WDR77

Summary

WDR77 (WD repeat domain 77, HGNC:29652) is a protein-coding gene on chromosome 1p13.2, encoding Methylosome protein WDR77 (Q9BQA1). Non-catalytic component of the methylosome complex, composed of PRMT5, WDR77 and CLNS1A, which modifies specific arginines to dimethylarginines in several spliceosomal Sm proteins and histones. It is a common-essential gene (DepMap: required in 97.8% of cancer cell lines).

The protein encoded by this gene is an androgen receptor coactivator that forms a complex with protein arginine methyltransferase 5, which modifies specific arginines to dimethylarginines in several spliceosomal Sm proteins. The encoded protein may be involved in the early stages of prostate cancer, with most of the protein being nuclear-localized in benign cells but cytoplasmic in cancer cells. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 79084 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 44 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 97.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_024102

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29652
Approved symbol	WDR77
Name	WD repeat domain 77
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Aliases	MEP50, p44
Ensembl gene	ENSG00000116455
Ensembl biotype	protein_coding
OMIM	611734
Entrez	79084

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000235090, ENST00000449340, ENST00000459665, ENST00000497278

RefSeq mRNA: 4 — MANE Select: NM_024102 NM_001317062, NM_001317063, NM_001317064, NM_024102

CCDS: CCDS835

Canonical transcript exons

ENST00000235090 — 10 exons

Exon	Start	End
ENSE00000783706	111448619	111448804
ENSE00000958112	111439890	111441389
ENSE00001450728	111449055	111449256
ENSE00003494985	111447435	111447576
ENSE00003539233	111442025	111442093
ENSE00003591702	111444054	111444124
ENSE00003612847	111447095	111447144
ENSE00003615062	111443867	111443921
ENSE00003625110	111443323	111443394
ENSE00003654035	111442653	111442761

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 99.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.4471 / max 142.0891, expressed in 1810 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13817	14.1772	1788
13816	5.1345	1695
13815	1.4935	1010
13818	0.6419	391

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.06	gold quality
apex of heart	UBERON:0002098	94.10	gold quality
gastrocnemius	UBERON:0001388	93.86	gold quality
right adrenal gland cortex	UBERON:0035827	93.23	gold quality
muscle of leg	UBERON:0001383	92.97	gold quality
right adrenal gland	UBERON:0001233	92.95	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.66	gold quality
esophagus mucosa	UBERON:0002469	92.64	gold quality
body of stomach	UBERON:0001161	92.62	gold quality
heart left ventricle	UBERON:0002084	92.42	gold quality
rectum	UBERON:0001052	92.38	gold quality
left adrenal gland	UBERON:0001234	92.38	gold quality
left adrenal gland cortex	UBERON:0035825	92.35	gold quality
cardiac ventricle	UBERON:0002082	92.18	gold quality
fallopian tube	UBERON:0003889	92.08	gold quality
left uterine tube	UBERON:0001303	91.78	gold quality
adrenal tissue	UBERON:0018303	91.67	gold quality
adrenal cortex	UBERON:0001235	91.66	gold quality
muscle organ	UBERON:0001630	91.58	gold quality
skeletal muscle organ	UBERON:0014892	91.58	gold quality
minor salivary gland	UBERON:0001830	91.41	gold quality
right atrium auricular region	UBERON:0006631	91.41	gold quality
body of pancreas	UBERON:0001150	91.40	gold quality
stromal cell of endometrium	CL:0002255	91.35	gold quality
left coronary artery	UBERON:0001626	91.11	gold quality
esophagus	UBERON:0001043	91.06	gold quality
heart	UBERON:0000948	91.03	gold quality
spleen	UBERON:0002106	90.98	gold quality
stomach	UBERON:0000945	90.93	gold quality
adrenal gland	UBERON:0002369	90.90	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)

57 targeting WDR77, 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-7110-3P	100.00	73.18	2486
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4762-3P	99.43	69.72	2363

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 30)

• Here, we describe a novel component of the methylosome, a 50-kilodalton WD repeat protein termed methylosome protein 50 (MEP50). (PMID:11756452)
• SUZ12 might have a role in transcriptional regulation through physical interaction with MEP50 that can be an adaptor between PRMT5 and its substrate H2A (PMID:16712789)
• Forced nuclear localization of p44 inhibited prostate cancer cell growth by G1 cell-cycle arrest. (PMID:17032745)
• results suggest distinct functions of the nuclear and the p44/protein arginine methyltransferase 5 complexes in the developing fetal testis and in the oncogenesis of testicular tumors. (PMID:17437848)
• nuclear p44 and cytoplasmic p44 have distinct and opposing functions in the regulation of prostate cancer cell proliferation (PMID:18356297)
• expression and function of p44 in breast cancer; expression of p44 shows strong cytoplasmic expression in morphologically normal terminal ductal lobular units, while nuclear p44 is observed in both ductal carcinoma in situ and invasive carcinoma (PMID:19840198)
• These results provide a basis for understanding subcellular transport of p44/WDR77 during prostate development and tumorigenesis. (PMID:21789256)
• p44 plays a role in mediating the effects of hormones during ovarian tumorigenesis. (PMID:22022581)
• structure of the surprising hetero-octameric complex reveals the close interaction between the seven-bladed beta-propeller MEP50 and the N-terminal domain of PRMT5, and delineates the structural elements of substrate recognition. (PMID:23071334)
• These studies suggest a novel mechanism by which proliferation and differentiation of prostate epithelial cells are controlled by WDR77’s location in the cell. (PMID:23145110)
• Data indicate a transcription complex androgen receptor (AR)-p44-Smad1, and confirmed for physical interaction by co-immunoprecipitaion. (PMID:23734213)
• These findings characterize PKG as a novel regulator of AR-mediated transcription by enhancing AR cofactor p44/WDR77’s function. (PMID:23755100)
• MEP50 can transform cells independent of AR and ER. (PMID:25277535)
• Data indicate that MEP50 WD repeat protein is essential for methylation of histones H4 and H2A by PRMT5 arginine methyltransferase. (PMID:25713080)
• MEP50 genes reduces gene expression through histone arginine methylation in keratinocytes. (PMID:26763441)
• TSC22D2 protein might be a member of the PRMT5 complex via direct binding of WDR77. (PMID:27337956)
• Results provide evidence that PRMT5 and p44 regulate gene expression of growth and anti-growth factors to promote lung tumorigenesis. (PMID:27480244)
• SFN treatment of tumors results in reduced MEP50 level and H4R3me2s formation, confirming that that SFN impacts this complex in vivo. These studies suggest that the PRMT5/MEP50 is required for tumor growth and that reduced expression of this complex is a part of the mechanism of SFN suppression of tumor formation. (PMID:28854561)
• Data indicate that ZNF326 is an interaction partner and substrate of the PRMT5/WDR77 complex. (PMID:28977470)
• In an in vitro assay of vascular smooth muscle cells, circRNA WDR77 silencing significantly inhibited cell proliferation and migration. Bioinformatics methods revealed that miR-124 and fibroblast growth factor 2 (FGF-2) were downstream targets of circRNA WDR77. (PMID:29042195)
• A 3.7 A structure of PRMT5, solved in complex with regulatory binding subunit MEP50 (methylosome associated protein 50, WDR77, p44), by single particle (SP) cryo-Electron Microscopy (cryo-EM) using micrographs of particles that are visibly crowded and aggregated. The catalytic PRMT5 subunits form a core tetramer and the MEP50 subunits are arranged peripherally in complex with the PRMT5 N-terminal domain. (PMID:29518110)
• Deacetylation of WDR77 at Lys-3 and Lys-243 suppresses cancer cell growth by reducing WDR77/PRMT5 transmethylase complex activity. (PMID:30282801)
• curcumin affects the PRMT5-MEP50 methyltransferase expression might be explored for its therapeutic application. (PMID:30392062)
• These results suggest that MEP50/PRMT5 is important for HH signal-induced GLI1 activation, especially in cancers. (PMID:30675521)
• WD Repeat Domain 77 Protein Regulates Translation of E2F1 and E2F3 mRNA. (PMID:33020149)
• Biochemical Investigation of the Interaction of pICln, RioK1 and COPR5 with the PRMT5-MEP50 Complex. (PMID:33624332)
• Germ-line mutations in WDR77 predispose to familial papillary thyroid cancer. (PMID:34326253)
• HBx represses WDR77 to enhance HBV replication by DDB1-mediated WDR77 degradation in the liver. (PMID:34373747)
• HNRNPC promotes estrogen receptor-positive breast cancer cell cycle by stabilizing WDR77 mRNA in an m6A-dependent manner. (PMID:38353359)
• Inhibition of PRMT5/MEP50 Arginine Methyltransferase Activity Causes Cancer Vulnerability in NDRG2[low] Adult T-Cell Leukemia/Lymphoma. (PMID:38474089)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000101347
mus_musculus	Wdr77	ENSMUSG00000000561
rattus_norvegicus	Wdr77	ENSRNOG00000016394

Paralogs (9): ERCC8 (ENSG00000049167), GEMIN5 (ENSG00000082516), RBBP7 (ENSG00000102054), WDR59 (ENSG00000103091), GRWD1 (ENSG00000105447), PEX7 (ENSG00000112357), WDR24 (ENSG00000127580), RBBP4 (ENSG00000162521), WDR73 (ENSG00000177082)

Protein

Protein identifiers

Methylosome protein WDR77 — Q9BQA1 (reviewed: Q9BQA1)

Alternative names: Androgen receptor cofactor p44, Methylosome protein 50, WD repeat-containing protein 77, p44/Mep50

All UniProt accessions (3): A0A024R0H7, Q9BQA1, H0Y711

UniProt curated annotations — full annotation on UniProt →

Function. Non-catalytic component of the methylosome complex, composed of PRMT5, WDR77 and CLNS1A, which modifies specific arginines to dimethylarginines in several spliceosomal Sm proteins and histones. This modification targets Sm proteins to the survival of motor neurons (SMN) complex for assembly into small nuclear ribonucleoprotein core particles. Might play a role in transcription regulation. The methylosome complex also methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), methylation of Piwi proteins being required for the interaction with Tudor domain-containing proteins and subsequent localization to the meiotic nuage.

Subunit / interactions. Component of the methylosome complex composed of PRMT5, WDR77 and CLNS1A. Found in a complex composed of PRMT5, WDR77 and RIOK1. RIOK1 and CLNS1A bound directly to PRMT5 at the same binding site, in a mutually exclusive manner, which allows the recruitment of distinct methylation substrates, such as nucleolin/NCL and Sm proteins, respectively. Found in a complex with the component of the methylosome, PRMT5, CLNS1A, WDR77, PRMT1 and ERH. Directly interacts with PRMT5, as well as with several Sm proteins, including SNRPB and SNRPD2 and, more weakly, SNRPD3 and SNRPE. Forms a compact hetero-octamer with PRMT5, decorating the outer surface of a PRMT5 tetramer. Interacts with SUZ12 and histone H2A/H2AC20, but not with histones H2B, H3 nor H4. Interacts with CTDP1 and LSM11. Interacts with APEX1, AR and NKX3-1. Interacts with CHTOP. Interacts with FAM47E. Interacts with TSC22D2.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Highly expressed in heart, skeletal muscle, spleen, testis, uterus, prostate and thymus. In testis, expressed in germ cells and Leydig cells, but not in peritubular myocytes, nor in Sertoli cells. Expressed in prostate cancers, in seminomas and in Leydig cell tumors.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BQA1-1	1	yes
Q9BQA1-2	2

RefSeq proteins (4): NP_001303991, NP_001303992, NP_001303993, NP_077007* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR052139	Methylosome_Comp_WDR77	Family

Pfam: PF00400

UniProt features (57 total): strand 38, repeat 7, turn 4, sequence conflict 2, helix 2, chain 1, sequence variant 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

88 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9ZL3	X-RAY DIFFRACTION	1.71
9MGQ	X-RAY DIFFRACTION	1.85
6V0P	X-RAY DIFFRACTION	1.88
7ZVU	X-RAY DIFFRACTION	1.95
9ZL4	X-RAY DIFFRACTION	1.95
7ZUY	X-RAY DIFFRACTION	2
7S0U	X-RAY DIFFRACTION	2.01
7ZUP	X-RAY DIFFRACTION	2.01
7ZV2	X-RAY DIFFRACTION	2.01
8VEO	X-RAY DIFFRACTION	2.03
4GQB	X-RAY DIFFRACTION	2.06
9MGR	X-RAY DIFFRACTION	2.07
7ZUU	X-RAY DIFFRACTION	2.09
7S1R	X-RAY DIFFRACTION	2.1
6V0N	X-RAY DIFFRACTION	2.11
7SER	X-RAY DIFFRACTION	2.14
9EYV	X-RAY DIFFRACTION	2.15
9EYX	X-RAY DIFFRACTION	2.2
9PCA	X-RAY DIFFRACTION	2.2
7S1P	X-RAY DIFFRACTION	2.21
6RLL	X-RAY DIFFRACTION	2.22
9MGL	X-RAY DIFFRACTION	2.25
9MGM	X-RAY DIFFRACTION	2.25
9MRE	X-RAY DIFFRACTION	2.25
5EMJ	X-RAY DIFFRACTION	2.27
9EYW	X-RAY DIFFRACTION	2.3
5FA5	X-RAY DIFFRACTION	2.34
4X60	X-RAY DIFFRACTION	2.35
9EYU	X-RAY DIFFRACTION	2.35
5C9Z	X-RAY DIFFRACTION	2.36

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQA1-F1	91.35	0.83

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): 5

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-191859	snRNP Assembly
R-HSA-3214858	RMTs methylate histone arginines
R-HSA-194441	Metabolism of non-coding RNA
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 253 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, PID_HDAC_CLASSI_PATHWAY, ELVIDGE_HYPOXIA_DN, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_RIBOSOME_BIOGENESIS, GOBP_EPITHELIUM_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_POSITIVE_REGULATION_OF_RNA_SPLICING, GOBP_POSITIVE_REGULATION_OF_MRNA_PROCESSING, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, TGACCTY_ERR1_Q2, YY1_Q6

GO Biological Process (12): protein polyubiquitination (GO:0000209), spliceosomal snRNP assembly (GO:0000387), regulation of transcription by RNA polymerase II (GO:0006357), ubiquitin-dependent protein catabolic process (GO:0006511), oocyte axis specification (GO:0007309), positive regulation of cell population proliferation (GO:0008284), positive regulation of mRNA splicing, via spliceosome (GO:0048026), secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development (GO:0060528), epithelial cell proliferation involved in prostate gland development (GO:0060767), negative regulation of epithelial cell proliferation involved in prostate gland development (GO:0060770), negative regulation of cell population proliferation (GO:0008285), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (4): transcription coactivator activity (GO:0003713), methyl-CpG binding (GO:0008327), ubiquitin-like ligase-substrate adaptor activity (GO:1990756), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), Cul4B-RING E3 ubiquitin ligase complex (GO:0031465), methylosome (GO:0034709), transferase complex (GO:1990234)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Metabolism of non-coding RNA	1
Chromatin modifying enzymes	1
Metabolism of RNA	1
Chromatin organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	3
protein ubiquitination	2
mRNA splicing, via spliceosome	2
regulation of DNA-templated transcription	2
cell population proliferation	2
regulation of cell population proliferation	2
intracellular membrane-bounded organelle	2
protein-RNA complex assembly	1
transcription by RNA polymerase II	1
modification-dependent protein catabolic process	1
developmental process involved in reproduction	1
oocyte construction	1
axis specification	1
positive regulation of cellular process	1
positive regulation of RNA splicing	1
regulation of mRNA splicing, via spliceosome	1
positive regulation of mRNA processing	1
glandular epithelial cell differentiation	1
prostate glandular acinus development	1
epithelial cell differentiation involved in prostate gland development	1
prostate gland development	1
epithelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
negative regulation of developmental process	1
negative regulation of multicellular organismal process	1
epithelial cell proliferation involved in prostate gland development	1
regulation of epithelial cell proliferation involved in prostate gland development	1
negative regulation of reproductive process	1
negative regulation of cellular process	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
nucleotide binding	1
sequence-specific DNA binding	1
enzyme-substrate adaptor activity	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3464 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WDR77	PRMT5	O14744	999
WDR77	CLNS1A	P54105	928
WDR77	SNRPD3	P43331	912
WDR77	RIOK1	Q9BRS2	793
WDR77	SNRPB	P14678	785
WDR77	CTDP1	Q9Y5B0	747
WDR77	PRMT1	Q99873	746
WDR77	TP53	P04637	745
WDR77	SNRPD1	P13641	718
WDR77	H2AC19	P20670	715
WDR77	H2AC20	Q16777	715
WDR77	SNAI1	O95863	671
WDR77	SNRPE	P08578	657
WDR77	H4C7	Q99525	647
WDR77	H4C16	P02304	646

IntAct

201 interactions, top by confidence:

A	B	Type	Score
PRMT5	WDR77	psi-mi:“MI:0915”(physical association)	0.960
WDR77	PRMT5	psi-mi:“MI:0407”(direct interaction)	0.960
PRMT5	WDR77	psi-mi:“MI:0407”(direct interaction)	0.960
WDR77	PRMT5	psi-mi:“MI:0915”(physical association)	0.960
WDR77	PRMT5	psi-mi:“MI:0914”(association)	0.960
PRMT5	CLNS1A	psi-mi:“MI:0914”(association)	0.830
CLNS1A	PRMT5	psi-mi:“MI:0914”(association)	0.830
COPRS	PRMT5	psi-mi:“MI:0914”(association)	0.770
PRMT5	H4C16	psi-mi:“MI:0915”(physical association)	0.760
PRMT5	H4C16	psi-mi:“MI:0213”(methylation reaction)	0.760
CCT2	TXNDC9	psi-mi:“MI:0914”(association)	0.730
RIOK1	PRMT5	psi-mi:“MI:0914”(association)	0.710
PRMT5	PRMT5	psi-mi:“MI:0914”(association)	0.690
SNRPB	PRMT5	psi-mi:“MI:0914”(association)	0.670
IFT88	IFT56	psi-mi:“MI:0914”(association)	0.640
CCT3	TXNDC9	psi-mi:“MI:0914”(association)	0.640
SMN1	PRMT5	psi-mi:“MI:0914”(association)	0.600
N	WDR77	psi-mi:“MI:0915”(physical association)	0.580

BioGRID (572): WDR77 (Affinity Capture-MS), WDR77 (Affinity Capture-MS), WDR77 (Affinity Capture-MS), WDR77 (Affinity Capture-MS), PRKG2 (Two-hybrid), PRKG2 (Reconstituted Complex), WDR77 (Reconstituted Complex), WDR77 (Affinity Capture-Western), PRKG1 (Affinity Capture-Western), WDR77 (Biochemical Activity), WDR77 (Affinity Capture-MS), WDR77 (Affinity Capture-MS), WDR77 (Co-fractionation), WDR77 (Affinity Capture-MS), WDR77 (Two-hybrid)

ESM2 similar proteins: A0A1L8HX76, A0JP70, A5D8Q8, A7Z052, E9Q349, P57081, Q13216, Q2T9T9, Q32KQ2, Q32P44, Q4QR85, Q567G2, Q5BIM8, Q5E9I7, Q5RB07, Q5RBZ2, Q5U4D9, Q5XFW6, Q5XJS5, Q64LD2, Q6AY87, Q6NPN9, Q6NUD0, Q6P4I2, Q6ZJX0, Q6ZPG2, Q7Z5U6, Q7ZVF0, Q7ZVR1, Q7ZY78, Q86W42, Q8BX17, Q8C5V5, Q8CBW4, Q8CFD5, Q8NA23, Q8TEQ6, Q8VC03, Q96KV7, Q99J09

Diamond homologs: A1CF18, A1CUD6, A3LQ86, A4R3M4, A5DL92, A5DST9, A5E6M3, A8XEN7, B3MC74, B4JW81, B4KTK4, B4LJT7, B6QC56, B8AP31, B8M0Q1, C0S902, C1GB49, E9Q349, O13286, O94423, O94527, P18851, P93339, P93397, P93398, P93563, Q04225, Q16959, Q1JQD2, Q2HBX6, Q2KJJ5, Q32LP9, Q40507, Q40687, Q54ED4, Q54WA3, Q54YD8, Q58E77, Q5A7Q3, Q5APF0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CDK4	“up-regulates activity”	WDR77	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 176 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
Metabolism of non-coding RNA	6	29.5×	3e-06
MicroRNA (miRNA) biogenesis	6	21.2×	1e-05
Signaling by TGFBR3	6	17.1×	4e-05
Formation of tubulin folding intermediates by CCT/TriC	5	16.4×	2e-04
Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding	5	15.8×	3e-04
Prefoldin mediated transfer of substrate to CCT/TriC	5	15.3×	3e-04
Gene Silencing by RNA	5	13.8×	5e-04
Beta-catenin independent WNT signaling	6	13.6×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
pre-miRNA processing	5	36.0×	4e-05
spliceosomal snRNP assembly	9	33.5×	2e-09
miRNA-mediated gene silencing by inhibition of translation	5	28.4×	1e-04
U2-type prespliceosome assembly	6	24.0×	4e-05
spliceosomal complex assembly	5	19.3×	5e-04
negative regulation of Notch signaling pathway	5	13.8×	2e-03
mRNA splicing, via spliceosome	21	12.3×	3e-14
protein targeting	5	11.7×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1323 predictions. Top by Δscore:

Variant	Effect	Δscore
1:111442758:TCAC:T	acceptor_gain	1.0000
1:111442759:CAC:C	acceptor_gain	1.0000
1:111442759:CACC:C	acceptor_gain	1.0000
1:111442760:ACCT:A	acceptor_loss	1.0000
1:111442761:CC:C	acceptor_loss	1.0000
1:111442761:CCTG:C	acceptor_gain	1.0000
1:111442762:C:A	acceptor_loss	1.0000
1:111442762:C:CC	acceptor_gain	1.0000
1:111444049:CTTA:C	donor_loss	1.0000
1:111444050:TTA:T	donor_loss	1.0000
1:111444051:TA:T	donor_loss	1.0000
1:111444121:TGAG:T	acceptor_gain	1.0000
1:111444122:GAG:G	acceptor_gain	1.0000
1:111444125:C:CC	acceptor_gain	1.0000
1:111447090:CTCA:C	donor_loss	1.0000
1:111447091:TCAC:T	donor_loss	1.0000
1:111447092:CACCT:C	donor_loss	1.0000
1:111447093:A:AC	donor_gain	1.0000
1:111447093:A:T	donor_loss	1.0000
1:111447094:C:CA	donor_loss	1.0000
1:111447094:C:CC	donor_gain	1.0000
1:111447143:TG:T	acceptor_gain	1.0000
1:111447144:GC:G	acceptor_loss	1.0000
1:111447145:C:CC	acceptor_gain	1.0000
1:111447145:CTA:C	acceptor_loss	1.0000
1:111447447:C:CT	donor_gain	1.0000
1:111447448:T:TT	donor_gain	1.0000
1:111447486:A:AC	donor_gain	1.0000
1:111447487:C:CC	donor_gain	1.0000
1:111441498:CATT:C	donor_gain	0.9900

AlphaMissense

2214 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:111447452:A:C	S142R	1.000
1:111447452:A:T	S142R	1.000
1:111447454:T:G	S142R	1.000
1:111443903:A:G	W195R	0.999
1:111443903:A:T	W195R	0.999
1:111441346:A:G	W305R	0.998
1:111441346:A:T	W305R	0.998
1:111447134:A:G	W152R	0.998
1:111447134:A:T	W152R	0.998
1:111447562:A:G	W106R	0.998
1:111447562:A:T	W106R	0.998
1:111447570:A:T	V103D	0.998
1:111448720:G:T	A67D	0.998
1:111443901:C:A	W195C	0.997
1:111443901:C:G	W195C	0.997
1:111447132:C:A	W152C	0.997
1:111447132:C:G	W152C	0.997
1:111447442:C:G	D146H	0.997
1:111447446:G:C	S144R	0.997
1:111447446:G:T	S144R	0.997
1:111447447:C:A	S144I	0.997
1:111447448:T:G	S144R	0.997
1:111447456:A:T	V141D	0.997
1:111447576:C:T	G101D	0.997
1:111448658:A:G	W88R	0.997
1:111448658:A:T	W88R	0.997
1:111448717:G:T	P68H	0.997
1:111448737:A:C	F61L	0.997
1:111448737:A:T	F61L	0.997
1:111448738:A:G	F61S	0.997

dbSNP variants (sampled 300 via entrez): RS1000142370 (1:111448548 C>G), RS1000195140 (1:111448116 G>A), RS1000369635 (1:111446229 A>G), RS1000417950 (1:111441243 C>T), RS1000419911 (1:111449783 A>AGAGCCTGGCGGG), RS1000526200 (1:111449540 C>T), RS1000687099 (1:111442954 C>T), RS1000766390 (1:111441518 C>T), RS1000864210 (1:111440672 G>A,C), RS1001192071 (1:111445362 A>G), RS10014 (1:111440525 C>T), RS1001938899 (1:111440551 C>T), RS1002178904 (1:111451115 C>T), RS1002356874 (1:111444691 G>A), RS1002409143 (1:111444480 C>T)

Disease associations

OMIM: gene MIM:611734 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3108649 (SINGLE PROTEIN), CHEMBL3137261 (PROTEIN COMPLEX), CHEMBL4748230 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,256 (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
CHEMBL1088977	ADEMETIONINE	3	1,522
CHEMBL4466233	PEMRAMETOSTAT	2	542
CHEMBL4249337	ONAMETOSTAT	1	192

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

Binding affinities (BindingDB)

570 measured of 1024 human assays (1024 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2S,3S,4R,5R)-2-[(1R)-1-(3,4-dichlorocyclohexa-2,4-dien-1-yl)-1-hydroxyethyl]-5-[(4E)-4-hydroxyimino-4aH-pyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	0.2 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(1S,2R,3S,5R)-3-[2-(2-amino-3-chloroquinolin-7-yl)ethyl]-5-[(4Z)-4-methoxyimino-4aH-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentane-1,2-diol	IC50	0.2 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(2R,3S,4R,5R)-2-[(R)-(3,4-dichlorophenyl)-hydroxymethyl]-5-[4-(2-methylhydrazinyl)-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	0.3 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(1S,2R,3S,5R)-3-[2-[2-(cyclopropylmethylamino)quinolin-7-yl]ethyl]-5-[(4Z)-4-hydroxyimino-4aH-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentane-1,2-diol	IC50	0.33 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
6-(5,8-dioxa-2-azatricyclo[4.3.0.03,7]nonane-2-carbonyl)-2-[(2R)-2-hydroxy-2-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]ethyl]-4,4-dimethyl-3H-isoquinolin-1-one	IC50	0.35 nM	US-11098059
(2R,3S,4R,5R)-2-[(R)-(3,4-dichlorophenyl)-hydroxymethyl]-5-[4-(hydroxyamino)-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	0.4 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
2-[(2R)-2-hydroxy-2-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]ethyl]-6-[(1R,5S)-3-methoxy-8-azabicyclo[3.2.1]octane-8-carbonyl]-4,4-dimethyl-3H-isoquinolin-1-one	IC50	0.44 nM	US-11098059
2-[(2R)-2-hydroxy-2-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]ethyl]-6-[(1R,5S)-3-methoxy-8-azabicyclo[3.2.1]octane-8-carbonyl]-4,4-dimethyl-3H-isoquinolin-1-one	IC50	0.5 nM	US-11098059
6-[(1R,5S)-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carbonyl]-2-[(2R)-2-hydroxy-2-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]ethyl]-4,4-dimethyl-3H-isoquinolin-1-one	IC50	0.52 nM	US-11098059
US11220524, Example 20	IC50	0.6 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(2R,3S,4R,5R)-2-[(R)-(3,4-difluorophenyl)-hydroxymethyl]-5-[4-(hydroxyamino)-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	0.6 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(1S,2R,3S,5R)-3-[2-(2-aminoquinolin-7-yl)ethyl]-5-[(4Z)-4-methoxyimino-4aH-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentane-1,2-diol	IC50	0.64 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
US11220524, Example 63	IC50	0.7 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
US11220524, Example 80	IC50	0.7 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(1S,2R,3S,5R)-3-[2-[2-(cyclopropylmethylamino)quinolin-7-yl]ethyl]-5-[(4Z)-4-methoxyimino-4aH-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentane-1,2-diol	IC50	0.82 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(2R,3S,4R,5R)-2-[(R)-(3,4-dichlorophenyl)-hydroxymethyl]-5-[4-(methoxyamino)-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	1.8 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
US11220524, Example 65	IC50	1.9 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
US11220524, Example 93-B	IC50	2.3 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
US11220524, Example 37	IC50	2.4 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
US11220524, Example 99	IC50	2.4 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(2S,3S,4R,5R)-2-[(1R)-1-(3,4-dichlorophenyl)-1-hydroxyethyl]-5-[4-(methoxyamino)-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	2.6 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(2R,3R,4S,5R)-2-(4-hydrazinyl-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl)-5-[(R)-hydroxy-[4-(trifluoromethyl)phenyl]methyl]oxolane-3,4-diol	IC50	2.7 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(1R,2S,3R,5S)-3-[(4Z)-4-methoxyimino-4aH-pyrrolo[2,3-d]pyrimidin-7-yl]-5-[2-[2-(methylamino)quinolin-7-yl]ethyl]cyclopentane-1,2-diol	IC50	2.7 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(2S,3S,4R,5R)-2-[(1R)-1-(4-chlorophenyl)-1-hydroxyethyl]-5-[4-(hydroxyamino)-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	2.8 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
US11220524, Example 72	IC50	2.8 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
US11220524, Example 78	IC50	3.1 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(1S,2R,3S,5R)-3-[2-[2-(cyclopropylmethylamino)quinolin-7-yl]ethyl]-5-[(4Z)-4-(methylhydrazinylidene)-4aH-pyrrolo[2,3-d]pyrimidin-7-yl]cyclopentane-1,2-diol	IC50	3.2 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(1S,2R,3S,5R)-3-[(1S)-1-(3,4-dichlorophenyl)-1-hydroxyethyl]-5-[4-(hydroxyamino)-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]cyclopentane-1,2-diol	IC50	3.4 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(2R,3S,4R,5R)-2-[(R)-(3,4-dichlorophenyl)-hydroxymethyl]-5-[4-(ethoxyamino)-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	3.9 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
4-(aminomethyl)-6-[5-[hydroxy(phenyl)methyl]-3-pyridinyl]-3,4,4a,5,6,7,8,8a-octahydro-2H-phthalazin-1-one	IC50	5.8 nM	US-11479551: MTA-cooperative PRMT5 inhibitors
US11220524, Example 37-B	IC50	6.3 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(2R,3S,4R,5R)-2-[(R)-(4-chlorophenyl)-hydroxymethyl]-5-[4-(2-methylhydrazinyl)-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	8.3 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(2R,3S,4R,5R)-2-[(R)-hydroxy-[3-methyl-4-(trifluoromethyl)phenyl]methyl]-5-[4-(methoxyamino)-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	8.4 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
US11220524, Example 62	IC50	8.6 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(2S,3S,4R,5R)-2-[(1R)-1-(3,4-dichlorophenyl)-1-hydroxyethyl]-5-[4-(hydroxyamino)-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	9.6 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
US11220524, Example 73	IC50	9.7 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(S)-6-((1-acetylpiperidin-4-yl)amino)-N-(2-hydroxy-3-(1,3,4,9-tetrahydro-2H-pyrido [3,4-b]indol-2-yl)propyl)pyrimidine-4-carboxamide	IC50	10 nM	US-11274098: Tricyclic compounds for use in treatment of proliferative disorders
(2R,3S,4R,5R)-2-[(R)-(3,4-difluorophenyl)-hydroxymethyl]-5-[4-(methoxyamino)-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	10.2 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(2R,3S,4R,5R)-2-[(R)-(3,4-dichlorophenyl)-hydroxymethyl]-5-[5-ethynyl-4-(methoxyamino)-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	10.2 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
2-[(2S)-2-hydroxy-2-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]ethyl]-6-[(1R,5S)-3-methoxy-8-azabicyclo[3.2.1]octane-8-carbonyl]-4,4-dimethyl-3H-isoquinolin-1-one	IC50	11.3 nM	US-11098059
US11220524, Example 50-B	IC50	11.7 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
CHEMBL4634826	EC50	12 nM
4-(aminomethyl)-6-[5-(benzenesulfinyl)-3-pyridinyl]-3,4,4a,5,6,7,8,8a-octahydro-2H-phthalazin-1-one	IC50	12 nM	US-11479551: MTA-cooperative PRMT5 inhibitors
(2R,3S,4R,5R)-2-[(R)-(4-chlorophenyl)-hydroxymethyl]-5-[4-(hydroxyamino)-2-methyl-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	13.9 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(1S,2R,3R,5R)-3-[(S)-(3,4-dichlorophenyl)-hydroxymethyl]-5-[4-(methoxyamino)-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]cyclopentane-1,2-diol	IC50	19.9 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
2-[(2S)-2-hydroxy-2-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]ethyl]-6-[(1R,5S)-3-methoxy-8-azabicyclo[3.2.1]octane-8-carbonyl]-4,4-dimethyl-3H-isoquinolin-1-one	IC50	24.3 nM	US-11098059
US11220524, Example 54	IC50	25.6 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(2S,3S,4R,5R)-2-[(1R)-1-(3,4-dichlorophenyl)-1-hydroxyethyl]-5-[5-fluoro-4-(methoxyamino)-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	28 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(2S,3S,4R,5R)-2-[(1R)-1-(4-chlorophenyl)-1-hydroxyethyl]-5-[4-(ethoxyamino)-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	29.1 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)
(2R,3S,4R,5R)-2-[(R)-(3,4-dichlorophenyl)-hydroxymethyl]-5-[4-(2,2,2-trifluoroethoxyamino)-1,2,4a,7a-tetrahydropyrrolo[2,3-d]pyrimidin-7-yl]oxolane-3,4-diol	IC50	29.6 nM	US-11220524: Selective inhibitors of protein arginine methyltransferase 5 (PRMT5)

ChEMBL bioactivities

3472 potent at pChembl≥5 of 3694 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.94	Kd	0.0114	nM	CHEMBL4563402
10.30	Ki	0.05	nM	CHEMBL5426836
10.00	Ki	0.1	nM	CHEMBL6163998
10.00	Ki	0.1	nM	CHEMBL6166947
10.00	Ki	0.1	nM	CHEMBL6143724
10.00	Ki	0.1	nM	CHEMBL6143495
10.00	Ki	0.1	nM	CHEMBL6148651
9.89	IC50	0.13	nM	ONAMETOSTAT
9.80	IC50	0.16	nM	CHEMBL4564327
9.70	IC50	0.2	nM	CHEMBL5865819
9.70	IC50	0.2	nM	CHEMBL5796835
9.70	Ki	0.2	nM	CHEMBL6145605
9.70	Ki	0.2	nM	CHEMBL6168533
9.68	IC50	0.21	nM	CHEMBL5757382
9.62	Kd	0.241	nM	CHEMBL4441584
9.62	IC50	0.24	nM	CHEMBL5790903
9.60	IC50	0.25	nM	CHEMBL4541714
9.54	IC50	0.29	nM	CHEMBL5747648
9.52	IC50	0.3	nM	CHEMBL5861732
9.51	IC50	0.31	nM	CHEMBL5810961
9.49	IC50	0.32	nM	CHEMBL4577464
9.48	IC50	0.33	nM	CHEMBL5894143
9.46	IC50	0.35	nM	CHEMBL5863900
9.44	IC50	0.36	nM	CHEMBL5774632
9.40	IC50	0.4	nM	CHEMBL4454890
9.40	IC50	0.4	nM	CHEMBL5973136
9.40	IC50	0.4	nM	CHEMBL5761913
9.40	Ki	0.4	nM	CHEMBL6133844
9.38	IC50	0.42	nM	CHEMBL5613744
9.36	IC50	0.44	nM	CHEMBL5755426
9.33	IC50	0.47	nM	CHEMBL6055014
9.30	IC50	0.5	nM	CHEMBL6007359
9.30	IC50	0.5	nM	CHEMBL5945691
9.30	IC50	0.5	nM	CHEMBL5076664
9.30	IC50	0.5	nM	CHEMBL5789744
9.30	IC50	0.5	nM	CHEMBL5965955
9.30	IC50	0.5	nM	CHEMBL5886237
9.30	IC50	0.5	nM	CHEMBL5800665
9.30	IC50	0.5	nM	CHEMBL5080751
9.30	IC50	0.5	nM	CHEMBL5994189
9.30	Ki	0.5	nM	CHEMBL6152797
9.28	IC50	0.53	nM	CHEMBL6046886
9.28	IC50	0.52	nM	CHEMBL5998088
9.22	IC50	0.6	nM	CHEMBL4536042
9.22	IC50	0.6	nM	CHEMBL5910147
9.22	IC50	0.6	nM	CHEMBL6041499
9.22	IC50	0.6	nM	CHEMBL5759950
9.22	Ki	0.6	nM	CHEMBL6167929
9.21	IC50	0.61	nM	CHEMBL5745612
9.20	IC50	0.63	nM	CHEMBL5967412

PubChem BioAssay actives

311 with measured affinity, of 548 total; 50 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
(1S,2S,3S,5R)-3-[[6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl]oxy]-5-(4-methylpyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol	1997206: Binding affinity to N-terminal 6xHis-tagged full length human PRMT5/MEP50 expressed in sf21 cells using S-Adenosyl-L-methionine as substrate assessed as dissociation constant incubated for 25 to 60 mins by liquid scintillation analysis	kd	<0.0001	uM
(1S,2R,3S,5R)-3-[2-(2-amino-3-bromoquinolin-7-yl)ethyl]-5-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol	1593844: Inhibition of full-length human N-terminal FLAG-tagged PRMT5/full length N-terminal His6-tagged MEP50 (unknown origin) expressed in baculovirus infected Sf9 insect cells assessed as reduction of S-adenosyl-L-homocysteine formation using human recombinant histone H2A (1 to 130 residues) as substrate after 1 hr in the presence of S-adenosyl-L-methionine by high throughput mass spectrometry	ic50	0.0001	uM
2-amino-3-methyl-N-[(4R)-4,5,6,7-tetrahydro-1H-indazol-4-yl]-N-[[5-(trifluoromethyl)-2-pyridinyl]methyl]quinoline-6-carboxamide	1997247: Binding affinity to PRMT5/MEP50 (unknown origin) using histone H4 peptide assessed as inhibition constant preincubated for 24 hrs followed by substrate addition and measured for 2 hrs in the presence of SAM by MTase-Glo Methyl Transferase Assay	ki	0.0001	uM
(2R,3R,4S,5R)-2-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[(R)-(4-chloro-3-fluorophenyl)-hydroxymethyl]oxolane-3,4-diol	1997206: Binding affinity to N-terminal 6xHis-tagged full length human PRMT5/MEP50 expressed in sf21 cells using S-Adenosyl-L-methionine as substrate assessed as dissociation constant incubated for 25 to 60 mins by liquid scintillation analysis	kd	0.0002	uM
(1R,2S,3R,5S)-3-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[2-(6-chloro-3-methylimidazo[1,2-a]pyridin-7-yl)ethyl]cyclopentane-1,2-diol	1593844: Inhibition of full-length human N-terminal FLAG-tagged PRMT5/full length N-terminal His6-tagged MEP50 (unknown origin) expressed in baculovirus infected Sf9 insect cells assessed as reduction of S-adenosyl-L-homocysteine formation using human recombinant histone H2A (1 to 130 residues) as substrate after 1 hr in the presence of S-adenosyl-L-methionine by high throughput mass spectrometry	ic50	0.0002	uM
(1R,2S,3R,5S)-3-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[2-(2,3-dimethylimidazo[1,2-a]pyridin-7-yl)ethyl]cyclopentane-1,2-diol	1593844: Inhibition of full-length human N-terminal FLAG-tagged PRMT5/full length N-terminal His6-tagged MEP50 (unknown origin) expressed in baculovirus infected Sf9 insect cells assessed as reduction of S-adenosyl-L-homocysteine formation using human recombinant histone H2A (1 to 130 residues) as substrate after 1 hr in the presence of S-adenosyl-L-methionine by high throughput mass spectrometry	ic50	0.0002	uM
(1R,2S,3R,5S)-3-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[2-(2-aminoquinolin-7-yl)ethyl]cyclopentane-1,2-diol	1593844: Inhibition of full-length human N-terminal FLAG-tagged PRMT5/full length N-terminal His6-tagged MEP50 (unknown origin) expressed in baculovirus infected Sf9 insect cells assessed as reduction of S-adenosyl-L-homocysteine formation using human recombinant histone H2A (1 to 130 residues) as substrate after 1 hr in the presence of S-adenosyl-L-methionine by high throughput mass spectrometry	ic50	0.0003	uM
(1R,2S,3R,5S)-3-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[2-(6-fluoro-3-methylimidazo[1,2-a]pyridin-7-yl)ethyl]cyclopentane-1,2-diol	1593844: Inhibition of full-length human N-terminal FLAG-tagged PRMT5/full length N-terminal His6-tagged MEP50 (unknown origin) expressed in baculovirus infected Sf9 insect cells assessed as reduction of S-adenosyl-L-homocysteine formation using human recombinant histone H2A (1 to 130 residues) as substrate after 1 hr in the presence of S-adenosyl-L-methionine by high throughput mass spectrometry	ic50	0.0003	uM
(1S,2R,3S,5R)-3-[4-(6-amino-2-pyridinyl)butyl]-5-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol	1593844: Inhibition of full-length human N-terminal FLAG-tagged PRMT5/full length N-terminal His6-tagged MEP50 (unknown origin) expressed in baculovirus infected Sf9 insect cells assessed as reduction of S-adenosyl-L-homocysteine formation using human recombinant histone H2A (1 to 130 residues) as substrate after 1 hr in the presence of S-adenosyl-L-methionine by high throughput mass spectrometry	ic50	0.0004	uM
(2S)-2-[[(2S)-5-amino-2-[[2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]pentanoyl]amino]-5-[[N’-[3-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]propyl]carbamimidoyl]amino]pentanoic acid	2127549: Inhibition of human PRMT5/MEP50 using Histone H2 as substrate and SAM as cofactor by radiometric HotSpot assay	ic50	0.0004	uM
(2R,3S,4R,5R)-2-[(R)-(4-chlorophenyl)-hydroxymethyl]-5-(4-hydrazinylpyrrolo[2,3-d]pyrimidin-7-yl)oxolane-3,4-diol	1593838: Inhibition of PRMT5 (unknown origin)/MEP50 (unknown origin) using histone H2 as substrate preincubated for 15 to 20 mins followed by S-[methyl-3H]adenosyl-L-methionine addition measured after 60 mins by liquid scintillation counting	ic50	0.0006	uM
(1R,2S,3R,5S)-3-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[2-[2-(cyclopropylmethylamino)quinolin-7-yl]ethyl]cyclopentane-1,2-diol	1593844: Inhibition of full-length human N-terminal FLAG-tagged PRMT5/full length N-terminal His6-tagged MEP50 (unknown origin) expressed in baculovirus infected Sf9 insect cells assessed as reduction of S-adenosyl-L-homocysteine formation using human recombinant histone H2A (1 to 130 residues) as substrate after 1 hr in the presence of S-adenosyl-L-methionine by high throughput mass spectrometry	ic50	0.0008	uM
(1R,2S,3R,5S)-3-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[2-(3-methylimidazo[1,2-a]pyridin-7-yl)ethyl]cyclopentane-1,2-diol	1593844: Inhibition of full-length human N-terminal FLAG-tagged PRMT5/full length N-terminal His6-tagged MEP50 (unknown origin) expressed in baculovirus infected Sf9 insect cells assessed as reduction of S-adenosyl-L-homocysteine formation using human recombinant histone H2A (1 to 130 residues) as substrate after 1 hr in the presence of S-adenosyl-L-methionine by high throughput mass spectrometry	ic50	0.0008	uM
(2R,3R,3aS,6S,6aR)-6-[(2-amino-3-bromoquinolin-7-yl)methyl]-2-(4-methylpyrrolo[2,3-d]pyrimidin-7-yl)-3,4,6,6a-tetrahydro-2H-furo[3,4-b]furan-3,3a-diol	2106926: Inhibition of PRMT5/MEP50 (unknown origin)	ic50	0.0008	uM
1-[4-[[4-[(3S,4S)-4-(3,4-dihydro-1H-isoquinolin-2-yl)-3-hydroxypiperidine-1-carbonyl]-5-fluoro-2-pyridinyl]amino]piperidin-1-yl]ethanone	1997243: Inhibition of full-length recombinant PRMT5/full-length recombinant MEP50 (unknown origin) expressed in baculovirus infected Sf21 cells using biotinylated H4R3(Mel) peptide as substrate preincubated for 60 mins followed by substrate addition and measured for 150 minutes in the presence of SAM by methylation assay	ec50	0.0009	uM
(2R,3R,4S,5R)-2-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[(R)-(3,4-difluorophenyl)-hydroxymethyl]oxolane-3,4-diol	1593836: Inhibition of full length N-terminal FLAG-tagged PRMT5 (unknown origin)/MEP50 (unknown origin) expressed in baculovirus infected Sf21 insect cells using H4(1-21) peptide SGRGKGGKGLGKGGAKRHRKV as substrate measured after 25 minutes in the presence of [3H]SAM by liquid scintillation counting	ic50	0.0010	uM
(2R,3R,4S,5R)-2-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[(R)-(4-chlorophenyl)-hydroxymethyl]oxolane-3,4-diol	1593836: Inhibition of full length N-terminal FLAG-tagged PRMT5 (unknown origin)/MEP50 (unknown origin) expressed in baculovirus infected Sf21 insect cells using H4(1-21) peptide SGRGKGGKGLGKGGAKRHRKV as substrate measured after 25 minutes in the presence of [3H]SAM by liquid scintillation counting	ic50	0.0010	uM
N-(6-amino-5-methyl-3-pyridinyl)-2-[(2R,5S)-2-(1,3-benzothiazol-5-yl)-5-methylpiperidin-1-yl]-2-oxoacetamide	2104822: Substrate competitive inhibition of human PRMT5/MEP50 complex preincubated for 30 mins with [3H]SAM followed by incubation with 1 uM histone H4 (1 to 21) peptide for 2.5 hrs by radioactive flash plate based scintillation counting analysis	ki	0.0010	uM
(2R,3R,4S,5R)-2-(4-amino-5-fluoropyrrolo[2,3-d]pyrimidin-7-yl)-5-[(R)-(3,4-difluorophenyl)-hydroxymethyl]oxolane-3,4-diol	1593836: Inhibition of full length N-terminal FLAG-tagged PRMT5 (unknown origin)/MEP50 (unknown origin) expressed in baculovirus infected Sf21 insect cells using H4(1-21) peptide SGRGKGGKGLGKGGAKRHRKV as substrate measured after 25 minutes in the presence of [3H]SAM by liquid scintillation counting	ic50	0.0020	uM
(1R,2S,3R,5R)-3-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[(S)-(3,4-difluorophenyl)-hydroxymethyl]cyclopentane-1,2-diol	1593838: Inhibition of PRMT5 (unknown origin)/MEP50 (unknown origin) using histone H2 as substrate preincubated for 15 to 20 mins followed by S-[methyl-3H]adenosyl-L-methionine addition measured after 60 mins by liquid scintillation counting	ic50	0.0020	uM
2-(cyclobutylamino)-N-[(2S)-3-(3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxypropyl]pyridine-4-carboxamide	2156116: Inhibition of Flag-tagged human PRMT5/his-tagged MEP50 (unknown origin) expressed in baculovirus expression system using Sm3d as substrate assessed as apparent inhibition constant preincubated for 60 mins followed by substrate addition and measured after 30 mins by Cheng-Prusoff plot analysis	ki	0.0024	uM
6-(6-azaspiro[2.5]octane-6-carbonyl)-2-[(2R)-2-hydroxy-2-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]ethyl]-4,4-dimethyl-3H-isoquinolin-1-one	1997232: Inhibition of PRMT5/MEP50 (unknown origin) using histone H4 peptide as substrate preincubated for 30 mins followed by substrate addition and measured for 60 mins by AlphaScreen analysis	ic50	0.0028	uM
(2R,3S,4R,5R)-2-[(R)-(3,4-difluorophenyl)-hydroxymethyl]-5-(4-methylpyrrolo[2,3-d]pyrimidin-7-yl)oxolane-3,4-diol	1593836: Inhibition of full length N-terminal FLAG-tagged PRMT5 (unknown origin)/MEP50 (unknown origin) expressed in baculovirus infected Sf21 insect cells using H4(1-21) peptide SGRGKGGKGLGKGGAKRHRKV as substrate measured after 25 minutes in the presence of [3H]SAM by liquid scintillation counting	ic50	0.0030	uM
(2R,3R,4S,5R)-2-(6-aminopurin-9-yl)-5-[(R)-(3,4-difluorophenyl)-hydroxymethyl]oxolane-3,4-diol	1593836: Inhibition of full length N-terminal FLAG-tagged PRMT5 (unknown origin)/MEP50 (unknown origin) expressed in baculovirus infected Sf21 insect cells using H4(1-21) peptide SGRGKGGKGLGKGGAKRHRKV as substrate measured after 25 minutes in the presence of [3H]SAM by liquid scintillation counting	ic50	0.0030	uM
(3S)-2-[(5-amino-1H-pyrrolo[3,2-b]pyridin-2-yl)methyl]-6-fluoro-1’-[(4-fluorophenyl)methyl]spiro[isoindole-3,3’-pyrrolidine]-1,2’-dione	2113476: Inhibition of PRMT5 (1 to 637 residues)/MEP504 (2 to 342 residues)(unknown origin) expressed in baculovirus infected Sf21 insect cells using histone H4/SAM as substrate incubated for 5 hrs in presence of MTA by MTase Glo assay	ic50	0.0030	uM
6-[(1-acetylpiperidin-4-yl)amino]-N-[(2S)-3-(3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxypropyl]pyrimidine-4-carboxamide	2156115: Inhibition of Flag-tagged human PRMT5/his-tagged MEP50 (unknown origin) expressed in baculovirus expression system using H2A as substrate assessed as apparent inhibition constant preincubated for 60 mins followed by substrate addition and measured after 30 mins by Cheng-Prusoff plot analysis	ki	0.0030	uM
(1S,2R,3S,5R)-3-[2-(6-amino-3-pyridinyl)ethyl]-5-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol	1593844: Inhibition of full-length human N-terminal FLAG-tagged PRMT5/full length N-terminal His6-tagged MEP50 (unknown origin) expressed in baculovirus infected Sf9 insect cells assessed as reduction of S-adenosyl-L-homocysteine formation using human recombinant histone H2A (1 to 130 residues) as substrate after 1 hr in the presence of S-adenosyl-L-methionine by high throughput mass spectrometry	ic50	0.0050	uM
(2R,3R,4S,5R)-2-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[(R)-hydroxy(phenyl)methyl]oxolane-3,4-diol	1356237: Inhibition of PRMT5/MEP50 complex (unknown origin) expressed in Sf9 insect cells using SGRGKGGKGLGKGGAKRHRKVLRDK-Biotin as substrate by surface plasmon resonance assay	kd	0.0060	uM
(1R,2S,3R,5S)-3-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-(2-quinolin-7-ylethyl)cyclopentane-1,2-diol	1593844: Inhibition of full-length human N-terminal FLAG-tagged PRMT5/full length N-terminal His6-tagged MEP50 (unknown origin) expressed in baculovirus infected Sf9 insect cells assessed as reduction of S-adenosyl-L-homocysteine formation using human recombinant histone H2A (1 to 130 residues) as substrate after 1 hr in the presence of S-adenosyl-L-methionine by high throughput mass spectrometry	ic50	0.0063	uM
(2R,3R,4S,5R)-2-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[(8-methyl-1,8-diazaspiro[4.5]decan-1-yl)methyl]oxolane-3,4-diol	1725892: Binding affinity to N-terminal FLAG-tagged human PRMT5 (1 to 637 residues)/N-terminal thrombin His-tagged MEP50 (2 to 342 residues) expressed in baculovirus infected Sf21 cells by streptavidin coated sensor chip based surface plasmon resonance analysis	kd	0.0076	uM
(1R,2S,3R,5R)-3-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-[(E)-2-quinolin-7-ylethenyl]cyclopentane-1,2-diol	1593844: Inhibition of full-length human N-terminal FLAG-tagged PRMT5/full length N-terminal His6-tagged MEP50 (unknown origin) expressed in baculovirus infected Sf9 insect cells assessed as reduction of S-adenosyl-L-homocysteine formation using human recombinant histone H2A (1 to 130 residues) as substrate after 1 hr in the presence of S-adenosyl-L-methionine by high throughput mass spectrometry	ic50	0.0079	uM
2-[[2-(diaminomethylideneamino)-1,3-thiazol-5-yl]methyl]-5-fluoro-N-[(4-fluorophenyl)methyl]-3-oxo-1H-isoindole-1-carboxamide	2113476: Inhibition of PRMT5 (1 to 637 residues)/MEP504 (2 to 342 residues)(unknown origin) expressed in baculovirus infected Sf21 insect cells using histone H4/SAM as substrate incubated for 5 hrs in presence of MTA by MTase Glo assay	ic50	0.0080	uM
(3S)-6-fluoro-1’-[(4-fluorophenyl)methyl]-2-(1H-pyrrolo[3,2-b]pyridin-2-ylmethyl)spiro[isoindole-3,3’-pyrrolidine]-1,2’-dione	2113476: Inhibition of PRMT5 (1 to 637 residues)/MEP504 (2 to 342 residues)(unknown origin) expressed in baculovirus infected Sf21 insect cells using histone H4/SAM as substrate incubated for 5 hrs in presence of MTA by MTase Glo assay	ic50	0.0080	uM
2-(4-bromobenzoyl)-N-[(2S)-3-(3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxypropyl]-3,4-dihydro-1H-isoquinoline-6-carboxamide	1613956: Inhibition of recombinant human N-terminal FLAG-tagged PRMT5 (2 to end residues)/human N-terminal His-tagged MEP50 (2 to end residues) expressed in HEK293F cells using H4 peptide as substrate preincubated for 15 mins followed by substrate and [3H]SAM addition and measured after 1 hr by scintillation counting method	ic50	0.0085	uM
(2R,3S,4R,5R)-2-[(R)-amino-(3,4-difluorophenyl)methyl]-5-(4-methylpyrrolo[2,3-d]pyrimidin-7-yl)oxolane-3,4-diol	1593836: Inhibition of full length N-terminal FLAG-tagged PRMT5 (unknown origin)/MEP50 (unknown origin) expressed in baculovirus infected Sf21 insect cells using H4(1-21) peptide SGRGKGGKGLGKGGAKRHRKV as substrate measured after 25 minutes in the presence of [3H]SAM by liquid scintillation counting	ic50	0.0090	uM
N-cyclopropyl-2-[[2-(diaminomethylideneamino)-1,3-thiazol-5-yl]methyl]-N-[(4-fluorophenyl)methyl]-3-oxo-1H-isoindole-1-carboxamide	2113476: Inhibition of PRMT5 (1 to 637 residues)/MEP504 (2 to 342 residues)(unknown origin) expressed in baculovirus infected Sf21 insect cells using histone H4/SAM as substrate incubated for 5 hrs in presence of MTA by MTase Glo assay	ic50	0.0090	uM
(3S)-2-[(6-amino-1H-pyrrolo[2,3-b]pyridin-2-yl)methyl]-6-fluoro-1’-[(4-fluorophenyl)methyl]spiro[isoindole-3,3’-pyrrolidine]-1,2’-dione	2113476: Inhibition of PRMT5 (1 to 637 residues)/MEP504 (2 to 342 residues)(unknown origin) expressed in baculovirus infected Sf21 insect cells using histone H4/SAM as substrate incubated for 5 hrs in presence of MTA by MTase Glo assay	ic50	0.0090	uM
(2R,3R,4S,5R)-2-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-5-(1,8-diazaspiro[4.5]decan-1-ylmethyl)oxolane-3,4-diol	1725890: Inhibition of full-length human N-terminal FLAG-tagged PRMT5/full length N-terminal His6-tagged MEP50 (unknown origin) expressed in baculovirus infected Sf9 insect cells assessed as reduction of S-adenosyl-L-homocysteine formation using human recombinant histone H2A (1 to 130 residues) and S-adenosyl-L-methionine as substrate after 60 mins by rapidfire mass spectrometry analysis	ic50	0.0095	uM
2-[[2-(diaminomethylideneamino)-1,3-thiazol-5-yl]methyl]-N-[(4-fluorophenyl)methyl]-N-methyl-3-oxo-1H-isoindole-1-carboxamide	2113476: Inhibition of PRMT5 (1 to 637 residues)/MEP504 (2 to 342 residues)(unknown origin) expressed in baculovirus infected Sf21 insect cells using histone H4/SAM as substrate incubated for 5 hrs in presence of MTA by MTase Glo assay	ic50	0.0100	uM
(2R,3S,4R,5R)-2-[(R)-(4-chlorophenyl)-hydroxymethyl]-5-(5-hydroxy-3,6,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1(9),2,7,11-tetraen-10-yl)oxolane-3,4-diol	1510878: Inhibition of human recombinant PRMT5/MEP50 expressed in baculovirus infected High-five cells using histone 4 peptide as substrate in presence of [3H]SAM preincubated for 20 mins followed by [3H]SAM addition and measured after 30 mins by scintillation counting method	ic50	0.0110	uM
2-(4-bromobenzoyl)-N-[3-(3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxypropyl]-3,4-dihydro-1H-isoquinoline-6-carboxamide	1613956: Inhibition of recombinant human N-terminal FLAG-tagged PRMT5 (2 to end residues)/human N-terminal His-tagged MEP50 (2 to end residues) expressed in HEK293F cells using H4 peptide as substrate preincubated for 15 mins followed by substrate and [3H]SAM addition and measured after 1 hr by scintillation counting method	ic50	0.0110	uM
N-[(2S)-3-(3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxypropyl]-2-[4-(dimethylamino)benzoyl]-3,4-dihydro-1H-isoquinoline-6-carboxamide	1613956: Inhibition of recombinant human N-terminal FLAG-tagged PRMT5 (2 to end residues)/human N-terminal His-tagged MEP50 (2 to end residues) expressed in HEK293F cells using H4 peptide as substrate preincubated for 15 mins followed by substrate and [3H]SAM addition and measured after 1 hr by scintillation counting method	ic50	0.0110	uM
N-[(2R)-3-(3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxypropyl]-2-quinolin-8-yloxyacetamide	1685690: Inhibition of human full length FLAG-tagged PRMT5/human His6-tagged MEP50 expressed in baculovirus-infected Sf9 cells assessed as reduction in tritium incorporation into peptide substrate using human Histone H4 (1 to 15 residues) and [3H]SAM as substrate preincubated with enzyme and H4 for 30 mins followed by [3H]SAM addition and measured after 120 mins by radioactive flashplate assay	ic50	0.0110	uM
(5R)-5-(1-adamantyl)-2-amino-3-methyl-5-phenylimidazol-4-one	1662036: Inhibition of recombinant Avi-tagged PRMT5 (2 to 637)/ His-tagged MEP50 (2 to 342) (unknown origin) expressed in baculovirus infected Sf21 cells using biotinylated H4R3 (Me1) peptide as substrate in presence of SAM preincubated for 60 mins followed by substrate addition after 150 mins by biochemical methylation assay	ec50	0.0120	uM
N-[(2S)-3-(3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxypropyl]-6-[[1-[2-[2-[2-[2-[2-[2-[[(2S)-1-[(2R,4S)-4-hydroxy-2-[[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-2-oxoethoxy]ethoxy]ethoxy]ethoxy]ethoxy]acetyl]azetidin-3-yl]amino]pyrimidine-4-carboxamide	1722836: Inhibition of human PRMT5/MEP50 assessed as reduction in methyltransferase activity using histone 4 peptide as substrate in presence of [3H]SAM incubated for 30 mins	ic50	0.0120	uM
2-[[2-(diaminomethylideneamino)-1,3-thiazol-5-yl]methyl]-N-[(4-fluorophenyl)methyl]-5-methoxy-3-oxo-1H-isoindole-1-carboxamide	2113476: Inhibition of PRMT5 (1 to 637 residues)/MEP504 (2 to 342 residues)(unknown origin) expressed in baculovirus infected Sf21 insect cells using histone H4/SAM as substrate incubated for 5 hrs in presence of MTA by MTase Glo assay	ic50	0.0120	uM
N-[(2S)-3-(3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxypropyl]-2-(4-methoxybenzoyl)-3,4-dihydro-1H-isoquinoline-6-carboxamide	1613956: Inhibition of recombinant human N-terminal FLAG-tagged PRMT5 (2 to end residues)/human N-terminal His-tagged MEP50 (2 to end residues) expressed in HEK293F cells using H4 peptide as substrate preincubated for 15 mins followed by substrate and [3H]SAM addition and measured after 1 hr by scintillation counting method	ic50	0.0130	uM
N-[3-(3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxypropyl]-3-pyridin-2-ylbenzamide	1685690: Inhibition of human full length FLAG-tagged PRMT5/human His6-tagged MEP50 expressed in baculovirus-infected Sf9 cells assessed as reduction in tritium incorporation into peptide substrate using human Histone H4 (1 to 15 residues) and [3H]SAM as substrate preincubated with enzyme and H4 for 30 mins followed by [3H]SAM addition and measured after 120 mins by radioactive flashplate assay	ic50	0.0130	uM
N-[(2S)-3-(3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxypropyl]-3-pyridin-2-ylbenzamide	1685690: Inhibition of human full length FLAG-tagged PRMT5/human His6-tagged MEP50 expressed in baculovirus-infected Sf9 cells assessed as reduction in tritium incorporation into peptide substrate using human Histone H4 (1 to 15 residues) and [3H]SAM as substrate preincubated with enzyme and H4 for 30 mins followed by [3H]SAM addition and measured after 120 mins by radioactive flashplate assay	ic50	0.0130	uM
5-fluoro-N-[(4-fluorophenyl)methyl]-2-[[2-[(N’-methylcarbamimidoyl)amino]-1,3-thiazol-5-yl]methyl]-3-oxo-1H-isoindole-1-carboxamide	2113476: Inhibition of PRMT5 (1 to 637 residues)/MEP504 (2 to 342 residues)(unknown origin) expressed in baculovirus infected Sf21 insect cells using histone H4/SAM as substrate incubated for 5 hrs in presence of MTA by MTase Glo assay	ic50	0.0140	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
sodium arsenite	decreases expression, increases expression	3
cobaltous chloride	decreases expression	2
bisphenol S	increases expression	2
GSK-J4	decreases expression	1
afuresertib	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
nickel chloride	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
celastrol	decreases expression	1
CGP 52608	affects binding, increases reaction	1
gedunin	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, 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
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Microplastics	increases abundance, increases expression	1
Cisplatin	increases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1

ChEMBL screening assays

202 unique, capped per target: 202 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118736	Binding	Binding affinity to WDR77 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8AF	Abcam Raji WDR77 KO	Cancer cell line	Male
CVCL_C0BA	Abcam THP-1 WDR77 KO	Cancer cell line	Male
CVCL_C7CX	Abcam PC-3 WDR77 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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