quality
mouth mucosa	UBERON:0003729	96.63	gold quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	2620.68
E-MTAB-10662	yes	1911.08
E-MTAB-6678	yes	1342.40
E-MTAB-6819	yes	1206.06
E-HCAD-4	yes	232.12
E-CURD-122	yes	80.11
E-MTAB-10553	yes	37.79
E-MTAB-6701	yes	36.00
E-HCAD-10	yes	34.36
E-MTAB-9467	yes	33.58
E-MTAB-9221	yes	29.66
E-HCAD-9	yes	25.02
E-CURD-112	yes	24.22
E-GEOD-125970	yes	15.90
E-CURD-88	yes	13.23

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	630.1	high
Spinal cord	tissue	213.0
Corpus callosum	tissue	181.6
Medulla oblongata	tissue	166.1
Midbrain	tissue	158.0
Thalamus	tissue	146.6
Substantia nigra	tissue	144.3
Adipose tissue	tissue	142.8	medium
Pons	tissue	140.7
Pancreas	tissue	137.3	high
Superior colliculi	tissue	134.1
Locus coeruleus	tissue	123.9
Hypothalamus	tissue	113.0
Cerebral cortex	tissue	110.5	medium
Somatosensory cortex	tissue	110.5
Periaqueductal gray	tissue	110.3
Esophagus	tissue	105.8	high
Thyroid gland	tissue	103.6	high
Hippocampal formation	tissue	98.3
Occipital cortex	tissue	95.3
Motor cortex	tissue	95.2
Ventral forebrain	tissue	91.5
Gallbladder	tissue	91.2	high
Prefrontal cortex	tissue	91.1
Putamen	tissue	90.0
Temporal cortex	tissue	87.5
Septum	tissue	87.3
Entorhinal cortex	tissue	86.3
Lung	tissue	85.2	medium
Retrosplenial and cingulate cortex	tissue	85.1
Retrosplenial cortex	tissue	84.1
Vagina	tissue	83.0	medium
Spleen	tissue	81.7	medium
Ovary	tissue	79.7	medium
Nucleus accumbens	tissue	79.3
Duodenum	tissue	79.2	medium
Insular cortex	tissue	78.1
Thymus	tissue	76.7
Amygdala	tissue	76.5
Urinary bladder	tissue	76.4	high
Hippocampus	tissue	76.3	medium
Basal ganglia	tissue	65.6	high
Cerebellum	tissue	65.6	high
Lymph node	tissue	64.7	low
Olfactory bulb	tissue	63.8
Tonsil	tissue	62.9	medium
Appendix	tissue	62.4	medium
Adrenal gland	tissue	58.3	medium
Colon	tissue	57.7	medium
Placenta	tissue	57.2	medium
Small intestine	tissue	54.8	medium
Postcentral gyrus	tissue	54.7
Choroid plexus	tissue	51.6
Fallopian tube	tissue	50.6	medium
Breast	tissue	48.2	medium
Smooth muscle	tissue	48.1	low
Seminal vesicle	tissue	48.0	medium
Stomach 1	tissue	47.8	medium
Salivary gland	tissue	47.5	high
Rectum	tissue	45.5	medium

Brain sub-regions (HPA Brain Atlas): detected in 292; highest nTPM — Ventral spinal cord (213.0), White matter (181.6), Dorsal spinal cord (179.6), Mammillary body (129.0), Dorsal funiculus (white matter) (126.4).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, CEBPB, EGR1, ESR1, FOXN1, FOXO1, JUN, KAT5, KLF4, MAX, MITF, MYC, MYF6, NFE2L2, NFKB, PAX1, PAX6, PDX1, PITX2, PRDM2, SP1, STAT5B, TBP, TCF12, TCF15, THRA, THRB, TP53

miRNA regulators (miRDB)

Targeting TKT by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

16 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-1266-5P	97.71	66.92	1052
HSA-MIR-3127-5P	97.52	65.24	786
HSA-MIR-3918	96.13	64.65	1300

Functional genomics

gnomAD constraint: pLI 5.22e-12, LOEUF 0.923, missense Z 1.66 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000462138 — one region, missense o/e 0.85. DepMap (CRISPR cell-line fitness): dependent in 38.2% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): OCUM-1 (-1.845), SNU-738 (-1.728), KPL-1 (-1.694), KON (-1.613), WM793 (-1.581), NCI-H322 (-1.539), IHH-4 (-1.505), CAL-29 (-1.459), DLD-1 (-1.452), COLO-800 (-1.437), JURL-MK1 (-1.417), KCI-MOH1 (-1.406), Panc 04.03 (-1.405), NCI-H2023 (-1.343), HCC-461 (-1.336).

Literature-anchored findings (GeneRIF, showing 28)

