THAP9

Summary

THAP9 (THAP domain containing 9, HGNC:23192) is a protein-coding gene on chromosome 4q21.22, encoding DNA transposase THAP9 (Q9H5L6). Active transposase that specifically recognizes the bipartite 5’-TXXGGGX(A/T)-3’ consensus motif and mediates transposition.

Enables sequence-specific DNA binding activity and transposase activity. Involved in DNA integration and DNA transposition. Predicted to be located in nucleoplasm.

Source: NCBI Gene 79725 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 112 total
• MANE Select transcript: NM_024672

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23192
Approved symbol	THAP9
Name	THAP domain containing 9
Location	4q21.22
Locus type	gene with protein product
Status	Approved
Aliases	FLJ34093
Ensembl gene	ENSG00000168152
Ensembl biotype	protein_coding
OMIM	612537
Entrez	79725

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 nonsense_mediated_decay, 1 protein_coding

ENST00000302236, ENST00000505901, ENST00000506208, ENST00000509353, ENST00000514244, ENST00000514440

RefSeq mRNA: 2 — MANE Select: NM_024672 NM_001317776, NM_024672

CCDS: CCDS3598

Canonical transcript exons

ENST00000302236 — 5 exons

Exon	Start	End
ENSE00001150266	82916944	82919969
ENSE00001246538	82904736	82904931
ENSE00001246544	82900735	82900882
ENSE00003614950	82906324	82906627
ENSE00003682600	82907785	82907935

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 90.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.6254 / max 405.9647, expressed in 1535 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48587	3.9912	1279
48589	0.9999	221
203270	0.9130	482
48588	0.6876	264
48590	0.5512	138
48592	0.2622	76
48591	0.2202	68

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	90.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.76	gold quality
male germ cell	CL:0000015	86.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.46	gold quality
ventricular zone	UBERON:0003053	83.50	gold quality
right testis	UBERON:0004534	83.13	gold quality
left testis	UBERON:0004533	82.32	gold quality
ganglionic eminence	UBERON:0004023	82.12	gold quality
testis	UBERON:0000473	81.60	gold quality
calcaneal tendon	UBERON:0003701	80.81	gold quality
hindlimb stylopod muscle	UBERON:0004252	79.84	gold quality
biceps brachii	UBERON:0001507	79.43	gold quality
secondary oocyte	CL:0000655	79.16	gold quality
muscle of leg	UBERON:0001383	77.85	gold quality
gastrocnemius	UBERON:0001388	77.84	gold quality
adrenal tissue	UBERON:0018303	77.15	gold quality
muscle organ	UBERON:0001630	75.56	gold quality
corpus callosum	UBERON:0002336	75.55	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	74.50	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	74.44	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	74.10	gold quality
cortical plate	UBERON:0005343	73.48	gold quality
islet of Langerhans	UBERON:0000006	73.07	gold quality
right lobe of thyroid gland	UBERON:0001119	72.78	gold quality
tendon	UBERON:0000043	71.59	gold quality
right lobe of liver	UBERON:0001114	71.46	gold quality
thyroid gland	UBERON:0002046	71.33	gold quality
left lobe of thyroid gland	UBERON:0001120	71.17	gold quality
left ovary	UBERON:0002119	71.11	gold quality
spinal cord	UBERON:0002240	71.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.64

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
IL21
IL9
SPI1

miRNA regulators (miRDB)

55 targeting THAP9, 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-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-5190	99.15	67.76	1234

Literature-anchored findings (GeneRIF, showing 5)

• results indicate that human THAP9 is an active DNA transposase that, although “domesticated,” still retains the catalytic activity to mobilize P transposable elements across species (PMID:23349291)
• THAP9-AS1/miR-133b/SOX4 positive feedback loop facilitates the progression of esophageal squamous cell carcinoma. (PMID:33854048)
• Oligomerization of THAP9 Transposase via Amino-Terminal Domains. (PMID:34033475)
• THAP9 Transposase Cleaves DNA via Conserved Acidic Residues in an RNaseH-Like Domain. (PMID:34072453)
• THAP9-AS1 Promotes Tumorigenesis and Reduces ROS Generation through the JAK2/STAT3 Signaling Pathway by Increasing SOCS3 Promoter Methylation in Osteosarcoma. (PMID:34691358)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

DNA transposase THAP9 — Q9H5L6 (reviewed: Q9H5L6)

Alternative names: THAP domain-containing protein 9

All UniProt accessions (6): D6R957, D6RCT5, D6REM3, Q9H5L6, F2Z371, H0Y9F3

UniProt curated annotations — full annotation on UniProt →

Function. Active transposase that specifically recognizes the bipartite 5’-TXXGGGX(A/T)-3’ consensus motif and mediates transposition.

