RBBP5

Summary

RBBP5 (RB binding protein 5, histone lysine methyltransferase complex subunit, HGNC:9888) is a protein-coding gene on chromosome 1q32.1, encoding Retinoblastoma-binding protein 5 (Q15291). In embryonic stem (ES) cells, plays a crucial role in the differentiation potential, particularly along the neural lineage, regulating gene induction and H3 ‘Lys-4’ methylation at key developmental loci, including that mediated by retinoic acid. It is a common-essential gene (DepMap: required in 97.6% of cancer cell lines).

This gene encodes a ubiquitously expressed nuclear protein which belongs to a highly conserved subfamily of WD-repeat proteins. The encoded protein binds directly to retinoblastoma protein, which regulates cell proliferation. It interacts preferentially with the underphosphorylated retinoblastoma protein via the E1A-binding pocket B. Three alternatively spliced transcript variants that encode different protein isoforms have been described for this gene.

Source: NCBI Gene 5929 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 13
• Clinical variants (ClinVar): 41 total — 2 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 97.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_005057

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9888
Approved symbol	RBBP5
Name	RB binding protein 5, histone lysine methyltransferase complex subunit
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	RBQ3, SWD1
Ensembl gene	ENSG00000117222
Ensembl biotype	protein_coding
OMIM	600697
Entrez	5929

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000264515, ENST00000367164, ENST00000484379, ENST00000861177, ENST00000861178, ENST00000861179, ENST00000861180, ENST00000861181, ENST00000912403, ENST00000912404, ENST00000955070

RefSeq mRNA: 3 — MANE Select: NM_005057 NM_001193272, NM_001193273, NM_005057

CCDS: CCDS30983, CCDS53463

Canonical transcript exons

ENST00000264515 — 14 exons

Exon	Start	End
ENSE00000791733	205105028	205105168
ENSE00001040274	205099741	205099812
ENSE00001040279	205099911	205100064
ENSE00001040282	205103857	205104019
ENSE00001040284	205101600	205101709
ENSE00001040285	205098989	205099106
ENSE00001040291	205097326	205097395
ENSE00001040293	205096682	205096911
ENSE00001040298	205094873	205095064
ENSE00001040300	205100152	205100271
ENSE00001267748	205115858	205115883
ENSE00001408697	205086142	205088815
ENSE00003636473	205114789	205114961
ENSE00003851070	205121855	205121978

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 94.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.1395 / max 473.9439, expressed in 1807 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16954	11.8015	1772
16955	7.6973	1754
16953	0.6407	359

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	94.57	gold quality
secondary oocyte	CL:0000655	88.65	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.74	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.23	gold quality
oocyte	CL:0000023	85.09	gold quality
calcaneal tendon	UBERON:0003701	85.05	gold quality
islet of Langerhans	UBERON:0000006	84.03	gold quality
ganglionic eminence	UBERON:0004023	82.62	gold quality
ventricular zone	UBERON:0003053	82.53	gold quality
cortical plate	UBERON:0005343	82.34	gold quality
stromal cell of endometrium	CL:0002255	81.60	gold quality
monocyte	CL:0000576	80.22	gold quality
gastrocnemius	UBERON:0001388	80.18	gold quality
leukocyte	CL:0000738	80.11	gold quality
blood	UBERON:0000178	80.03	gold quality
muscle of leg	UBERON:0001383	79.82	gold quality
tendon	UBERON:0000043	79.80	gold quality
mononuclear cell	CL:0000842	79.75	gold quality
lymph node	UBERON:0000029	79.69	gold quality
rectum	UBERON:0001052	79.38	gold quality
right adrenal gland	UBERON:0001233	79.16	gold quality
adrenal tissue	UBERON:0018303	78.97	gold quality
prefrontal cortex	UBERON:0000451	78.95	gold quality
left adrenal gland	UBERON:0001234	78.90	gold quality
adrenal gland	UBERON:0002369	78.75	gold quality
right adrenal gland cortex	UBERON:0035827	78.68	gold quality
pancreas	UBERON:0001264	78.29	gold quality
left adrenal gland cortex	UBERON:0035825	78.24	gold quality
granulocyte	CL:0000094	78.10	gold quality
adrenal cortex	UBERON:0001235	77.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, KMT2A

miRNA regulators (miRDB)

129 targeting RBBP5, 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-5692A	100.00	74.40	6850
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-570-3P	99.96	72.41	4910

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 17)