• Almost all multiple sclerosis patients had cerebrospinal fluid IgG directed to isoforms of one of the oligodendroglial molecules, transketolase, 2’,3’-cyclic-nucleotide 3’-phosphodiesterase type I, collapsin response mediator protein 2, and tubulin beta4. (PMID:18676363)
• This protein has been found differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19110265)
• This protein has been found differentially expressed in thalami from patients with schizophrenia. (PMID:20471030)
• The crystal structure of human transketolase and new insights into its mode of action. (PMID:20667822)
• Single Nucleotide Polymorphism in transketolase is associated with diabetic nephropathy. (PMID:20826743)
• TKT is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. (PMID:21555518)
• Structure and function of the transketolase from Mycobacterium tuberculosis and comparison with the human enzyme. (PMID:22645655)
• No transketolase activity of TKTDelta38 can be detected for conversion of physiological sugar substrates thus arguing against an intrinsically encoded enzymatic function of TKTL1 in tumor cell metabolism (PMID:23118983)
• Data indicate that transketolase (hTKT). shares 61% sequence identity with transketolase-like protein (TKTL1). (PMID:23261987)
• TKT rs3736156 identified significant differences in the onset of cardiovascular event in patients having genotypes AG + AA versus GG (PMID:23492569)
• basal TK activity was decreased in cases with diabetic neuropathy (PMID:24114639)
• Akt1 phosphorylates TKT on Thr382, markedly enhancing enzyme activity. (PMID:24981175)
• Transketolase is upregulated in metastatic peritoneal implants and promotes ovarian cancer cell proliferation. (PMID:25895698)
• transketolase (TKT)is required for cancer growth because of its ability to affect the production of NAPDH to counteract oxidative stress. (PMID:26811478)
• The observed associations of genetic variation in transketolase enzyme with neuropathic symptoms and reduced thermal sensation in recent-onset diabetes suggest a role of pathways metabolizing glycolytic intermediates in early diabetic neuropathy. (PMID:27103086)
• Mutations in TKT gene is associated with a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects. (PMID:27259054)
• reduced expression of transketolase in pyrimidine 5’-nucleotidase deficient patients (PMID:27381654)
• Over-expressed and hypo-methylated TKT gene is associated with hepatocellular carcinoma. (PMID:27760737)
• results suggest that SH2D5 is an HBV-induced protein capable of binding to TKT, leading to induction of HCC cell proliferation. (PMID:30659097)
• The regulation of TKT by oxythiamine and/or vitamin B1 may therefore be associated with response to the modulation of NET formation by preventing generation of excessive NETs in inflammatory diseases. (PMID:31415630)
• Transketolase Activity in the Formation of the Azinomycin Azabicycle Moiety (PMID:31424204)
• Erythrocyte transketolase deficiency in patients suffering from Crohn’s disease. (PMID:31646581)
• The nuclear translocation of transketolase inhibits the farnesoid receptor expression by promoting the binding of HDAC3 to FXR promoter in hepatocellular carcinoma cell lines. (PMID:31949131)
• Genetic variants in TKT and DERA in the nicotinamide adenine dinucleotide phosphate pathway predict melanoma survival. (PMID:32659474)
• Untargeted metabolomics as an unbiased approach to the diagnosis of inborn errors of metabolism of the non-oxidative branch of the pentose phosphate pathway. (PMID:32828637)
• QM/MM Study of Human Transketolase: Thiamine Diphosphate Activation Mechanism and Complete Catalytic Cycle. (PMID:34161071)
• Transketolase promotes colorectal cancer metastasis through regulating AKT phosphorylation. (PMID:35110545)
• TKT-PARP1 axis induces radioresistance by promoting DNA double-strand break repair in hepatocellular carcinoma. (PMID:38216672)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tkta	ENSDARG00000029689
mus_musculus	Tkt	ENSMUSG00000021957
rattus_norvegicus	Tkt	ENSRNOG00000016064

Paralogs (4): TKTL1 (ENSG00000007350), BCKDHB (ENSG00000083123), TKTL2 (ENSG00000151005), PDHB (ENSG00000168291)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:105992) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 16 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased body weight	1
microphthalmia	1
postnatal growth retardation	1
decreased white adipose tissue amount	1
reduced fertility	1
decreased brain weight	1
abnormal sexual interaction	1
decreased heart weight	1
decreased liver weight	1
decreased kidney weight	1
decreased testis weight	1
increased red blood cell distribution width	1
embryonic lethality before implantation, complete penetrance	1
preweaning lethality, complete penetrance	1
embryonic lethality prior to organogenesis	1
embryonic lethality prior to tooth bud stage	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Escherichia coli K-12	P0AFG8	100.0%	Diamond
Escherichia coli O157:H7	P0AFG9	100.0%	Diamond
Thermus thermophilus HB8	Q5SLR3	99.7%	Diamond
Thermus thermophilus HB27	Q72GU2	99.7%	Diamond
Pan troglodytes	Q5R1W6	99.4%	Diamond
Macaca fascicularis	Q60HC7	98.9%	Diamond
Pongo abelii	Q5R4C1	98.7%	Diamond
Bos taurus	Q6B855	93.6%	Diamond
Bacillus subtilis subsp. subtilis str. 168	P21882	86.8%	Diamond
Buchnera aphidicola str. APS (Acyrthosiphon pisum)	P57301	86.6%	Diamond
Haemophilus influenzae Rd KW20	P45119	68.6%	Diamond
Cupriavidus necator H16	Q59097	65.1%	Diamond
Clostridium sp. MSTE9	J0MXK0	54.2%	Diamond
Methanocaldococcus jannaschii DSM 2661	Q58094	49.4%	Diamond
Rhodococcoides fascians	P46374	48.3%	Diamond
Phocaeicola vulgatus ATCC 8482	A6KXB4	46.7%	Diamond
Actinobacillus succinogenes 130Z	A6VKQ4	42.4%	Diamond
Sinorhizobium fredii NGR234	P55574	40.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SNORD38C	snoRNA	109617024
PRKCD	protein-coding	5580
DCP1A	protein-coding	55802
RFT1	protein-coding	91869
SFMBT1	protein-coding	51460

Protein

Protein identifiers

Transketolase — P29401 (reviewed: P29401)

All UniProt accessions (5): E9PFF2, P29401, F8W888, F8WAX4, V9HWD9

UniProt curated annotations — full annotation on UniProt →

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. Thus, catalyzes the reversible transfer of a two-carbon ketol group from sedoheptulose-7-phosphate to glyceraldehyde-3-phosphate, producing xylulose-5-phosphate and ribose-5-phosphate. The phosphate group of the substrate plays a role in stabilizing the substrate-thiamine intermediate while preventing the formation of the reactive enamine intermediate (Ref.28). Can also use fructose-6-phosphate as a ketose donor.

Subunit / interactions. Homodimer.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. In contrast to E.coli transketolase, human transketolase is not inhibited by 2’-methoxy-thiamine diphosphate.

Cofactor. Binds 1 Mg(2+) ion per subunit (PubMed:20667822, PubMed:23965678, PubMed:31534226, PubMed:3248678, Ref.28). Can also utilize other divalent metal cations, such as Ca(2+), Mn(2+) and Co(2+). Binds 1 thiamine pyrophosphate per subunit.

Pathway. Carbohydrate degradation; pentose phosphate pathway.

