THRAP3

Summary

THRAP3 (thyroid hormone receptor associated protein 3, HGNC:22964) is a protein-coding gene on chromosome 1p34.3, encoding Thyroid hormone receptor-associated protein 3 (Q9Y2W1). Involved in pre-mRNA splicing.

Enables nuclear thyroid hormone receptor binding activity; phosphoprotein binding activity; and transcription coactivator activity. Involved in positive regulation of circadian rhythm and regulation of gene expression. Acts upstream of or within positive regulation of transcription by RNA polymerase II. Located in exon-exon junction complex and nuclear speck. Part of mediator complex.

Source: NCBI Gene 9967 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 139 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_005119

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22964
Approved symbol	THRAP3
Name	thyroid hormone receptor associated protein 3
Location	1p34.3
Locus type	gene with protein product
Status	Approved
Aliases	TRAP150, BCLAF2
Ensembl gene	ENSG00000054118
Ensembl biotype	protein_coding
OMIM	603809
Entrez	9967

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 23 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000354618, ENST00000466743, ENST00000469141, ENST00000648638, ENST00000884179, ENST00000884180, ENST00000884181, ENST00000884182, ENST00000884183, ENST00000939503, ENST00000939504, ENST00000939505, ENST00000939506, ENST00000939507, ENST00000939508, ENST00000939509, ENST00000939510, ENST00000939511, ENST00000939512, ENST00000939513, ENST00000939514, ENST00000954118, ENST00000954119, ENST00000954120

RefSeq mRNA: 3 — MANE Select: NM_005119 NM_001321471, NM_001321473, NM_005119

CCDS: CCDS405

Canonical transcript exons

ENST00000354618 — 12 exons

Exon	Start	End
ENSE00000766231	36296583	36296770
ENSE00000955947	36289060	36289764
ENSE00001079144	36301553	36301696
ENSE00001079145	36300886	36301084
ENSE00001291272	36286368	36287270
ENSE00001298923	36282533	36282700
ENSE00001354450	36259382	36259484
ENSE00001402345	36303796	36305357
ENSE00001459618	36224443	36224505
ENSE00003479354	36292598	36292709
ENSE00003566879	36291374	36291546
ENSE00003660836	36293851	36293935

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 96.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 61.8941 / max 507.5059, expressed in 1822 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2164	58.7043	1822
2177	1.5853	838
2163	1.1039	810
2165	0.5006	268

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	96.97	gold quality
ventricular zone	UBERON:0003053	96.92	gold quality
calcaneal tendon	UBERON:0003701	96.84	gold quality
muscle of leg	UBERON:0001383	96.44	gold quality
ganglionic eminence	UBERON:0004023	96.24	gold quality
adrenal tissue	UBERON:0018303	96.07	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.97	gold quality
stromal cell of endometrium	CL:0002255	95.96	gold quality
lower esophagus	UBERON:0013473	95.96	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.86	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.67	gold quality
descending thoracic aorta	UBERON:0002345	95.60	gold quality
mucosa of stomach	UBERON:0001199	95.57	gold quality
right lobe of thyroid gland	UBERON:0001119	95.46	gold quality
right coronary artery	UBERON:0001625	95.46	gold quality
popliteal artery	UBERON:0002250	95.45	gold quality
tibial artery	UBERON:0007610	95.44	gold quality
cortical plate	UBERON:0005343	95.29	gold quality
tendon	UBERON:0000043	95.25	gold quality
aorta	UBERON:0000947	95.21	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.15	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.13	gold quality
left lobe of thyroid gland	UBERON:0001120	95.10	gold quality
right adrenal gland cortex	UBERON:0035827	95.10	gold quality
gall bladder	UBERON:0002110	95.02	gold quality
vagina	UBERON:0000996	94.98	gold quality
thoracic aorta	UBERON:0001515	94.98	gold quality
esophagus	UBERON:0001043	94.97	gold quality
body of uterus	UBERON:0009853	94.97	gold quality
right adrenal gland	UBERON:0001233	94.94	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10553	yes	7.08
E-MTAB-7303	no	668.59
E-MTAB-8060	no	205.60
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CNBP, MYC

miRNA regulators (miRDB)

70 targeting THRAP3, 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-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-3679-3P	99.64	69.88	1599

Literature-anchored findings (GeneRIF, showing 12)

