THAP3

Summary

THAP3 (THAP domain containing 3, HGNC:20855) is a protein-coding gene on chromosome 1p36.31, encoding THAP domain-containing protein 3 (Q8WTV1). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1.

Predicted to enable DNA binding activity and zinc ion binding activity. Involved in positive regulation of transcription by RNA polymerase II.

Source: NCBI Gene 90326 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_001195753

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20855
Approved symbol	THAP3
Name	THAP domain containing 3
Location	1p36.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000041988
Ensembl biotype	protein_coding
OMIM	612532
Entrez	90326

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000054650, ENST00000307896, ENST00000377627, ENST00000472925, ENST00000480647, ENST00000484669, ENST00000484676, ENST00000487819, ENST00000866303, ENST00000866304, ENST00000866305, ENST00000866306, ENST00000922198, ENST00000922199, ENST00000922200, ENST00000953195

RefSeq mRNA: 8 — MANE Select: NM_001195753 NM_001195752, NM_001195753, NM_001394496, NM_001394497, NM_001394498, NM_001394499, NM_001394500, NM_138350

CCDS: CCDS55572, CCDS55573, CCDS86

Canonical transcript exons

ENST00000054650 — 6 exons

Exon	Start	End
ENSE00001402591	6625150	6625292
ENSE00001474647	6624868	6624954
ENSE00002956509	6632796	6633562
ENSE00003406981	6628499	6628691
ENSE00003477092	6630288	6630353
ENSE00003674101	6632391	6632495

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 91.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.8813 / max 93.0240, expressed in 1784 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
413	6.9615	1766
412	0.9197	310

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	91.59	gold quality
lower esophagus mucosa	UBERON:0035834	89.97	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.16	gold quality
cerebellar hemisphere	UBERON:0002245	87.97	gold quality
mucosa of transverse colon	UBERON:0004991	87.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.89	gold quality
cerebellar cortex	UBERON:0002129	87.80	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.70	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.50	gold quality
endocervix	UBERON:0000458	87.49	gold quality
lower esophagus	UBERON:0013473	87.49	gold quality
right adrenal gland cortex	UBERON:0035827	87.44	gold quality
cortical plate	UBERON:0005343	87.34	gold quality
granulocyte	CL:0000094	87.19	gold quality
right adrenal gland	UBERON:0001233	87.17	gold quality
popliteal artery	UBERON:0002250	87.14	gold quality
tibial artery	UBERON:0007610	87.13	gold quality
frontal pole	UBERON:0002795	87.08	silver quality
hindlimb stylopod muscle	UBERON:0004252	87.07	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.01	gold quality
body of uterus	UBERON:0009853	86.92	gold quality
aorta	UBERON:0000947	86.72	gold quality
right coronary artery	UBERON:0001625	86.62	gold quality
right lobe of thyroid gland	UBERON:0001119	86.61	gold quality
gastrocnemius	UBERON:0001388	86.61	gold quality
descending thoracic aorta	UBERON:0002345	86.59	gold quality
ascending aorta	UBERON:0001496	86.45	gold quality
thoracic aorta	UBERON:0001515	86.44	gold quality
right frontal lobe	UBERON:0002810	86.33	gold quality
left adrenal gland	UBERON:0001234	86.32	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-110499	no	36.17
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting THAP3, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-6512-5P	98.76	69.29	1195
HSA-MIR-6516-5P	98.42	70.19	1551
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-1263	98.13	69.18	459
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-6511A-3P	97.60	66.61	713
HSA-MIR-6511B-3P	97.60	66.61	713
HSA-MIR-3200-5P	97.34	65.97	826
HSA-MIR-6854-3P	90.99	65.18	155

Literature-anchored findings (GeneRIF, showing 1)

• THAP3 recruits SMYD3 to OXPHOS genes and epigenetically promotes mitochondrial respiration in hepatocellular carcinoma. (PMID:38664231)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-69l10.4	ENSDARG00000098036
danio_rerio	si:dkey-50i6.5	ENSDARG00000101320
mus_musculus	Thap3	ENSMUSG00000039759
rattus_norvegicus	Thap3	ENSRNOG00000026840
drosophila_melanogaster	CG13894	FBGN0035157

Paralogs (7): THAP1 (ENSG00000131931), ARL14EP (ENSG00000152219), THAP8 (ENSG00000161277), THAP2 (ENSG00000173451), THAP6 (ENSG00000174796), THAP7 (ENSG00000184436), ARL14EPL (ENSG00000268223)

Protein

Protein identifiers

THAP domain-containing protein 3 — Q8WTV1 (reviewed: Q8WTV1)

All UniProt accessions (3): Q8WTV1, K7EIZ2, R4GNH0

UniProt curated annotations — full annotation on UniProt →

Function. Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1.

Subunit / interactions. Component of a THAP1/THAP3-HCFC1-OGT complex that contains at least, either THAP1 or THAP3, HCFC1 and OGT. Interacts directly with OGT and HCFC1 (via its HBM).

Tissue specificity. Highly expressed in heart, skeletal muscle and placenta. Weaker expression in brain, kidney and liver.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8WTV1-1	1	yes
Q8WTV1-3	2
Q8WTV1-4	3

RefSeq proteins (8): NP_001182681, NP_001182682, NP_001381425, NP_001381426, NP_001381427, NP_001381428, NP_001381429, NP_612359 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006612	THAP_Znf	Domain
IPR026520	THAP3	Family

Pfam: PF05485

UniProt features (13 total): splice variant 4, mutagenesis site 3, chain 1, zinc finger region 1, sequence conflict 1, region of interest 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WTV1-F1	71.57	0.37

Functional residue map

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

Post-translational modifications (1): 122

Mutagenesis-validated functional residues (3):

Position	Phenotype
178	abolishes interaction with hcfc1.
180	abolishes interaction with hcfc1.
177–180	abolishes interaction with hcfc1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 50 (showing top): DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, RAY_TUMORIGENESIS_BY_ERBB2_CDC25A_DN, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_DN, chr1p36, GOBP_POSITIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, WAKABAYASHI_ADIPOGENESIS_PPARG_BOUND_8D, ALK_DN.V1_UP, PRKDC_TARGET_GENES, SETD7_TARGET_GENES, UBN1_TARGET_GENES, ZNF423_TARGET_GENES, ZNF711_TARGET_GENES, ZNF843_TARGET_GENES, ZSCAN30_TARGET_GENES

GO Biological Process (1): positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (4): DNA binding (GO:0003677), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
nucleic acid binding	1
transition metal ion binding	1
binding	1
cation binding	1

Protein interactions and networks

STRING

370 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
THAP3	THAP12	O43422	882
THAP3	THAP11	Q96EK4	877
THAP3	DNAJC11	Q9NVH1	625
THAP3	THAP6	Q8TBB0	621
THAP3	THAP4	Q8WY91	574
THAP3	THAP10	Q9P2Z0	570
THAP3	RRM1	P23921	537
THAP3	THAP8	Q8NA92	490
THAP3	PAWR	Q96IZ0	469
THAP3	OGT	O15294	459
THAP3	KLHL21	Q9UJP4	424
THAP3	HCFC1	P51610	405
THAP3	TNFRSF25	P78507	385
THAP3	ZNF251	Q9BRH9	373
THAP3	SZRD1	Q7Z422	370

IntAct

81 interactions, top by confidence:

A	B	Type	Score
GTF2H4	GTF2H1	psi-mi:“MI:0914”(association)	0.670
THAP3	GTF2H4	psi-mi:“MI:0915”(physical association)	0.620
NUTF2	THAP3	psi-mi:“MI:0915”(physical association)	0.560
THAP3	UBL5	psi-mi:“MI:0915”(physical association)	0.560
CHAT	THAP3	psi-mi:“MI:0915”(physical association)	0.560
FGFR3	THAP3	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	THAP3	psi-mi:“MI:0915”(physical association)	0.560
LSAMP	THAP3	psi-mi:“MI:0915”(physical association)	0.560
NDUFS1	THAP3	psi-mi:“MI:0915”(physical association)	0.560
POLR2A	THAP3	psi-mi:“MI:0915”(physical association)	0.560
PKN1	THAP3	psi-mi:“MI:0915”(physical association)	0.560
RAC1	THAP3	psi-mi:“MI:0915”(physical association)	0.560
SNRPB	THAP3	psi-mi:“MI:0915”(physical association)	0.560
TYR	THAP3	psi-mi:“MI:0915”(physical association)	0.560
UQCRB	THAP3	psi-mi:“MI:0915”(physical association)	0.560
UQCRC1	THAP3	psi-mi:“MI:0915”(physical association)	0.560
VBP1	THAP3	psi-mi:“MI:0915”(physical association)	0.560
EZR	THAP3	psi-mi:“MI:0915”(physical association)	0.560
	THAP3	psi-mi:“MI:0915”(physical association)	0.560
DNALI1	THAP3	psi-mi:“MI:0915”(physical association)	0.560
BAG6	THAP3	psi-mi:“MI:0915”(physical association)	0.560
KLF11	THAP3	psi-mi:“MI:0915”(physical association)	0.560
DNAJB6	THAP3	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	THAP3	psi-mi:“MI:0915”(physical association)	0.560
TARDBP	THAP3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (85): THAP3 (Affinity Capture-MS), THAP3 (Reconstituted Complex), THAP3 (Two-hybrid), THAP3 (Affinity Capture-MS), THAP3 (Affinity Capture-RNA), THAP3 (Negative Genetic), THAP3 (Negative Genetic), THAP3 (Negative Genetic), THAP3 (Negative Genetic), THAP3 (Positive Genetic), THAP3 (Positive Genetic), THAP3 (Positive Genetic), NUTF2 (Two-hybrid), UBL5 (Two-hybrid), THAP3 (Two-hybrid)

ESM2 similar proteins: A2AGX3, A4Q9F3, A6QPH9, D3YYI7, E9PGG2, P29590, Q0P5B4, Q0VC73, Q2TBI2, Q3T0G1, Q45KJ4, Q45KJ6, Q4R7H0, Q5BJT4, Q5E9N3, Q5NVM3, Q5PPH4, Q5U208, Q5XI57, Q642B6, Q6P3Z3, Q6P9L4, Q6ZN17, Q6ZVT0, Q70EL4, Q7L4P6, Q8AVK2, Q8BJ25, Q8BUM9, Q8C6D4, Q8CDF7, Q8CE64, Q8CHW1, Q8N554, Q8NA92, Q8NFT6, Q8TC41, Q8VCZ3, Q8WTV1, Q8WY91

Diamond homologs: B5XCB8, Q0IHI7, Q0P5B4, Q1JPT7, Q1RMM0, Q2TBI2, Q3T0G1, Q4R3Q6, Q4R7M0, Q5RCE4, Q5U208, Q5U560, Q5ZHN5, Q642B6, Q6DDT6, Q6DIN8, Q6P3Z3, Q7Z6K1, Q8BJ25, Q8CHW1, Q8WTV1, Q8WY91, Q9D305, Q9H0W7, Q9NVV9, Q8NA92, Q9H5L6, Q8VCZ3, Q9BT49, Q8TBB0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

988 predictions. Top by Δscore:

Variant	Effect	Δscore
1:6625272:G:GT	donor_gain	1.0000
1:6625290:CCG:C	donor_gain	1.0000
1:6625292:GGT:G	donor_loss	1.0000
1:6625293:G:GG	donor_gain	1.0000
1:6625293:GT:G	donor_loss	1.0000
1:6628494:CTTA:C	acceptor_loss	1.0000
1:6628495:TTA:T	acceptor_loss	1.0000
1:6628496:TA:T	acceptor_loss	1.0000
1:6628497:A:AG	acceptor_gain	1.0000
1:6628498:G:GG	acceptor_gain	1.0000
1:6628689:CAGGT:C	donor_loss	1.0000
1:6625288:CACCG:C	donor_gain	0.9900
1:6625289:ACCG:A	donor_gain	0.9900
1:6625291:CG:C	donor_gain	0.9900
1:6625292:GG:G	donor_gain	0.9900
1:6628494:CTTAG:C	acceptor_gain	0.9900
1:6628495:TTAGG:T	acceptor_gain	0.9900
1:6628496:TAG:T	acceptor_gain	0.9900
1:6628497:AG:A	acceptor_gain	0.9900
1:6628497:AGGTT:A	acceptor_gain	0.9900
1:6628498:G:T	acceptor_gain	0.9900
1:6628498:GG:G	acceptor_gain	0.9900
1:6628498:GGT:G	acceptor_gain	0.9900
1:6628498:GGTT:G	acceptor_gain	0.9900
1:6628498:GGTTT:G	acceptor_gain	0.9900
1:6630286:A:AG	acceptor_gain	0.9900
1:6630287:G:GG	acceptor_gain	0.9900
1:6633002:G:GT	donor_gain	0.9900
1:6628490:T:TA	acceptor_gain	0.9800
1:6628493:CCTTA:C	acceptor_gain	0.9800

AlphaMissense

1571 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:6625285:T:C	F23L	1.000
1:6625287:C:A	F23L	1.000
1:6625287:C:G	F23L	1.000
1:6628533:T:A	W37R	1.000
1:6628533:T:C	W37R	1.000
1:6628535:G:C	W37C	1.000
1:6628535:G:T	W37C	1.000
1:6628599:T:C	F59L	1.000
1:6628600:T:C	F59S	1.000
1:6628601:C:A	F59L	1.000
1:6628601:C:G	F59L	1.000
1:6625231:T:C	C5R	0.999
1:6625288:C:G	H24D	0.999
1:6628501:T:C	F26S	0.999
1:6628585:T:A	I54N	0.999
1:6628587:T:A	C55S	0.999
1:6628587:T:C	C55R	0.999
1:6628588:G:A	C55Y	0.999
1:6628588:G:C	C55S	0.999
1:6628589:C:G	C55W	0.999
1:6628600:T:G	F59C	0.999
1:6628659:C:A	P79T	0.999
1:6628659:C:T	P79S	0.999
1:6628660:C:A	P79H	0.999
1:6628668:T:C	F82L	0.999
1:6628670:C:A	F82L	0.999
1:6628670:C:G	F82L	0.999
1:6625286:T:C	F23S	0.998
1:6625288:C:A	H24N	0.998
1:6628500:T:C	F26L	0.998

dbSNP variants (sampled 300 via entrez): RS1000102480 (1:6628854 C>A), RS1000160269 (1:6634153 G>A,C), RS1000165263 (1:6624830 C>A), RS1000851247 (1:6633613 A>C), RS1001039185 (1:6624080 A>C,G), RS1001167064 (1:6625734 G>T), RS1001263963 (1:6634912 G>A), RS1001906718 (1:6634369 T>C), RS1002438719 (1:6630093 A>G), RS1002448009 (1:6629634 CT>C), RS1003159593 (1:6631926 T>C), RS1003440822 (1:6631092 C>A,T), RS1003507983 (1:6626993 G>A), RS1003641621 (1:6626409 C>G,T), RS1004005229 (1:6631078 C>T)

Disease associations

OMIM: gene MIM:612532 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010988_520	Adult body size	3.000000e-08
GCST011769_1	Schizophrenia	8.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
bisphenol A	affects cotreatment, increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	affects splicing, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
abrine	increases expression	1
bisphenol S	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Valproic Acid	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A7L4	SEES3-1V human THAP3, clone1	Embryonic stem cell	Male
CVCL_A7L5	SEES3-1V human THAP3, clone2	Embryonic stem cell	Male
CVCL_A7L6	SEES3-1V human THAP3, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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