RYBP

Summary

RYBP (RING1 and YY1 binding protein, HGNC:10480) is a protein-coding gene on chromosome 3p13, encoding RING1 and YY1-binding protein (Q8N488). Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development.

Enables nucleic acid binding activity. Involved in chromatin remodeling; positive regulation of apoptotic process; and regulation of primary metabolic process. Located in nucleoplasm. Part of PcG protein complex.

Source: NCBI Gene 23429 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Moderate, GenCC)
• GWAS associations: 38
• Clinical variants (ClinVar): 7 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_012234

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10480
Approved symbol	RYBP
Name	RING1 and YY1 binding protein
Location	3p13
Locus type	gene with protein product
Status	Approved
Aliases	YEAF1, AAP1, DEDAF
Ensembl gene	ENSG00000163602
Ensembl biotype	protein_coding
OMIM	607535
Entrez	23429

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 retained_intron, 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000477973, ENST00000676660, ENST00000676841, ENST00000677329

RefSeq mRNA: 1 — MANE Select: NM_012234 NM_012234

Canonical transcript exons

ENST00000477973 — 4 exons

Exon	Start	End
ENSE00001204361	72379040	72379138
ENSE00001204363	72379251	72379427
ENSE00001826994	72371825	72378637
ENSE00001930429	72446496	72446621

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 96.47.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2686 / max 20.8486, expressed in 107 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
43145	0.2686	107

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower lobe of lung	UBERON:0008949	96.47	gold quality
cartilage tissue	UBERON:0002418	96.04	gold quality
endothelial cell	CL:0000115	95.90	gold quality
trabecular bone tissue	UBERON:0002483	95.58	gold quality
urethra	UBERON:0000057	95.51	gold quality
CA1 field of hippocampus	UBERON:0003881	95.17	gold quality
middle frontal gyrus	UBERON:0002702	95.07	gold quality
cranial nerve II	UBERON:0000941	94.96	gold quality
placenta	UBERON:0001987	94.67	gold quality
inferior vagus X ganglion	UBERON:0005363	94.63	gold quality
choroid plexus epithelium	UBERON:0003911	94.58	gold quality
visceral pleura	UBERON:0002401	94.38	gold quality
sperm	CL:0000019	94.35	gold quality
pigmented layer of retina	UBERON:0001782	94.34	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.34	gold quality
adult organism	UBERON:0007023	94.34	gold quality
mucosa of urinary bladder	UBERON:0001259	94.12	gold quality
cortical plate	UBERON:0005343	94.07	gold quality
superficial temporal artery	UBERON:0001614	93.70	gold quality
male germ cell	CL:0000015	93.66	gold quality
nipple	UBERON:0002030	93.60	gold quality
mammary duct	UBERON:0001765	93.58	gold quality
skin of hip	UBERON:0001554	93.52	gold quality
pleura	UBERON:0000977	93.41	gold quality
saphenous vein	UBERON:0007318	93.35	gold quality
cauda epididymis	UBERON:0004360	93.33	gold quality
epithelium of mammary gland	UBERON:0003244	93.18	gold quality
parietal pleura	UBERON:0002400	93.17	gold quality
subthalamic nucleus	UBERON:0001906	93.15	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.15	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.49
E-MTAB-3929	no	126.69

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
CDC6	Unknown

miRNA regulators (miRDB)

262 targeting RYBP, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548N	99.98	71.94	4170
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-4775	99.98	75.00	6394
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834

Literature-anchored findings (GeneRIF, showing 29)

• YEAF1/RYBP and YAF-2 are functionally distinct members of a cofactor family for the YY1 and E4TF1/hGABP transcription factors. (PMID:11953439)
• interacts specifically with the E2F2 and E2F3 family members, dependent on the marked box domain in these proteins (PMID:12411495)
• Apoptin is efficiently delivered and induced apoptosis in cancer cells when fused to the HIV-TAT protein transduction domain. (PMID:14691460)
• DEDAF associates with a DED-containing DNA-binding protein in the nucleus and regulates the transcription activity [DEDAF human] (PMID:14765135)
• Adenovirus expressing Rybp synergistically cooperates with the death receptor ligand, tumor necrosis factor-alpha, in the induction of apoptosis, and thus may have clinical applicability for the treatment of cancer. (PMID:18551146)
• RYBP interacts with MDM2 via residues 1-73 and 144-228 & decreases MDM2-mediated p53 ubiquitination, stabilizing p53 increasing its activity. RYBP is decreased in human cancer tissues. (PMID:19098711)
• Polymorphisms in RYBP and AOAH genes are associated with chronic rhinosinusitis in a Chinese population. (PMID:22723975)
• RYBP has a role in survival of patients with hepatocellular carcinoma (HCC) and responsiveness to chemotherapy (PMID:25344099)
• Results identify a novel YY1 ~ miR-9 ~ RYBP axis involved in melanoma tumorigenesis and reinforce the idea that regulatory circuitries involving miRNAs and TFs are prevalent mechanisms. (PMID:26104682)
• RYBP activates FANK1-mediated activator protein 1 (AP-1) signaling pathway which contributes to tumor cell apoptosis. (PMID:27060496)
• overexpression of RYBP suppresses breast cancer growth and metastasis both in vitro and in vivo. (PMID:27748911)
• This study revealed the molecular mechanism responsible for RYBP nuclear translocation. (PMID:27989698)
• findings support the idea that RYBP may represent a target for cancer therapy and suggest that it may be useful as a prognostic biomarker for HCC, either alone or in combination with KLF4 and Sp1 (PMID:28028181)
• this is the first study to show the correlation between RYBP polymorphisms with the risk and prognosis of HCC. We found that the RYBP SNP, rs2118593 can be a new predictor for poor prognosis of HCC, providing a scientific basis for improving the treatment and prognosis of HCC. (PMID:28369212)
• This review also discusses the role of RYBP in apoptosis through non-epigenetic mechanisms as well as recent investigations linking the role of RYBP to apoptosis and cancer. (PMID:29665352)
• Mechanistic dissection further disclosed that RYBP directly binds to ubiquitin protein ligase E3A (UBE3A) to promote its ubiquitination and proteasomal degradation in an autoubiquitination-independent manner (PMID:30040487)
• upregulation of RYBP decreased the phosphorylation of EGFR and ERK1/2 in anaplastic thyroid cancer (ATC) cells. Taken together, our data indicated that RYBP might be considered as a promising therapeutic target for the treatment of ATC. (PMID:30431689)
• ETS1 up-regulates human RYBP expression at transcriptional level. ETS1 binds to RYBP promoter region through a multiple of conserved ETS1 binding sites in RYBP promoter region. RYBP is required for ETS1-induced human tumor cell growth inhibition. (PMID:30638661)
• RYBP expression level in tumor tissues was applied to predict the prognosis of hepatocellular carcinoma patients more accurately (PMID:31113915)
• the up-regulated expression of miR-769-5p contributed to Hepatocellular carcinoma progression possibly by targeting RYBP. (PMID:31545279)
• RYBP suppresses esophageal squamous cell carcinoma proliferation by downregulating CDC6 and CDC45, thus inhibiting the G1-S transition (PMID:32209426)
• Upregulated miR4115p levels promote lymph node metastasis by targeting RYBP in head and neck squamous cell carcinoma. (PMID:33537835)
• The nuclear localization sequence of the epigenetic factor RYBP binds to human importin alpha3. (PMID:33945888)
• Re-expression of circ_0043610 contributes to trophoblast dysfunction through the miR-558/RYBP pathway in preeclampsia. (PMID:35908953)
• RYBP Sensitizes Cancer Cells to PARP Inhibitors by Regulating ATM Activity. (PMID:36233063)
• Deficiency of the Polycomb Protein RYBP and TET Methylcytosine Oxidases Promotes Extensive CpG Island Hypermethylation and Malignant Transformation. (PMID:37272752)
• Structural basis of the histone ubiquitination read-write mechanism of RYBP-PRC1. (PMID:38528151)
• Glucose-induced RYBP suppresses tumor cell aerobic glycolysis and migration. (PMID:38735205)
• Unveiling the Binding between the Armadillo-Repeat Domain of Plakophilin 1 and the Intrinsically Disordered Transcriptional Repressor RYBP. (PMID:38785968)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rybpa	ENSDARG00000037773
danio_rerio	rybpb	ENSDARG00000053459
mus_musculus	Rybp	ENSMUSG00000072872
rattus_norvegicus	Rybp	ENSRNOG00000005353
drosophila_melanogaster	RYBP	FBGN0034763
caenorhabditis_elegans		WBGENE00016937

Paralogs (1): YAF2 (ENSG00000015153)

Protein

Protein identifiers

RING1 and YY1-binding protein — Q8N488 (reviewed: Q8N488)

Alternative names: Apoptin-associating protein 1, Death effector domain-associated factor, YY1 and E4TF1-associated factor 1

All UniProt accessions (1): Q8N488

UniProt curated annotations — full annotation on UniProt →

Function. Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1-like complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A ‘Lys-119’, rendering chromatin heritably changed in its expressibility. Component of a PRC1-like complex that mediates monoubiquitination of histone H2A ‘Lys-119’ on the X chromosome and is required for normal silencing of one copy of the X chromosome in XX females. May stimulate ubiquitination of histone H2A ‘Lys-119’ by recruiting the complex to target sites. Inhibits ubiquitination and subsequent degradation of TP53, and thereby plays a role in regulating transcription of TP53 target genes. May also regulate the ubiquitin-mediated proteasomal degradation of other proteins like FANK1 to regulate apoptosis. May be implicated in the regulation of the transcription as a repressor of the transcriptional activity of E4TF1. May bind to DNA. May play a role in the repression of tumor growth and metastasis in breast cancer by down-regulating SRRM3.

Subunit / interactions. Monomer. Component of repressive BCOR complex containing Polycomb group subcomplex at least composed of BCOR, PCGF1, RING1 and RNF2/RING2. Component of PCR1-like complexes. Interacts with PCGF1. Part of a PCR1-like complex that contains AUTS2, PCGF5, RNF2, CSNK2B and RYBP. Interacts with RNF2; the interaction is direct. Interacts with CBX2, YAF2, RING1 and RNF2. Interacts with ubiquitin and ubiquitinated proteins. Interacts with ubiquitinated histone H2A. Interacts with apoptin, DEDD, FADD, CASP8, CASP10, YY1 and GABPB1. Together with GABPB1 and YY1, it forms a ternary complex, probably being the bridge factor between these two transcription factors. Interacts with MDM2, and thereby inhibits ubiquitination of TP53. Identified in a ternary complex containing MDM2, TP53 and RYBP. Interacts with FANK1; may prevent the ubiquitin-mediated proteasomal degradation of FANK1. Interacts with IFT57.

Subcellular location. Nucleus. Cytoplasm. Nucleoplasm.

Tissue specificity. Down-regulated in breast cancer tissues and in several breast cancer cell lines (at protein level). Widely expressed with highest levels in lymphoid tissues and placenta.

Post-translational modifications. Monoubiquitinated.

Domain organisation. Intrinsically unstructured in the absence of binding partners. Folds upon binding to DNA or RNF2.

RefSeq proteins (1): NP_036366* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001876	Znf_RanBP2	Domain
IPR033774	YAF2_RYBP	Conserved_site
IPR036443	Znf_RanBP2_sf	Homologous_superfamily
IPR039958	RYBP/YAF2	Family

Pfam: PF00641, PF17219

UniProt features (22 total): modified residue 5, strand 4, region of interest 4, compositionally biased region 4, chain 1, zinc finger region 1, cross-link 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
3IXS	X-RAY DIFFRACTION	1.7
9DBY	ELECTRON MICROSCOPY	2.8
8PP6	ELECTRON MICROSCOPY	3.18
9DDE	ELECTRON MICROSCOPY	3.2
9DG3	ELECTRON MICROSCOPY	3.46

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N488-F1	66.89	0.25

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 (6): 99, 123, 127, 130, 227, 77

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-8939243	RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known
R-HSA-8953750	Transcriptional Regulation by E2F6
R-HSA-212436	Generic Transcription Pathway
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878171	Transcriptional regulation by RUNX1