• analysis of menin’s role as a tumor suppressor and binding sites of Rbbp5 and MLL1 (PMID:16604156)
• The identified components revealed factors involved in histone methylation and cell cycle control and include Ash2L, RbBP5, WDR5, HCF-1, DBC-1, and EMSY. (PMID:19131338)
• Results show that Depletion of CHD8 enhances HOXA2 expression and a loss of the WDR5/Ash2L/RbBP5 subcomplex. (PMID:20085832)
• MLL1 SET domain make direct contacts with the substrates and contribute to the formation of a joint catalytic center. (PMID:21124902)
• structural and biochemical analyses reveal a basic surface on Ash2L as the RbBP5-binding interface, and this interface is crucial for both RbBP5 binding and MLL1 methyltransferase activity regulation (PMID:22231628)
• Data indicate that MLL1 methylates Ash2L in the absence of histone H3, but only when assembled within a complex with WDR5 and RbBP5. (PMID:24235145)
• Non active site mutations in the MLL1 SET domain render the protein defective for H3K4 dimethylation by the MLL1 core complex, which is associated with a loss of the ability of MLL1 to interact with WRAD or with the RbBP5/Ash2L heterodimer. (PMID:24680668)
• Results from a study on gene expression variability markers in early-stage human embryos shows that RBBP5 is a putative expression variability marker for the 3-day, 8-cell embryo stage. (PMID:26288249)
• This study demonstrated that RBQ3 might play an important role in glioma, and RBQ3 inhibitors might be novel anti-tumor agents. (PMID:26671109)
• role of RBQ3 in the development of multiple myeloma (PMID:27189701)
• this study shows that during epithelial-mesenchymal transition in the prostate cancer cell line RbBP5 binding is increased in the vicinity of Snail transcription start site (PMID:27566588)
• different cancer mutations in MLL1 lead to a loss or increase in activity, illustrating the complex and tumor-specific role of MLL1 in carcinogenesis. (PMID:28182322)
• Our nuclear magnetic resonance binding data supports the hypothesis that in addition to the role of RbBP5 in catalytic activation, its beta-propeller domain is a platform for the recruitment of the MLL complexes to chromatin targets through its direct interaction with nucleic acids. (PMID:29897600)
• RBBP5 plays an important role in the progression of hepatocellular carcinoma. (PMID:30533424)
• We used a hybrid methods approach to study the assembly and biochemical function of the minimally active MLL1 complex (MLL1, WDR5 and RbBP5)..We identified a new interaction site between the MLL1 SET domain and the WD40 beta-propeller domain of RbBP5, and demonstrate the susceptibility of the catalytic function of the complex to disruption of individual interaction sites. (PMID:31400120)
• We identified an internal interaction between the WD40 propeller and the C-terminal distal region in RBBP5, which assisted the maintenance of the compact conformation of the MLL1 complex. We also discovered a vertebrate-specific motif in the C-terminal distal region of RBBP5 that contributed to nucleosome recognition and methylation of nucleosomes by the MLL1 complex. (PMID:31544921)
• Long noncoding RNA AC245100.4 promotes prostate cancer tumorigenesis via the microRNA1455p/RBBP5 axis. (PMID:33416179)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbbp5	ENSDARG00000042147
mus_musculus	Rbbp5	ENSMUSG00000026439
rattus_norvegicus	Rbbp5	ENSRNOG00000021289
drosophila_melanogaster	Rbbp5	FBGN0036973
caenorhabditis_elegans		WBGENE00017683

Paralogs (2): VPS8 (ENSG00000156931), WDR72 (ENSG00000166415)

Protein

Protein identifiers

Retinoblastoma-binding protein 5 — Q15291 (reviewed: Q15291)

Alternative names: Retinoblastoma-binding protein RBQ-3

All UniProt accessions (1): Q15291

UniProt curated annotations — full annotation on UniProt →

Function. In embryonic stem (ES) cells, plays a crucial role in the differentiation potential, particularly along the neural lineage, regulating gene induction and H3 ‘Lys-4’ methylation at key developmental loci, including that mediated by retinoic acid. Does not affect ES cell self-renewal. Component or associated component of some histone methyltransferase complexes which regulates transcription through recruitment of those complexes to gene promoters. As part of the MLL1/MLL complex, involved in mono-, di- and trimethylation at ‘Lys-4’ of histone H3. Histone H3 ‘Lys-4’ methylation represents a specific tag for epigenetic transcriptional activation. In association with ASH2L and WDR5, stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and SETD1B.

Subunit / interactions. Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30. Core component of several methyltransferase-containing complexes including MLL1/MLL, MLL2/3 (also named ASCOM complex) and MLL4/WBP7. Each complex is at least composed of ASH2L, RBBP5, WDR5, DPY30, one or more specific histone methyltransferases (KMT2A/MLL1, KMT2D/MLL2, KMT2C/MLL3 and KMT2B/MLL4), and the facultative components PAGR1, BACC1, CHD8, E2F6, HCFC1, HCFC2, HSP70, INO80C, KDM6A, KANSL1, LAS1L, MAX, MCRS1, MEN1, MGA, MYST1/MOF, NCOA6, PAXIP1/PTIP, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9, TEX10 and alpha- and beta-tubulin. Component of a histone methylation complex composed of at least ZNF335, RBBP5, ASH2L and WDR5; the complex may have histone H3-specific methyltransferase activity, however does not have specificity for ‘Lys-4’ of histone H3. Interacts with ZNF335. Interacts with ASH2L; the interaction is direct. Interacts with WDR5; the interaction is direct. Components of the ZNF335-RBBP5-ASH2L-WDR5 histone methylation complex may associate with components of a nuclear receptor-mediated transcription complex to form a complex at least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and WDR5. Within this complex interacts with EMSY. Found in a complex with RBBP5, ASH2L, DPY30, KMT2A, KMT2D and WDR5. Interacts with SETD1A. Interacts with WDR82.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitously expressed.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15291-1	1	yes
Q15291-2	2