Miscellaneous. Able to mediate mobilization of P-elements when transfected in Drosophila.

RefSeq proteins (2): NP_001304705, NP_078948* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006612	THAP_Znf	Domain
IPR021896	THAP9-like_HTH	Domain
IPR038441	THAP_Znf_sf	Homologous_superfamily
IPR048365	TNP-like_RNaseH_N	Domain
IPR048366	TNP-like_GBD	Domain
IPR048367	TNP-like_RNaseH_C	Domain
IPR055035	THAP9_C	Domain

Pfam: PF05485, PF12017, PF21787, PF21788, PF21789, PF22824

UniProt features (10 total): sequence variant 4, sequence conflict 3, chain 1, zinc finger region 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H5L6-F1	73.49	0.24

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 60 (showing top): GOBP_DNA_INTEGRATION, chr4q21, TGGAAA_NFAT_Q4_01, GOBP_DNA_METABOLIC_PROCESS, GOBP_DNA_RECOMBINATION, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_TRANSPOSITION, GOMF_CATALYTIC_ACTIVITY_ACTING_ON_DNA, TAVAZOIE_METASTASIS, KRAS.600.LUNG.BREAST_UP.V1_DN, KRAS.LUNG_UP.V1_DN, BANP_TARGET_GENES, E2F2_TARGET_GENES, ELF2_TARGET_GENES, NFE2L1_TARGET_GENES

GO Biological Process (5): DNA recombination (GO:0006310), DNA transposition (GO:0006313), DNA integration (GO:0015074), endothelial cell proliferation (GO:0001935), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (8): DNA binding (GO:0003677), transposase activity (GO:0004803), zinc ion binding (GO:0008270), transferase activity (GO:0016740), sequence-specific DNA binding (GO:0043565), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	2
DNA recombination	1
transposition	1
epithelial cell proliferation	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
nucleic acid binding	1
catalytic activity, acting on DNA	1
transition metal ion binding	1
catalytic activity	1
DNA binding	1
transcription cis-regulatory region binding	1
regulation of DNA-templated transcription	1
transcription regulator activity	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

450 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
THAP9	PGBD5	Q8N414	789
THAP9	THAP12	O43422	607
THAP9	THAP10	Q9P2Z0	599
THAP9	HARBI1	Q96MB7	589
THAP9	THAP8	Q8NA92	582
THAP9	A0A1B0GW23	A0A1B0GW23	573
THAP9	PGBD2	Q6P3X8	555
THAP9	THAP11	Q96EK4	546
THAP9	GIN1	Q9NXP7	531
THAP9	PGBD1	Q96JS3	530
THAP9	THAP1	Q9NVV9	517
THAP9	ZBED8	Q8IZ13	477
THAP9	MPHOSPH6	Q99547	471
THAP9	SETMAR	Q53H47	469
THAP9	DBF4B	Q8NFT6	465

IntAct

14 interactions, top by confidence:

A	B	Type	Score
rep	THAP9	psi-mi:“MI:0915”(physical association)	0.560
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
KCTD17	CBX4	psi-mi:“MI:0914”(association)	0.530
Kctd5		psi-mi:“MI:0914”(association)	0.350
MRPL50	MRPL43	psi-mi:“MI:0914”(association)	0.350
MRPL9	MRPL43	psi-mi:“MI:0914”(association)	0.350
KCTD17	CBX4	psi-mi:“MI:0914”(association)	0.350
KCTD17	PXDNL	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): THAP9 (Affinity Capture-MS), THAP9 (Affinity Capture-MS), THAP9 (Affinity Capture-MS), THAP9 (Affinity Capture-MS), THAP9 (Affinity Capture-MS), THAP9 (Affinity Capture-MS), THAP9 (Affinity Capture-MS), THAP9 (Affinity Capture-MS), THAP9 (Affinity Capture-MS), THAP9 (Two-hybrid), THAP9 (Two-hybrid)

ESM2 similar proteins: A3KMX0, A4IFA3, A4IGY9, A4Z943, A4Z944, B8QB46, D2EAC2, E1C2V1, O43422, O60290, P10911, P35125, P86452, Q13075, Q2NKX8, Q3UPF5, Q49AG3, Q5FWF4, Q5SVZ6, Q5T890, Q5TKR9, Q6DJS0, Q6EKJ0, Q6R2W3, Q6YI93, Q7Z2W4, Q80WE4, Q86UP8, Q86VD1, Q8BZ21, Q8N8K9, Q8QMP8, Q8TDB6, Q8WML3, Q92794, Q96JM7, Q96JS3, Q99388, Q99NI3, Q9CUX1

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	106
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1213 predictions. Top by Δscore:

Variant	Effect	Δscore
4:82900883:G:GG	donor_gain	1.0000
4:82906320:ATAG:A	acceptor_loss	1.0000
4:82906321:TA:T	acceptor_loss	1.0000
4:82906322:A:G	acceptor_loss	1.0000
4:82906623:TTCAG:T	donor_loss	1.0000
4:82906624:TCAG:T	donor_loss	1.0000
4:82906625:CAG:C	donor_loss	1.0000
4:82906626:AGGT:A	donor_loss	1.0000
4:82906627:GGTA:G	donor_loss	1.0000
4:82906628:G:A	donor_loss	1.0000
4:82906629:T:G	donor_loss	1.0000
4:82900859:G:GT	donor_gain	0.9900
4:82900880:CCA:C	donor_gain	0.9900
4:82900881:CA:C	donor_gain	0.9900
4:82900892:G:GT	donor_gain	0.9900
4:82901123:A:T	donor_gain	0.9900
4:82906318:TCATA:T	acceptor_gain	0.9900
4:82906319:CATAG:C	acceptor_gain	0.9900
4:82906320:ATAGA:A	acceptor_gain	0.9900
4:82906321:TAG:T	acceptor_gain	0.9900
4:82906322:A:AG	acceptor_gain	0.9900
4:82906322:AGA:A	acceptor_gain	0.9900
4:82906323:G:GG	acceptor_gain	0.9900
4:82907932:GAAC:G	donor_gain	0.9900
4:82907936:G:GG	donor_gain	0.9900
4:82900843:ACACC:A	donor_gain	0.9800
4:82900878:CACCA:C	donor_gain	0.9800
4:82900879:ACCA:A	donor_gain	0.9800
4:82900880:CCAG:C	donor_loss	0.9800
4:82900881:CAG:C	donor_loss	0.9800

AlphaMissense

5973 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:82904767:T:A	W38R	0.999
4:82904767:T:C	W38R	0.999
4:82904839:T:C	C62R	0.999
4:82900815:T:C	C5R	0.998
4:82900878:C:G	H26D	0.998
4:82904769:G:C	W38C	0.998
4:82904769:G:T	W38C	0.998
4:82904852:T:C	F66S	0.998
4:82904738:T:C	F28S	0.997
4:82904768:G:C	W38S	0.997
4:82904812:T:A	W53R	0.997
4:82904812:T:C	W53R	0.997
4:82904839:T:A	C62S	0.997
4:82904840:G:C	C62S	0.997
4:82904759:G:C	R35P	0.996
4:82904841:T:G	C62W	0.996
4:82904851:T:C	F66L	0.996
4:82904853:T:A	F66L	0.996
4:82904853:T:G	F66L	0.996
4:82900815:T:A	C5S	0.995
4:82900816:G:A	C5Y	0.995
4:82900816:G:C	C5S	0.995
4:82900817:C:G	C5W	0.995
4:82900830:T:C	C10R	0.995
4:82904837:T:C	L61P	0.995
4:82904912:C:A	P86H	0.995
4:82900875:T:C	F25L	0.994
4:82900877:C:A	F25L	0.994
4:82900877:C:G	F25L	0.994
4:82904837:T:A	L61Q	0.994

dbSNP variants (sampled 300 via entrez): RS1000019032 (4:82900290 T>C), RS1000154176 (4:82899867 A>C), RS1000224887 (4:82919785 A>G,T), RS1000554053 (4:82912486 A>G), RS1000859753 (4:82908996 T>C), RS1000920858 (4:82902174 T>C), RS1000943217 (4:82905075 TA>T,TAA), RS1001078565 (4:82908700 T>G), RS1001095538 (4:82905414 CTG>C), RS1001182844 (4:82920083 TTTG>T), RS1001193035 (4:82907475 A>G), RS1001327965 (4:82919751 G>C,T), RS1001376284 (4:82901879 A>T), RS1001849434 (4:82919856 T>G), RS1001880703 (4:82919559 A>C,T)

Disease associations

OMIM: gene MIM:612537 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012490_87	Femur bone mineral density x serum urate levels interaction	3.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	7
trichostatin A	decreases expression, affects cotreatment	3
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
cupric oxide	increases phosphorylation	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
clothianidin	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Sunitinib	decreases expression	1
Leflunomide	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ethyl Methanesulfonate	increases expression	1
Folic Acid	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Tretinoin	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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