MSigDB gene sets: 291 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, RACCACAR_AML_Q6, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, NFKB_Q6, AGTCTTA_MIR499, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, ACCAATC_MIR509, chr3p13, MILI_PSEUDOPODIA_HAPTOTAXIS_UP

GO Biological Process (7): negative regulation of transcription by RNA polymerase II (GO:0000122), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), apoptotic process (GO:0006915), negative regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032435), positive regulation of apoptotic process (GO:0043065), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (7): nucleic acid binding (GO:0003676), DNA binding (GO:0003677), transcription coregulator activity (GO:0003712), transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), PcG protein complex (GO:0031519)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Generic Transcription Pathway	2
Transcriptional regulation by RUNX1	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of DNA-templated transcription	2
DNA-templated transcription	2
binding	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
chromatin organization	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
negative regulation of proteasomal protein catabolic process	1
negative regulation of ubiquitin-dependent protein catabolic process	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
nucleic acid binding	1
transcription regulator activity	1
transcription coregulator activity	1
transition metal ion binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

1820 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RYBP	RING1	Q06587	998
RYBP	YY1	P25490	997
RYBP	PCGF1	Q9BSM1	996
RYBP	RNF2	Q99496	996
RYBP	KDM2B	Q8NHM5	995
RYBP	BMI1	P35226	964
RYBP	R4GMX3	R4GMX3	964
RYBP	SKP1	P34991	955
RYBP	PCGF6	Q9BYE7	954
RYBP	PCGF5	Q86SE9	952
RYBP	YAF2	Q8IY57	948
RYBP	CBX2	Q14781	930
RYBP	PCGF2	P35227	924
RYBP	PCGF3	Q3KNV8	921
RYBP	E2F6	O75461	845

IntAct

314 interactions, top by confidence:

A	B	Type	Score
RNF2	RYBP	psi-mi:“MI:0915”(physical association)	0.970
RNF2	RYBP	psi-mi:“MI:0407”(direct interaction)	0.970
RYBP	RNF2	psi-mi:“MI:0915”(physical association)	0.970
RYBP	RING1	psi-mi:“MI:0915”(physical association)	0.950
RING1	RYBP	psi-mi:“MI:0915”(physical association)	0.950
RYBP	CSNK2A2	psi-mi:“MI:0914”(association)	0.900
PCGF5	CSNK2A2	psi-mi:“MI:0914”(association)	0.880
RYBP	BMI1	psi-mi:“MI:0914”(association)	0.850
PCGF2	CBX4	psi-mi:“MI:0914”(association)	0.840
CSNK2A2	EIF3J	psi-mi:“MI:0914”(association)	0.790
AUTS2	CSNK2B	psi-mi:“MI:0914”(association)	0.760
E2F6	WDR5	psi-mi:“MI:0914”(association)	0.730
RING1	CBX4	psi-mi:“MI:0914”(association)	0.730
FUS	RYBP	psi-mi:“MI:0915”(physical association)	0.670
PCGF6	CBX4	psi-mi:“MI:0914”(association)	0.640
YAF2	E2F6	psi-mi:“MI:0914”(association)	0.640
EAF1	RYBP	psi-mi:“MI:0915”(physical association)	0.560
RYBP	BANP	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (482): RYBP (Two-hybrid), RYBP (Affinity Capture-MS), RYBP (Affinity Capture-MS), RYBP (Affinity Capture-MS), RYBP (Affinity Capture-MS), RYBP (Affinity Capture-MS), RYBP (Affinity Capture-MS), RYBP (Affinity Capture-MS), PCGF3 (Affinity Capture-MS), USP7 (Affinity Capture-MS), BCOR (Affinity Capture-MS), BCORL1 (Affinity Capture-MS), MORC4 (Affinity Capture-MS), TFDP1 (Affinity Capture-MS), KDM2B (Affinity Capture-MS)

ESM2 similar proteins: A0A8I6G705, A1L3K1, B5DFF2, B5DFI8, G3MWR8, O19048, O19137, O88508, P06730, P29338, P57721, P57722, P60335, Q12800, Q13888, Q15365, Q15366, Q16763, Q1LZ53, Q1RML1, Q28D01, Q2TBV5, Q4W5Z4, Q5E9A3, Q5FVR7, Q5NVP9, Q5TDH0, Q61990, Q6AYU1, Q6DH13, Q6P1K8, Q6ZRY4, Q7RTP6, Q8C6G8, Q8CCI5, Q8CJ19, Q8IY57, Q8N488, Q8VC52, Q921J4

Diamond homologs: Q5EG55, Q7SYB3, Q8CCI5, Q8IY57, Q8N488, Q99LW6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RYBP	down-regulates	ABL1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 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
SUMOylation of DNA methylation proteins	5	57.9×	3e-06
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	9	46.6×	8e-11
Transcriptional Regulation by E2F6	7	35.3×	2e-07
SUMOylation of transcription cofactors	5	20.9×	4e-04
SUMOylation of RNA binding proteins	5	20.5×	4e-04
SUMOylation of chromatin organization proteins	5	13.7×	2e-03
SUMOylation of DNA damage response and repair proteins	5	12.6×	3e-03
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	5	12.6×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of apoptotic signaling pathway	5	38.0×	2e-04
cerebral cortex development	5	13.9×	5e-03
negative regulation of neuron apoptotic process	7	10.5×	2e-03
chromatin remodeling	8	7.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	2
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
441945	GRCh37/hg19 3p13-12.3(chr3:70433832-77012164)x1	Pathogenic

SpliceAI

972 predictions. Top by Δscore:

Variant	Effect	Δscore
3:72378635:GGCC:G	acceptor_loss	1.0000
3:72378637:CCTAG:C	acceptor_loss	1.0000
3:72378638:C:CA	acceptor_loss	1.0000
3:72378638:C:CC	acceptor_gain	1.0000
3:72378651:C:CT	acceptor_gain	1.0000
3:72379035:AGTAC:A	donor_loss	1.0000
3:72379036:GTAC:G	donor_loss	1.0000
3:72379037:TA:T	donor_loss	1.0000
3:72379038:ACCTT:A	donor_loss	1.0000
3:72379039:C:CG	donor_loss	1.0000
3:72379134:TTGGT:T	acceptor_gain	1.0000
3:72379135:TGGT:T	acceptor_gain	1.0000
3:72379136:GGT:G	acceptor_gain	1.0000
3:72379137:GT:G	acceptor_gain	1.0000
3:72379139:C:CC	acceptor_gain	1.0000
3:72379143:A:AC	acceptor_gain	1.0000
3:72379143:A:C	acceptor_gain	1.0000
3:72379152:A:AC	acceptor_gain	1.0000
3:72379152:A:C	acceptor_gain	1.0000
3:72379155:C:CT	acceptor_gain	1.0000
3:72379156:A:T	acceptor_gain	1.0000
3:72379160:C:CT	acceptor_gain	1.0000
3:72379246:CTTAC:C	donor_loss	1.0000
3:72379249:A:AC	donor_gain	1.0000
3:72379250:C:CA	donor_gain	1.0000
3:72379250:CT:C	donor_gain	1.0000
3:72379250:CTT:C	donor_gain	1.0000
3:72379250:CTTG:C	donor_gain	1.0000
3:72379250:CTTGG:C	donor_gain	1.0000
3:72379423:GTTTT:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000008590 (3:72438495 A>G,T), RS1000046401 (3:72394988 A>G), RS1000094419 (3:72448680 C>T), RS1000146249 (3:72410939 G>A), RS1000165018 (3:72434031 T>A,C), RS1000339555 (3:72411495 T>C), RS1000381503 (3:72400268 T>A,C,G), RS1000388470 (3:72432237 C>A), RS1000414755 (3:72438146 C>G), RS1000449724 (3:72405399 A>C), RS1000487213 (3:72400834 T>C), RS1000598123 (3:72444956 T>C), RS1000606219 (3:72415673 A>G), RS1000640904 (3:72437901 C>A,T), RS1000657787 (3:72377116 T>A)

Disease associations

OMIM: gene MIM:607535 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Moderate	Autosomal dominant

Mondo (1): complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

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

GWAS associations

38 associations (top):

Study	Trait	p-value
GCST000817_86	Height	4.000000e-13
GCST001956_60	Height	5.000000e-13
GCST002647_91	Height	3.000000e-22
GCST002702_38	Height	5.000000e-10
GCST004063_156	Waist circumference adjusted for body mass index	3.000000e-08
GCST004063_99	Waist circumference adjusted for body mass index	4.000000e-07
GCST004500_44	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	2.000000e-06
GCST004562_17	Waist circumference adjusted for body mass index	8.000000e-07
GCST004562_176	Waist circumference adjusted for body mass index	2.000000e-09
GCST004562_218	Waist circumference adjusted for body mass index	7.000000e-08
GCST004562_74	Waist circumference adjusted for body mass index	1.000000e-06
GCST004562_90	Waist circumference adjusted for body mass index	1.000000e-08
GCST004563_1	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	1.000000e-06
GCST004563_181	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	4.000000e-07
GCST004563_226	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	2.000000e-08
GCST004563_67	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	7.000000e-08
GCST004563_81	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	3.000000e-06
GCST004564_132	Waist circumference adjusted for BMI in active individuals	5.000000e-07
GCST004564_133	Waist circumference adjusted for BMI in active individuals	9.000000e-09
GCST004564_134	Waist circumference adjusted for BMI in active individuals	2.000000e-06
GCST004564_135	Waist circumference adjusted for BMI in active individuals	1.000000e-07
GCST004564_95	Waist circumference adjusted for BMI in active individuals	5.000000e-06
GCST005038_28	Allergic disease (asthma, hay fever or eczema)	9.000000e-11
GCST006138_9	Resting-state electroencephalogram vigilance	2.000000e-07
GCST007927_6	Medication use (beta blocking agents)	2.000000e-08
GCST008163_40	Height	5.000000e-06
GCST008163_558	Height	2.000000e-06
GCST008359_8	Response to cognitive-behavioural therapy in anxiety disorder	7.000000e-06
GCST008839_556	Height	1.000000e-22
GCST009391_596	Metabolite levels	5.000000e-08

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0004357	electroencephalogram measurement
EFO:0009929	Beta blocking agent use measurement
EFO:0007820	cognitive behavioural therapy
EFO:0010502	indoxyl sulfate measurement
EFO:0004327	electrocardiography
EFO:0009819	comparative body size at age 10, self-reported
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066053 (PROTEIN-PROTEIN INTERACTION)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression	3
Acetaminophen	increases expression	2
Copper	decreases expression, increases expression, affects binding	2
Hydrogen Peroxide	affects expression	2
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
salinomycin	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	affects expression	1
sodium arsenite	increases expression	1
cupric chloride	affects expression	1
cupric oxide	increases expression	1
CD 437	decreases expression	1
chloropicrin	increases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	affects binding, increases expression	1
PCI 5002	increases expression, affects cotreatment	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	increases expression	1
Vehicle Emissions	increases methylation	1
Cadmium	increases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5548052	Binding	PROTAC activity at CRBN/RYBP in human K562 cells assessed as degradation of RYBP protein expression at 1 to 10 uM incubated for 24 hrs by Western blotting analysis	Discovery and Characterization of a Novel Cereblon-Recruiting PRC1 Bridged PROTAC Degrader. — J Med Chem

Cellosaurus cell lines

8 cell lines: 5 cancer cell line, 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A6A3	SEES3-1V human RYBP, clone1	Embryonic stem cell	Male
CVCL_A6A4	SEES3-1V human RYBP, clone2	Embryonic stem cell	Male
CVCL_A6A5	SEES3-1V human RYBP, clone3	Embryonic stem cell	Male
CVCL_B7Z8	Abcam Raji RYBP KO	Cancer cell line	Male
CVCL_C0A0	Abcam THP-1 RYBP KO	Cancer cell line	Male
CVCL_C7BP	Abcam PC-3 RYBP KO	Cancer cell line	Male
CVCL_E2JM	HAP1 RYBP (-) 1	Cancer cell line	Male
CVCL_E2JN	HAP1 RYBP (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder