RBBP7

Summary

RBBP7 (RB binding protein 7, chromatin remodeling factor, HGNC:9890) is a protein-coding gene on chromosome Xp22.2, encoding Histone-binding protein RBBP7 (Q16576). Core histone-binding subunit that may target chromatin remodeling factors, histone acetyltransferases and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA.

This protein is a ubiquitously expressed nuclear protein and belongs to a highly conserved subfamily of WD-repeat proteins. It is found among several proteins that binds directly to retinoblastoma protein, which regulates cell proliferation. The encoded protein is found in many histone deacetylase complexes, including mSin3 co-repressor complex. It is also present in protein complexes involved in chromatin assembly. This protein can interact with BRCA1 tumor-suppressor gene and may have a role in the regulation of cell proliferation and differentiation. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5931 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure, X-linked, 9 (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 143 total — 1 pathogenic
• Phenotypes (HPO): 12
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002893

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9890
Approved symbol	RBBP7
Name	RB binding protein 7, chromatin remodeling factor
Location	Xp22.2
Locus type	gene with protein product
Status	Approved
Aliases	RbAp46
Ensembl gene	ENSG00000102054
Ensembl biotype	protein_coding
OMIM	300825
Entrez	5931

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 31 protein_coding, 4 retained_intron

ENST00000330735, ENST00000380084, ENST00000380087, ENST00000404022, ENST00000416035, ENST00000425696, ENST00000444437, ENST00000465244, ENST00000468092, ENST00000481586, ENST00000486166, ENST00000493145, ENST00000863745, ENST00000863746, ENST00000863747, ENST00000863748, ENST00000863749, ENST00000863750, ENST00000863751, ENST00000863752, ENST00000863753, ENST00000863754, ENST00000863755, ENST00000919334, ENST00000919335, ENST00000919336, ENST00000919337, ENST00000919338, ENST00000967933, ENST00000967934, ENST00000967935, ENST00000967936, ENST00000967937, ENST00000967938, ENST00000967939

RefSeq mRNA: 2 — MANE Select: NM_002893 NM_001198719, NM_002893

CCDS: CCDS14179, CCDS56598

Canonical transcript exons

ENST00000380087 — 12 exons

Exon	Start	End
ENSE00001256635	16852749	16852875
ENSE00001483695	16844341	16845103
ENSE00001608413	16869076	16869220
ENSE00001760546	16853682	16853842
ENSE00001906795	16870038	16870362
ENSE00003347279	16862955	16863100
ENSE00003419639	16858676	16858849
ENSE00003479052	16852551	16852628
ENSE00003501021	16857594	16857709
ENSE00003629010	16845828	16845938
ENSE00003635327	16849244	16849301
ENSE00003783962	16852046	16852122

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 75.8697 / max 621.5736, expressed in 1826 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198576	37.7760	1819
198575	35.0133	1815
198573	1.2136	793
198574	0.9744	646
198577	0.8924	559

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.73	gold quality
secondary oocyte	CL:0000655	99.69	gold quality
right adrenal gland	UBERON:0001233	99.45	gold quality
right adrenal gland cortex	UBERON:0035827	99.44	gold quality
adrenal cortex	UBERON:0001235	99.39	gold quality
adrenal tissue	UBERON:0018303	99.38	gold quality
left adrenal gland cortex	UBERON:0035825	99.38	gold quality
corpus epididymis	UBERON:0004359	99.35	gold quality
left adrenal gland	UBERON:0001234	99.34	gold quality
adrenal gland	UBERON:0002369	99.30	gold quality
seminal vesicle	UBERON:0000998	99.18	gold quality
endothelial cell	CL:0000115	99.15	gold quality
right testis	UBERON:0004534	99.04	gold quality
left ovary	UBERON:0002119	98.99	gold quality
left testis	UBERON:0004533	98.92	gold quality
right ovary	UBERON:0002118	98.86	gold quality
right uterine tube	UBERON:0001302	98.77	gold quality
cauda epididymis	UBERON:0004360	98.61	gold quality
ovary	UBERON:0000992	98.58	gold quality
body of uterus	UBERON:0009853	98.57	gold quality
testis	UBERON:0000473	98.54	gold quality
male germ cell	CL:0000015	98.47	gold quality
endocervix	UBERON:0000458	98.46	gold quality
sperm	CL:0000019	98.44	gold quality
cervix squamous epithelium	UBERON:0006922	98.44	gold quality
mucosa of stomach	UBERON:0001199	98.40	gold quality
parotid gland	UBERON:0001831	98.37	gold quality
ventricular zone	UBERON:0003053	98.32	gold quality
lower esophagus	UBERON:0013473	98.28	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.28	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	120.10
E-GEOD-134144	yes	31.45
E-MTAB-10283	no	244.67
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
CDH1	Repression