Similarity. Belongs to the transketolase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P29401-1	1	yes
P29401-2	2

RefSeq proteins (3): NP_001055, NP_001128527, NP_001244957 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005474	Transketolase_N	Domain
IPR005475	Transketolase-like_Pyr-bd	Domain
IPR009014	Transketo_C/PFOR_II	Homologous_superfamily
IPR020826	Transketolase_BS	Binding_site
IPR029061	THDP-binding	Homologous_superfamily
IPR033248	Transketolase_C	Domain
IPR049557	Transketolase_CS	Conserved_site
IPR051424	Transketolase-like	Family

Pfam: PF00456, PF02779, PF02780

Enzyme classification (BRENDA)

• EC 2.2.1.1 — transketolase (BRENDA: 41 organisms, 197 substrates, 77 inhibitors, 215 Km, 72 kcat entries)

Substrate kinetics (BRENDA)

38 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-XYLULOSE 5-PHOSPHATE	0.0056–4.08	62
D-RIBOSE 5-PHOSPHATE	0.007–7	52
THIAMINE DIPHOSPHATE	0.0003–0.007	14
FRUCTOSE 6-PHOSPHATE	0.0002–11	11
GLYCOLALDEHYDE	0.13–200	8
HYDROXYPYRUVATE	—	7
D-FRUCTOSE 6-PHOSPHATE	0.029–0.72	6
3-FORMYLBENZOIC ACID	1.3–56	5
D-ERYTHROSE 4-PHOSPHATE	0.023–0.36	5
4-FORMYLBENZOIC ACID	13–251	4
XYLULOSE 5-PHOSPHATE	0.0004–0.16	4
3-HYDROXYBENZALDEHYDE	180–390	3
D-RIBOSE-5-PHOSPHATE	0.13–2.75	3
L-ERYTHRULOSE	4.9–8	3
SEDOHEPTULOSE 7-PHOSPHATE	0.031–4	3

Catalyzed reactions (Rhea)

• D-sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate = aldehydo-D-ribose 5-phosphate + D-xylulose 5-phosphate (RHEA:10508)

UniProt features (128 total): helix 36, binding site 29, strand 21, modified residue 16, sequence conflict 7, mutagenesis site 6, turn 5, site 2, sequence variant 2, chain 1, active site 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

13 structures by resolution:

PDB	Title	Method	Resolution (Å)
4KXV	Human transketolase in covalent complex with donor ketose D-xylulose-5-phosphate, crystal …	X-RAY DIFFRACTION	0.97
4KXW	Human transketolase in covalent complex with donor ketose D-xylulose-5-phosphate, crystal …	X-RAY DIFFRACTION	0.97
4KXU	Human transketolase in covalent complex with donor ketose D-fructose-6-phosphate	X-RAY DIFFRACTION	0.98
4KXX	Human transketolase in covalent complex with donor ketose D-sedoheptulose-7-phosphate	X-RAY DIFFRACTION	1.03
6HAD	Human transketolase variant E160Q	X-RAY DIFFRACTION	1.04
6HA3	Human transketolase variant E160Q in covalent complex with donor ketose …	X-RAY DIFFRACTION	1.08
6RJB	Human transketolase variant T382E	X-RAY DIFFRACTION	1.15
4KXY	Human transketolase in complex with ThDP analogue (R)-2-(1,2-dihydroxyethyl)-3-deaza-ThDP	X-RAY DIFFRACTION	1.26
8WA8	Human transketolase in complex with phosphite	X-RAY DIFFRACTION	1.48
8WA9	Human transketolase soaked with donor ketose D-fructose	X-RAY DIFFRACTION	1.5
8WAA	Human transketolase soaked with donor ketose D-xylulose	X-RAY DIFFRACTION	1.5
3MOS	The structure of human Transketolase	X-RAY DIFFRACTION	1.75
3OOY	Crystal structure of human Transketolase (TKT)	X-RAY DIFFRACTION	2.05

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29401-F1	97.11	0.97

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of carbohydrate metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; nuclear bodies; nuclear speckles

Antibody reliability (HPA): IH enhanced · IF enhanced

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3)

Position	Role
366	proton donor
37	important for catalytic activity
258	important for catalytic activity

Ligand- & substrate-binding residues (29)

Position	Role
125	thiamine diphosphate
155	Ca(2+)
155	Mg(2+)
155	thiamine diphosphate
156	thiamine diphosphate
157	thiamine diphosphate
185	Ca(2+)
185	Mg(2+)
185	thiamine diphosphate
187	Ca(2+)
37	D-fructose 6-phosphate
187	Mg(2+)
189	D-fructose 6-phosphate
189	thiamine diphosphate
244	thiamine diphosphate
258	D-fructose 6-phosphate
258	D-xylulose 5-phosphate
258	thiamine diphosphate
318	D-glyceraldehyde 3-phosphate
392	thiamine diphosphate
416	D-glyceraldehyde 3-phosphate
37	D-xylulose 5-phosphate
474	D-glyceraldehyde 3-phosphate
40	thiamine diphosphate
75	thiamine diphosphate
77	thiamine diphosphate
110	D-fructose 6-phosphate
110	D-xylulose 5-phosphate
123	thiamine diphosphate

Post-translational modifications (17)

Type	Positions
N-acetylmethionine	1
Phosphoserine	3, 104, 295, 345
N6-acetyllysine	6, 11, 144, 204, 232, 241, 260, 538, 603
Phosphotyrosine	275
Phosphothreonine	287
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	352

Mutagenesis-validated functional residues (6)

Position	Phenotype
160	reduces the catalytic efficiency by 10-fold.
160	reduces the catalytic efficiency by 5-fold.
165	reduces the catalytic efficiency by about 50-fold.
366	reduces the catalytic efficiency by about 5000-fold, probably due to the disruption of the low-barrier hydrogen bonding shown to play a …
382	increases the catalytic activity by 1.5-fold.
382	reduces the catalytic activity by 10-fold.

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 11; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

11 pathways:

ID	Pathway	Evidence
R-HSA-163754	Insulin effects increased synthesis of Xylulose-5-Phosphate	curated
R-HSA-9818028	NFE2L2 regulates pentose phosphate pathway genes	curated
R-HSA-71336	Pentose phosphate pathway	curated
R-HSA-9711123	Cellular response to chemical stress	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-163685	Integration of energy metabolism	—
R-HSA-9755511	KEAP1-NFE2L2 pathway	—
R-HSA-1430728	Metabolism	—
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives	—
R-HSA-9759194	Nuclear events mediated by NFE2L2	—

MSigDB gene sets: 350 (showing top): GOBP_NADPPLUS_METABOLIC_PROCESS, GOBP_GROWTH, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, RIZKI_TUMOR_INVASIVENESS_3D_DN, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_GLUCOSE_6_PHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, ACATTCC_MIR1_MIR206, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_DN

GO Biological Process (5): pentose-phosphate shunt (GO:0006098), pentose-phosphate shunt, non-oxidative branch (GO:0009052), glyceraldehyde-3-phosphate biosynthetic process (GO:0046166), D-xylulose 5-phosphate biosynthetic process (GO:1901159), glyceraldehyde-3-phosphate metabolic process (GO:0019682)

GO Molecular Function (9): magnesium ion binding (GO:0000287), transketolase activity (GO:0004802), calcium ion binding (GO:0005509), thiamine pyrophosphate binding (GO:0030976), protein homodimerization activity (GO:0042803), protein binding (GO:0005515), transferase activity (GO:0016740), transketolase or transaldolase activity (GO:0016744), metal ion binding (GO:0046872)

