THTPA

Summary

THTPA (thiamine triphosphatase, HGNC:18987) is a protein-coding gene on chromosome 14q11.2, encoding Thiamine-triphosphatase (Q9BU02). Hydrolase highly specific for thiamine triphosphate (ThTP).

This gene encodes an enzyme which catalyzes the biosynthesis of thiamine disphophate (vitamin B1) by hydrolysis of thiamine triphosphate. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 79178 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 597 total — 1 pathogenic
• MANE Select transcript: NM_024328

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18987
Approved symbol	THTPA
Name	thiamine triphosphatase
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	THTPASE
Ensembl gene	ENSG00000259431
Ensembl biotype	protein_coding
OMIM	611612
Entrez	79178

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000288014, ENST00000404535, ENST00000554789, ENST00000554970, ENST00000555446, ENST00000556015, ENST00000556545, ENST00000557630

RefSeq mRNA: 6 — MANE Select: NM_024328 NM_001126339, NM_001256062, NM_001256321, NM_001256322, NM_001256323, NM_024328

CCDS: CCDS32053, CCDS58306, CCDS58307

Canonical transcript exons

ENST00000288014 — 2 exons

Exon	Start	End
ENSE00001031748	23556271	23557304
ENSE00002486634	23558695	23560271

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 92.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.8389 / max 112.5685, expressed in 1797 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138940	9.0486	1783
138938	2.4691	1270
138937	1.4865	843
138935	0.5755	100
138939	0.5460	320
138941	0.1829	62
138942	0.1058	32
138934	0.0984	44
138933	0.0155	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	92.89	gold quality
frontal cortex	UBERON:0001870	91.32	gold quality
amygdala	UBERON:0001876	90.31	gold quality
temporal lobe	UBERON:0001871	90.29	gold quality
cerebral cortex	UBERON:0000956	90.12	gold quality
anterior cingulate cortex	UBERON:0009835	90.08	gold quality
putamen	UBERON:0001874	89.49	gold quality
right frontal lobe	UBERON:0002810	89.48	gold quality
Ammon’s horn	UBERON:0001954	89.47	gold quality
substantia nigra	UBERON:0002038	89.40	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.25	gold quality
nucleus accumbens	UBERON:0001882	89.16	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.71	gold quality
caudate nucleus	UBERON:0001873	88.56	gold quality
superior frontal gyrus	UBERON:0002661	88.29	gold quality
gastrocnemius	UBERON:0001388	88.24	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.16	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.10	gold quality
apex of heart	UBERON:0002098	87.98	gold quality
right adrenal gland	UBERON:0001233	87.88	gold quality
brain	UBERON:0000955	87.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.45	gold quality
muscle of leg	UBERON:0001383	87.38	gold quality
skeletal muscle organ	UBERON:0014892	87.32	gold quality
right adrenal gland cortex	UBERON:0035827	87.26	gold quality
ganglionic eminence	UBERON:0004023	87.23	gold quality
primary visual cortex	UBERON:0002436	86.84	gold quality
left adrenal gland	UBERON:0001234	86.80	gold quality
hypothalamus	UBERON:0001898	86.78	gold quality
cortical plate	UBERON:0005343	86.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting THTPA, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-573	99.55	67.44	955
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-1207-5P	99.49	69.11	2983

Literature-anchored findings (GeneRIF, showing 1)

• The untagged recombinant human ThTPase (hThTPase) was expressed in E. coli and purified to homogeneity. (PMID:15109578)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	thtpa	ENSDARG00000063049
danio_rerio	si:dkey-191c17.2	ENSDARG00000095445
mus_musculus	Thtpa	ENSMUSG00000045691
rattus_norvegicus	Thtpa	ENSRNOG00000018105

Protein

Protein identifiers

Thiamine-triphosphatase — Q9BU02 (reviewed: Q9BU02)

All UniProt accessions (4): G3V5B9, G3V5Q5, Q9BU02, H0YJU8

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolase highly specific for thiamine triphosphate (ThTP).

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm.

Tissue specificity. Widely expressed but at a low level.

Cofactor. Binds 1 Mg(2+) ion per subunit.

Similarity. Belongs to the ThTPase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BU02-1	1	yes
Q9BU02-2	2

RefSeq proteins (6): NP_001119811, NP_001242991, NP_001243250, NP_001243251, NP_001243252, NP_077304* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012177	ThTPase_euk	Family
IPR023577	CYTH_domain	Domain
IPR033469	CYTH-like_dom_sf	Homologous_superfamily
IPR039582	THTPA	Family

Pfam: PF01928

Enzyme classification (BRENDA):

• EC 3.6.1.28 — thiamine-triphosphatase (BRENDA: 10 organisms, 32 substrates, 58 inhibitors, 46 Km, 13 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
THIAMINE TRIPHOSPHATE	0.008–2.8	32
THIAMIN TRIPHOSPHATE	0.0211–0.126	9
ATP	3.7	1
ITP	0.1043	1
MG2+-THIAMINE TRIPHOSPHATE COMPLEX	0.6	1

Catalyzed reactions (Rhea), 1 shown:

• thiamine triphosphate + H2O = thiamine diphosphate + phosphate + H(+) (RHEA:11744)

UniProt features (47 total): binding site 12, mutagenesis site 9, strand 9, helix 9, splice variant 2, initiator methionine 1, chain 1, modified residue 1, sequence variant 1, domain 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3BHD	X-RAY DIFFRACTION	1.5
3TVL	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BU02-F1	87.22	0.70

Functional residue map

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

Ligand- & substrate-binding residues (12): 145; 157; 157; 159; 193; 7; 9; 11; 55; 57; 65; 125

Post-translational modifications (1): 2

Mutagenesis-validated functional residues (9):

Position	Phenotype
11	mildly decreases enzyme activity.
37	strongly decreases affinity for thiamine triphosphate and enzyme activity.
39	strongly decreases affinity for thiamine triphosphate and enzyme activity.
53	strongly decreases affinity for thiamine triphosphate and enzyme activity.
65	strongly decreases enzyme activity. no effect on affinity for thiamine triphosphate.
79	decreases enzyme activity.
81	mildly decreases enzyme activity.
147	strongly decreases affinity for thiamine triphosphate and enzyme activity.
193	strongly decreases affinity for thiamine triphosphate and enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-196819	Vitamin B1 (thiamin) metabolism
R-HSA-1430728	Metabolism
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors
R-HSA-196854	Metabolism of vitamins and cofactors

MSigDB gene sets: 86 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GCM_GSPT1, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_VITAMIN_BIOSYNTHETIC_PROCESS, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_DEPHOSPHORYLATION, CAGCCTC_MIR4855P, GOBP_VITAMIN_METABOLIC_PROCESS, GOBP_PRIMARY_ALCOHOL_METABOLIC_PROCESS, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_ALCOHOL_METABOLIC_PROCESS

GO Biological Process (7): generation of precursor metabolites and energy (GO:0006091), thiamine metabolic process (GO:0006772), thiamine diphosphate biosynthetic process (GO:0009229), dephosphorylation (GO:0016311), thiamine diphosphate metabolic process (GO:0042357), phosphate-containing compound metabolic process (GO:0006796), thiamine-containing compound metabolic process (GO:0042723)

GO Molecular Function (6): magnesium ion binding (GO:0000287), hydrolase activity (GO:0016787), thiamine triphosphate phosphatase activity (GO:0050333), protein binding (GO:0005515), pyrophosphatase activity (GO:0016462), metal ion binding (GO:0046872)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	1
Metabolism of vitamins and cofactors	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metabolic process	2
thiamine-containing compound metabolic process	2
cellular anatomical structure	2
primary alcohol metabolic process	1
thiamine diphosphate metabolic process	1
thiamine-containing compound biosynthetic process	1
organophosphate biosynthetic process	1
phosphate-containing compound metabolic process	1
organophosphate metabolic process	1
sulfur compound metabolic process	1
pyrimidine-containing compound metabolic process	1
metal ion binding	1
catalytic activity	1
pyrophosphatase activity	1
binding	1
hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides	1
cation binding	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

988 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
THTPA	TPK1	Q9H3S4	602
THTPA	TMEM139	Q8IV31	506
THTPA	MELTF	P08582	464
THTPA	SLC19A2	O60779	457
THTPA	ZNF786	Q8N393	423
THTPA	ITPK1	Q13572	408
THTPA	TLCD1	Q96CP7	405
THTPA	SLC19A3	Q9BZV2	404
THTPA	ENTPD5	O75356	394
THTPA	SLC25A19	Q9HC21	381
THTPA	MOCOS	Q96EN8	378
THTPA	ANXA10	Q9UJ72	375
THTPA	UBAP2L	Q14157	360
THTPA	HACL1	Q9UJ83	348
THTPA	SELENOT	P62341	338

IntAct

27 interactions, top by confidence:

A	B	Type	Score
RAD51D	RAD51C	psi-mi:“MI:0914”(association)	0.860
KLK5	DENND11	psi-mi:“MI:0914”(association)	0.640
RCCD1	SPAG9	psi-mi:“MI:0914”(association)	0.640
TSPYL6	USP12	psi-mi:“MI:0914”(association)	0.640
TLX3	THTPA	psi-mi:“MI:0915”(physical association)	0.560
THTPA	RTL8C	psi-mi:“MI:0914”(association)	0.530
ORF10	PPT1	psi-mi:“MI:0914”(association)	0.530
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
TEX13B	ARID1A	psi-mi:“MI:0914”(association)	0.350
AFG2B	RCCD1	psi-mi:“MI:0914”(association)	0.350
ZNF44	ZNF195	psi-mi:“MI:0914”(association)	0.350
THTPA	GTPBP6	psi-mi:“MI:0914”(association)	0.350
AQP12B	TIPRL	psi-mi:“MI:0914”(association)	0.350
DCAKD	P3H1	psi-mi:“MI:0914”(association)	0.350
SFXN3	ACSL1	psi-mi:“MI:0914”(association)	0.350
SLC25A13	A2ML1	psi-mi:“MI:0914”(association)	0.350
SLC22A11	CNOT1	psi-mi:“MI:0914”(association)	0.350
SLC2A5	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC35D3	ERLIN2	psi-mi:“MI:0914”(association)	0.350
SLC35E2A	ADCY3	psi-mi:“MI:0914”(association)	0.350
TLX3	THTPA	psi-mi:“MI:0915”(physical association)	0.000
THTPA		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (78): DIMT1 (Affinity Capture-MS), GTPBP6 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS), CLPX (Affinity Capture-MS), WDR59 (Affinity Capture-MS), TUBA1A (Affinity Capture-MS), ITIH3 (Affinity Capture-MS), THTPA (Affinity Capture-MS), THTPA (Affinity Capture-MS), CLPX (Affinity Capture-MS), ARF6 (Affinity Capture-MS), ITIH3 (Affinity Capture-MS), FAM127A (Affinity Capture-MS), THTPA (Affinity Capture-MS), THTPA (Affinity Capture-MS)

ESM2 similar proteins: A5PK74, A6H751, B3STU3, D3ZBP4, D4ABH7, E2RDP2, F1MH07, O00411, O95382, P48760, P49753, Q05932, Q1L5Z9, Q29S19, Q2VPK5, Q3U269, Q3U5Q7, Q4KMJ1, Q58CQ5, Q5SPB6, Q643R3, Q66H85, Q684M2, Q68DD2, Q68G58, Q6ICH7, Q6NVG1, Q6PAT0, Q76MJ5, Q80UU1, Q84MC1, Q84QC1, Q86TL0, Q8BKF1, Q8GY54, Q8IUH8, Q8NFF5, Q8R3J5, Q8TDZ2, Q8VDP3

Diamond homologs: Q8CGV7, Q8JZL3, Q8MKF1, Q9BGW0, Q9BU02

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	479
Likely benign	74
Benign	21

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
487556	NM_033400.3(ZFHX2):c.5738G>A (p.Arg1913Lys)	Pathogenic

SpliceAI

825 predictions. Top by Δscore:

Variant	Effect	Δscore
14:23557310:G:GT	donor_gain	1.0000
14:23558690:TGTA:T	acceptor_loss	1.0000
14:23558691:GTAG:G	acceptor_loss	1.0000
14:23558692:TAGGT:T	acceptor_loss	1.0000
14:23558694:GGT:G	acceptor_gain	1.0000
14:23559846:GGGGC:G	acceptor_gain	1.0000
14:23559847:GGGC:G	acceptor_gain	1.0000
14:23559848:GGC:G	acceptor_gain	1.0000
14:23559849:GC:G	acceptor_gain	1.0000
14:23559849:GCCTA:G	acceptor_loss	1.0000
14:23559850:CC:C	acceptor_gain	1.0000
14:23559851:C:CC	acceptor_gain	1.0000
14:23559857:A:AC	acceptor_gain	1.0000
14:23559932:GCTCA:G	donor_loss	1.0000
14:23559933:CTCA:C	donor_loss	1.0000
14:23559934:TCA:T	donor_loss	1.0000
14:23559935:CAC:C	donor_loss	1.0000
14:23559936:ACCTT:A	donor_loss	1.0000
14:23559937:C:A	donor_loss	1.0000
14:23560251:AAACC:A	donor_loss	1.0000
14:23560252:AACCT:A	donor_loss	1.0000
14:23560254:C:CG	donor_loss	1.0000
14:23556989:GAGTA:G	donor_gain	0.9900
14:23557300:GCTTG:G	donor_gain	0.9900
14:23558693:A:AG	acceptor_gain	0.9900
14:23558694:G:GG	acceptor_gain	0.9900
14:23558694:GGTGT:G	acceptor_gain	0.9900
14:23559857:A:C	acceptor_gain	0.9900
14:23560035:CT:C	acceptor_gain	0.9900
14:23560037:C:CC	acceptor_gain	0.9900

AlphaMissense

1463 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:23556791:T:C	F12L	0.987
14:23556793:C:A	F12L	0.987
14:23556793:C:G	F12L	0.987
14:23557208:T:C	F151L	0.984
14:23557210:T:A	F151L	0.984
14:23557210:T:G	F151L	0.984
14:23556941:T:A	W62R	0.982
14:23556941:T:C	W62R	0.982
14:23556952:A:C	K65N	0.973
14:23556952:A:T	K65N	0.973
14:23556943:G:C	W62C	0.970
14:23556943:G:T	W62C	0.970
14:23558726:G:C	K193N	0.969
14:23558726:G:T	K193N	0.969
14:23556792:T:C	F12S	0.968
14:23556784:G:C	E9D	0.966
14:23556784:G:T	E9D	0.966
14:23556866:G:C	D37H	0.965
14:23556867:A:C	D37A	0.961
14:23556948:T:C	L64P	0.961
14:23557118:T:C	F121L	0.961
14:23557120:T:A	F121L	0.961
14:23557120:T:G	F121L	0.961
14:23556878:G:C	D41H	0.956
14:23556868:C:A	D37E	0.955
14:23556868:C:G	D37E	0.955
14:23558736:T:G	Y197D	0.955
14:23557119:T:C	F121S	0.953
14:23556880:C:A	D41E	0.952
14:23556880:C:G	D41E	0.952

dbSNP variants (sampled 300 via entrez): RS1000070652 (14:23521059 A>G), RS1000180700 (14:23516573 A>G), RS1000308389 (14:23526376 C>T), RS1000375875 (14:23550211 T>C), RS1000420254 (14:23520965 T>C), RS1000476809 (14:23550969 C>T), RS1000481365 (14:23532123 C>T), RS1000514459 (14:23518186 G>A), RS1000546550 (14:23524446 C>T), RS1000577393 (14:23556646 A>G,T), RS1000586695 (14:23517775 C>T), RS1000718292 (14:23530530 G>A), RS1000788397 (14:23511891 C>G,T), RS1000813340 (14:23530774 T>C), RS1000917911 (14:23524768 A>C)

Disease associations

OMIM: gene MIM:611612 | 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

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
sodium arsenate	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Valproic Acid	decreases expression	1
Cyclosporine	decreases expression	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KU09	HeLa SilenciX THTPA	Cancer cell line	Female

Clinical trials (associated diseases)

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