THAP5

Summary

THAP5 (THAP domain containing 5, HGNC:23188) is a protein-coding gene on chromosome 7q31.1, encoding THAP domain-containing protein 5 (Q7Z6K1). Has sequence-specific DNA-binding activity and can function as transcriptional repressor (in vitro).

Enables protease binding activity. Involved in negative regulation of cell cycle and negative regulation of transcription by RNA polymerase II. Located in chromatin and nucleoplasm.

Source: NCBI Gene 168451 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 60 total
• MANE Select transcript: NM_001130475

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23188
Approved symbol	THAP5
Name	THAP domain containing 5
Location	7q31.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp313O1132
Ensembl gene	ENSG00000177683
Ensembl biotype	protein_coding
OMIM	612534
Entrez	168451

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding_CDS_not_defined, 3 protein_coding, 1 retained_intron

ENST00000313516, ENST00000412935, ENST00000415914, ENST00000438865, ENST00000446771, ENST00000468884, ENST00000484452, ENST00000493722

RefSeq mRNA: 5 — MANE Select: NM_001130475 NM_001130475, NM_001287598, NM_001287599, NM_001287601, NM_182529

CCDS: CCDS34734, CCDS47687

Canonical transcript exons

ENST00000415914 — 3 exons

Exon	Start	End
ENSE00001706172	108562132	108565105
ENSE00001718704	108569490	108569706
ENSE00003595442	108565830	108566022

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 95.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.8349 / max 208.8044, expressed in 1804 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85693	27.8349	1804
85692	0.3484	123
85691	0.0632	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	95.72	gold quality
endothelial cell	CL:0000115	94.39	gold quality
epithelial cell of pancreas	CL:0000083	93.62	gold quality
epithelium of nasopharynx	UBERON:0001951	92.55	gold quality
germinal epithelium of ovary	UBERON:0001304	92.12	gold quality
palpebral conjunctiva	UBERON:0001812	91.86	gold quality
inferior vagus X ganglion	UBERON:0005363	91.78	gold quality
corpus callosum	UBERON:0002336	91.65	gold quality
subthalamic nucleus	UBERON:0001906	91.11	gold quality
layer of synovial tissue	UBERON:0007616	90.91	gold quality
dorsal plus ventral thalamus	UBERON:0001897	90.80	gold quality
islet of Langerhans	UBERON:0000006	90.39	gold quality
adrenal tissue	UBERON:0018303	90.39	gold quality
medulla oblongata	UBERON:0001896	90.21	gold quality
trigeminal ganglion	UBERON:0001675	90.03	gold quality
superior vestibular nucleus	UBERON:0007227	90.02	gold quality
amniotic fluid	UBERON:0000173	90.00	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.94	gold quality
pons	UBERON:0000988	89.84	gold quality
lateral nuclear group of thalamus	UBERON:0002736	89.40	gold quality
tendon	UBERON:0000043	89.30	gold quality
oviduct epithelium	UBERON:0004804	89.26	gold quality
cortical plate	UBERON:0005343	89.03	gold quality
ventricular zone	UBERON:0003053	88.98	gold quality
dorsal root ganglion	UBERON:0000044	88.85	gold quality
synovial joint	UBERON:0002217	88.83	gold quality
kidney epithelium	UBERON:0004819	88.83	gold quality
ventral tegmental area	UBERON:0002691	88.56	gold quality
ganglionic eminence	UBERON:0004023	88.41	gold quality
embryo	UBERON:0000922	88.40	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)

108 targeting THAP5, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-1297	99.91	73.41	3162

Literature-anchored findings (GeneRIF, showing 3)

• THAP5 and its regulation by Omi/HtrA2 provide a new link between cell cycle control and apoptosis in cardiomyocytes (PMID:19502560)
• this work suggests that THAP5 is a DNA-binding protein and a transcriptional repressor. THAP5 has a pro-apoptotic function and it was induced in melanoma cells under conditions that promoted cell death. (PMID:21110952)
• Study identified Abro1 as a specific interactor of THAP5, a zinc finger transcription factor that is involved in G2/M control and apoptosis. (PMID:21195082)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

THAP domain-containing protein 5 — Q7Z6K1 (reviewed: Q7Z6K1)

All UniProt accessions (2): C9JIH7, Q7Z6K1

UniProt curated annotations — full annotation on UniProt →

Function. Has sequence-specific DNA-binding activity and can function as transcriptional repressor (in vitro). May be a regulator of cell cycle: THAP5 overexpression in human cell lines causes cell cycle arrest at G2/M phase.

Subunit / interactions. Interacts with HTRA2; under apoptotic conditions. Interacts with ABRAXAS2.

Subcellular location. Nucleus.