GO Cellular Component (8): nucleoplasm (GO:0005654), peroxisome (GO:0005777), cytosol (GO:0005829), nuclear body (GO:0016604), nuclear speck (GO:0016607), vesicle (GO:0031982), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

8 top-level categories:

Category	Pathways
Metabolism	2
Integration of energy metabolism	1
Metabolism of carbohydrates and carbohydrate derivatives	1
Nuclear events mediated by NFE2L2	1
Cellular responses to stimuli	1
Cellular responses to stress	1
Cellular response to chemical stress	1
KEAP1-NFE2L2 pathway	1

GO top-level categories

41 GO namespaces:

Category	Terms
cellular anatomical structure	3
glyceraldehyde-3-phosphate metabolic process	2
organophosphate biosynthetic process	2
carbohydrate derivative biosynthetic process	2
metal ion binding	2
cation binding	2
NADPH regeneration	1
pentose-phosphate shunt, oxidative branch	1
pentose-phosphate shunt, non-oxidative branch	1
glucose 6-phosphate metabolic process	1
D-ribulose-phosphate 3-epimerase activity	1
ribose-5-phosphate isomerase activity	1
transaldolase activity	1
transketolase activity	1
generation of precursor metabolites and energy	1
pentose-phosphate shunt	1
aldehyde biosynthetic process	1
D-xylulose 5-phosphate metabolic process	1
aldehyde metabolic process	1
organophosphate metabolic process	1
carbohydrate derivative metabolic process	1
transketolase or transaldolase activity	1
vitamin binding	1
anion binding	1
quaternary ammonium group binding	1
heterocyclic compound binding	1
sulfur compound binding	1
identical protein binding	1
protein dimerization activity	1
binding	1
catalytic activity	1
transferase activity	1
nuclear lumen	1
microbody	1
cytoplasm	1
nucleoplasm	1
intracellular membraneless organelle	1
nuclear ribonucleoprotein granule	1
membrane-bounded organelle	1
extracellular vesicle	1
intracellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 11 of 22 annotations. The rest are phylogenetic / computational / electronic (IEA).

11 experimentally-supported GO terms:

GO term	NS	Evidence
glyceraldehyde-3-phosphate biosynthetic process	BP	direct assay
pentose-phosphate shunt	BP	direct assay
extracellular exosome	CC	high-throughput assay
nuclear body	CC	direct assay
nuclear speck	CC	direct assay
nucleoplasm	CC	direct assay
vesicle	CC	high-throughput assay
calcium ion binding	MF	direct assay
magnesium ion binding	MF	direct assay
protein homodimerization activity	MF	direct assay
transketolase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,835 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TKT	TPK1	Q9H3S4	955
TKT	TALDO1	P37837	905
TKT	H6PD	O95479	838
TKT	PGD	P52209	818
TKT	RPIA	P49247	818
TKT	RPE	Q96AT9	797
TKT	G6PD	P11413	793
TKT	RPEL1	Q2QD12	774
TKT	TPI1	P00938	746
TKT	GPI	P06744	743
TKT	PGLS	O95336	686
TKT	XYLB	O75191	678
TKT	PKM	P14618	655
TKT	PGK1	P00558	622
TKT	PGK2	P07205	613

IntAct

Human interaction partners of TKT in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

18 partners by confidence:

Partner	Interaction type	MIscore	Records
ATG2B	association	0.530	2
POTEF	association	0.530	2
TERF1	physical association	0.510	2
YWHAZ	physical association	0.400	1
GOLGA4	association	0.350	1
TUBA4A	association	0.350	1
ACTR6	physical association	0.000	1
EIF1B	physical association	0.000	1
FBXO11	physical association	0.000	1
FTSJ1	physical association	0.000	1
GABARAPL2	physical association	0.000	1
GH1	physical association	0.000	1
HLA-B	physical association	0.000	1
IKBKE	physical association	0.000	1
ITGB1BP2	physical association	0.000	1
MCC	physical association	0.000	1
TNFRSF10D	physical association	0.000	1
VHL	physical association	0.000	1

BioGRID (437 interactions; top human partners by supporting records): TKTL1 (Cross-Linking-MS (XL-MS); 7 records), AGR2 (Proximity Label-MS; 3 records), MYC (Affinity Capture-MS; 3 records), SOD1 (Co-fractionation; 3 records), AR (Affinity Capture-MS; 2 records), ATG2B (Affinity Capture-MS; 2 records), BRD4 (Affinity Capture-MS; 2 records), CALR (Co-fractionation; 2 records), CAMK2B (Affinity Capture-MS; 2 records), CCNF (Proximity Label-MS; 2 records), DMWD (Affinity Capture-MS; 2 records), EIF2AK4 (Affinity Capture-MS; 2 records), ENO1 (Co-fractionation; 2 records), GREB1 (Affinity Capture-MS; 2 records), ISG15 (Affinity Capture-MS; 2 records)

SIGNOR signaling

9 signaling interactions:

A	Effect	B	Mechanism
AKT1	“up-regulates activity”	TKT	phosphorylation
AKT	“up-regulates activity”	TKT	phosphorylation
TKT	“down-regulates quantity”	“D-xylulose 5-phosphate(2-)”	“chemical modification”
TKT	“down-regulates quantity”	“D-ribofuranose 5-phosphate(2-)”	“chemical modification”
TKT	“up-regulates quantity”	“sedoheptulose 7-phosphate”	“chemical modification”
TKT	“up-regulates quantity”	“D-glyceraldehyde 3-phosphate(2-)”	“chemical modification”
NFE2L2	“up-regulates quantity by expression”	TKT	“transcriptional regulation”
VRK2	“up-regulates activity”	TKT	phosphorylation
FBXL6	“up-regulates activity”	TKT	ubiquitination

Disease & clinical

Genetic variants

Variant evidence for TKT: 136 ClinVar records (4 pathogenic / likely pathogenic); 20 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

136 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	71
Likely benign	25
Benign	11

Top pathogenic / likely-pathogenic (4)

Showing all 4 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
3235058	NM_001064.4(TKT):c.181C>T (p.Gln61Ter)	Likely pathogenic	criteria provided, single submitter	1
4277802	NM_001064.4(TKT):c.1697-1G>A	Likely pathogenic	criteria provided, single submitter	1
223089	NM_001064.4(TKT):c.633G>A (p.Trp211Ter)	Pathogenic	no assertion criteria provided	1
223091	NM_001064.4(TKT):c.952C>T (p.Arg318Cys)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore TKT’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 1,271):

Position(s)	Effect	Δscore	Sites
3:53225800	donor_gain	1.0000
3:53225932–53225933	acceptor_loss	1.0000	3
3:53225938	acceptor_gain	1.0000
3:53226879–53226880	acceptor_loss	1.0000	5
3:53226881	acceptor_gain	1.0000
3:53228054–53228055	donor_loss	1.0000	5
3:53228150–53228151	acceptor_loss	1.0000	4
3:53228156	acceptor_gain	1.0000
3:53228275	donor_loss	1.0000	3
3:53228360	acceptor_gain	1.0000

AlphaMissense

1,801 missense substitutions predicted likely pathogenic (of 4,120 scored), across 460 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M429	9	0.978	0.996
D424	8	0.998	0.999
H110	8	0.992	0.999
H416	8	0.992	0.999
F389	8	0.991	1.000
H77	8	0.989	0.996
D183	8	0.989	0.995
D398	8	0.988	0.997
D339	8	0.987	0.995
F392	8	0.987	1.000
H258	8	0.985	0.993
H37	8	0.984	0.997
D69	8	0.984	0.995
D155	8	0.981	0.995
D341	8	0.981	0.996
D433	8	0.980	0.996
D561	8	0.974	0.998
H562	8	0.964	0.989
D533	8	0.960	0.980
D450	8	0.952	0.986

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

6 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	5.22e-07
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	8.71e-06
Ovary Serous Cystadenocarcinoma (validation)	unfavorable	9.83e-06
Liver Hepatocellular Carcinoma (validation)	unfavorable	1.38e-05
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000435
Bladder Urothelial Carcinoma (TCGA)	unfavorable	0.000865

Disease associations

OMIM: gene MIM:606781 | disease phenotypes: MIM:617044

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
transketolase deficiency	Strong	Autosomal recessive	3

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (6 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

6 panels:

Panel	Rating
DDG2P	green
Fetal anomalies	amber
Hypotonic infant	amber
Intellectual disability	amber
Leukodystrophy, childhood onset	amber
Paediatric disorders	amber

Mondo (1): transketolase deficiency (MONDO:0014881)

Orphanet (1): Transketolase deficiency (Orphanet:488618)

HPO phenotypes

32 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000107	Renal cyst
HP:0000365	Hearing impairment
HP:0000486	Strabismus
HP:0000509	Conjunctivitis
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000554	Uveitis
HP:0000722	Compulsive behaviors
HP:0000733	Motor stereotypy
HP:0000750	Delayed speech and language development
HP:0000869	Secondary amenorrhea
HP:0001051	Seborrheic dermatitis
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001344	Absent speech
HP:0001627	Abnormal heart morphology
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001643	Patent ductus arteriosus
HP:0001655	Patent foramen ovale
HP:0002240	Hepatomegaly
HP:0003508	Proportionate short stature
HP:0003577	Congenital onset
HP:0007018	Attention deficit hyperactivity disorder
HP:0011686	Abnormal coronary artery course
HP:0025550	Elevated circulating ribitol concentration
HP:0100651	Type I diabetes mellitus
HP:0100716	Self-injurious behavior
HP:0410072	Increased level of ribose in urine

GWAS associations

20 associations:

Study	Trait	p-value
GCST010002_424	Refractive error	9e-24
GCST007104_8	QRS duration	4e-23
GCST010796_1875	Electrocardiogram morphology (amplitude at temporal datapoints)	7e-22
GCST010796_1874	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-18
GCST012020_576	Serum metabolite levels	1e-16
GCST010796_1873	Electrocardiogram morphology (amplitude at temporal datapoints)	7e-14
GCST012020_575	Serum metabolite levels	5e-13
GCST90020024_373	A body shape index	9e-12
GCST90020029_796	Waist circumference adjusted for body mass index	2e-11
GCST005951_60	Body mass index	5e-11
GCST90020025_1748	Waist-to-hip ratio adjusted for BMI	3e-10
GCST90020027_832	Waist-hip index	4e-10
GCST003844_44	QRS duration	7e-10
GCST90020027_831	Waist-hip index	5e-9
GCST003598_35	QRS duration	6e-9
GCST90020029_795	Waist circumference adjusted for body mass index	7e-9
GCST90020024_372	A body shape index	1e-8
GCST90020025_1747	Waist-to-hip ratio adjusted for BMI	1e-8
GCST007103_8	QRS duration	2e-8
GCST003598_31	QRS duration	3e-6

EFO canonical traits (from GWAS)

5 canonical traits:

EFO ID	Trait name
EFO:0005054	QRS complex
EFO:0004340	body mass index
EFO:0004327	electrocardiography
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4983 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,601 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,601

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

57 measured of 58 human assays (63 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL403691	EC50	4.7 nM
N-(2-amino-6-chloro-pyridin-3-ylmethyl)-N-{2-[2-[(2-amino-6-chloro-pyridin-3-ylmethyl)-formyl-amino]-1-(2-hydroxy-ethyl)-propenyldisulfanyl]-4-hydroxy-1-methyl-but-1-enyl}-formamide	EC50	8 nM
3-(acetylthio)-4-(N-((2-amino-6-methylpyridin-3-yl)methyl)formamido)pent-3-enyl acetate	EC50	8 nM
CHEMBL271044	EC50	8.3 nM
CHEMBL256627	EC50	8.7 nM
3-(2-amino-6-chloro-pyridin-3-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-thiazol-3-ium; chloride	EC50	9 nM
N-(2-amino-6-methyl-pyridin-3-ylmethyl)-N-{2-[2-[(2-amino-6-methyl-pyridin-3-ylmethyl)-formyl-amino]-1-(2-hydroxy-ethyl)-propenyldisulfanyl]-4-hydroxy-1-methyl-but-1-enyl}-formamide	EC50	12 nM
N-((2-amino-6-methylpyridin-3-yl)methyl)-N-(5-hydroxy-3-(2-(2-hydroxyethyl)disulfanyl)pent-2-en-2-yl)formamide	EC50	13 nM
N-((2-amino-6-methylpyridin-3-yl)methyl)-N-(1-(2-oxo-1,3-oxathian-4-ylidene)ethyl)formamide	EC50	15 nM
CHEMBL403021	KD	16 nM
3-(6-methyl-2-amino-pyridin-3-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-thiazol-3-ium chloride	EC50	18 nM
CHEMBL403212	EC50	21 nM
CHEMBL401817	KD	22 nM
3-(2-amino-6-methyl-pyridin-3-ylmethyl)-5-(2-hydroxy-ethyl)-2,4-dimethyl-thiazol-3-ium; chloride	EC50	28 nM
4-(N-((2-amino-6-methylpyridin-3-yl)methyl)formamido)-3-(benzoylthio)pent-3-enyl benzoate	EC50	28 nM
CHEMBL255339	EC50	30 nM
N-{2-[2-[acetyl-(2-amino-6-methyl-pyridin-3-ylmethyl)-amino]-1-(2-hydroxy-ethyl)-propenyldisulfanyl]-4-hydroxy-1-methyl-but-1-enyl}-N-(2-amino-6-methyl-pyridin-3-ylmethyl)-acetamide	EC50	32 nM
3-(2-(4-(N-((2-amino-6-methylpyridin-3-yl)methyl)formamido)-1-hydroxypent-3-en-3-yl)disulfanyl)propanoic acid	EC50	52 nM
3-(2-amino-pyridin-3-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-thiazol-3-ium; chloride	EC50	110 nM
(4-(N-((2-amino-6-methylpyridin-3-yl)methyl)formamido)-1-hydroxypent-3-en-3-ylthio)methyl pivalate	EC50	116 nM
CHEMBL270168	EC50	160 nM
CHEMBL430409	KD	170 nM
CHEMBL258077	EC50	300 nM
CHEMBL429246	EC50	360 nM
CHEMBL257929	EC50	470 nM
N-(2-amino-pyridin-3-ylmethyl)-N-{2-[2-[(2-amino-pyridin-3-ylmethyl)-formyl-amino]-1-(2-hydroxy-ethyl)-propenyldisulfanyl]-4-hydroxy-1-methyl-but-1-enyl}-formamide	EC50	479 nM
CHEMBL270632	EC50	490 nM
CHEMBL402566	EC50	570 nM
CHEMBL256177	EC50	660 nM
CHEMBL256831	EC50	800 nM
CHEMBL404163	EC50	840 nM
CHEMBL255541	EC50	950 nM
CHEMBL270384	EC50	1000 nM
CHEMBL257254	EC50	1100 nM
CHEMBL404300	EC50	1300 nM
CHEMBL5653589	KD	1440 nM
CHEMBL270385	KD	1460 nM
CHEMBL255603	EC50	1600 nM
CHEMBL255340	EC50	2000 nM
CHEMBL272095	EC50	2200 nM
CHEMBL257883	EC50	2300 nM
CHEMBL255550	EC50	2600 nM
CHEMBL256803	EC50	2710 nM
CHEMBL402065	EC50	3100 nM
CHEMBL402764	EC50	3240 nM
CHEMBL257253	EC50	4700 nM
N-((2-amino-6-methylpyridin-3-yl)methyl)-N-(3-(butylthio)-5-hydroxypent-2-en-2-yl)formamide	EC50	6000 nM
CHEMBL255138	EC50	6300 nM
CHEMBL255345	EC50	8500 nM
3-(2-amino-6-methyl-pyridin-3-ylmethyl)-5-(2-hydroxy-ethyl)-thiazol-3-ium; chloride	EC50	9500 nM

ChEMBL bioactivities

94 potent at pChembl≥5 of 102 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.52	Kd	3	nM	CHEMBL255138
8.33	EC50	4.7	nM	CHEMBL403691
8.15	Kd	7	nM	CHEMBL255603
8.10	EC50	8	nM	CHEMBL252843
8.10	EC50	8	nM	CHEMBL402594
8.08	EC50	8.3	nM	CHEMBL271044
8.06	EC50	8.7	nM	CHEMBL256627
8.05	EC50	9	nM	CHEMBL401948
8.05	EC50	9	nM	CHEMBL270613
8.00	Kd	10	nM	CHEMBL256627
7.92	EC50	12	nM	CHEMBL440237
7.92	Kd	12	nM	3-DEAZATHIAMINE
7.89	EC50	13	nM	CHEMBL253045
7.82	EC50	15	nM	CHEMBL252845
7.80	Kd	16	nM	CHEMBL403021
7.75	EC50	18	nM	CHEMBL252086
7.68	EC50	21	nM	CHEMBL403212
7.66	Kd	22	nM	CHEMBL401817
7.64	Kd	23	nM	CHEMBL256831
7.60	Kd	25	nM	CHEMBL402329
7.60	Kd	25	nM	CHEMBL402566
7.58	EC50	26	nM	CHEMBL252086
7.57	Kd	27	nM	CHEMBL255340
7.55	EC50	28	nM	CHEMBL252844
7.55	EC50	28	nM	CHEMBL252441
7.55	Kd	28	nM	CHEMBL258077
7.54	Kd	29	nM	CHEMBL256454
7.52	EC50	30	nM	CHEMBL255339
7.50	EC50	32	nM	CHEMBL251888
7.48	Kd	33	nM	CHEMBL252086
7.47	Kd	34	nM	CHEMBL271044
7.44	Kd	36	nM	CHEMBL270632
7.44	Kd	36	nM	CHEMBL403365
7.40	Kd	40	nM	CHEMBL255541
7.34	Kd	46	nM	CHEMBL270613
7.30	EC50	50	nM	CHEMBL258077
7.28	EC50	52	nM	CHEMBL401965
7.28	Kd	53	nM	CHEMBL255542
7.25	EC50	56	nM	CHEMBL402329
7.24	Kd	57	nM	CHEMBL429246
7.22	Kd	60	nM	CHEMBL256177
7.20	Kd	63	nM	CHEMBL401572
7.19	Kd	64	nM	CHEMBL255550
7.19	Kd	64	nM	CHEMBL271521
7.12	Kd	75	nM	CHEMBL403212
6.98	Kd	104	nM	CHEMBL270168
6.96	EC50	110	nM	CHEMBL252637
6.96	Kd	109	nM	CHEMBL270384
6.96	EC50	110	nM	CHEMBL403365
6.94	EC50	116	nM	CHEMBL253044

PubChem BioAssay actives

92 with measured affinity, of 118 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[4-amino-5-[[5-(2-hydroxyethyl)-4-methylthiophen-3-yl]methyl]pyrimidin-2-yl]acetamide	320591: Inhibition of apo-transketolase by coupled TPPK/Apo-TK enzymatic assay	kd	0.0030	uM
2-[3-[(2-amino-6-methyl-3-pyridinyl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethyl acetate	320379: Inhibition of human transketolase in HCT116 cells	ec50	0.0047	uM
2-[3-[(6-amino-3-pyridinyl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethanol	320378: Inhibition of transketolase by TPPK/apo-TK coupled assay	kd	0.0070	uM
N-[(2-amino-6-chloro-3-pyridinyl)methyl]-N-[(Z)-3-[[(Z)-2-[(2-amino-6-chloro-3-pyridinyl)methyl-formylamino]-5-hydroxypent-2-en-3-yl]disulfanyl]-5-hydroxypent-2-en-2-yl]formamide	313901: Inhibition of transketolase in human HCT116 cells	ec50	0.0080	uM
[(Z)-3-acetylsulfanyl-4-[(2-amino-6-methyl-3-pyridinyl)methyl-formylamino]pent-3-enyl] acetate	313901: Inhibition of transketolase in human HCT116 cells	ec50	0.0080	uM
2-[3-[(2-amino-4,6-dimethyl-3-pyridinyl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethanol	320379: Inhibition of human transketolase in HCT116 cells	ec50	0.0083	uM
2-[3-[(2-amino-6-ethyl-3-pyridinyl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethanol	320379: Inhibition of human transketolase in HCT116 cells	ec50	0.0087	uM
2-[3-[(2-amino-6-chloro-3-pyridinyl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethanol chloride	313901: Inhibition of transketolase in human HCT116 cells	ec50	0.0090	uM
2-[3-[(2-amino-6-chloro-3-pyridinyl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethanol	320379: Inhibition of human transketolase in HCT116 cells	ec50	0.0090	uM
2-[4-[(4-amino-2-methylpyrimidin-5-yl)methyl]-3-methylthiophen-2-yl]ethanol	320591: Inhibition of apo-transketolase by coupled TPPK/Apo-TK enzymatic assay	kd	0.0120	uM
N-[(2-amino-6-methyl-3-pyridinyl)methyl]-N-[(Z)-3-[[(Z)-2-[(2-amino-6-methyl-3-pyridinyl)methyl-formylamino]-5-hydroxypent-2-en-3-yl]disulfanyl]-5-hydroxypent-2-en-2-yl]formamide	313901: Inhibition of transketolase in human HCT116 cells	ec50	0.0120	uM
N-[(2-amino-6-methyl-3-pyridinyl)methyl]-N-[(Z)-5-hydroxy-3-(2-hydroxyethyldisulfanyl)pent-2-en-2-yl]formamide	313901: Inhibition of transketolase in human HCT116 cells	ec50	0.0130	uM
N-[(2-amino-6-methyl-3-pyridinyl)methyl]-N-[(1Z)-1-(2-oxo-1,3-oxathian-4-ylidene)ethyl]formamide	313901: Inhibition of transketolase in human HCT116 cells	ec50	0.0150	uM
2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-2-oxo-1,3-thiazol-5-yl]ethyl phosphono hydrogen phosphate	320588: Inhibition of apo-transketolase	kd	0.0160	uM
2-[3-[(2-amino-6-methyl-3-pyridinyl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethanol chloride	313901: Inhibition of transketolase in human HCT116 cells	ec50	0.0180	uM
2-[3-[(2-amino-6-methyl-3-pyridinyl)methyl]-2-ethyl-4-methyl-1,3-thiazol-3-ium-5-yl]ethanol	320379: Inhibition of human transketolase in HCT116 cells	ec50	0.0210	uM
2-[3-[(2-amino-6-methyl-3-pyridinyl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethyl phosphono hydrogen phosphate	320377: Binding affinity to apo-transketolase	kd	0.0220	uM
N-[6-amino-5-[[5-(2-hydroxyethyl)-4-methyl-1,3-thiazol-3-ium-3-yl]methyl]-2-pyridinyl]acetamide	320378: Inhibition of transketolase by TPPK/apo-TK coupled assay	kd	0.0230	uM
2-[3-[(2-amino-6-methyl-3-pyridinyl)methyl]-2,4-dimethyl-1,3-thiazol-3-ium-5-yl]ethanol	320378: Inhibition of transketolase by TPPK/apo-TK coupled assay	kd	0.0250	uM
2-[3-[(2-amino-6-methyl-3-pyridinyl)methyl]-4-(hydroxymethyl)-1,3-thiazol-3-ium-5-yl]ethanol	320378: Inhibition of transketolase by TPPK/apo-TK coupled assay	kd	0.0250	uM
(1S)-1-[3-[(2-amino-6-methyl-3-pyridinyl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethane-1,2-diol	320378: Inhibition of transketolase by TPPK/apo-TK coupled assay	kd	0.0270	uM
2-[3-[(2-amino-6-methyl-3-pyridinyl)methyl]-2,4-dimethyl-1,3-thiazol-3-ium-5-yl]ethanol chloride	313901: Inhibition of transketolase in human HCT116 cells	ec50	0.0280	uM
[(Z)-4-[(2-amino-6-methyl-3-pyridinyl)methyl-formylamino]-3-benzoylsulfanylpent-3-enyl] benzoate	313901: Inhibition of transketolase in human HCT116 cells	ec50	0.0280	uM
(1R)-1-[3-[(2-amino-6-methyl-3-pyridinyl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethane-1,2-diol	320378: Inhibition of transketolase by TPPK/apo-TK coupled assay	kd	0.0280	uM
2-[3-[(2-amino-6-methyl-3-pyridinyl)methyl]-1,3-thiazol-3-ium-5-yl]ethanol	320378: Inhibition of transketolase by TPPK/apo-TK coupled assay	kd	0.0290	uM
1-[3-[(2-amino-6-methyl-3-pyridinyl)methyl]-5-(2-hydroxyethyl)-4-methyl-1,3-thiazol-3-ium-2-yl]ethanol	320379: Inhibition of human transketolase in HCT116 cells	ec50	0.0300	uM
N-[(Z)-3-[[(Z)-2-[acetyl-[(2-amino-6-methyl-3-pyridinyl)methyl]amino]-5-hydroxypent-2-en-3-yl]disulfanyl]-5-hydroxypent-2-en-2-yl]-N-[(2-amino-6-methyl-3-pyridinyl)methyl]acetamide	313901: Inhibition of transketolase in human HCT116 cells	ec50	0.0320	uM
2-[3-[(2-amino-3-pyridinyl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethanol	320378: Inhibition of transketolase by TPPK/apo-TK coupled assay	kd	0.0360	uM
2-[3-[(2-amino-6-methyl-3-pyridinyl)methyl]-2-methyl-1,3-thiazol-3-ium-5-yl]ethanol	320378: Inhibition of transketolase by TPPK/apo-TK coupled assay	kd	0.0360	uM
2-[3-[(2-amino-6-methyl-3-pyridinyl)methyl]-4-ethyl-1,3-thiazol-3-ium-5-yl]ethanol	320378: Inhibition of transketolase by TPPK/apo-TK coupled assay	kd	0.0400	uM
3-[[(Z)-2-[(2-amino-6-methyl-3-pyridinyl)methyl-formylamino]-5-hydroxypent-2-en-3-yl]disulfanyl]propanoic acid	313901: Inhibition of transketolase in human HCT116 cells	ec50	0.0520	uM
1-[3-[(2-amino-6-methyl-3-pyridinyl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethane-1,2-diol	320378: Inhibition of transketolase by TPPK/apo-TK coupled assay	kd	0.0530	uM
6-amino-5-[[5-(2-hydroxyethyl)-4-methyl-1,3-thiazol-3-ium-3-yl]methyl]pyridine-2-carbonitrile	320378: Inhibition of transketolase by TPPK/apo-TK coupled assay	kd	0.0570	uM
2-[4-[(4-amino-2-cyclopropylpyrimidin-5-yl)methyl]-3-methylthiophen-2-yl]ethanol	320591: Inhibition of apo-transketolase by coupled TPPK/Apo-TK enzymatic assay	kd	0.0600	uM
2-[4-[[4-amino-2-(trifluoromethyl)pyrimidin-5-yl]methyl]-3-methylthiophen-2-yl]ethanol	320591: Inhibition of apo-transketolase by coupled TPPK/Apo-TK enzymatic assay	kd	0.0630	uM
2-[3-[(4-amino-3-pyridinyl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethanol	320378: Inhibition of transketolase by TPPK/apo-TK coupled assay	kd	0.0640	uM
2-[4-[(4-amino-2-propan-2-ylpyrimidin-5-yl)methyl]-3-methylthiophen-2-yl]ethanol	320591: Inhibition of apo-transketolase by coupled TPPK/Apo-TK enzymatic assay	kd	0.0640	uM
2-[3-[[2-amino-6-(trifluoromethyl)-3-pyridinyl]methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethanol	320378: Inhibition of transketolase by TPPK/apo-TK coupled assay	kd	0.1040	uM
2-[3-[(2-amino-5-iodo-3-pyridinyl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethanol	320378: Inhibition of transketolase by TPPK/apo-TK coupled assay	kd	0.1090	uM
2-[3-[(2-amino-3-pyridinyl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethanol chloride	313901: Inhibition of transketolase in human HCT116 cells	ec50	0.1100	uM
[(Z)-2-[(2-amino-6-methyl-3-pyridinyl)methyl-formylamino]-5-hydroxypent-2-en-3-yl]sulfanylmethyl 2,2-dimethylpropanoate	313901: Inhibition of transketolase in human HCT116 cells	ec50	0.1160	uM
2-[5-[[5-(2-hydroxyethyl)-4-methyl-1,3-thiazol-3-ium-3-yl]methyl]pyridine-2-carbonyl]benzoic acid	320378: Inhibition of transketolase by TPPK/apo-TK coupled assay	kd	0.1400	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149594: Binding affinity to human TKT incubated for 45 mins by Kinobead based pull down assay	kd	0.1513	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149594: Binding affinity to human TKT incubated for 45 mins by Kinobead based pull down assay	kd	0.1669	uM
[2-[3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl]ethoxy-methylphosphoryl] dihydrogen phosphate	320588: Inhibition of apo-transketolase	kd	0.1700	uM
2-[4-methyl-3-[(5-methyl-3-pyridinyl)methyl]-1,3-thiazol-3-ium-5-yl]ethanol	320378: Inhibition of transketolase by TPPK/apo-TK coupled assay	kd	0.2200	uM
2-[4-[(4-amino-2-phenylpyrimidin-5-yl)methyl]-3-methylthiophen-2-yl]ethanol	320591: Inhibition of apo-transketolase by coupled TPPK/Apo-TK enzymatic assay	kd	0.2300	uM
2-[4-methyl-3-[[6-(trifluoromethyl)-3-pyridinyl]methyl]-1,3-thiazol-3-ium-5-yl]ethanol	320378: Inhibition of transketolase by TPPK/apo-TK coupled assay	kd	0.3100	uM
N-[(2-amino-3-pyridinyl)methyl]-N-[(Z)-3-[[(Z)-2-[(2-amino-3-pyridinyl)methyl-formylamino]-5-hydroxypent-2-en-3-yl]disulfanyl]-5-hydroxypent-2-en-2-yl]formamide	313901: Inhibition of transketolase in human HCT116 cells	ec50	0.4790	uM
2-[3-[(2-amino-6-methyl-3-pyridinyl)methyl]-4-methyl-2-(pyridin-3-ylmethyl)-1,3-thiazol-3-ium-5-yl]ethanol	320379: Inhibition of human transketolase in HCT116 cells	ec50	0.8400	uM

CTD chemical–gene interactions

84 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Arsenic	increases expression, increases abundance, affects cotreatment	3
Tobacco Smoke Pollution	decreases expression, increases expression, affects expression	3
Tretinoin	affects cotreatment, increases expression	3
Particulate Matter	increases abundance, increases expression, affects cotreatment	3
sodium arsenate	increases abundance, increases expression	2
cobaltous chloride	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Arsenic Trioxide	decreases reaction, affects cotreatment, increases expression, affects binding	2
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	increases abundance, increases expression	2
Cadmium	increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	affects expression, increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment, affects localization	1
arsenite	decreases reaction, affects binding	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	decreases methylation	1
lead chloride	increases expression	1
cupric chloride	increases expression	1

ChEMBL screening assays

18 unique, capped per target: 18 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4270851	Binding	Binding affinity to transketolase in human Hela cells lysates assessed as protein enrichment by measuring normalized heavy/light ratio at by nano-LC-ESIMS/MS analysis	Determination of Gymnemic Acid I as a Protein Biosynthesis Inhibitor Using Chemical Proteomics. — *J Nat Prod*

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1ZC	Abcam A-549 TKT KO	Cancer cell line	Male
CVCL_D2DD	Abcam HCT 116 TKT KO	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TKT across ~30M SureChEMBL compounds — explore on Sugi Predict.