TKTL2

Summary

TKTL2 (transketolase like 2, HGNC:25313) is a protein-coding gene on chromosome 4q32.2, encoding Transketolase-like protein 2 (Q9H0I9). Plays an essential role in total transketolase activity and cell proliferation in cancer cells; after transfection with anti-TKTL1 siRNA, total transketolase activity dramatically decreases and proliferation was significantly inhibited in cancer cells.

Predicted to enable thiamine pyrophosphate binding activity and transketolase activity. Located in cytoplasm.

Source: NCBI Gene 84076 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 97 total
• MANE Select transcript: NM_032136

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25313
Approved symbol	TKTL2
Name	transketolase like 2
Location	4q32.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32975, DKFZP434L1717
Ensembl gene	ENSG00000151005
Ensembl biotype	protein_coding
Entrez	84076

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000280605

RefSeq mRNA: 1 — MANE Select: NM_032136 NM_032136

CCDS: CCDS3805

Canonical transcript exons

ENST00000280605 — 1 exons

Exon	Start	End
ENSE00000997198	163471095	163473754

Expression profiles

Bgee: expression breadth broad, 19 present calls, max score 96.34.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2292 / max 184.9448, expressed in 3 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54671	0.1894	3
54672	0.0158	3
54674	0.0107	3
54673	0.0097	3
54670	0.0036	1

Top tissues by expression

219 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adult organism	UBERON:0007023	96.34	gold quality
sperm	CL:0000019	94.50	gold quality
left testis	UBERON:0004533	88.29	gold quality
right testis	UBERON:0004534	87.82	gold quality
testis	UBERON:0000473	86.38	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	65.02	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
epithelial cell of pancreas	CL:0000083	53.30	gold quality
deltoid	UBERON:0001476	50.46	gold quality
myocardium	UBERON:0002349	50.25	gold quality
ileal mucosa	UBERON:0000331	50.06	silver quality
pancreatic ductal cell	CL:0002079	48.89	silver quality
cerebellar vermis	UBERON:0004720	48.32	gold quality
quadriceps femoris	UBERON:0001377	47.43	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
monocyte	CL:0000576	46.36	silver quality
upper leg skin	UBERON:0004262	45.95	silver quality
vastus lateralis	UBERON:0001379	45.40	gold quality
leukocyte	CL:0000738	45.37	silver quality
bone marrow cell	CL:0002092	44.50	gold quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
bone marrow	UBERON:0002371	42.40	gold quality
thymus	UBERON:0002370	42.31	gold quality
muscle tissue	UBERON:0002385	41.86	gold quality
skeletal muscle tissue	UBERON:0001134	41.39	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting TKTL2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-548O-3P	99.74	69.30	2228

Literature-anchored findings (GeneRIF, showing 1)

• Homology modelling of TKTL1 and TKTL2 using transketolase (TKT) as template, revealed that both could assume a folded structure like TKT. TKTL1/2 presented a cleft of suitable dimensions between the homodimer surfaces that could accommodate the co-factor-substrate. An appropriate cavity and a hydrophobic nodule were also present in TKTL1/2 and implicated in aminopyrimidine and thiazole ring binding in TKT, respectively. (PMID:30646877)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tktb	ENSDARG00000006019
mus_musculus	Tktl2	ENSMUSG00000025519
rattus_norvegicus	Tktl2	ENSRNOG00000014185

Paralogs (4): TKTL1 (ENSG00000007350), BCKDHB (ENSG00000083123), TKT (ENSG00000163931), PDHB (ENSG00000168291)

Protein

Protein identifiers

Transketolase-like protein 2 — Q9H0I9 (reviewed: Q9H0I9)

All UniProt accessions (2): Q9H0I9, A0A140VKC2

UniProt curated annotations — full annotation on UniProt →

Function. Plays an essential role in total transketolase activity and cell proliferation in cancer cells; after transfection with anti-TKTL1 siRNA, total transketolase activity dramatically decreases and proliferation was significantly inhibited in cancer cells. Plays a pivotal role in carcinogenesis.

Subunit / interactions. Homodimer.

Tissue specificity. Overexpressed in hepatoma cancer cells.

Cofactor. Binds 1 Mg(2+) ion per subunit. Can also utilize other divalent metal cations, such as Ca(2+), Mn(2+) and Co(2+). Binds 1 thiamine pyrophosphate per subunit.

Similarity. Belongs to the transketolase family.

