TDRD3

Summary

TDRD3 (tudor domain containing 3, HGNC:20612) is a protein-coding gene on chromosome 13q21.2, encoding Tudor domain-containing protein 3 (Q9H7E2). Scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins.

Enables chromatin binding activity; methylated histone binding activity; and transcription coactivator activity. Predicted to be involved in DNA topological change. Located in Golgi apparatus; cytosol; and nucleus. Part of DNA topoisomerase III-beta-TDRD3 complex.

Source: NCBI Gene 81550 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 102 total
• Druggable target: yes
• MANE Select transcript: NM_001146070

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20612
Approved symbol	TDRD3
Name	tudor domain containing 3
Location	13q21.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21007
Ensembl gene	ENSG00000083544
Ensembl biotype	protein_coding
OMIM	614392
Entrez	81550

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000196169, ENST00000377881, ENST00000377882, ENST00000377894, ENST00000463109, ENST00000471710, ENST00000484389, ENST00000621840, ENST00000648252, ENST00000886801, ENST00000886802, ENST00000886803, ENST00000886804, ENST00000962458

RefSeq mRNA: 3 — MANE Select: NM_001146070 NM_001146070, NM_001146071, NM_030794

CCDS: CCDS53872, CCDS9441

Canonical transcript exons

ENST00000377881 — 14 exons

Exon	Start	End
ENSE00000923619	60509763	60509919
ENSE00000923621	60528367	60529217
ENSE00000923622	60535108	60535233
ENSE00000923623	60567525	60567650
ENSE00001205834	60483775	60483846
ENSE00001205839	60467238	60467379
ENSE00001475406	60573616	60573871
ENSE00003475615	60397220	60397405
ENSE00003479746	60439688	60439772
ENSE00003500698	60485799	60485948
ENSE00003512857	60494435	60494575
ENSE00003550160	60460380	60460540
ENSE00003621645	60444683	60444748
ENSE00003672678	60510630	60510755

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 93.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.4240 / max 271.3708, expressed in 1735 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
135279	3.4492	1412
135282	2.6708	1261
135283	2.6665	1075
135281	1.1017	672
135280	0.5358	279

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	93.90	gold quality
tendon	UBERON:0000043	91.58	gold quality
cortical plate	UBERON:0005343	89.79	gold quality
ventricular zone	UBERON:0003053	88.98	gold quality
colonic epithelium	UBERON:0000397	88.88	gold quality
tendon of biceps brachii	UBERON:0008188	88.51	gold quality
gastrocnemius	UBERON:0001388	87.92	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.88	gold quality
muscle of leg	UBERON:0001383	87.87	gold quality
ganglionic eminence	UBERON:0004023	87.82	gold quality
sural nerve	UBERON:0015488	87.51	gold quality
adrenal tissue	UBERON:0018303	87.16	gold quality
body of pancreas	UBERON:0001150	87.01	gold quality
corpus callosum	UBERON:0002336	86.94	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.81	gold quality
periodontal ligament	UBERON:0008266	86.19	gold quality
right uterine tube	UBERON:0001302	85.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.75	gold quality
muscle organ	UBERON:0001630	85.61	gold quality
rectum	UBERON:0001052	85.26	gold quality
pancreas	UBERON:0001264	84.66	gold quality
pigmented layer of retina	UBERON:0001782	84.61	gold quality
tibia	UBERON:0000979	84.37	gold quality
tibial nerve	UBERON:0001323	84.33	gold quality
left ovary	UBERON:0002119	84.32	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.27	gold quality
lower esophagus mucosa	UBERON:0035834	84.22	gold quality
mucosa of transverse colon	UBERON:0004991	83.92	gold quality
mucosa of stomach	UBERON:0001199	83.88	gold quality
right atrium auricular region	UBERON:0006631	83.75	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	24.34
E-ANND-3	yes	5.19
E-ENAD-17	no	258.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting TDRD3, 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-3671	99.90	73.04	3897
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-219A-1-3P	98.91	67.87	639
HSA-MIR-16-1-3P	98.70	69.23	1538
HSA-MIR-943	97.81	64.42	694
HSA-MIR-585-5P	97.54	69.02	955
HSA-MIR-6818-5P	97.50	67.10	1167
HSA-MIR-6500-3P	97.42	67.20	867

Literature-anchored findings (GeneRIF, showing 13)