Upstream regulators (CollecTRI, top): ATF3, BCL6, LHX2

miRNA regulators (miRDB)

65 targeting RBBP7, 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-4533	100.00	69.48	2758
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-526B-3P	99.88	74.06	2587

Literature-anchored findings (GeneRIF, showing 23)

• RbAp46 expression suppresses the transformed phenotypes of breast cancer cells, and dysregulation of RbAp46 expression may contribute to breast cancer tumorigenesis. (PMID:14666671)
• RbAp46 inhibits cell growth and suppresses the transformed phenotypes of tumor cell lines. (PMID:14981905)
• RT-PCR data show high expression of putative tumor suppressor genes Rsk4 and RbAp46 in 47% and 79% of breast carcinoma cases, respectively, whereas Cldn2 was down-regulated in 52% of breast cancer cases compared with normal adjacent tissues. (PMID:17314274)
• RbAp46 folds into a seven-bladed beta propeller structure and binds histone H4 in a groove formed between an N-terminal alpha helix and an extended loop inserted into blade six. (PMID:18571423)
• Data show that RbAp46 and RbAp48 interact with estrogen receptor (ER)alpha at endogenous, estrogen-responsive genes and alter expression of endogenous, ERalpha-activated and -repressed genes in MCF-7 breast cancer cells. (PMID:18577416)
• Both of RbAp46 mRNA and protein levels were upregulated significantly in NSCLC cancer tissues. Serum levels of RbAp46 were markedly higher in NSCLC patients than in healthy controls. (PMID:19655816)
• the CRL4 complex containing RBBP7 (CRL4(RBBP7)) might regulate mitosis by promoting ubiquitin-dependent loading of newly synthesized CENP-A during the G1 phase of the cell cycle. (PMID:25795299)
• Ras induced RbAp46 expression increases invasion of bladder cancer cells. (PMID:25885317)
• NKX6.1 directly enhances the mRNA level of E-cadherin by recruiting BAF155 coactivator and represses that of vimentin and N-cadherin by recruiting RBBP7 (retinoblastoma binding protein 7) corepressor. (PMID:26257059)
• The MTA1 subunit of the nucleosome remodeling and deacetylase complex can recruit two copies of RBBP4/RBBP7. (PMID:27144666)
• Results show a novel interaction of the Lsm4 RGG domain with HAT1 and RBBP7, leading to the possibility of a posttranslational modifications network involved in mRNP regulation. (PMID:27247266)
• AMPK phosphorylates DNMT1, RBBP7, and HAT1 and increases interactions of DNMT1, RBBP7, and HAT1. (PMID:28143904)
• Taken together with previous findings this suggests, that MTA-RBBP is a stable complex, with a central role in the initial assembly of the human NuRD complex. (PMID:28179136)
• show that BCL11A(2-16) pulls down RBBP4, RBBP7, and other components of PRC2, NuRD, and SIN3A from the cell lysate of the TNBC cell line SUM149 (PMID:29263092)
• results support a model in which the activation of the TNF-alpha/NF-kappaB axis contributes to an increase in CRL4B(DCAF)(11) activity and a decrease in p21(Cip1) protein levels, thereby controlling cell cycle progression in human osteosarcoma cells. (PMID:29377600)
• RBBP7 controls the stability of HUWE1.RBBP7 is the E3 ligase responsible for the proteasomal degradation of HUWE1. (PMID:29738775)
• Circular RNA hsa_circ_0006168 contributes to cell proliferation, migration and invasion in esophageal cancer by regulating miR-384/RBBP7 axis via activation of S6K/S6 pathway. (PMID:31957828)
• Overlapping functions of RBBP4 and RBBP7 in regulating cell proliferation and histone H3.3 deposition during mouse preimplantation development. (PMID:34709113)
• Hypoxia-induced RBBP7 promotes esophagus cancer progression by inducing CDK4 expression. (PMID:35538026)
• FIT links c-Myc and P53 acetylation by recruiting RBBP7 during colorectal carcinogenesis. (PMID:37225855)
• X-linked RBBP7 mutation causes maturation arrest and testicular tumors. (PMID:37843278)
• RBBP7, regulated by SP1, enhances the Warburg effect to facilitate the proliferation of hepatocellular carcinoma cells via PI3K/AKT signaling. (PMID:38368381)
• Interpreting the molecular mechanisms of RBBP4/7 and their roles in human diseases (Review). (PMID:38577935)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbb4l	ENSDARG00000015208
mus_musculus	Rbbp7	ENSMUSG00000031353
rattus_norvegicus	Rbbp7	ENSRNOG00000005157
drosophila_melanogaster	Caf1-55	FBGN0263979
caenorhabditis_elegans	lin-53	WBGENE00003036
caenorhabditis_elegans	rba-1	WBGENE00004312

Paralogs (9): ERCC8 (ENSG00000049167), GEMIN5 (ENSG00000082516), WDR59 (ENSG00000103091), GRWD1 (ENSG00000105447), PEX7 (ENSG00000112357), WDR77 (ENSG00000116455), WDR24 (ENSG00000127580), RBBP4 (ENSG00000162521), WDR73 (ENSG00000177082)

Protein

Protein identifiers

Histone-binding protein RBBP7 — Q16576 (reviewed: Q16576)

Alternative names: Histone acetyltransferase type B subunit 2, Nucleosome-remodeling factor subunit RBAP46, Retinoblastoma-binding protein 7, Retinoblastoma-binding protein p46

All UniProt accessions (8): Q16576, C9J7L0, C9JAJ9, E9PC52, Q5JNZ6, Q5JP01, Q5JP02, Q6FHQ0

UniProt curated annotations — full annotation on UniProt →

Function. Core histone-binding subunit that may target chromatin remodeling factors, histone acetyltransferases and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA. Component of several complexes which regulate chromatin metabolism. These include the type B histone acetyltransferase (HAT) complex, which is required for chromatin assembly following DNA replication; the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression; the nucleosome remodeling and histone deacetylase complex (the NuRD complex), which promotes transcriptional repression by histone deacetylation and nucleosome remodeling; and the PRC2/EED-EZH2 complex, which promotes repression of homeotic genes during development; and the NURF (nucleosome remodeling factor) complex.

Subunit / interactions. Binds directly to helix 1 of the histone fold of histone H4, a region that is not accessible when H4 is in chromatin. Subunit of the type B histone acetyltransferase (HAT) complex, composed of RBBP7 and HAT1. Subunit of the core histone deacetylase (HDAC) complex, which is composed of HDAC1, HDAC2, RBBP4 and RBBP7. The core HDAC complex associates with SIN3A, ARID4B/SAP180, SAP18, SAP30, SAP130, SUDS3/SAP45 and possibly ARID4A/RBP1 and ING1 to form the SIN3 HDAC complex. Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5. The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes. The NuRD complex may interact with MBD3L1. The NuRD complex may interact with MBD3L2. Subunit of the PRC2/EED-EZH2 complex, which is composed of at least EED, EZH2, RBBP4, RBBP7 and SUZ12. The PRC2/EED-EZH2 complex may also associate with HDAC1. Component of the NURF-1 ISWI chromatin remodeling complex (also called the nucleosome-remodeling factor (NURF) complex) at least composed of SMARCA1 (isoform 2), BPTF, RBBP4 and RBBP7. Within the complex interacts with isoform 2 of SMARCA1. Component of the BPFT-SMARCA1 complex at least composed of SMARCA1 (isoform 1), BPFT, RBBP4 and RBBP7; the complex is catalytically inactive and does not remodel chromatin. Within the complex interacts with isoform 1 of SMARCA1. Interacts with BRCA1. Interacts with CDK2AP1. Interacts with CENPA. Interacts with CHD3. Interacts with CHD4. Interacts with CREBBP, and this interaction may be enhanced by the binding of phosphorylated CREB1 to CREBBP. Interacts with HDAC7. Interacts with MTA1. Interacts with PWWP2B. Interacts with RB1 (via viral protein-binding domain). Interacts with SUV39H1.

Subcellular location. Nucleus.

Disease relevance. Spermatogenic failure, X-linked, 9 (SPGFX9) [MIM:301137] A male infertility disorder characterized by spermatogenesis maturation arrest and non-obstructive azoospermia. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the WD repeat RBAP46/RBAP48/MSI1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16576-1	1	yes
Q16576-2	2

RefSeq proteins (2): NP_001185648, NP_002884* (*=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
IPR020472	WD40_PAC1	Repeat
IPR022052	Histone-bd_RBBP4-like_N	Domain
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR050459	WD_repeat_RBAP46/RBAP48/MSI1	Family

Pfam: PF00400, PF12265

UniProt features (72 total): strand 34, modified residue 10, repeat 7, sequence variant 6, helix 6, cross-link 5, initiator methionine 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7M3X	X-RAY DIFFRACTION	1.46
3CFS	X-RAY DIFFRACTION	2.4
3CFV	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16576-F1	91.26	0.85

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 (15): 3, 4, 10, 95, 119, 159, 354, 4, 4, 101, 155, 159, 2, 13, 2

Function

Pathways and Gene Ontology

Reactome pathways

25 pathways

ID	Pathway
R-HSA-212300	PRC2 methylates histones and DNA
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-3214815	HDACs deacetylate histones
R-HSA-3214841	PKMTs methylate histone lysines
R-HSA-3214847	HATs acetylate histones
R-HSA-3214858	RMTs methylate histone arginines
R-HSA-427389	ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-606279	Deposition of new CENPA-containing nucleosomes at the centromere
R-HSA-6804758	Regulation of TP53 Activity through Acetylation
R-HSA-73762	RNA Polymerase I Transcription Initiation
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-8951664	Neddylation
R-HSA-8953750	Transcriptional Regulation by E2F6
R-HSA-9609690	HCMV Early Events
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-9710421	Defective pyroptosis
R-HSA-9764725	Negative Regulation of CDH1 Gene Transcription
R-HSA-9843940	Regulation of endogenous retroelements by KRAB-ZFP proteins
R-HSA-9844594	Transcriptional regulation of brown and beige adipocyte differentiation by EBF2
R-HSA-9845323	Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)
R-HSA-9909649	Regulation of PD-L1(CD274) transcription
R-HSA-9937850	NuRD complex assembly
R-HSA-9940951	Interaction of NuRD complexes with transcription factors
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)

MSigDB gene sets: 403 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, AHRARNT_01, PID_HDAC_CLASSI_PATHWAY, AP1_01, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, BENPORATH_ES_WITH_H3K27ME3, PID_TELOMERASE_PATHWAY, E2F4DP1_01, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GCANCTGNY_MYOD_Q6, SP3_Q3, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, GOBP_GROWTH

GO Biological Process (17): negative regulation of transcription by RNA polymerase II (GO:0000122), DNA replication (GO:0006260), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), brain development (GO:0007420), negative regulation of cell growth (GO:0030308), negative regulation of cell migration (GO:0030336), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), regulation of cell fate specification (GO:0042659), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), response to steroid hormone (GO:0048545), cellular heat acclimation (GO:0070370), negative regulation of stem cell population maintenance (GO:1902455), positive regulation of stem cell population maintenance (GO:1902459), regulation of stem cell differentiation (GO:2000736), chromatin organization (GO:0006325)

GO Molecular Function (3): RNA binding (GO:0003723), histone binding (GO:0042393), protein binding (GO:0005515)

GO Cellular Component (10): histone deacetylase complex (GO:0000118), chromosome, telomeric region (GO:0000781), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), NuRD complex (GO:0016581), NURF complex (GO:0016589), ESC/E(Z) complex (GO:0035098), Sin3-type complex (GO:0070822), ATPase complex (GO:1904949)

Reactome top-level categories

Rollup of top-17 pathways:

Category	Pathways
Chromatin modifying enzymes	4
Epigenetic regulation of gene expression	1
Cellular Senescence	1
Positive epigenetic regulation of rRNA expression	1
Activation of HOX genes during differentiation	1
Nucleosome assembly	1
Regulation of TP53 Activity	1
RNA Polymerase I Promoter Clearance	1
PTEN Regulation	1
Post-translational protein modification	1
Generic Transcription Pathway	1
HCMV Infection	1
SARS-CoV Infections	1
Diseases of programmed cell death	1
Regulation of CDH1 Gene Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	3
regulation of DNA-templated transcription	2
stem cell population maintenance	2
regulation of stem cell population maintenance	2
catalytic complex	2
cellular anatomical structure	2
histone deacetylase complex	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
DNA metabolic process	1
DNA biosynthetic process	1
chromatin organization	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
central nervous system development	1
animal organ development	1
head development	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
cell fate specification	1
regulation of cell fate commitment	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
response to hormone	1
response to lipid	1
heat acclimation	1
cellular response to heat	1
negative regulation of developmental process	1
negative regulation of multicellular organismal process	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1

Protein interactions and networks

STRING

4318 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBBP7	MTA2	O94776	997
RBBP7	SAP30	O75446	997
RBBP7	SUZ12	Q15022	997
RBBP7	MTA1	Q13330	997
RBBP7	HDAC1	Q13547	997
RBBP7	SAP18	O00422	997
RBBP7	CHD4	Q14839	997
RBBP7	HDAC2	Q92769	997
RBBP7	EED	O75530	996
RBBP7	EZH2	Q15910	995
RBBP7	CHD3	Q12873	995
RBBP7	AEBP2	Q6ZN18	994
RBBP7	EZH1	Q92800	994
RBBP7	GATAD2B	Q8WXI9	993
RBBP7	GATAD2A	Q86YP4	993

IntAct

265 interactions, top by confidence:

A	B	Type	Score
MTA2	RBBP7	psi-mi:“MI:0915”(physical association)	0.920
SUZ12	EED	psi-mi:“MI:0914”(association)	0.910
HDAC1	KDM1A	psi-mi:“MI:0914”(association)	0.910
MTA2	RBBP4	psi-mi:“MI:0914”(association)	0.890
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
BRMS1	HDAC1	psi-mi:“MI:0914”(association)	0.830
HAT1	RBBP4	psi-mi:“MI:0914”(association)	0.800
H4C16	RBBP7	psi-mi:“MI:0407”(direct interaction)	0.790
CHD3	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
GATAD2B	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
H4C16	RBBP7	psi-mi:“MI:0915”(physical association)	0.790
PHF1	EED	psi-mi:“MI:0914”(association)	0.790
SIN3A	RBBP4	psi-mi:“MI:0914”(association)	0.790
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
SMARCA1	RBBP4	psi-mi:“MI:0914”(association)	0.770
H3C1	HAT1	psi-mi:“MI:0914”(association)	0.770
BPTF	SMARCA1	psi-mi:“MI:0914”(association)	0.750

BioGRID (1354): RBBP7 (Affinity Capture-MS), RBBP7 (Affinity Capture-Western), RBBP7 (Affinity Capture-MS), RBBP7 (Affinity Capture-MS), RBBP7 (Affinity Capture-MS), RBBP7 (Affinity Capture-MS), RBBP7 (Affinity Capture-MS), RBBP7 (Affinity Capture-MS), RBBP7 (Affinity Capture-MS), RBBP7 (Reconstituted Complex), RBBP7 (Affinity Capture-MS), RBBP7 (Affinity Capture-MS), RBBP7 (Affinity Capture-MS), RBBP7 (Affinity Capture-MS), RBBP7 (Affinity Capture-MS)

ESM2 similar proteins: A5GFZ5, A8MWD9, C9WPN6, O35900, O60762, O70152, P02362, P50894, P62084, P62306, P62307, P62308, P62309, P62310, P62311, P62314, P62315, P62318, P62320, P62321, P62323, P62487, P62488, P62489, P82931, Q16576, Q1JQ93, Q24572, Q2TBV5, Q2VIR3, Q32PE9, Q3SWX8, Q3T0Z8, Q3ZBL0, Q3ZC10, Q4R304, Q4R5F6, Q5E9B8, Q5ZMS3, Q60973

Diamond homologs: A1CUD6, A2AH22, A7TLU2, A8IZG4, A8X8C6, B0R0D7, B0XAF3, B4GDM7, B4JW81, B4LJT7, E7FAG6, F1LTR1, G0SA60, G0SC29, O13046, O13923, O22468, O75717, O76071, O93377, O94527, P0CS38, P0CS39, P0DPA1, P25382, P25569, P26309, P57737, Q06440, Q08E38, Q09028, Q16576, Q1DZQ0, Q24572, Q28D01, Q28DW0, Q292E8, Q3MHL3, Q3SWX8, Q4KLI9

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
RBBP7	“form complex”	“MBD2/NuRD complex”	binding
RBBP7	“form complex”	“MBD3/NuRD complex”	binding
RBBP7	“form complex”	HNuRF	binding
PRKAA1	“up-regulates activity”	RBBP7	phosphorylation
RBBP7	“down-regulates activity”	DNMT1	binding
RBBP7	“up-regulates activity”	HAT1	binding
AMPK	“up-regulates activity”	RBBP7	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 169 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of TP53 Activity through Acetylation	8	30.7×	6e-09
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	9	28.8×	1e-09
Regulation of PTEN gene transcription	17	25.5×	4e-17
NuRD complex assembly	17	20.1×	2e-15
Interaction of NuRD complexes with transcription factors	17	18.1×	8e-15
PRC2 methylates histones and DNA	14	17.9×	4e-12
Transcriptional Regulation by E2F6	7	17.2×	4e-06
RNA Polymerase I Transcription Initiation	9	16.9×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of stem cell population maintenance	9	46.6×	2e-11
regulation of stem cell differentiation	9	46.6×	2e-11
DNA methylation-dependent constitutive heterochromatin formation	6	22.0×	1e-05
negative regulation of gene expression, epigenetic	8	21.7×	2e-07
positive regulation of stem cell population maintenance	9	20.9×	4e-08
heterochromatin formation	12	20.7×	8e-11
protein localization to chromatin	5	19.6×	2e-04
epigenetic regulation of gene expression	7	18.1×	7e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	24
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3544365	NM_002893.4(RBBP7):c.1200dup (p.Trp401fs)	Pathogenic

SpliceAI

2248 predictions. Top by Δscore:

Variant	Effect	Δscore
X:16841423:TACA:T	acceptor_loss	1.0000
X:16841424:ACAG:A	acceptor_loss	1.0000
X:16841425:CAGAA:C	acceptor_loss	1.0000
X:16841426:A:AG	acceptor_gain	1.0000
X:16841427:G:GG	acceptor_gain	1.0000
X:16841427:GA:G	acceptor_gain	1.0000
X:16841427:GAA:G	acceptor_gain	1.0000
X:16841427:GAAAA:G	acceptor_gain	1.0000
X:16845939:C:CC	acceptor_gain	1.0000
X:16849297:TTTTA:T	acceptor_gain	1.0000
X:16849298:TTTA:T	acceptor_gain	1.0000
X:16849299:TTA:T	acceptor_gain	1.0000
X:16849299:TTACT:T	acceptor_loss	1.0000
X:16849300:TA:T	acceptor_gain	1.0000
X:16849302:C:CC	acceptor_gain	1.0000
X:16849303:T:A	acceptor_loss	1.0000
X:16852752:AT:A	donor_gain	1.0000
X:16853680:A:AC	donor_gain	1.0000
X:16853681:C:CC	donor_gain	1.0000
X:16853681:CAT:C	donor_gain	1.0000
X:16853839:CAGT:C	acceptor_gain	1.0000
X:16853843:C:CC	acceptor_gain	1.0000
X:16857592:A:AC	donor_gain	1.0000
X:16857593:C:CC	donor_gain	1.0000
X:16857710:C:CC	acceptor_gain	1.0000
X:16858672:ATAC:A	donor_loss	1.0000
X:16858673:TAC:T	donor_loss	1.0000
X:16858674:ACCTG:A	donor_loss	1.0000
X:16858855:G:C	acceptor_gain	1.0000
X:16858855:G:GC	acceptor_gain	1.0000

AlphaMissense

2832 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:16845836:A:G	W401R	1.000
X:16845836:A:T	W401R	1.000
X:16845849:G:C	N396K	1.000
X:16845849:G:T	N396K	1.000
X:16845853:T:A	D395V	1.000
X:16845853:T:G	D395A	1.000
X:16845854:C:G	D395H	1.000
X:16845859:G:A	S393F	1.000
X:16845860:A:G	S393P	1.000
X:16845866:A:G	S391P	1.000
X:16845896:A:G	W381R	1.000
X:16845896:A:T	W381R	1.000
X:16845923:G:C	H372D	1.000
X:16845925:C:A	G371V	1.000
X:16845925:C:T	G371E	1.000
X:16845926:C:G	G371R	1.000
X:16845926:C:T	G371R	1.000
X:16845928:C:T	G370E	1.000
X:16845932:G:C	H369D	1.000
X:16845936:A:C	F367L	1.000
X:16845936:A:T	F367L	1.000
X:16845937:A:G	F367S	1.000
X:16845938:A:G	F367L	1.000
X:16845938:A:T	F367I	1.000
X:16849248:A:G	L365P	1.000
X:16849260:C:T	G361E	1.000
X:16852054:C:A	W344C	1.000
X:16852054:C:G	W344C	1.000
X:16852055:C:G	W344S	1.000
X:16852056:A:G	W344R	1.000

dbSNP variants (sampled 300 via entrez): RS1000078108 (X:16846144 G>A), RS1000084735 (X:16862459 C>T), RS1000248276 (X:16858367 C>T), RS1000306588 (X:16866163 A>G), RS1000359868 (X:16866332 C>T), RS1000639122 (X:16864388 G>A,T), RS1000717234 (X:16851603 T>C), RS1001145290 (X:16864727 C>G), RS1001197749 (X:16856287 T>C,G), RS1001198977 (X:16868943 G>T), RS1001533090 (X:16868232 A>G), RS1001791927 (X:16857706 G>A), RS1001796384 (X:16849571 G>A), RS1001868781 (X:16859937 T>C), RS1002188692 (X:16860436 C>A,T)

Disease associations

OMIM: gene MIM:300825 | disease phenotypes: MIM:301137

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure, X-linked, 9	Limited	X-linked

Mondo (1): spermatogenic failure, X-linked, 9 (MONDO:0976123)

Orphanet (0):

HPO phenotypes

12 total (12 of 12 shown, HPO-id order):

HPO	Term
HP:0001417	X-linked inheritance
HP:0002664	Neoplasm
HP:0002716	Lymphadenopathy
HP:0003251	Male infertility
HP:0008232	Elevated circulating follicle stimulating hormone level
HP:0008734	Decreased testicular size
HP:0011462	Young adult onset
HP:0011961	Non-obstructive azoospermia
HP:0011969	Elevated circulating luteinizing hormone level
HP:0031038	Spermatogenesis maturation arrest
HP:0040171	Decreased serum testosterone concentration
HP:0100618	Leydig cell neoplasia

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_86	Refractive error	1.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3286065 (SINGLE PROTEIN), CHEMBL3301388 (PROTEIN COMPLEX), CHEMBL5465253 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 137,701 (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
CHEMBL1534	RIBOFLAVIN	4	136,163
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

12 potent at pChembl≥5 of 19 total, top 12 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.22	Ki	0.6	nM	CHEMBL2204997
8.92	Ki	1.2	nM	CHEMBL2204995
8.40	IC50	4	nM	CHEMBL2204995
8.40	IC50	4	nM	CHEMBL2204997
8.10	Ki	7.9	nM	CHEMBL2204998
7.85	Ki	14	nM	CHEMBL2204996
7.70	IC50	20	nM	CHEMBL2204998
7.13	Ki	74	nM	CHEMBL2204999
6.83	Ki	149	nM	CHEMBL1608462
6.71	Ki	194	nM	CHEMBL3287734
6.11	IC50	780	nM	MOLIBRESIB
5.28	Kd	5200	nM	CHEMBL5406943

PubChem BioAssay actives

12 with measured affinity, of 78 total; 9 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-[(6-methyl-2-oxo-4-propyl-1H-pyridin-3-yl)methyl]-6-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]-1-propan-2-ylindazole-4-carboxamide	711407: Inhibition of PRC2 complex of FLAG-EZH2, EED, SUZ12, AEBP2 and RbAp48 using histone H3 peptide (21 to 44) as substrate and [3H]SAM after 30 mins	ki	0.0006	uM
N-[(6-methyl-2-oxo-4-propyl-1H-pyridin-3-yl)methyl]-6-[2-(4-methylpiperazin-1-yl)-4-pyridinyl]-1-propan-2-ylindazole-4-carboxamide	711407: Inhibition of PRC2 complex of FLAG-EZH2, EED, SUZ12, AEBP2 and RbAp48 using histone H3 peptide (21 to 44) as substrate and [3H]SAM after 30 mins	ki	0.0012	uM
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-6-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]-1-propan-2-ylindazole-4-carboxamide	711407: Inhibition of PRC2 complex of FLAG-EZH2, EED, SUZ12, AEBP2 and RbAp48 using histone H3 peptide (21 to 44) as substrate and [3H]SAM after 30 mins	ki	0.0079	uM
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-6-[2-(4-methylpiperazin-1-yl)-4-pyridinyl]-1-propan-2-ylindazole-4-carboxamide	711407: Inhibition of PRC2 complex of FLAG-EZH2, EED, SUZ12, AEBP2 and RbAp48 using histone H3 peptide (21 to 44) as substrate and [3H]SAM after 30 mins	ki	0.0140	uM
6-cyclopropyl-N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-1-propan-2-ylindazole-4-carboxamide	711407: Inhibition of PRC2 complex of FLAG-EZH2, EED, SUZ12, AEBP2 and RbAp48 using histone H3 peptide (21 to 44) as substrate and [3H]SAM after 30 mins	ki	0.0740	uM
6-cyclopropyl-N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[5,4-b]pyridine-4-carboxamide	711407: Inhibition of PRC2 complex of FLAG-EZH2, EED, SUZ12, AEBP2 and RbAp48 using histone H3 peptide (21 to 44) as substrate and [3H]SAM after 30 mins	ki	0.1490	uM
(6R,7R)-6,7-dihydroxy-1,6-dimethyl-8,9-dihydro-7H-naphtho[1,2-g][1]benzofuran-10,11-dione	1151969: Competitive inhibition of EZH2 histone methyltransferase activity in EZH2/SUZ12/EED/RbAp46/48 (unknown origin) using histone H3 peptide/varying concentration of S-adenosylmethionine as substrate after 2 hrs by Lineweaver-Burk plot analysis	ki	0.1940	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	2179047: Inhibition of RBBP7 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.7800	uM
7-chloro-8-ethyl-10-[2-(2-methylpropoxy)ethyl]benzo[g]pteridine-2,4-dione	2030513: Binding affinity to CM5 sensor chip immobilized C-terminal FLAG tagged full length human HAT1/Rbap46 assessed as dissociation constant by SPR analysis	kd	5.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects expression	3
sodium arsenite	decreases expression, increases abundance	2
cobaltous chloride	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Estradiol	affects binding, increases reaction, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
uranyl acetate	affects expression	1
decabromobiphenyl ether	decreases expression	1
methoxyacetic acid	increases expression, increases reaction	1
sodium bichromate	increases expression	1
afimoxifene	decreases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	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
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Temozolomide	decreases expression	1
Fulvestrant	decreases expression	1
Leflunomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	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
CHEMBL5652242	Binding	Binding affinity to human RBBP7 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

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1E2	Abcam HCT 116 RBBP7 KO	Cancer cell line	Male
CVCL_B2DH	Abcam HeLa RBBP7 KO	Cancer cell line	Female
CVCL_TI60	HAP1 RBBP7 (-) 1	Cancer cell line	Male
CVCL_TI61	HAP1 RBBP7 (-) 2	Cancer cell line	Male
CVCL_TI62	HAP1 RBBP7 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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