RBBP6

Summary

RBBP6 (RB binding protein 6, ubiquitin ligase, HGNC:9889) is a protein-coding gene on chromosome 16p12.1, encoding E3 ubiquitin-protein ligase RBBP6 (Q7Z6E9). E3 ubiquitin-protein ligase which promotes ubiquitination of YBX1, leading to its degradation by the proteasome. It is a common-essential gene (DepMap: required in 91.4% of cancer cell lines).

The retinoblastoma tumor suppressor (pRB) protein binds with many other proteins. In various human cancers, pRB suppresses cellular proliferation and is inactivated. Cell cycle-dependent phosphorylation regulates the activity of pRB. This gene encodes a protein which binds to underphosphorylated but not phosphorylated pRB. Multiple alternatively spliced transcript variants that encode different isoforms have been found for this gene.

Source: NCBI Gene 5930 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 255 total
• Cancer dependency (DepMap): dependent in 91.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_006910

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9889
Approved symbol	RBBP6
Name	RB binding protein 6, ubiquitin ligase
Location	16p12.1
Locus type	gene with protein product
Status	Approved
Aliases	P2P-R, PACT, SNAMA
Ensembl gene	ENSG00000122257
Ensembl biotype	protein_coding
OMIM	600938
Entrez	5930

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000319715, ENST00000348022, ENST00000381039, ENST00000452655, ENST00000562430, ENST00000562683, ENST00000564314, ENST00000564726, ENST00000567686, ENST00000568015, ENST00000568316, ENST00000570185, ENST00000613729, ENST00000646282, ENST00000937827

RefSeq mRNA: 3 — MANE Select: NM_006910 NM_006910, NM_018703, NM_032626

CCDS: CCDS10621, CCDS10622, CCDS45444

Canonical transcript exons

ENST00000319715 — 18 exons

Exon	Start	End
ENSE00001690982	24548945	24548981
ENSE00001732323	24546163	24546262
ENSE00001745967	24567792	24567893
ENSE00001856595	24570876	24572863
ENSE00001944481	24539566	24540792
ENSE00003465136	24563199	24563295
ENSE00003480203	24561824	24562161
ENSE00003480512	24559505	24559677
ENSE00003503032	24553513	24553557
ENSE00003505451	24563610	24563664
ENSE00003557876	24555615	24555703
ENSE00003584415	24563423	24563501
ENSE00003643132	24555821	24555917
ENSE00003659353	24561612	24561715
ENSE00003663697	24556308	24556447
ENSE00003671939	24567143	24567505
ENSE00003684768	24564797	24564865
ENSE00003690349	24568745	24570499

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 97.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.4934 / max 2746.5905, expressed in 1822 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153232	28.1447	1812
153231	4.1590	1652
153233	4.0707	1439
153236	0.6401	335
153230	0.2684	90
153228	0.2016	74
153229	0.0089	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.91	gold quality
cervix squamous epithelium	UBERON:0006922	97.79	gold quality
sperm	CL:0000019	96.94	gold quality
mucosa of stomach	UBERON:0001199	95.87	gold quality
left ovary	UBERON:0002119	95.81	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.63	gold quality
male germ cell	CL:0000015	95.39	gold quality
right ovary	UBERON:0002118	95.07	gold quality
right uterine tube	UBERON:0001302	94.97	gold quality
left testis	UBERON:0004533	94.96	gold quality
right testis	UBERON:0004534	94.91	gold quality
skin of abdomen	UBERON:0001416	94.83	gold quality
cerebellar hemisphere	UBERON:0002245	94.70	gold quality
left uterine tube	UBERON:0001303	94.63	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.62	gold quality
cerebellar cortex	UBERON:0002129	94.57	gold quality
body of uterus	UBERON:0009853	94.37	gold quality
monocyte	CL:0000576	94.27	gold quality
tongue squamous epithelium	UBERON:0006919	94.25	gold quality
right lung	UBERON:0002167	94.22	gold quality
cerebellum	UBERON:0002037	94.17	gold quality
skin of leg	UBERON:0001511	94.10	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.01	gold quality
ovary	UBERON:0000992	93.98	gold quality
testis	UBERON:0000473	93.91	gold quality
adenohypophysis	UBERON:0002196	93.83	gold quality
calcaneal tendon	UBERON:0003701	93.75	gold quality
cervix epithelium	UBERON:0004801	93.67	gold quality
mononuclear cell	CL:0000842	93.66	gold quality
sural nerve	UBERON:0015488	93.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting RBBP6, 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-4673	100.00	66.64	1490
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-320A-3P	99.77	69.73	2107

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 91.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 25)

• P2P-R expression may be translationally regulated by PUM2 and that P2P-R may modulate translation by influencing ribosomal protein gene expression (PMID:15617101)
• RBBP6 has a role in mRNA processing and ubiquitin-like pathways (PMID:16396680)
• The authors showed that RBBP6 and its isolated RING finger domain were able to ubiquitinate YB-1, resulting in its degradation in the proteosome. As a result, RBBP6 was able to suppress the levels of YB-1 in vivo and reduce its transactivational ability. (PMID:18851979)
• RBBP6 may be involved in the degradation of p53, thereby enhancing cell proliferation and inhibiting apoptosis in lung cancer. (PMID:21676486)
• Taken together with the structural similarities to U-box-containing proteins, our data suggest that RBBP6 plays a role in chaperone-mediated ubiquitination and possibly in protein quality control. (PMID:22130672)
• these findings suggest that RBBP6 isoform 3 is a cell cycle regulator and may be deregulated in carcinogenesis (PMID:22139301)
• AGO2, PACT and TRBP are required for the efficient functioning of Dicer in cells (PMID:22163034)
• gene silencing sensitises breast cancer cells to staurosporine and camptothecin-induced cell death (PMID:24703106)
• RBBP6 prevents DNA damage by destabilizing the transcriptional repressor ZBTB38. (PMID:24726359)
• RBBP6 gene variants are associated with glioma and contribute to glioma susceptibility (PMID:25127414)
• implicate RBBP6 and iso3 as novel regulators of 3’ processing, especially of RNAs with AU-rich 3’ UTRs. (PMID:25319826)
• High expression levels of RBBP6 and high apoptosis levels were found in HIV-associated nephropathy (HIVAN) cases. This direct association between RBBP6 expression and apoptosis levels suggests that RBBP6 play a role in HIVAN pathogenesis. (PMID:25910411)
• Results from a study on gene expression variability markers in early-stage human embryos shows that RBBP6 is a putative expression variability marker for the 3-day, 8-cell embryo stage. (PMID:26288249)
• RBBP6 is a candidate gene for myeloproliferative neoplasms (MPNs) susceptibility in a subset of pedigrees with familial MPN. (PMID:26574608)
• These results suggest that the RBBP6-3 isoform may be involved in promoting apoptosis in cancerous cells. (PMID:26905308)
• RBBP6 overexpression could resist colorectal cancer cells against radiation. (PMID:29369481)
• RBBP6 might potentiate cervical carcinoma cell viability. (PMID:29501043)
• A crystal structure of the VP30-RBBP6 peptide complex revealed that RBBP6 mimics the viral nucleoprotein (NP) binding to the same interface of VP30. (PMID:30550789)
• In the present study, elevated expression of PACT was detected in cisplatin-resistant A2780/CP cells relative to cisplatin-sensitive A2780cells. (PMID:30827507)
• RBBP6, a RING finger-domain E3 ubiquitin ligase, induces epithelial-mesenchymal transition and promotes metastasis of colorectal cancer. (PMID:31685801)
• Analysis of the expression and association of retinoblastoma binding protein 6 with the JNK signaling pathway in prostate cancers. (PMID:32662898)
• RBBP6 aggravates the progression of ovarian cancer by targeting PIK3R6. (PMID:33155192)
• The lncRNA SLCO4A1-AS1/miR-876-3p/RBBP6 axis regulates cell proliferation and apoptosis in acute lymphocytic leukemia via the JNK signaling pathway. (PMID:33683013)
• RBBP6 activates the pre-mRNA 3’ end processing machinery in humans. (PMID:35177536)
• Abnormal expression of long non-coding RNA FGD5-AS1 affects the development of ovarian cancer through regulating miR-107/RBBP6 axis. (PMID:37322627)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rbbp6	ENSMUSG00000030779
rattus_norvegicus	Rbbp6	ENSRNOG00000012806

Paralogs (1): ZCCHC24 (ENSG00000165424)

Protein

Protein identifiers

E3 ubiquitin-protein ligase RBBP6 — Q7Z6E9 (reviewed: Q7Z6E9)

Alternative names: Proliferation potential-related protein, Protein P2P-R, RING-type E3 ubiquitin transferase RBBP6, Retinoblastoma-binding Q protein 1, Retinoblastoma-binding protein 6, p53-associated cellular protein of testis

All UniProt accessions (6): A0A087WY32, A0A2R8Y880, Q7Z6E9, H3BSK8, H3BUN0, I3L3Y2

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase which promotes ubiquitination of YBX1, leading to its degradation by the proteasome. May play a role as a scaffold protein to promote the assembly of the p53/TP53-MDM2 complex, resulting in increase of MDM2-mediated ubiquitination and degradation of p53/TP53; may function as negative regulator of p53/TP53, leading to both apoptosis and cell growth. Regulates DNA-replication and the stability of chromosomal common fragile sites (CFSs) in a ZBTB38- and MCM10-dependent manner. Controls ZBTB38 protein stability and abundance via ubiquitination and proteasomal degradation, and ZBTB38 in turn negatively regulates the expression of MCM10 which plays an important role in DNA-replication. (Microbial infection) [Isoform 1]: Restricts ebolavirus replication probably by impairing the vp30-NP interaction, and thus viral transcription.

Subunit / interactions. Interacts with p53/TP53 and RB1. Interacts also with MDM2 and YBX1. Interacts with NEK6. Interacts with ZBTB38. (Microbial infection) [Isoform 1]: Interacts with ebolavirus VP30.

Subcellular location. Nucleus. Nucleolus. Chromosome. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Tissue specificity. Highly expressed in the placenta and testis. Expressed at lower levels in the brain, heart, kidney, liver and lung. Overexpressed in esophageal cancer.

Post-translational modifications. Phosphorylated by NEK6.

Domain organisation. Contains a N-terminus DWNN domain, a zinc-finger domain and a C4C4 zinc-binding RING finger domain. The ring finger may indeed be a U-box domain.

Pathway. Protein modification; protein ubiquitination.

Isoforms (4)

UniProt ID	Names	Canonical?
Q7Z6E9-1	1	yes
Q7Z6E9-2	2
Q7Z6E9-3	3
Q7Z6E9-4	4

RefSeq proteins (3): NP_008841, NP_061173, NP_116015 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR001878	Znf_CCHC	Domain
IPR003613	Ubox_domain	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR014891	DWNN_domain	Domain
IPR025829	Zn_knuckle_CX2CX3GHX4C	Domain
IPR033489	RBBP6	Family
IPR036875	Znf_CCHC_sf	Homologous_superfamily

Pfam: PF04564, PF08783, PF13696

UniProt features (106 total): compositionally biased region 32, modified residue 27, region of interest 12, strand 10, helix 6, splice variant 4, turn 3, sequence variant 3, zinc finger region 2, cross-link 2, sequence conflict 2, chain 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6E5X	X-RAY DIFFRACTION	1.5
2C7H	SOLUTION NMR
2YSA	SOLUTION NMR
2YUR	SOLUTION NMR
3ZTG	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z6E9-F1	46.97	0.06

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 (29): 130, 244, 245, 246, 247, 360, 516, 768, 770, 772, 780, 815, 861, 873, 957, 984, 1179, 1221, 1271, 1277 …

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9013422	RHOBTB1 GTPase cycle
R-HSA-9770562	mRNA Polyadenylation
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation

MSigDB gene sets: 264 (showing top): RNGTGGGC_UNKNOWN, BROWNE_HCMV_INFECTION_4HR_UP, MYAATNNNNNNNGGC_UNKNOWN, MODULE_97, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, PAX4_01, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, BROWNE_HCMV_INFECTION_8HR_UP, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, TGCACTT_MIR519C_MIR519B_MIR519A, LFA1_Q6

GO Biological Process (10): in utero embryonic development (GO:0001701), DNA replication (GO:0006260), regulation of DNA replication (GO:0006275), mRNA processing (GO:0006397), ubiquitin-dependent protein catabolic process (GO:0006511), DNA damage response (GO:0006974), protein ubiquitination (GO:0016567), multicellular organism growth (GO:0035264), embryonic organ development (GO:0048568), somite development (GO:0061053)

GO Molecular Function (9): RNA binding (GO:0003723), ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), protein kinase binding (GO:0019901), ubiquitin protein ligase activity (GO:0061630), nucleic acid binding (GO:0003676), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (9): nucleus (GO:0005634), chromosome (GO:0005694), nucleolus (GO:0005730), centrosome (GO:0005813), cytosol (GO:0005829), nuclear speck (GO:0016607), protein-containing complex (GO:0032991), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
RHOBTB GTPase Cycle	1
mRNA 3’-end processing	1
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	3
embryo development	2
binding	2
cellular anatomical structure	2
chordate embryonic development	1
DNA metabolic process	1
DNA biosynthetic process	1
DNA replication	1
regulation of DNA metabolic process	1
RNA processing	1
mRNA metabolic process	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
cellular response to stress	1
protein modification by small protein conjugation	1
multicellular organismal process	1
developmental growth	1
animal organ development	1
epithelium development	1
nucleic acid binding	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
kinase binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
centriole	1
microtubule organizing center	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
cellular_component	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1668 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBBP6	TP53	P04637	976
RBBP6	CPSF3	Q9UKF6	801
RBBP6	ZBTB38	Q8NAP3	800
RBBP6	SYMPK	Q92797	782
RBBP6	SON	P18583	769
RBBP6	MDM2	Q00987	752
RBBP6	WDR33	Q9C0J8	736
RBBP6	PAPOLG	Q9BWT3	722
RBBP6	ARID4A	P29374	687
RBBP6	CPSF1	Q10570	682
RBBP6	CSTF3	Q12996	677
RBBP6	PAPOLA	P51003	670
RBBP6	PAPOLB	Q9NRJ5	657
RBBP6	PCF11	O94913	649
RBBP6	CPSF2	Q9P2I0	649
RBBP6	KDM5A	P29375	649

IntAct

137 interactions, top by confidence:

A	B	Type	Score
CPSF6	NUDT21	psi-mi:“MI:0914”(association)	0.740
SRSF7	RBBP6	psi-mi:“MI:0915”(physical association)	0.660
RBBP6	SRSF7	psi-mi:“MI:0403”(colocalization)	0.660
PNN	CASC3	psi-mi:“MI:0914”(association)	0.640
ZNF576	ZBED1	psi-mi:“MI:0914”(association)	0.640
GSPT2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
ZC3H18	AQR	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
TRPC4AP	SMCHD1	psi-mi:“MI:0914”(association)	0.530
SRPK2	RRP9	psi-mi:“MI:0914”(association)	0.530
RBBP6	HNRNPC	psi-mi:“MI:0914”(association)	0.530
EZH1	EPOP	psi-mi:“MI:0914”(association)	0.530
RNPS1	CASC3	psi-mi:“MI:0914”(association)	0.530
HNRNPC	CASC3	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
RPL13	RRP8	psi-mi:“MI:0914”(association)	0.530
SRSF5	CBX6	psi-mi:“MI:0914”(association)	0.530
ZC3H18	SRPK2	psi-mi:“MI:0914”(association)	0.530
LRRK2	DFFA	psi-mi:“MI:0914”(association)	0.530
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
RBBP6	CPSF3	psi-mi:“MI:0407”(direct interaction)	0.440
MDM2	RBBP6	psi-mi:“MI:0915”(physical association)	0.400
RBBP6	ZFYVE9	psi-mi:“MI:0915”(physical association)	0.370
Plk2	NES	psi-mi:“MI:0914”(association)	0.350

BioGRID (304): CSTF2 (Affinity Capture-Western), CSTF3 (Affinity Capture-Western), CPSF1 (Affinity Capture-Western), CPSF2 (Affinity Capture-Western), CPSF4 (Affinity Capture-Western), RBBP6 (Affinity Capture-MS), RBBP6 (Affinity Capture-MS), RBBP6 (Affinity Capture-MS), RBBP6 (Co-fractionation), RBBP6 (Co-fractionation), RBBP6 (Co-fractionation), UFM1 (Co-fractionation), RBBP6 (Affinity Capture-MS), RB1 (Affinity Capture-Western), TP53 (Affinity Capture-Western)

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

Diamond homologs: B9DFV2, F4JP52, O94264, P43254, P97868, Q7Z6E9, P35728, Q4KLY4, Q5R9J5, Q803I4, Q99496, Q9CQJ4

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RBBP6	ubiquitination
RBBP6	“down-regulates quantity by destabilization”	YBX1	ubiquitination
RBBP6	“down-regulates quantity by destabilization”	ZBTB38	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 151 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
Transport of Mature Transcript to Cytoplasm	8	29.0×	1e-08
RNA Polymerase II Transcription Termination	13	27.2×	1e-13
mRNA 3’-end processing	12	22.5×	1e-11
mRNA Splicing	17	17.8×	1e-14
Processing of Capped Intron-Containing Pre-mRNA	20	15.7×	6e-16
mRNA Polyadenylation	18	15.1×	2e-14
Transport of Mature mRNA derived from an Intron-Containing Transcript	8	11.6×	2e-05
mRNA Splicing - Major Pathway	22	11.4×	4e-15

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	6	34.0×	3e-06
regulation of alternative mRNA splicing, via spliceosome	9	16.3×	1e-06
mRNA splicing, via spliceosome	16	10.8×	1e-09
ribosomal small subunit biogenesis	6	10.1×	4e-03
RNA processing	6	9.7×	5e-03
negative regulation of translation	6	8.7×	6e-03
RNA splicing	13	8.5×	1e-06
mRNA processing	13	7.6×	3e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	202
Likely benign	24
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1666 predictions. Top by Δscore:

Variant	Effect	Δscore
16:24540789:GAAG:G	donor_gain	1.0000
16:24540791:AGGTA:A	donor_loss	1.0000
16:24540792:GGTAA:G	donor_loss	1.0000
16:24540793:GT:G	donor_loss	1.0000
16:24546155:A:AG	acceptor_gain	1.0000
16:24546156:T:G	acceptor_gain	1.0000
16:24546158:TACAG:T	acceptor_loss	1.0000
16:24546160:CAGAA:C	acceptor_loss	1.0000
16:24546161:A:AC	acceptor_loss	1.0000
16:24546161:A:AG	acceptor_gain	1.0000
16:24546162:G:GG	acceptor_gain	1.0000
16:24546162:GA:G	acceptor_gain	1.0000
16:24546162:GAA:G	acceptor_gain	1.0000
16:24546162:GAAT:G	acceptor_gain	1.0000
16:24546162:GAATA:G	acceptor_gain	1.0000
16:24546258:GTTAT:G	donor_gain	1.0000
16:24546259:TTAT:T	donor_gain	1.0000
16:24546260:TAT:T	donor_gain	1.0000
16:24546261:AT:A	donor_gain	1.0000
16:24546261:ATG:A	donor_loss	1.0000
16:24546263:G:GA	donor_loss	1.0000
16:24546263:G:GG	donor_gain	1.0000
16:24546264:TAA:T	donor_loss	1.0000
16:24548935:T:TA	acceptor_gain	1.0000
16:24548937:T:TA	acceptor_gain	1.0000
16:24548943:A:AG	acceptor_gain	1.0000
16:24548944:G:GA	acceptor_gain	1.0000
16:24548944:GA:G	acceptor_gain	1.0000
16:24548944:GAA:G	acceptor_gain	1.0000
16:24548977:AAGCA:A	donor_gain	1.0000

AlphaMissense

11744 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:24540639:C:G	H5D	1.000
16:24540642:T:C	Y6H	1.000
16:24540642:T:G	Y6D	1.000
16:24540647:A:C	K7N	1.000
16:24540647:A:T	K7N	1.000
16:24540648:T:A	F8I	1.000
16:24540648:T:C	F8L	1.000
16:24540648:T:G	F8V	1.000
16:24540649:T:C	F8S	1.000
16:24540649:T:G	F8C	1.000
16:24540650:T:A	F8L	1.000
16:24540650:T:G	F8L	1.000
16:24540676:T:A	V17D	1.000
16:24540681:T:C	F19L	1.000
16:24540682:T:C	F19S	1.000
16:24540683:T:A	F19L	1.000
16:24540683:T:G	F19L	1.000
16:24540687:G:A	G21R	1.000
16:24540687:G:C	G21R	1.000
16:24540687:G:T	G21W	1.000
16:24540688:G:A	G21E	1.000
16:24540688:G:T	G21V	1.000
16:24540697:T:A	I24N	1.000
16:24540712:T:C	L29S	1.000
16:24540716:G:C	K30N	1.000
16:24540716:G:T	K30N	1.000
16:24540724:T:A	I33N	1.000
16:24540724:T:C	I33T	1.000
16:24540724:T:G	I33S	1.000
16:24540742:T:C	L39P	1.000

dbSNP variants (sampled 300 via entrez): RS1000269271 (16:24543724 A>G), RS1000374616 (16:24538124 C>G), RS1000506391 (16:24557605 A>C), RS1000566712 (16:24553762 A>G), RS1000811883 (16:24558829 C>G,T), RS1000910554 (16:24541962 T>C), RS1001138118 (16:24547288 T>C), RS1001213974 (16:24557955 A>G), RS1001491347 (16:24541673 A>G), RS1001491512 (16:24562743 T>C), RS1001749954 (16:24563993 G>A), RS1001936967 (16:24558361 A>C,G), RS1001978452 (16:24558339 C>A,T), RS1002191612 (16:24541277 C>T), RS1002225778 (16:24571527 T>C)

Disease associations

OMIM: gene MIM:600938 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000597_3	Brain structure	6.000000e-07
GCST001762_422	Obesity-related traits	9.000000e-06
GCST004904_182	Body mass index	1.000000e-08
GCST007096_88	Pulse pressure	8.000000e-08
GCST007099_75	Systolic blood pressure	9.000000e-09
GCST007576_217	Chronotype	5.000000e-10
GCST010988_39	Adult body size	1.000000e-08
GCST010989_6	Body size at age 10	3.000000e-10
GCST90007526_11	Low hand grip strength (60 years and older) (EWGSOP)	3.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0003940	physical activity
EFO:0004340	body mass index
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0008328	chronotype measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0006941	grip strength measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression, affects expression	4
Valproic Acid	affects expression, decreases expression	4
Benzo(a)pyrene	increases expression	3
Doxorubicin	affects response to substance, decreases expression, affects phosphorylation	2
Estradiol	decreases expression, affects cotreatment	2
Nicotine	decreases expression, decreases reaction, increases expression	2
Tobacco Smoke Pollution	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
Asbestos, Crocidolite	increases expression	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases reaction, decreases expression	1
alpha-cobratoxin	decreases expression, decreases reaction	1
coumarin	decreases phosphorylation	1
cupric oxide	increases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	1
beta-methylcholine	affects expression	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
torcetrapib	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
PCI 5002	increases expression, affects cotreatment	1
Leflunomide	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A5T5	SEES3-1V human RBBP6, clone1	Embryonic stem cell	Male
CVCL_A5T6	SEES3-1V human RBBP6, clone2	Embryonic stem cell	Male
CVCL_A5T7	SEES3-1V human RBBP6, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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