RefSeq proteins (3): NP_001180201, NP_001180202, NP_005048* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR037850	RBBP5/Swd1	Family

Pfam: PF00400

UniProt features (70 total): strand 32, turn 8, repeat 6, modified residue 6, region of interest 4, mutagenesis site 4, compositionally biased region 3, sequence conflict 3, chain 1, cross-link 1, splice variant 1, helix 1

Structure

Experimental structures (PDB)

32 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6KM7	X-RAY DIFFRACTION	1.8
5F6L	X-RAY DIFFRACTION	1.9
4X8N	X-RAY DIFFRACTION	2.1
7W67	X-RAY DIFFRACTION	2.19
4X8P	X-RAY DIFFRACTION	2.2
7W6A	X-RAY DIFFRACTION	2.21
7W6L	X-RAY DIFFRACTION	2.26
3P4F	X-RAY DIFFRACTION	2.35
5F6K	X-RAY DIFFRACTION	2.41
7W6I	X-RAY DIFFRACTION	2.56
7W6J	X-RAY DIFFRACTION	2.68
7BRE	X-RAY DIFFRACTION	2.8
6KIU	ELECTRON MICROSCOPY	3.2
9YM8	ELECTRON MICROSCOPY	3.43
9YMF	ELECTRON MICROSCOPY	3.45
9YL3	ELECTRON MICROSCOPY	3.5
8DU4	ELECTRON MICROSCOPY	3.55
9YLE	ELECTRON MICROSCOPY	3.63
9YLY	ELECTRON MICROSCOPY	3.77
6KIV	ELECTRON MICROSCOPY	4
6KIW	ELECTRON MICROSCOPY	4
7MBN	ELECTRON MICROSCOPY	4.02
6KIX	ELECTRON MICROSCOPY	4.1
6PWX	ELECTRON MICROSCOPY	4.2
7UD5	ELECTRON MICROSCOPY	4.25
6PWW	ELECTRON MICROSCOPY	4.4
6KIZ	ELECTRON MICROSCOPY	4.5
6W5M	ELECTRON MICROSCOPY	4.6
7MBM	ELECTRON MICROSCOPY	4.76
6W5N	ELECTRON MICROSCOPY	6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15291-F1	78.41	0.56

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 (7): 252, 350, 388, 389, 497, 525, 129

Mutagenesis-validated functional residues (4):

Position	Phenotype
374	significant reduction in its ability to stimulate kmt2a methyltransferase activity in association with wdr5 and ash2l.
375	significant reduction in its ability to stimulate kmt2a methyltransferase activity in association with wdr5 and ash2l.
376	reduced ability to stimulate kmt2a methyltransferase activity in association with wdr5 and ash2l.
377	reduced ability to stimulate kmt2a methyltransferase activity in association with wdr5 and ash2l.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-201722	Formation of the beta-catenin:TCF transactivating complex
R-HSA-3214841	PKMTs methylate histone lysines
R-HSA-3769402	Deactivation of the beta-catenin transactivating complex
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-8936459	RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
R-HSA-8951664	Neddylation
R-HSA-9772755	Formation of WDR5-containing histone-modifying complexes
R-HSA-9818564	Epigenetic regulation of gene expression by MLL3 and MLL4 complexes
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis
R-HSA-9909649	Regulation of PD-L1(CD274) transcription
R-HSA-9944997	Loss of Function of KMT2D in MLL4 Complex Formation in Kabuki Syndrome
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)

MSigDB gene sets: 242 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, BROWNE_HCMV_INFECTION_8HR_UP, AAGTCCA_MIR422B_MIR422A, HOFMANN_CELL_LYMPHOMA_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_RESPONSE_TO_ESTROGEN, GOBP_DNA_DAMAGE_RESPONSE, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, CLIMENT_BREAST_CANCER_COPY_NUMBER_UP, GOBP_RESPONSE_TO_HORMONE, TCCAGAG_MIR518C, ZHANG_BREAST_CANCER_PROGENITORS_UP, ACEVEDO_LIVER_CANCER_UP, GOBP_CHROMATIN_REMODELING

GO Biological Process (4): DNA damage response (GO:0006974), response to estrogen (GO:0043627), transcription initiation-coupled chromatin remodeling (GO:0045815), chromatin organization (GO:0006325)