• Tudor domain of TDRD3 was required for its recruitment to cytoplasmic stress granules. (PMID:18632687)
• propose a contribution of Tdrd3 to FMRP-mediated translational repression and suggest that the loss of the FMRP-Tdrd3 interaction caused by the I304N mutation might contribute to the pathogenesis of Fragile X syndrome (PMID:18664458)
• The TDRD3 is an effector molecule that promotes transcription by binding methylarginine marks on histone tails. (PMID:21172665)
• The binding specificity and affinity of the Tudor domains of TDRD3, SMN and SPF30 proteins were characterized quantitatively. (PMID:22363433)
• Top3b proteins from several animals associate with polyribosomes, which are units of mRNA translation, whereas the Top3 homologs from E. coli and yeast lack the association. The Top3b-polyribosome association requires TDRD3, which directly interacts with Top3beta and is present in animals but not bacteria or yeast. (PMID:27257063)
• Structural basis of the interaction between TOP3B and the TDRD3 auxiliary factor has been reported. (PMID:28176834)
• Study reports TDRD3 as a novel regulator of cell proliferation and invasion in breast cancer cells. Its depletion inhibits tumor formation and metastasis to the lung in vivo. Furthermore, TDRD3 regulates the expression of a number of key genes associated with promotion of breast cancer tumorigenesis and disease progression at the level of translation. (PMID:28698590)
• Our work depicts the structural plasticity of the TDRD3 Tudor domain and paves the way for the subsequent structure-guided discovery of selective inhibitors targeting Tudor domains (PMID:29645362)
• TDRD3 promotes DHX9 chromatin recruitment and R-loop resolution. (PMID:34329467)
• TDRD3 is an antiviral restriction factor that promotes IFN signaling with G3BP1. (PMID:35085371)
• A dual-activity topoisomerase complex regulates mRNA translation and turnover. (PMID:35748872)
• Involvement of SYCP2L and TDRD3 gene variants on ovarian reserve and reproductive outcomes: a cross-sectional study. (PMID:37417852)
• PRMT1 and TDRD3 promote stress granule assembly by rebuilding the protein-RNA interaction network. (PMID:39097054)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tdrd3	ENSDARG00000025421
mus_musculus	Tdrd3	ENSMUSG00000022019
rattus_norvegicus	Tdrd3	ENSRNOG00000009034
drosophila_melanogaster	Tdrd3	FBGN0036450
caenorhabditis_elegans		WBGENE00021748

Protein

Protein identifiers

Tudor domain-containing protein 3 — Q9H7E2 (reviewed: Q9H7E2)

All UniProt accessions (3): Q9H7E2, B1AMN9, F2Z2Y2

UniProt curated annotations — full annotation on UniProt →

Function. Scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins. Plays a role in the regulation of translation of target mRNAs by binding Arg/Gly-rich motifs (GAR) in dimethylarginine-containing proteins. In nucleus, acts as a coactivator: recognizes and binds asymmetric dimethylation on the core histone tails associated with transcriptional activation (H3R17me2a and H4R3me2a) and recruits proteins at these arginine-methylated loci. In cytoplasm, acts as an antiviral factor that participates in the assembly of stress granules together with G3BP1.

Subunit / interactions. Component of mRNA stress granules. Interacts with FMR1, FXR1, FXR2, EWSR1, FUS, SERBP1, EEF1A1 and DDX3X or DDX3Y, and with the small nuclear ribonucleoprotein-associated proteins SNRPB and SNRPN. Interacts with ‘Lys-48’-linked tetra-ubiquitin, but not with monoubiquitin or ‘Lys-63’-linked ubiquitin chains. May interact with the exon junction complex (EJC) composed at least of CASC3, EIF4A3, MAGOH and RBM8A. Interacts with POLR2A (via the C-terminal domain (CTD)).

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Detected in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Post-translational modifications. Probably cleaved by enteroviral 2A proteinase.

Domain organisation. The Tudor domain specifically recognizes and binds asymmetric dimethylation of histone H3 ‘Arg-17’ (H3R17me2a) and histones H4 ‘Arg-3’, 2 tags for epigenetic transcriptional activation.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H7E2-1	1	yes
Q9H7E2-2	2, Long
Q9H7E2-3	3

RefSeq proteins (3): NP_001139542, NP_001139543, NP_110421 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002999	Tudor	Domain
IPR009060	UBA-like_sf	Homologous_superfamily
IPR013894	RMI1_OB	Domain
IPR015940	UBA	Domain
IPR041915	UBA_TDRD3	Domain
IPR042470	RMI1_N_C_sf	Homologous_superfamily
IPR047379	Tudor_TDRD3	Domain

Pfam: PF00567, PF08585, PF22562

UniProt features (42 total): strand 11, helix 6, turn 5, region of interest 5, compositionally biased region 3, domain 2, modified residue 2, splice variant 2, mutagenesis site 2, sequence conflict 2, chain 1, cross-link 1

Structure

Experimental structures (PDB)

20 structures.

PDB	Method	Resolution (Å)
5GVD	X-RAY DIFFRACTION	1.62
5YJ8	X-RAY DIFFRACTION	1.76
3S6W	X-RAY DIFFRACTION	1.78
3PMT	X-RAY DIFFRACTION	1.8
8JTN	X-RAY DIFFRACTION	1.8
3PNW	X-RAY DIFFRACTION	2.05
6V9T	X-RAY DIFFRACTION	2.15
9CA4	ELECTRON MICROSCOPY	3.01
9CAK	ELECTRON MICROSCOPY	3.01
9CAL	ELECTRON MICROSCOPY	3.15
9CAH	ELECTRON MICROSCOPY	3.16
9CA1	ELECTRON MICROSCOPY	3.26
9CAG	ELECTRON MICROSCOPY	3.33
9C9Y	ELECTRON MICROSCOPY	3.35
9CA0	ELECTRON MICROSCOPY	3.48
9CAJ	ELECTRON MICROSCOPY	3.51
5GVE	X-RAY DIFFRACTION	3.61
9C9W	ELECTRON MICROSCOPY	4.25
1WJI	SOLUTION NMR
2LTO	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H7E2-F1	58.62	0.22

Antibody-complex structures (SAbDab): 1 — 3PNW

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 (3): 256, 345, 470

Mutagenesis-validated functional residues (2):

Position	Phenotype
598	abolishes interaction with dimethylarginine-containing protein motifs and reduces association with mrna stress granules.
638–644	loss of interaction with the ejc.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 126 (showing top): chr13q21, GOBP_CHROMOSOME_ORGANIZATION, BROWNE_HCMV_INFECTION_6HR_DN, AREB6_01, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_DNA_CONFORMATION_CHANGE, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, AACTTT_UNKNOWN, GOBP_CHROMATIN_REMODELING, GOBP_HETEROCHROMATIN_ORGANIZATION, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, P53_DECAMER_Q2, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOMF_CHROMATIN_BINDING, GOCC_EXON_EXON_JUNCTION_COMPLEX

GO Biological Process (3): DNA topological change (GO:0006265), chromatin organization (GO:0006325), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (6): chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), RNA binding (GO:0003723), histone H3 reader activity (GO:0140006), histone H4 reader activity (GO:0140008), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), cytosol (GO:0005829), DNA topoisomerase III-beta-TDRD3 complex (GO:0140225), cytoplasm (GO:0005737), exon-exon junction complex (GO:0035145)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	2
histone reader activity	2
intracellular membrane-bounded organelle	2
cytoplasm	2
DNA metabolic process	1
DNA conformation change	1
cellular component organization	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
nucleic acid binding	1
nuclear lumen	1
endomembrane system	1
protein-containing complex	1
intracellular anatomical structure	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

1328 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TDRD3	TOP3B	O95985	929
TDRD3	FXR2	P51116	839
TDRD3	FMR1	Q06787	799
TDRD3	TCERG1	O14776	753
TDRD3	CARM1	Q86X55	738
TDRD3	PRMT1	Q99873	726
TDRD3	SMNDC1	O75940	673
TDRD3	FXR1	P51114	668
TDRD3	MED12	Q93074	653
TDRD3	DDX3X	O00571	648
TDRD3	NOM1	Q5C9Z4	632
TDRD3	EIF3G	O75821	605
TDRD3	H4C7	Q99525	584
TDRD3	H4C16	P02304	581
TDRD3	G3BP1	Q13283	581

IntAct

39 interactions, top by confidence:

A	B	Type	Score
POLR2A	TDRD3	psi-mi:“MI:0915”(physical association)	0.700
TDRD3	POLR2A	psi-mi:“MI:0407”(direct interaction)	0.700
POLR2A	SMN1	psi-mi:“MI:0914”(association)	0.660
TOP3B	TDRD3	psi-mi:“MI:0914”(association)	0.640
KIF1C	KIF1B	psi-mi:“MI:2364”(proximity)	0.480
CC2D2A	OFD1	psi-mi:“MI:2364”(proximity)	0.420
TDRD3	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
FUS	TDRD3	psi-mi:“MI:0915”(physical association)	0.370
PB2		psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
TDRD3	PTMA	psi-mi:“MI:0914”(association)	0.350
TOP3B	HMGN4	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
NPM1	RPS3A	psi-mi:“MI:0914”(association)	0.350
TOP3B	PRMT5	psi-mi:“MI:0914”(association)	0.350
YBX1	NOP56	psi-mi:“MI:0914”(association)	0.350
LCA5	DVL2	psi-mi:“MI:2364”(proximity)	0.270
DCTN1	NACA	psi-mi:“MI:2364”(proximity)	0.270
POC1A	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
NINL	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
FBL	ZNF850	psi-mi:“MI:2364”(proximity)	0.270
CDC14A	CEP290	psi-mi:“MI:2364”(proximity)	0.270
DGCR8	VWA8	psi-mi:“MI:2364”(proximity)	0.270
FASTKD2	MED19	psi-mi:“MI:2364”(proximity)	0.270
FXR2	RPSA2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (320): PABPC1 (Affinity Capture-Western), MAGOH (Affinity Capture-Western), RBM8A (Affinity Capture-Western), TDRD3 (Co-fractionation), TDRD3 (Co-fractionation), TDRD3 (Co-fractionation), TDRD3 (Proximity Label-MS), TDRD3 (Proximity Label-MS), TDRD3 (Proximity Label-MS), TDRD3 (Proximity Label-MS), TDRD3 (Proximity Label-MS), TDRD3 (Affinity Capture-MS), TDRD3 (Affinity Capture-MS), TDRD3 (Affinity Capture-MS), TDRD3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IZ84, A0A1L8H8C0, A0A1L8HFX9, A2RUV4, F1LP90, F5HSE3, O43310, O60237, O75167, O88453, P41110, P61406, Q12830, Q1LVF3, Q2HJG4, Q2PFD7, Q3TLH4, Q5RAK6, Q5ZMS6, Q66HC1, Q6A0A2, Q6NRP6, Q6NZL0, Q6P1U3, Q6PKG0, Q75N33, Q7TN02, Q7TPM1, Q7YZA2, Q7Z6E9, Q80TN7, Q80XI3, Q86UR5, Q86US8, Q8IVL0, Q8IVL1, Q8K0V4, Q8N4C8, Q90YL3, Q90YY5

Diamond homologs: A4IF98, Q2HJG4, Q5ZHV8, Q5ZMS6, Q66HC1, Q6DDH2, Q6NRP6, Q6NYG6, Q6P1U3, Q7ZVM9, Q91W18, Q9D4G9, Q9H7E2, Q9H9A7, O18870, O75940, Q16637, Q3T045, Q4QQU6, Q4R4F8, Q58EK5, Q5R591, Q6DEY1, Q8BGT7, A9CPT4, Q99MV1, Q9BXT4, Q9FLT0, Q9Y2W6, P91399, Q8HYB8, Q9W6S8, O02771, O35876, P97801, Q5RE18, Q7SXW2, Q7ZV80, Q9VV74

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TDRD3	“form complex”	“TDRD3-TOP3B type IA topoisomerase complex”	binding
TDRD3	unknown	SNRPN	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 49 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
Anchoring of the basal body to the plasma membrane	5	20.2×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
RNA splicing	6	12.0×	1e-03
cilium assembly	6	10.0×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	87
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4113 predictions. Top by Δscore:

Variant	Effect	Δscore
13:60439685:CAG:C	acceptor_loss	1.0000
13:60439687:GGT:G	acceptor_gain	1.0000
13:60439771:AT:A	donor_gain	1.0000
13:60439773:G:GG	donor_gain	1.0000
13:60444682:GACA:G	acceptor_gain	1.0000
13:60460466:G:GT	donor_gain	1.0000
13:60460497:A:AG	donor_gain	1.0000
13:60460497:A:G	donor_gain	1.0000
13:60467236:A:AG	acceptor_gain	1.0000
13:60467237:G:GA	acceptor_gain	1.0000
13:60467237:GCCT:G	acceptor_gain	1.0000
13:60467367:G:GT	donor_gain	1.0000
13:60467376:GAGA:G	donor_gain	1.0000
13:60467377:AGA:A	donor_gain	1.0000
13:60467378:GA:G	donor_gain	1.0000
13:60467378:GAG:G	donor_gain	1.0000
13:60467378:GAGT:G	donor_loss	1.0000
13:60467379:AGTA:A	donor_loss	1.0000
13:60467380:G:GG	donor_gain	1.0000
13:60467380:GTA:G	donor_loss	1.0000
13:60467381:T:C	donor_loss	1.0000
13:60467382:AAGTG:A	donor_loss	1.0000
13:60467383:AGTGT:A	donor_loss	1.0000
13:60483774:GA:G	acceptor_gain	1.0000
13:60483843:ACAGG:A	donor_loss	1.0000
13:60483844:CAGGT:C	donor_loss	1.0000
13:60483845:AGGT:A	donor_loss	1.0000
13:60483846:GG:G	donor_loss	1.0000
13:60483847:G:GA	donor_loss	1.0000
13:60483848:T:A	donor_loss	1.0000

AlphaMissense

4274 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:60467365:T:A	W68R	1.000
13:60467365:T:C	W68R	1.000
13:60485912:G:C	R134S	1.000
13:60485912:G:T	R134S	1.000
13:60509830:T:C	L216P	1.000
13:60529195:C:A	A564E	1.000
13:60535160:T:A	V589D	1.000
13:60535166:T:C	F591S	1.000
13:60460510:C:A	A15E	0.999
13:60467254:G:A	G31R	0.999
13:60467254:G:C	G31R	0.999
13:60467255:G:A	G31E	0.999
13:60467262:A:C	K33N	0.999
13:60467262:A:T	K33N	0.999
13:60467367:G:C	W68C	0.999
13:60467367:G:T	W68C	0.999
13:60485898:T:C	F130L	0.999
13:60485899:T:G	F130C	0.999
13:60485900:T:A	F130L	0.999
13:60485900:T:G	F130L	0.999
13:60485911:G:C	R134T	0.999
13:60485916:G:C	A136P	0.999
13:60485919:G:C	A137P	0.999
13:60485923:T:A	I138N	0.999
13:60485923:T:G	I138S	0.999
13:60485925:G:C	A139P	0.999
13:60509803:T:C	F207S	0.999
13:60509826:G:C	A215P	0.999
13:60509830:T:A	L216H	0.999
13:60509863:T:C	L227P	0.999

dbSNP variants (sampled 300 via entrez): RS1000013214 (13:60414576 T>G), RS1000038966 (13:60569628 G>A), RS1000069730 (13:60510902 G>A,C,T), RS1000127480 (13:60516269 T>C,G), RS1000135090 (13:60504832 A>G), RS1000147536 (13:60498366 T>G), RS1000157907 (13:60444890 G>C,T), RS1000166544 (13:60530856 A>C), RS1000170785 (13:60437935 C>T), RS1000182743 (13:60453823 A>G), RS1000191196 (13:60402838 G>A), RS1000242776 (13:60498724 T>C), RS1000281372 (13:60474611 A>G), RS1000289881 (13:60406320 C>T), RS1000313767 (13:60555929 C>T)

Disease associations

OMIM: gene MIM:614392 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001381_3	Menopause (age at onset)	1.000000e-10
GCST001585_15	Breast size	2.000000e-06
GCST002701_41	Verbal declarative memory	1.000000e-06
GCST002701_5	Verbal declarative memory	1.000000e-06
GCST005312_32	Menopause (age at onset)	3.000000e-16

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004704	age at menopause
EFO:0004874	memory performance
EFO:0006806	paragraph delayed recall measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3879852 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, affects cotreatment, decreases expression	9
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
(+)-JQ1 compound	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Quercetin	decreases expression, increases phosphorylation	2
Tretinoin	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
arsenite	increases methylation	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
tamibarotene	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Cisplatin	affects expression	1
Coal	decreases expression, increases abundance	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3859084	Binding	Binding affinity to TDRD3 (unknown origin) at 200 uM by DSF assay	Discovery of a Potent, Selective, and Cell-Active Dual Inhibitor of Protein Arginine Methyltransferase 4 and Protein Arginine Methyltransferase 6. — J Med Chem

Clinical trials (associated diseases)

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