• TFIID and human mediator coactivator (TRAP150) complexes assemble cooperatively on promoter DNA (PMID:12130544)
• THRAP3 has a rold in the DNA damage response. (PMID:22424773)
• Thrap3 could play indispensable roles in terminal differentiation of adipocytes by enhancing PPARgamma-mediated gene activation cooperatively with Helz2. (PMID:23525231)
• BTF has functions distinct from TRAP150 in regulating the subcellular distribution of mRNAs in human cells. (PMID:23778535)
• Data indicate that distinct differences in proteins becoming Poly(ADP-ribose) PARylated upon various genotoxic insults are observed, exemplified by the PARylation of RNA-processing factors THRAP3 and TAF15 under oxidative stress. (PMID:24055347)
• Thrap3 plays a crucial role in controlling diabetic gene programming and may provide opportunities for the development of new therapeutics for obesity and type 2 diabetes. (PMID:25316675)
• The data suggest a model in which TRAP150 interacts with dimeric PSF to block access of RNA to RRM2, thereby regulating the activity of PSF toward a broad set of splicing events in T cells. (PMID:26261210)
• These results indicate that THRAP3 negatively regulates SOX9 transcriptional activity as a cofactor of a SOX9 transcriptional complex during chondrogenesis. (PMID:28770354)
• Results indicate a role for the RNA processing factors THRAP3 and BCLAF1 in the regulation of the cellular DNA damage response (DDR) pathway. (PMID:29112714)
• Thrap3 promotes R-loop resolution via interaction with methylated DDX5. (PMID:34697388)
• Thrap3 promotes osteogenesis by inhibiting the degradation of Runx2. (PMID:35230719)
• Thrap3 promotes nonalcoholic fatty liver disease by suppressing AMPK-mediated autophagy. (PMID:37524868)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	thrap3b	ENSDARG00000098228
danio_rerio	thrap3a	ENSDARG00000101989
mus_musculus	Thrap3	ENSMUSG00000043962
rattus_norvegicus	Thrap3	ENSRNOG00000009977

Paralogs (2): BCLAF1 (ENSG00000029363), BCLAF3 (ENSG00000173681)

Protein

Protein identifiers

Thyroid hormone receptor-associated protein 3 — Q9Y2W1 (reviewed: Q9Y2W1)

Alternative names: BCLAF1 and THRAP3 family member 2, Thyroid hormone receptor-associated protein complex 150 kDa component

All UniProt accessions (2): A0A3B3ITZ9, Q9Y2W1

UniProt curated annotations — full annotation on UniProt →

Function. Involved in pre-mRNA splicing. Remains associated with spliced mRNA after splicing which probably involves interactions with the exon junction complex (EJC). Can trigger mRNA decay which seems to be independent of nonsense-mediated decay involving premature stop codons (PTC) recognition. May be involved in nuclear mRNA decay. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45 is proposed to sequester phosphorylated SFPQ from PTPRC/CD45 pre-mRNA in resting T-cells. Involved in cyclin-D1/CCND1 mRNA stability probably by acting as component of the SNARP complex which associates with both the 3’end of the CCND1 gene and its mRNA. Involved in response to DNA damage. Is excluced from DNA damage sites in a manner that parallels transcription inhibition; the function may involve the SNARP complex. Initially thought to play a role in transcriptional coactivation through its association with the TRAP complex; however, it is not regarded as a stable Mediator complex subunit. Cooperatively with HELZ2, enhances the transcriptional activation mediated by PPARG, maybe through the stabilization of the PPARG binding to DNA in presence of ligand. May play a role in the terminal stage of adipocyte differentiation. Plays a role in the positive regulation of the circadian clock. Acts as a coactivator of the CLOCK-BMAL1 heterodimer and promotes its transcriptional activator activity and binding to circadian target genes.

Subunit / interactions. Associated with the large multiprotein complex TRAP (Mediator complex-like). Interacts with SFPQ; the interaction is dependent on SFPQ phosphorylation at ‘Thr-687’ and inhibits binding of SFPQ to an ESS1 exonic splicing silencer element-containing RNA. Interacts with NXF1. Component of the SNARP complex which consists at least of SNIP1, SNW1, THRAP3, BCLAF1 and PNN. Associated with spliced mRNP complexes. Interacts with HELZ2 and PPARG. Interacts with CLOCK and BMAL1. Component of a MACOM-like complex, named WTAP complex, composed of WTAP, ZC3H13, CBLL1, KIAA1429, RBM15, BCLAF1 and THRAP3.

Subcellular location. Nucleus. Nucleoplasm. Nucleus speckle.

Tissue specificity. Ubiquitous.

Post-translational modifications. ADP-ribosylation during genotoxic stress promotes accumulation in nuclear speckles.

Similarity. Belongs to the BCLAF1/THRAP3 family.

RefSeq proteins (3): NP_001308400, NP_001308402, NP_005110* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029199	THRAP3_BCLAF1	Family

Pfam: PF15440

UniProt features (120 total): modified residue 51, cross-link 36, compositionally biased region 22, region of interest 5, mutagenesis site 2, initiator methionine 1, chain 1, sequence variant 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2W1-F1	46.40	0.02

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 (1): 552–559

Post-translational modifications (87): 461, 467, 470, 481, 486, 527, 551, 558, 602, 697, 705, 709, 711, 756, 759, 876, 879, 2, 17, 66 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
406	reduces phosphorylation upon dna damage; when associated with a-408.
408	reduces phosphorylation upon dna damage; when associated with a-406.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1989781	PPARA activates gene expression
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation

MSigDB gene sets: 214 (showing top): GOBP_CIRCADIAN_RHYTHM, REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_RNA_SPLICING, GOBP_POSITIVE_REGULATION_OF_MRNA_PROCESSING, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, CREBP1_Q2, GGGTGGRR_PAX4_03, GOBP_REGULATION_OF_CIRCADIAN_RHYTHM, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, MARTINEZ_RB1_TARGETS_UP, UEDA_PERIFERAL_CLOCK

GO Biological Process (11): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), nuclear-transcribed mRNA catabolic process (GO:0000956), mRNA processing (GO:0006397), circadian rhythm (GO:0007623), RNA splicing (GO:0008380), positive regulation of circadian rhythm (GO:0042753), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of mRNA splicing, via spliceosome (GO:0048026), mRNA stabilization (GO:0048255), rhythmic process (GO:0048511)

GO Molecular Function (11): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA binding (GO:0003677), transcription coregulator activity (GO:0003712), transcription coactivator activity (GO:0003713), RNA binding (GO:0003723), ATP binding (GO:0005524), nuclear vitamin D receptor binding (GO:0042809), nuclear thyroid hormone receptor binding (GO:0046966), phosphoprotein binding (GO:0051219), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), mediator complex (GO:0016592), nuclear speck (GO:0016607), extracellular exosome (GO:0070062), exon-exon junction complex (GO:0035145)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Regulation of lipid metabolism by PPARalpha	1
Adipogenesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of mRNA splicing, via spliceosome	2
RNA processing	2
positive regulation of DNA-templated transcription	2
nucleic acid binding	2
nuclear receptor binding	2
nuclear protein-containing complex	2
alternative mRNA splicing, via spliceosome	1
mRNA catabolic process	1
mRNA metabolic process	1
rhythmic process	1
circadian rhythm	1
regulation of circadian rhythm	1
positive regulation of biological process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
mRNA splicing, via spliceosome	1
positive regulation of RNA splicing	1
positive regulation of mRNA processing	1
regulation of mRNA stability	1
RNA stabilization	1
negative regulation of mRNA catabolic process	1
biological_process	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
transcription regulator activity	1
transcription coregulator activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
core mediator complex	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

2598 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
THRAP3	BCLAF1	Q9NYF8	877
THRAP3	CBLL1	Q75N03	717
THRAP3	ZC3H13	Q5T200	704
THRAP3	VIRMA	Q69YN4	689
THRAP3	RBM15	Q96T37	659
THRAP3	ERH	P70659	595
THRAP3	PNN	Q9H307	566
THRAP3	HNRNPC	P07910	544
THRAP3	BRCA1	P38398	542
THRAP3	CDK5	Q00535	535
THRAP3	PPM1G	O15355	531
THRAP3	RNASEH1	O60930	493
THRAP3	PPARG	P37231	488
THRAP3	MED16	Q9Y2X0	473
THRAP3	DDX17	Q92841	461

IntAct

367 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
FOXK2	DVL2	psi-mi:“MI:0914”(association)	0.640
PNN	CASC3	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
MTA3	KDM1A	psi-mi:“MI:0914”(association)	0.530
DLD	PDHB	psi-mi:“MI:0914”(association)	0.530
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
SNIP1	CASC3	psi-mi:“MI:0914”(association)	0.530
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
DDX6	MCRIP1	psi-mi:“MI:0914”(association)	0.510
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
ESR1		psi-mi:“MI:0914”(association)	0.460
RBM45	HNRNPDL	psi-mi:“MI:0914”(association)	0.460
FUS	DDX3X	psi-mi:“MI:0914”(association)	0.430
THRAP3	FGF12	psi-mi:“MI:0403”(colocalization)	0.430
CEP126	THRAP3	psi-mi:“MI:0915”(physical association)	0.400
ABHD12B	THRAP3	psi-mi:“MI:0915”(physical association)	0.400
THRAP3	GORAB	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (597): THRAP3 (Affinity Capture-MS), THRAP3 (Affinity Capture-MS), THRAP3 (Affinity Capture-MS), THRAP3 (Affinity Capture-MS), THRAP3 (Affinity Capture-MS), THRAP3 (Affinity Capture-MS), THRAP3 (Affinity Capture-MS), THRAP3 (Affinity Capture-MS), THRAP3 (Affinity Capture-MS), THRAP3 (Affinity Capture-MS), THRAP3 (Affinity Capture-MS), THRAP3 (Affinity Capture-MS), THRAP3 (Affinity Capture-MS), THRAP3 (Affinity Capture-MS), THRAP3 (Affinity Capture-MS)

ESM2 similar proteins: A0JNI5, A2AJT4, D3ZTQ1, O35691, O75376, P79149, Q05519, Q12872, Q14241, Q149C2, Q3USH5, Q4KKX4, Q4R6F6, Q53F19, Q568R1, Q569Z6, Q5BJ39, Q5BL56, Q5HZB6, Q5M7V8, Q5R5X0, Q5SFM8, Q5T8P6, Q5ZM19, Q60974, Q63187, Q6DFQ2, Q6NZN0, Q6PJT7, Q6WKW9, Q6ZPZ3, Q8BZR9, Q8BZX4, Q8CB77, Q8CFC7, Q8K019, Q8K3W3, Q8K3X0, Q8N2M8, Q8QG78

Diamond homologs: A2AG58, A2AJT9, Q569Z6, Q5BJ39, Q5M7V8, Q9Y2W1, Q8K019, Q9NYF8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
THRAP3	down-regulates	SFPQ	binding
CDK11B	“up-regulates activity”	THRAP3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 219 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of pyruvate dehydrogenase (PDH) complex	6	29.5×	6e-06
Signaling by Retinoic Acid	7	19.7×	8e-06
mRNA 3’-end processing	10	13.6×	7e-07
mRNA Capping	5	13.1×	2e-03
Transport of Mature Transcript to Cytoplasm	5	13.1×	2e-03
Formation of the Early Elongation Complex	5	11.6×	2e-03
Formation of the HIV-1 Early Elongation Complex	5	11.6×	2e-03
HIV Transcription Elongation	5	11.6×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	6	23.9×	1e-04
negative regulation of protein ubiquitination	8	11.9×	1e-04
mRNA export from nucleus	7	10.8×	9e-04
mRNA splicing, via spliceosome	17	8.1×	6e-08
RNA splicing	13	6.0×	1e-04
mRNA processing	12	4.9×	1e-03
protein phosphorylation	12	4.2×	4e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — AML.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	113
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2828 predictions. Top by Δscore:

Variant	Effect	Δscore
1:36282686:G:GT	donor_gain	1.0000
1:36286361:A:AG	acceptor_gain	1.0000
1:36286366:A:AG	acceptor_gain	1.0000
1:36286367:G:GG	acceptor_gain	1.0000
1:36286367:GT:G	acceptor_gain	1.0000
1:36286367:GTT:G	acceptor_gain	1.0000
1:36286367:GTTCT:G	acceptor_gain	1.0000
1:36291369:TTCA:T	acceptor_loss	1.0000
1:36291370:TCA:T	acceptor_loss	1.0000
1:36291372:A:AC	acceptor_loss	1.0000
1:36291372:A:AG	acceptor_gain	1.0000
1:36291372:AGACC:A	acceptor_gain	1.0000
1:36291373:G:A	acceptor_loss	1.0000
1:36291373:G:GA	acceptor_gain	1.0000
1:36291373:GA:G	acceptor_gain	1.0000
1:36291373:GAC:G	acceptor_gain	1.0000
1:36291373:GACC:G	acceptor_gain	1.0000
1:36291373:GACCC:G	acceptor_gain	1.0000
1:36291544:AAGG:A	donor_loss	1.0000
1:36291545:AGGTG:A	donor_loss	1.0000
1:36291546:GGTG:G	donor_loss	1.0000
1:36291547:G:C	donor_loss	1.0000
1:36292596:A:AG	acceptor_gain	1.0000
1:36292597:G:GG	acceptor_gain	1.0000
1:36292597:GA:G	acceptor_gain	1.0000
1:36292597:GAGC:G	acceptor_gain	1.0000
1:36292708:AGGT:A	donor_loss	1.0000
1:36292710:G:GA	donor_loss	1.0000
1:36292711:T:G	donor_loss	1.0000
1:36296768:GAA:G	donor_gain	1.0000

AlphaMissense

6219 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:36286472:G:C	R81T	1.000
1:36286475:G:C	R82T	1.000
1:36286475:G:T	R82M	1.000
1:36286476:G:C	R82S	1.000
1:36286476:G:T	R82S	1.000
1:36286561:T:A	W111R	1.000
1:36286561:T:C	W111R	1.000
1:36286563:G:C	W111C	1.000
1:36286563:G:T	W111C	1.000
1:36291418:T:C	L597P	1.000
1:36291447:T:C	F607L	1.000
1:36291448:T:C	F607S	1.000
1:36291449:T:A	F607L	1.000
1:36291449:T:G	F607L	1.000
1:36291459:T:C	F611L	1.000
1:36291460:T:C	F611S	1.000
1:36291461:C:A	F611L	1.000
1:36291461:C:G	F611L	1.000
1:36291507:T:C	F627L	1.000
1:36291508:T:C	F627S	1.000
1:36291508:T:G	F627C	1.000
1:36291509:T:A	F627L	1.000
1:36291509:T:G	F627L	1.000
1:36291511:C:A	A628D	1.000
1:36291516:C:G	H630D	1.000
1:36291517:A:C	H630P	1.000
1:36291520:T:A	I631K	1.000
1:36291520:T:G	I631R	1.000
1:36291529:T:A	I634N	1.000
1:36291529:T:G	I634S	1.000

dbSNP variants (sampled 300 via entrez): RS1000010642 (1:36274430 C>G), RS1000050607 (1:36250195 C>T), RS1000079332 (1:36280835 C>T), RS1000130909 (1:36241049 A>C), RS1000132971 (1:36239463 C>T), RS1000167548 (1:36260664 T>C), RS1000171424 (1:36300466 G>T), RS1000246996 (1:36216374 G>T), RS1000258979 (1:36297341 C>A,T), RS1000278292 (1:36207993 A>G,T), RS1000283828 (1:36247836 T>G), RS1000309225 (1:36207849 G>A), RS1000341185 (1:36297911 C>G), RS1000356632 (1:36228579 T>C), RS1000371081 (1:36236096 A>T)

Disease associations

OMIM: gene MIM:603809 | 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
GCST90002385_609	High light scatter reticulocyte count	4.000000e-15
GCST90002386_314	High light scatter reticulocyte percentage of red cells	1.000000e-14
GCST90002405_602	Reticulocyte count	3.000000e-13
GCST90002406_139	Reticulocyte fraction of red cells	3.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105820 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,213 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538
CHEMBL2140408	AMG-900	1	675

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

ChEMBL bioactivities

5 potent at pChembl≥5 of 5 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.40	IC50	40	nM	MOLIBRESIB
7.30	Kd	50	nM	MOLIBRESIB
5.90	Kd	1271	nM	CHEMBL5653589
5.90	ED50	1271	nM	CHEMBL5653589
5.56	Kd	2746	nM	AMG-900

PubChem BioAssay actives

4 with measured affinity, of 184 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178651: Inhibition of THRAP3 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.0400	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149584: Binding affinity to human THRAP3 incubated for 45 mins by Kinobead based pull down assay	kd	1.2706	uM
N-[4-[[3-(2-aminopyrimidin-4-yl)-2-pyridinyl]oxy]phenyl]-4-(4-methylthiophen-2-yl)phthalazin-1-amine	1425198: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	2.7460	uM

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
TAK-243	decreases sumoylation	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
coumarin	affects phosphorylation	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Irinotecan	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Vorinostat	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Caffeine	affects phosphorylation	1
Carcinogens	decreases expression	1
Clozapine	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	affects binding, increases reaction	1
Furaldehyde	increases expression, decreases expression, affects cotreatment, affects localization	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991911	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D6CR	HyCyte THP-1 KO-hTHRAP3	Cancer cell line	Male
CVCL_E1L7	HyCyte Hep-G2 KO-hTHRAP3	Cancer cell line	Male

Clinical trials (associated diseases)

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