GO Molecular Function (3): transcription cis-regulatory region binding (GO:0000976), histone binding (GO:0042393), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), histone methyltransferase complex (GO:0035097), MLL1/2 complex (GO:0044665), MLL3/4 complex (GO:0044666), Set1C/COMPASS complex (GO:0048188), MLL1 complex (GO:0071339)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
TCF dependent signaling in response to WNT	2
Epigenetic regulation by WDR5-containing histone modifying complexes	2
Chromatin modifying enzymes	1
Activation of HOX genes during differentiation	1
Transcriptional regulation by RUNX1	1
Post-translational protein modification	1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1
Regulation of PD-L1(CD274) expression	1
Loss of Function of KMT2D in Kabuki Syndrome	1
Differentiation of T cells	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
histone methyltransferase complex	3
nuclear lumen	2
cellular response to stress	1
response to hormone	1
transcription initiation at RNA polymerase II promoter	1
positive regulation of gene expression, epigenetic	1
cellular component organization	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
intracellular membraneless organelle	1
nucleoplasm	1
methyltransferase complex	1
nuclear protein-containing complex	1
MLL1/2 complex	1

Protein interactions and networks

STRING

2423 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBBP5	SETD1A	O15047	999
RBBP5	DPY30	Q9C005	999
RBBP5	ASH2L	Q9UBL3	999
RBBP5	WDR82	Q6UXN9	998
RBBP5	CXXC1	Q9P0U4	997
RBBP5	SETD1B	Q9UPS6	994
RBBP5	WDR5	P61964	993
RBBP5	SDC1	P18827	989
RBBP5	HCFC1	P51610	988
RBBP5	KMT2C	Q8NEZ4	985
RBBP5	KDM6A	O15550	968
RBBP5	PAXIP1	Q6ZW49	955
RBBP5	NCOA6	Q14686	946
RBBP5	KMT2A	Q03164	896
RBBP5	H3C1	P02295	880

IntAct

239 interactions, top by confidence:

A	B	Type	Score
ASH2L	RBBP5	psi-mi:“MI:0915”(physical association)	0.980
RBBP5	ASH2L	psi-mi:“MI:0915”(physical association)	0.980
RBBP5	ASH2L	psi-mi:“MI:0407”(direct interaction)	0.980
ASH2L	RBBP5	psi-mi:“MI:0914”(association)	0.980
ASH2L	RBBP5	psi-mi:“MI:0407”(direct interaction)	0.980
WDR5	RBBP5	psi-mi:“MI:0914”(association)	0.960
RBBP5	WDR5	psi-mi:“MI:0915”(physical association)	0.960
RBBP5	WDR5	psi-mi:“MI:0914”(association)	0.960
WDR5	RBBP5	psi-mi:“MI:0915”(physical association)	0.960
RBBP5	WDR5	psi-mi:“MI:0407”(direct interaction)	0.960
KMT2A	WDR5	psi-mi:“MI:0915”(physical association)	0.960
WDR5	RBBP5	psi-mi:“MI:0407”(direct interaction)	0.960
ASH2L	WDR5	psi-mi:“MI:0915”(physical association)	0.950
ASH2L	WDR5	psi-mi:“MI:0914”(association)	0.950
KMT2A	RBBP5	psi-mi:“MI:0915”(physical association)	0.940
RBBP5	KMT2A	psi-mi:“MI:0914”(association)	0.940
RBBP5	KMT2A	psi-mi:“MI:0407”(direct interaction)	0.940

BioGRID (768): RBBP5 (Affinity Capture-Western), RBBP5 (Reconstituted Complex), ASH2L (Two-hybrid), RBBP5 (Co-localization), RBBP5 (Affinity Capture-Western), RBBP5 (Affinity Capture-Western), RBBP5 (Affinity Capture-Western), RBBP5 (Affinity Capture-Western), RBBP5 (Affinity Capture-Western), RBBP5 (Affinity Capture-Western), RBBP5 (Affinity Capture-Western), RBBP5 (Affinity Capture-Western), RBBP5 (Reconstituted Complex), RBBP5 (Affinity Capture-MS), WDR33 (Co-fractionation)

ESM2 similar proteins: A0A2R8QPS5, A0A571BF63, A0A8M9QN10, A1A535, A1A5P5, A2BID5, A4D1P6, A9JRI0, B2RYI0, D3YVL2, F1QNV4, P97874, Q05B30, Q0WV90, Q15291, Q1LUT1, Q1LXR6, Q27GK7, Q2HJE1, Q32PH0, Q3TZ89, Q3U0M1, Q3UMY5, Q4V9P9, Q5NBT9, Q5PQS3, Q5R5R2, Q5R6T6, Q5ZLL7, Q6AI08, Q6DTM3, Q6PA97, Q6TEN6, Q7TMQ7, Q7Z3E5, Q7ZVL2, Q84JM4, Q8BL99, Q8CFJ9, Q8N957