RefSeq proteins (1): NP_115512* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005474	Transketolase_N	Domain
IPR005475	Transketolase-like_Pyr-bd	Domain
IPR009014	Transketo_C/PFOR_II	Homologous_superfamily
IPR029061	THDP-binding	Homologous_superfamily
IPR033248	Transketolase_C	Domain
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), 1 shown:

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

UniProt features (26 total): binding site 17, sequence conflict 4, sequence variant 2, chain 1, active site 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0I9-F1	96.64	0.96

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 (2): 370 (proton donor); 262 (important for catalytic activity)

Ligand- & substrate-binding residues (17): 248; 262; 262; 349; 370; 396; 420; 428; 432; 41; 78; 124–126 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 33 (showing top): chr4q32, OCT1_06, KEGG_PENTOSE_PHOSPHATE_PATHWAY, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOMF_SULFUR_COMPOUND_BINDING, GOMF_VITAMIN_BINDING, GOMF_QUATERNARY_AMMONIUM_GROUP_BINDING, MIKKELSEN_MEF_HCP_WITH_H3_UNMETHYLATED, MARTENS_TRETINOIN_RESPONSE_UP, WAGSCHAL_EHMT2_TARGETS_UP, GOMF_THIAMINE_PYROPHOSPHATE_BINDING, MODULE_426, MIR6124, MIR1323, MIR548O_3P

GO Biological Process (0):

GO Molecular Function (4): transketolase activity (GO:0004802), thiamine pyrophosphate binding (GO:0030976), metal ion binding (GO:0046872), transferase activity (GO:0016740)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cation binding	2
transketolase or transaldolase activity	1
vitamin binding	1
anion binding	1
quaternary ammonium group binding	1
heterocyclic compound binding	1
sulfur compound binding	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

3131 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TKTL2	TPK1	Q9H3S4	984
TKTL2	TALDO1	P37837	943
TKTL2	H6PD	O95479	844
TKTL2	PGD	P52209	833
TKTL2	G6PD	P11413	811
TKTL2	RPIA	P49247	799
TKTL2	RPEL1	Q2QD12	761
TKTL2	RPE	Q96AT9	760
TKTL2	TPI1	P00938	730
TKTL2	GAPDH	P00354	712
TKTL2	GPI	P06744	693
TKTL2	ENO1	P06733	656
TKTL2	XYLB	O75191	647
TKTL2	PGLS	O95336	636
TKTL2	PGK2	P07205	631

IntAct

14 interactions, top by confidence:

A	B	Type	Score
PRCC	BCAS2	psi-mi:“MI:0914”(association)	0.530
ZSWIM2	SEMG1	psi-mi:“MI:0914”(association)	0.530
RRP8	MAGEB2	psi-mi:“MI:0914”(association)	0.530
NFIC	TKTL2	psi-mi:“MI:0915”(physical association)	0.370
TKTL2	USP33	psi-mi:“MI:0914”(association)	0.350
TKTL2	BRME1	psi-mi:“MI:0914”(association)	0.350
ECD	NDC80	psi-mi:“MI:0914”(association)	0.350
PROZ	IDE	psi-mi:“MI:0914”(association)	0.350
SPG21	LRRC32	psi-mi:“MI:0914”(association)	0.350
SYT16	KBTBD7	psi-mi:“MI:0914”(association)	0.350
TKTL2	HSPA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (22): TKTL2 (Two-hybrid), ACP1 (Co-fractionation), AKR1B1 (Co-fractionation), ESD (Co-fractionation), FABP7 (Co-fractionation), GLRX (Co-fractionation), TALDO1 (Co-fractionation), TKTL2 (Co-fractionation), TKTL2 (Co-fractionation), TKTL2 (Co-fractionation), TKTL2 (Affinity Capture-MS), FBLN5 (Affinity Capture-MS), TKTL2 (Affinity Capture-MS), USP33 (Affinity Capture-MS), C19orf57 (Affinity Capture-MS)

ESM2 similar proteins: A0A2I2F2I5, A5A6L0, A7MB35, G0SHF3, O13366, O24457, P07342, P08559, P14874, P16387, P21839, P21953, P26267, P26268, P26284, P28838, P28839, P29803, P29804, P34385, P35486, P35487, P35738, P52899, P52900, P52901, P52902, P52903, Q06437, Q10489, Q2NL26, Q3ZC84, Q41768, Q41769, Q54C70, Q5R432, Q5R490, Q654V6, Q6K2E8, Q6P3A8

Diamond homologs: A0A0I9QGZ2, A6KXB4, A6VKQ4, A6YB01, D5AV94, F4IW47, J0MXK0, O20250, O67642, O83571, O94039, P0CZ16, P22976, P23254, P27302, P29277, P29401, P33315, P33570, P34736, P40142, P43757, P46374, P46708, P47312, P50137, P51010, P55574, P56900, P57927, P57958, P58333, P59956, P66962, P66963, P75611, P99161, P9WG24, P9WG25, Q12630

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	90
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

52 predictions. Top by Δscore:

Variant	Effect	Δscore
4:163471877:CGG:C	donor_gain	0.7900
4:163471394:ACTGC:A	acceptor_gain	0.6800
4:163472030:C:A	donor_gain	0.6800
4:163471395:CTGC:C	acceptor_gain	0.6600
4:163471396:T:A	acceptor_gain	0.6300
4:163471859:T:TA	donor_gain	0.5600
4:163472023:C:CT	donor_gain	0.4800
4:163471899:A:AC	donor_gain	0.4600
4:163471900:C:CC	donor_gain	0.4600
4:163471323:C:CC	acceptor_gain	0.4400
4:163471914:AT:A	donor_gain	0.4200
4:163472024:C:CT	donor_gain	0.4200
4:163471923:T:C	donor_gain	0.4100
4:163472378:T:TG	acceptor_gain	0.4100
4:163471322:A:AC	acceptor_gain	0.4000
4:163471988:C:CA	donor_gain	0.4000
4:163471393:AACTG:A	acceptor_gain	0.3800
4:163472378:T:C	acceptor_gain	0.3800
4:163471350:TGG:T	acceptor_gain	0.3700
4:163471415:A:AG	acceptor_gain	0.3400
4:163471416:T:TT	acceptor_gain	0.3200
4:163471856:A:AC	donor_gain	0.3200
4:163471857:C:CC	donor_gain	0.3200
4:163472147:CT:C	acceptor_gain	0.3100
4:163472148:TT:T	acceptor_gain	0.3100
4:163472471:C:CT	acceptor_gain	0.2900
4:163471349:TTGG:T	acceptor_gain	0.2800
4:163471377:CAAA:C	acceptor_gain	0.2700
4:163471858:T:C	donor_gain	0.2700
4:163472666:T:A	donor_gain	0.2700

AlphaMissense

4118 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:163472354:C:G	A461P	0.941
4:163472008:A:T	V576D	0.940
4:163473101:A:G	W212R	0.940
4:163473101:A:T	W212R	0.940
4:163472171:C:G	A522P	0.929
4:163472131:A:T	V535D	0.928
4:163472012:C:G	A575P	0.926
4:163472078:C:G	A553P	0.924
4:163473282:G:C	F151L	0.924
4:163473282:G:T	F151L	0.924
4:163473284:A:G	F151L	0.924
4:163472118:A:C	F539L	0.923
4:163472118:A:T	F539L	0.923
4:163472120:A:G	F539L	0.923
4:163472568:A:C	F389L	0.920
4:163472568:A:T	F389L	0.920
4:163472570:A:G	F389L	0.920
4:163472353:G:T	A461D	0.917
4:163472209:A:T	V509E	0.912
4:163472410:C:G	R442P	0.912
4:163472056:A:T	V560D	0.908
4:163472376:A:C	S453R	0.907
4:163472376:A:T	S453R	0.907
4:163472378:T:G	S453R	0.907
4:163472180:C:G	A519P	0.904
4:163472044:T:A	E564V	0.903
4:163472134:C:G	R534P	0.896
4:163472342:C:G	A465P	0.895
4:163473326:C:G	A137P	0.894
4:163472050:G:T	T562K	0.891

dbSNP variants (sampled 300 via entrez): RS1000088332 (4:163475113 T>C), RS1000119599 (4:163474913 A>G), RS10004056 (4:163475089 A>G), RS1001743997 (4:163473919 G>A,C), RS1002062433 (4:163473586 G>A,C), RS1002153177 (4:163472609 C>A,T), RS1002947232 (4:163470939 A>G), RS1003804148 (4:163471300 A>G), RS1004317396 (4:163475501 T>C), RS1005907413 (4:163473846 T>C), RS1006255491 (4:163473469 T>C,G), RS1006292336 (4:163474067 A>T), RS1006615459 (4:163472121 T>C), RS1007843273 (4:163471263 C>T), RS1007875700 (4:163470844 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.