Tissue specificity. Detected in heart. Detected in brain and muscle (at protein level). Highly expressed in the heart. Also found in brain and skeletal muscle.

Post-translational modifications. Cleaved by HTRA2 during apoptosis.

Induction. Up-regulated both in response to UV light treatment and cisplatin, agents that cause DNA damage (at protein level).

Isoforms (2)

UniProt ID	Names	Canonical?
Q7Z6K1-1	1	yes
Q7Z6K1-2	2

RefSeq proteins (5): NP_001123947, NP_001274527, NP_001274528, NP_001274530, NP_872335 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006612	THAP_Znf	Domain
IPR052224	THAP_domain_protein	Family

Pfam: PF05485

UniProt features (7 total): chain 1, zinc finger region 1, region of interest 1, coiled-coil region 1, short sequence motif 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z6K1-F1	59.63	0.28

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 67 (showing top): USF_C, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE, ELK1_01, NUYTTEN_EZH2_TARGETS_DN, chr7q31, MGGAAGTG_GABP_B, NUYTTEN_NIPP1_TARGETS_DN, GOMF_PROTEASE_BINDING, MARTENS_TRETINOIN_RESPONSE_DN, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, JOHNSTONE_PARVB_TARGETS_3_DN, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, FOXD2_TARGET_GENES

GO Biological Process (2): negative regulation of transcription by RNA polymerase II (GO:0000122), negative regulation of cell cycle (GO:0045786)

GO Molecular Function (4): protease binding (GO:0002020), DNA binding (GO:0003677), zinc ion binding (GO:0008270), metal ion binding (GO:0046872)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cell cycle	1
negative regulation of cellular process	1
regulation of cell cycle	1
enzyme binding	1
nucleic acid binding	1
transition metal ion binding	1
cation binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
THAP5	ABRAXAS2	Q15018	657
THAP5	THAP11	Q96EK4	652
THAP5	THAP12	O43422	644
THAP5	PNPLA8	Q9NP80	617
THAP5	THAP10	Q9P2Z0	583
THAP5	DNAJB9	Q9UBS3	569
THAP5	GPR141	Q7Z602	512
THAP5	IMMP2L	Q96T52	391
THAP5	BRCC3	P46736	380
THAP5	ANKRD40	Q6AI12	375
THAP5	THAP6	Q8TBB0	362
THAP5	DBNDD2	Q9BQY9	357
THAP5	ATP6V1E1	P36543	339
THAP5	ADCYAP1R1	P41586	339
THAP5	CCDC32	Q9BV29	324

IntAct

9 interactions, top by confidence:

A	B	Type	Score
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
THAP5	SKIL	psi-mi:“MI:0915”(physical association)	0.370
P		psi-mi:“MI:0914”(association)	0.350
S	IGLL5	psi-mi:“MI:0914”(association)	0.350
WHAMMP3	EXOC5	psi-mi:“MI:0914”(association)	0.350
INSR	BLTP3B	psi-mi:“MI:0914”(association)	0.350
EXOC1	THAP5	psi-mi:“MI:0915”(physical association)	0.000
rpoH	THAP5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): THAP5 (Affinity Capture-MS), THAP5 (Affinity Capture-RNA), THAP5 (Affinity Capture-MS), THAP5 (Affinity Capture-MS), THAP5 (Positive Genetic), THAP5 (Reconstituted Complex), THAP5 (Proximity Label-MS), THAP5 (Proximity Label-MS), THAP5 (Proximity Label-MS), THAP5 (Proximity Label-MS), THAP5 (Proximity Label-MS), THAP5 (Proximity Label-MS), THAP5 (Proximity Label-MS), THAP5 (Proximity Label-MS), THAP5 (Two-hybrid)

ESM2 similar proteins: A4IGQ8, B0BLU1, B5XCB8, O75113, O75132, P14629, Q0IIM1, Q0V8G8, Q17RS7, Q1JPT7, Q1RMM0, Q28GK6, Q28J92, Q3T0G1, Q4R3Q6, Q4R7M0, Q4V7W2, Q5FWF4, Q5NVM3, Q5QJC4, Q5RCE4, Q5SZJ8, Q5U208, Q5U560, Q5ZHN5, Q6A037, Q6DDT6, Q6DIN8, Q6INS5, Q6IR68, Q6NZP1, Q6PFX2, Q6TGZ4, Q7Z6K1, Q7ZYM8, Q80XJ2, Q86VD1, Q8BMI4, Q8BZ05, Q8C4P0

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, Q8VCZ3, Q9BT49, A0PT73, A0QIQ0, A0R6J8, A1KM55, A1T297, A3PTJ4, A5U669, B2HLY1, O64527, P9WFG6, P9WFG7, Q1BEZ2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

471 predictions. Top by Δscore:

Variant	Effect	Δscore
7:108565950:A:AC	donor_gain	1.0000
7:108565951:C:CC	donor_gain	1.0000
7:108569488:A:AC	donor_gain	1.0000
7:108569489:C:CC	donor_gain	1.0000
7:108566614:C:CT	donor_gain	0.9900
7:108566615:T:TT	donor_gain	0.9900
7:108566615:TA:T	donor_gain	0.9900
7:108569503:G:C	donor_gain	0.9900
7:108569731:GTT:G	donor_gain	0.9900
7:108569732:TTT:T	donor_gain	0.9900
7:108565930:C:CT	donor_gain	0.9800
7:108565931:T:TT	donor_gain	0.9800
7:108566030:T:C	acceptor_gain	0.9800
7:108569397:A:AC	donor_gain	0.9800
7:108569398:C:CC	donor_gain	0.9800
7:108569502:AGCTT:A	donor_gain	0.9800
7:108569506:T:TA	donor_gain	0.9800
7:108565952:TGGG:T	donor_gain	0.9700
7:108569483:AACTT:A	donor_loss	0.9700
7:108569484:ACTTA:A	donor_loss	0.9700
7:108569485:CTTA:C	donor_loss	0.9700
7:108569486:TTA:T	donor_loss	0.9700
7:108569487:T:TG	donor_loss	0.9700
7:108569488:ACGGA:A	donor_loss	0.9700
7:108565105:CCT:C	acceptor_loss	0.9600
7:108565107:T:A	acceptor_loss	0.9600
7:108566020:AATC:A	acceptor_loss	0.9600
7:108566021:ATCTG:A	acceptor_loss	0.9600
7:108566022:TCTG:T	acceptor_loss	0.9600
7:108566023:C:A	acceptor_loss	0.9600

AlphaMissense

2619 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:108565988:A:G	W39R	1.000
7:108565988:A:T	W39R	1.000
7:108565861:G:T	P81Q	0.999
7:108565879:A:G	L75S	0.999
7:108565920:A:C	F61L	0.999
7:108565920:A:T	F61L	0.999
7:108565921:A:G	F61S	0.999
7:108565922:A:G	F61L	0.999
7:108565932:A:C	C57W	0.999
7:108565934:A:G	C57R	0.999
7:108565986:C:A	W39C	0.999
7:108565986:C:G	W39C	0.999
7:108569557:A:G	C5R	0.999
7:108565862:G:A	P81S	0.998
7:108565921:A:C	F61C	0.998
7:108565923:A:C	H60Q	0.998
7:108565923:A:T	H60Q	0.998
7:108565933:C:G	C57S	0.998
7:108565933:C:T	C57Y	0.998
7:108565934:A:T	C57S	0.998
7:108565954:G:T	P50H	0.998
7:108565987:C:G	W39S	0.998
7:108566020:A:G	F28S	0.998
7:108569495:A:C	F25L	0.998
7:108569495:A:T	F25L	0.998
7:108569497:A:G	F25L	0.998
7:108569555:G:C	C5W	0.998
7:108565861:G:C	P81R	0.997
7:108565862:G:T	P81T	0.997
7:108565895:A:G	W70R	0.997

dbSNP variants (sampled 300 via entrez): RS1000042795 (7:108546281 T>G), RS1000056341 (7:108552850 G>A), RS1000153138 (7:108566102 A>G), RS1000484289 (7:108565858 G>A,T), RS1000530662 (7:108541362 T>A), RS1000562377 (7:108545889 A>G), RS1000873376 (7:108553809 G>C), RS1001085553 (7:108567434 G>C), RS1001167155 (7:108559546 T>A,C), RS1001283581 (7:108568753 G>T), RS1001304037 (7:108554146 T>C), RS1001374272 (7:108571118 T>C), RS1001376627 (7:108552169 G>A), RS1001454995 (7:108560013 T>C), RS1001508720 (7:108570772 G>A)

Disease associations

OMIM: gene MIM:612534 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001286_4	Smoking behavior	2.000000e-06
GCST001286_5	Smoking behavior	3.000000e-07
GCST001286_6	Smoking behavior	9.000000e-07
GCST004032_6	JT interval (sulfonylurea treatment interaction)	5.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004318	smoking behavior
EFO:0007885	JT interval
EFO:0007922	response to sulfonylurea

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
TAK-243	increases sumoylation	1
arsenite	decreases methylation	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
jinfukang	decreases expression	1
Cadmium	increases abundance, increases expression	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Folic Acid	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Phthalic Acids	increases methylation	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases expression, decreases methylation	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation, decreases expression	1
Aflatoxin M1	decreases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases abundance, increases expression	1

Clinical trials (associated diseases)

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