Diamond homologs: A0A1W2PR48, A6ZQL5, A8XZJ9, O02482, O13166, O13168, O42469, O42470, O42478, P16371, P40066, P47025, P63002, P63003, P79083, Q04724, Q04725, Q04726, Q04727, Q06078, Q07141, Q08117, Q08122, Q08924, Q0VA16, Q15291, Q54H44, Q54MZ3, Q5ZJH5, Q62440, Q62441, Q6AY87, Q6GPP0, Q7RXH4, Q86W42, Q8BX09, Q9H808, Q9JIT3, Q9WVB2, Q9WVB3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RBBP5	“form complex”	“MLL/SET subcomplex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 138 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
Formation of WDR5-containing histone-modifying complexes	21	51.6×	3e-29
Deactivation of the beta-catenin transactivating complex	10	21.6×	5e-09
Activation of HOX genes during differentiation	5	20.3×	2e-04
Epigenetic regulation by WDR5-containing histone modifying complexes	13	18.6×	6e-11
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	9	16.4×	3e-07
PKMTs methylate histone lysines	10	14.9×	1e-07
Formation of the beta-catenin:TCF transactivating complex	11	12.2×	1e-07
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	11	12.2×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
transcription initiation-coupled chromatin remodeling	7	21.1×	8e-06
positive regulation of miRNA transcription	6	13.7×	6e-04
cellular response to UV	5	11.6×	6e-03
positive regulation of transcription initiation by RNA polymerase II	5	10.7×	7e-03
methylation	6	8.0×	7e-03
chromatin remodeling	13	7.5×	6e-06
DNA damage response	12	5.0×	6e-04
transcription by RNA polymerase II	9	5.0×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	17
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
3384178	NM_005057.4(RBBP5):c.695C>T (p.Thr232Ile)	Pathogenic
3724725	NM_005057.4(RBBP5):c.1203T>G (p.Tyr401Ter)	Pathogenic

SpliceAI

2322 predictions. Top by Δscore:

Variant	Effect	Δscore
1:205095062:CTT:C	acceptor_gain	1.0000
1:205095065:C:CC	acceptor_gain	1.0000
1:205096928:C:CT	acceptor_gain	1.0000
1:205096929:A:T	acceptor_gain	1.0000
1:205096932:C:CT	acceptor_gain	1.0000
1:205096933:A:T	acceptor_gain	1.0000
1:205096939:T:C	acceptor_gain	1.0000
1:205096939:T:TC	acceptor_gain	1.0000
1:205097320:GCTCA:G	donor_loss	1.0000
1:205097321:CTCAC:C	donor_loss	1.0000
1:205097322:TCACC:T	donor_loss	1.0000
1:205097323:CACCT:C	donor_loss	1.0000
1:205097324:A:C	donor_loss	1.0000
1:205097325:C:CG	donor_loss	1.0000
1:205097325:CCTG:C	donor_gain	1.0000
1:205097391:AGCCC:A	acceptor_gain	1.0000
1:205097392:GCCC:G	acceptor_gain	1.0000
1:205097393:CCC:C	acceptor_gain	1.0000
1:205097393:CCCC:C	acceptor_gain	1.0000
1:205097394:CC:C	acceptor_gain	1.0000
1:205097394:CCC:C	acceptor_gain	1.0000
1:205097395:CC:C	acceptor_gain	1.0000
1:205097396:C:CC	acceptor_gain	1.0000
1:205097396:C:G	acceptor_loss	1.0000
1:205097399:C:CT	acceptor_gain	1.0000
1:205097400:A:T	acceptor_gain	1.0000
1:205097404:C:CT	acceptor_gain	1.0000
1:205097405:A:T	acceptor_gain	1.0000
1:205098985:GTA:G	donor_loss	1.0000
1:205098986:TA:T	donor_loss	1.0000

AlphaMissense

3522 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:205096873:A:G	L402S	1.000
1:205097362:A:T	V377D	1.000
1:205099026:A:C	D353E	1.000
1:205099026:A:T	D353E	1.000
1:205099027:T:A	D353V	1.000
1:205099027:T:C	D353G	1.000
1:205099027:T:G	D353A	1.000
1:205099028:C:G	D353H	1.000
1:205099029:A:C	F352L	1.000
1:205099029:A:T	F352L	1.000
1:205099030:A:C	F352C	1.000
1:205099030:A:G	F352S	1.000
1:205099031:A:C	F352V	1.000
1:205099031:A:G	F352L	1.000
1:205099031:A:T	F352I	1.000
1:205099038:T:A	E349D	1.000
1:205099038:T:G	E349D	1.000
1:205099039:T:A	E349V	1.000
1:205099044:T:A	E347D	1.000
1:205099044:T:G	E347D	1.000
1:205099045:T:A	E347V	1.000
1:205099046:C:T	E347K	1.000
1:205099051:T:C	Y345C	1.000
1:205099051:T:G	Y345S	1.000
1:205099052:A:G	Y345H	1.000
1:205099059:A:C	N342K	1.000
1:205099059:A:T	N342K	1.000
1:205099061:T:C	N342D	1.000
1:205099061:T:G	N342H	1.000
1:205099069:A:C	L339W	1.000

dbSNP variants (sampled 300 via entrez): RS1000108117 (1:205094053 T>C), RS1000218243 (1:205111640 C>T), RS1000226918 (1:205112728 T>C), RS1000244139 (1:205119058 G>A), RS1000270506 (1:205111249 C>A), RS1000383888 (1:205117577 T>A), RS1000393097 (1:205107070 G>A), RS1000441527 (1:205086910 C>T), RS1000512635 (1:205106186 A>C,T), RS1000533469 (1:205111926 T>C), RS1000573918 (1:205104746 C>A), RS1000659606 (1:205112639 T>G), RS1000671767 (1:205118876 T>C), RS1000713535 (1:205105850 A>G), RS1000761860 (1:205118568 G>A)

Disease associations

OMIM: gene MIM:600697 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST002184_3	Mean platelet volume	3.000000e-13
GCST004634_4	Basophil percentage of granulocytes	3.000000e-12
GCST010143_34	Meat-related diet	1.000000e-08
GCST010143_9	Meat-related diet	4.000000e-11
GCST010244_365	Triglyceride levels	4.000000e-11
GCST010697_12	Cortical surface area (min-P)	6.000000e-10
GCST010698_16	Subcortical volume (min-P)	8.000000e-09
GCST010699_52	Brain morphology (min-P)	5.000000e-08
GCST010700_66	Cortical thickness (MOSTest)	3.000000e-09
GCST010701_17	Cortical surface area (MOSTest)	5.000000e-08
GCST010702_2	Subcortical volume (MOSTest)	3.000000e-08
GCST010703_27	Brain morphology (MOSTest)	5.000000e-09
GCST90002395_551	Mean platelet volume	8.000000e-17

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007995	basophil percentage of granulocytes
EFO:0008111	diet measurement
EFO:0004530	triglyceride measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3108651 (SINGLE PROTEIN), CHEMBL3137282 (PROTEIN COMPLEX), CHEMBL4106124 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (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

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

ChEMBL bioactivities

47 potent at pChembl≥5 of 49 total, top 45 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.90	IC50	12.6	nM	CHEMBL4073865
7.90	IC50	12.7	nM	CHEMBL4103117
7.82	IC50	15.2	nM	CHEMBL4648206
7.66	IC50	21.8	nM	CHEMBL4646694
7.59	IC50	25.5	nM	CHEMBL4645555
7.53	IC50	29.6	nM	CHEMBL4632716
7.33	IC50	46.8	nM	CHEMBL4649421
7.25	IC50	55.6	nM	CHEMBL4633548
7.20	Kd	63	nM	MOLIBRESIB
7.18	IC50	66.5	nM	CHEMBL4641078
7.14	IC50	72.4	nM	CHEMBL4643465
7.10	IC50	80	nM	MOLIBRESIB
7.07	IC50	84.8	nM	CHEMBL4094433
7.00	IC50	99.5	nM	CHEMBL4637676
6.92	IC50	119	nM	CHEMBL4636460
6.91	IC50	124	nM	CHEMBL4102238
6.90	IC50	127	nM	CHEMBL4638858
6.88	IC50	132	nM	CHEMBL4647930
6.86	IC50	138	nM	CHEMBL4092028
6.86	IC50	138.4	nM	CHEMBL4638624
6.82	IC50	150.2	nM	CHEMBL4635991
6.72	IC50	190	nM	CHEMBL3884329
6.72	IC50	190	nM	CHEMBL4064300
6.70	IC50	201	nM	CHEMBL4649846
6.67	IC50	216	nM	CHEMBL4072805
6.63	IC50	234	nM	CHEMBL4635424
6.52	IC50	300	nM	CHEMBL3798088
6.52	IC50	300	nM	CHEMBL3884726
6.43	IC50	373	nM	CHEMBL4099772
6.40	IC50	400	nM	CHEMBL3883592
6.35	IC50	451	nM	CHEMBL4641985
6.34	IC50	452	nM	CHEMBL4084272
6.32	IC50	477	nM	CHEMBL4086696
6.24	IC50	578	nM	CHEMBL3799591
6.23	IC50	592	nM	CHEMBL4633905
6.14	IC50	724	nM	S-ADENOSYLHOMOCYSTEINE
6.13	IC50	744	nM	CHEMBL4078842
6.12	IC50	750	nM	CHEMBL3883592
6.05	IC50	900	nM	CHEMBL3883592
5.90	IC50	1259	nM	CHEMBL4065250
5.82	IC50	1527	nM	CHEMBL4099696
5.78	IC50	1650	nM	CHEMBL3885241
5.75	IC50	1800	nM	CHEMBL4078836
5.34	IC50	4600	nM	CHEMBL3907289
5.27	IC50	5400	nM	CHEMBL3957478

PubChem BioAssay actives

47 with measured affinity, of 68 total; 42 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
N-[(3R,6S,9S,12R)-9-[3-(diaminomethylideneamino)propyl]-6-ethyl-12-methyl-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclotetradec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.0126	uM
N-[(3R,6S,9S,12R)-6-ethyl-12-methyl-9-[3-[(N’-methylcarbamimidoyl)amino]propyl]-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclotetradec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.0127	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-(thiophen-3-ylmethyl)azetidin-3-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.0152	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-(furan-3-ylmethyl)azetidin-3-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.0218	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-(3-cyclopentylpropyl)azetidin-3-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.0255	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-(3-phenylpropyl)azetidin-3-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.0296	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[(1-benzylazetidin-3-yl)methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.0468	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-[(4-chlorophenyl)methyl]azetidin-3-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.0556	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179123: Binding affinity against RBBP5 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0630	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-(thiophen-2-ylmethyl)azetidin-3-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.0665	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[(1-butylazetidin-3-yl)methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.0724	uM
N-[(3R,6S,9S,12R)-9-[3-(diaminomethylideneamino)propyl]-6-ethyl-12-methyl-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclopentadec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.0848	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-[(3-chlorophenyl)methyl]azetidin-3-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.0995	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-(1-benzofuran-3-ylmethyl)azetidin-3-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.1190	uM
N-[(3R,6S,9S,12R)-3-(4-chlorophenyl)-9-[3-(diaminomethylideneamino)propyl]-6-ethyl-1,12-dimethyl-2,5,8,11-tetraoxo-1,4,7,10-tetrazacyclohexadec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.1240	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[3-(3-cyclopentylpropylamino)cyclobutyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.1270	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-(2-phenylethyl)triazol-4-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.1320	uM
N-[(3R,6S,9S,12R)-9-[3-(diaminomethylideneamino)propyl]-6-ethyl-3-(4-fluorophenyl)-1,12-dimethyl-2,5,8,11-tetraoxo-1,4,7,10-tetrazacyclohexadec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.1380	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-(3,3-diphenylpropyl)azetidin-3-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.1384	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[[1-[(2-chlorophenyl)methyl]azetidin-3-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.1502	uM
5-amino-N-[5-[4-(4-aminobutanoylamino)phenyl]-2-(4-methylpiperazin-1-yl)phenyl]-2-chloro-4-fluoro-3-methylbenzamide	1335471: Inhibition of recombinant MLL1/ASH2L/RBBP5/WDR5 complex histone methyltransferase activity (unknown origin) by AlphaScreen assay	ic50	0.1900	uM
N-[(3R,6S,9S,12R)-9-[3-(diaminomethylideneamino)propyl]-6-ethyl-1,12-dimethyl-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclohexadec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.1900	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[3-(3-phenylpropylamino)propyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.2010	uM
N-[(3R,6S,9S,12R)-6-ethyl-12-methyl-9-[3-[(N’-methylcarbamimidoyl)amino]propyl]-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclooctadec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.2160	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[1-(3-cyclopentylpropyl)azetidin-3-yl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.2340	uM
N-[4-[3-[(5-amino-2-chloro-4-fluoro-3-methylbenzoyl)amino]-4-(4-methylpiperazin-1-yl)phenyl]phenyl]piperidine-4-carboxamide	1335471: Inhibition of recombinant MLL1/ASH2L/RBBP5/WDR5 complex histone methyltransferase activity (unknown origin) by AlphaScreen assay	ic50	0.3000	uM
N-[(3R,6S,9S,12R)-9-[3-(diaminomethylideneamino)propyl]-6-ethyl-12-methyl-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclohexadec-12-yl]-2-methylpropanamide	1320620: Inhibition of His-SUMO-fused MLL1 (3762 to 3969 residues) interaction with His-SUMO-fused ASH2L/RBBP5/WDR5 (23 to 334 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 pLyss codon (+) assessed as decrease in methylation of Lys4 residue of histone H3 10-residue peptide using [3H]-S-adenosylmethionine as methyl donor after 2 hrs by scintillation counting method	ic50	0.3000	uM
N-[(3R,6S,9S,12R)-9-[3-(diaminomethylideneamino)propyl]-6-ethyl-12-methyl-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclohexadec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.3730	uM
N-[bis(4-fluorophenyl)methyl]-1-[[(2S)-5-(diaminomethylideneamino)-2-[[2-ethyl-2-(2-methylpropanoylamino)butanoyl]amino]pentanoyl]amino]cyclopentane-1-carboxamide	1320618: Inhibition of His-SUMO-fused MLL1 (3762 to 3969 residues) interaction with His-SUMO-fused ASH2L/RBBP5/WDR5 (23 to 334 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 pLyss codon (+) assessed as decrease in methylation of Lys4 residue of histone H3 10-residue peptide using [3H]-S-adenosylmethionine as methyl donor preincubated for 2 to 5 mins with ASH2L/RBBP5/WDR5 followed by MLL1 addition measured after 30 mins by scintillation counting method	ic50	0.4000	uM
(2S)-2-amino-4-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-[3-[(3-phenylpropylamino)methyl]cyclobutyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.4510	uM
N-[(3R,6S,9S,12R)-6-ethyl-12-methyl-9-[3-[(N’-methylcarbamimidoyl)amino]propyl]-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclohexadec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.4520	uM
N-[(3S,6S,9S,12R)-6-ethyl-12-methyl-9-[3-[(N’-methylcarbamimidoyl)amino]propyl]-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclotetradec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.4770	uM
N-benzhydryl-1-[[(2S)-5-(diaminomethylideneamino)-2-[[2-ethyl-2-(2-methylpropanoylamino)butanoyl]amino]pentanoyl]amino]cyclopentane-1-carboxamide	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.5780	uM
(2S)-2-amino-4-[2-aminoethyl-[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl]amino]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.5920	uM
(2S)-2-amino-4-[[(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]butanoic acid	1658842: Inhibition of recombinant human MLL1 complex (MLL1/Ash2L/RbBP5/WDR5/DPY-30) expressed in Escherichia coli Rosetta 2 (DE3) cells using H3 (1 to 21) peptide as substrate incubated for 1 hr in presence of 3[H] SAM by AlphaLISA assay	ic50	0.7240	uM
N-[(3R,6S,9S,12R)-6-ethyl-12-methyl-9-[3-[(N’-methylcarbamimidoyl)amino]propyl]-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacycloicos-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	0.7440	uM
N-[(3R,6S,9S,12R)-9-[3-[(N,N’-dimethylcarbamimidoyl)amino]propyl]-6-ethyl-12-methyl-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclohexadec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	1.2590	uM
N-[(3R,6S,9S,12R)-9-[3-(diaminomethylideneamino)propyl]-6-ethyl-12-methyl-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacycloheptadec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	1.5270	uM
5-amino-N-[5-(4-aminophenyl)-2-(4-methylpiperazin-1-yl)phenyl]-2-chloro-4-fluoro-3-methylbenzamide	1335471: Inhibition of recombinant MLL1/ASH2L/RBBP5/WDR5 complex histone methyltransferase activity (unknown origin) by AlphaScreen assay	ic50	1.6500	uM
N-[(3R,6S,9S,12R)-9-[3-(diaminomethylideneamino)propyl]-6-ethyl-2,5,8,11-tetraoxo-3-phenyl-1,4,7,10-tetrazacyclotetradec-12-yl]-2-methylpropanamide;2,2,2-trifluoroacetic acid	1449556: Inhibition of human N-terminal GST-tagged MLL1 (3735 to 3973 residues) interaction with human full length N-terminal 6xHis-tagged ASH2L/N-terminal 6xHis-tagged human full length RbBP5/human N-terminal 6xHis-tagged WDR5/human full length N-terminal 6xHis-tagged DPY30 assessed as decrease in H3K4me1-2 methylation preincubated for 30 mins followed by SAM/nucleosome mixture addition measured after 120 mins in absence of light by AlphaLISA assay	ic50	1.8000	uM
methyl 3-[(5-amino-2-chloro-4-fluoro-3-methylbenzoyl)amino]-4-(4-methylpiperazin-1-yl)benzoate	1320612: Inhibition of recombinant MLL1 (unknown origin) interaction with recombinant ASH2L/RBBP5/WDR5 (unknown origin) assessed as decrease in histone methylation after 60 mins by Alpha Screen assay	ic50	4.6000	uM
phenyl 3-[(5-amino-2-chloro-4-fluoro-3-methylbenzoyl)amino]-4-(4-methylpiperazin-1-yl)benzoate	1320612: Inhibition of recombinant MLL1 (unknown origin) interaction with recombinant ASH2L/RBBP5/WDR5 (unknown origin) assessed as decrease in histone methylation after 60 mins by Alpha Screen assay	ic50	5.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
FR900359	affects phosphorylation	1
ginger extract	affects cotreatment, affects expression, increases abundance	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, affects expression, increases abundance	1
deoxynivalenol	increases expression	1
trichostatin A	affects expression	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
U 0126	affects expression, affects reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Irinotecan	decreases expression, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	increases expression	1
Amphotericin B	decreases expression	1
Caffeine	increases phosphorylation	1
Daunorubicin	affects expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Menthol	decreases expression	1
Methylnitronitrosoguanidine	increases expression	1
Oils, Volatile	affects cotreatment, affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1

ChEMBL screening assays

19 unique, capped per target: 19 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652964	Binding	Binding affinity to human RBBP5 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A5T2	SEES3-1V human RBBP5, clone1	Embryonic stem cell	Male
CVCL_A5T3	SEES3-1V human RBBP5, clone2	Embryonic stem cell	Male
CVCL_A5T4	SEES3-1V human RBBP5, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice