RNF20

Summary

RNF20 (ring finger protein 20, HGNC:10062) is a protein-coding gene on chromosome 9q31.1, encoding E3 ubiquitin-protein ligase BRE1A (Q5VTR2). Component of the RNF20/40 E3 ubiquitin-protein ligase complex that mediates monoubiquitination of ‘Lys-120’ of histone H2B (H2BK120ub1). It is a selective cancer dependency (DepMap: 87.3% of cell lines).

The protein encoded by this gene shares similarity with BRE1 of S. cerevisiae. The protein encoded by this human gene is an E3 ubiquitin ligase that regulates chromosome structure by monoubiquitinating histone H2B. This protein acts as a putative tumor suppressor and positively regulates the p53 tumor suppressor as well as numerous histone H2A and H2B genes. In contrast, this protein also suppresses the expression of several protooncogenes and growth-related genes, including many genes that are induced by epidermal growth factor. This gene selectively suppresses the expression of some genes by interfering with chromatin recruitment of transcription elongation factor SII (TFIIS).

Source: NCBI Gene 56254 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 129 total
• Cancer dependency (DepMap): dependent in 87.3% of screened cell lines
• MANE Select transcript: NM_019592

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10062
Approved symbol	RNF20
Name	ring finger protein 20
Location	9q31.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20382, FLJ11189, KAIA2779, BRE1A, hBRE1, BRE1
Ensembl gene	ENSG00000155827
Ensembl biotype	protein_coding
OMIM	607699
Entrez	56254

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000374819, ENST00000389120, ENST00000466817, ENST00000478072, ENST00000479306, ENST00000481046, ENST00000888393, ENST00000888394, ENST00000888396, ENST00000912957

RefSeq mRNA: 1 — MANE Select: NM_019592 NM_019592

CCDS: CCDS35084

Canonical transcript exons

ENST00000389120 — 20 exons

Exon	Start	End
ENSE00001022954	101533853	101533914
ENSE00001090807	101560801	101560926
ENSE00001090811	101546820	101546966
ENSE00001090813	101554694	101554843
ENSE00001090815	101540793	101540975
ENSE00001090818	101552141	101552262
ENSE00001090819	101561910	101562011
ENSE00001090820	101550606	101550785
ENSE00001090821	101547399	101547518
ENSE00001090822	101561090	101561230
ENSE00001090824	101557384	101557596
ENSE00001090825	101553988	101554105
ENSE00001090826	101552383	101552753
ENSE00001090828	101547137	101547214
ENSE00001090830	101544767	101544885
ENSE00001504913	101540490	101540637
ENSE00001891221	101562246	101563344
ENSE00003274793	101551684	101551819
ENSE00003567521	101535398	101535552
ENSE00003786164	101540203	101540370

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 97.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.2992 / max 746.3879, expressed in 1790 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97761	14.8958	1772
97762	2.3386	1254
97768	0.8064	393
97767	0.5752	200
97766	0.5716	272
97763	0.0766	16
97764	0.0350	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	97.70	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.30	gold quality
left ventricle myocardium	UBERON:0006566	97.20	gold quality
ileal mucosa	UBERON:0000331	96.38	gold quality
deltoid	UBERON:0001476	96.23	gold quality
caput epididymis	UBERON:0004358	94.98	gold quality
myocardium	UBERON:0002349	94.97	gold quality
bronchial epithelial cell	CL:0002328	94.88	gold quality
parietal pleura	UBERON:0002400	94.67	gold quality
pigmented layer of retina	UBERON:0001782	94.66	gold quality
bronchus	UBERON:0002185	94.63	gold quality
corpus callosum	UBERON:0002336	94.42	gold quality
corpus epididymis	UBERON:0004359	94.41	gold quality
calcaneal tendon	UBERON:0003701	94.34	gold quality
superior vestibular nucleus	UBERON:0007227	94.17	gold quality
medulla oblongata	UBERON:0001896	94.08	gold quality
visceral pleura	UBERON:0002401	94.07	gold quality
cauda epididymis	UBERON:0004360	93.99	gold quality
inferior vagus X ganglion	UBERON:0005363	93.88	gold quality
mammary duct	UBERON:0001765	93.72	gold quality
epithelium of mammary gland	UBERON:0003244	93.72	gold quality
trabecular bone tissue	UBERON:0002483	93.48	gold quality
oral cavity	UBERON:0000167	93.44	gold quality
cerebellar vermis	UBERON:0004720	93.44	gold quality
ganglionic eminence	UBERON:0004023	93.31	gold quality
islet of Langerhans	UBERON:0000006	93.26	gold quality
subthalamic nucleus	UBERON:0001906	93.23	gold quality
lower lobe of lung	UBERON:0008949	93.21	gold quality
kidney epithelium	UBERON:0004819	93.12	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.11	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.18

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

86 targeting RNF20, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6785-5P	99.82	68.68	4428

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 87.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Functional analysis of the yeast counterpart (PMID:12535538)
• Functional analysis of the yeast counterpart (PMID:12535539)
• Functional analysis of the yeast counterpart (PMID:12876294)
• In humans, the 600 kDa RNF20/40 complex is the E3 ligase. (PMID:16307923)
• RNF20 overexpression leads to elevated histone 2B monoubiquitination, subsequently higher levels of methylation at H3 lysines 4 and 79, and stimulation of homeobox gene expression. (PMID:16307923)
• The Bre1 protein specifically increases the global level of H2B ubiquitylation at lysine 120 and enhances activator-dependent transcription. (PMID:16337599)
• identified as one of five genes containing 11 somatic mutations in a panel that included 132 colorectal cancers, then demonstrated that down-regulation of such homologs resulted in chromosomal instability and chromatid cohesion defects in human cells (PMID:18299561)
• RNF20 suppresses the expression of several proto-oncogenes, which reside preferentially in closed chromatin and are modestly transcribed despite bearing marks usually associated with high transcription rates. (PMID:18832071)
• hBre1 inhibits Ebp1’s tumor suppressive activity through mediating its polyubiquitination and degradation. (PMID:19037095)
• the observed defects in the radiation response of Bre1a/b-deficient cells (PMID:20738173)
• RNF20-mediated H2B ubiquitination at DSBs plays a critical role in HRR through chromatin remodeling (PMID:21362548)
• RNF20, presumably via H2Bub, selectively represses oncogenic genes by interfering with chromatin recruitment of TFIIS, a factor capable of relieving stalled RNA polymerase II. RNF20 inhibits the interaction between TFIIS and the PAF1 complex. (PMID:21596312)
• Studies indicate that H2B monoubiquitylation is driven primarily by an E3 ubiquitin ligase composed of the two RING finger proteins RNF20 and RNF40. (PMID:21827756)
• our results suggest that RNF20 and RNF40, either via ubiquitylation of H2B or other targets, are coupled to the proliferation of prostate cancer cells. (PMID:22155569)
• We show that Bre1 (human BRE1A/B (RNF20/40) and mouse Bre1a/b (Rnf20/40)) acts as an important suppressor of chromosomal instability (PMID:22354749)
• model whereby cotranscriptional recruitment of Rnf20 at MLL-fusion target genes leads to amplification of Dot1l-mediated H3K79 methylation, thereby rendering leukemia cells dependent on Rnf20 to maintain their oncogenic transcriptional program (PMID:23412334)
• The ability of E1A to target hBre1 to simultaneously repress cellular IFN dependent transcription while activating viral transcription (PMID:23785282)
• A primary role for FACT in RNF20 recruitment chromatin remodeling for initiation of homologous recombination repair. (PMID:24357716)
• Together, these results indicate that human adenovirus E1A uses hBre1 to recruit the hPaf1 complex in order to optimally activate viral early transcription by enhancing transcriptional elongation. (PMID:24600005)
• It was observed that RE-IIBP induces MEIS1-mediated apoptosis, which was dependent on H2BK120 ubiquitination by RNF20. (PMID:26206755)
• RNF20 and H2Bub1 promotes chronic colonic inflammation and inflammation-associated colorectal cancer in mice and humans, partly by augmenting NF-kappaB activity and attenuating the antitumoral T cell response. (PMID:26854224)
• the RNF20/40 complex, a major ubiquitin ligase catalysing histone H2B monoubiquitination, interacts with the motor protein Eg5 during mitosis and participates in spindle assembly. (PMID:27557628)
• The authors also show that the RING domains of RNF20 and RNF40 can form a stable heterodimer that is active. (PMID:27569044)
• Manipulation of key H2Bub1 E3 ubiquitin ligases, RNF20, RNF40 and BRCA1, in ovarian cancer cell line models modulated H2Bub1 levels, indicative of the role of these RING finger ligases in monoubiquitination of H2Bub1 in vitro (PMID:27798111)
• The effects of RNF20 on mammary tumorigenesis are subtype dependent: In basal-like cancers cells, RNF20 suppresses the NF-kappaB-dependent expression of cytokines, known to contribute to the growth of this tumor subtype. (PMID:28157208)
• data indicate that RNF20 and PARP1 are synthetic lethal interactors (PMID:28462496)
• ATG5 regulates histone H2B mono-ubiquitylation by translational control of RNF20 (PMID:29037992)
• RNF20 depletion stabilizes the ZSCAN4 protein half-life, suggesting that RNF20 negatively regulates ZSCAN4 stability. (PMID:29477841)
• This review summarized the current knowledge of RNF20 in chronic inflammation-driven cancers, DNA double-strand break, and apoptosis, and its impact on chromatin structure beyond the single nucleosome level. [review] (PMID:29934362)
• Low RNF20 expression is associated with initiation and progression of high-grade serous ovarian cancer. (PMID:30563893)
• Cooperative physical interactions among eEF1BdeltaL, RNF20/40, and HSF1 synergistically promote expression of heat shock-responsive genes. In addition, eEF1BdeltaL is a novel ubiquitylation target of RNF20/40 and elucidating its function. This provides a molecular mechanism for the cooperative function of distinct transcription factors in heat shock-responsive gene transcription. (PMID:30649429)
• The RNF20/40 complex regulates p53-dependent gene transcription and mRNA splicing. (PMID:31152661)
• SMURF2 prevents detrimental changes to chromatin, protecting human dermal fibroblasts from chromosomal instability and tumorigenesis. (PMID:32103168)
• CircRNF20 aggravates the progression of non-small-cell lung carcinoma by activating MAPK9. (PMID:33090403)
• Overexpression of ring finger protein 20 inhibits the progression of liver fibrosis via mediation of histone H2B lysine 120 ubiquitination. (PMID:33575967)
• Protease cleavage of RNF20 facilitates coronavirus replication via stabilization of SREBP1. (PMID:34452991)
• RNF20 deletion causes inflammation in model of sepsis through the NLRP3 activation. (PMID:36650938)
• The RPA-RNF20-SNF2H cascade promotes proper chromosome segregation and homologous recombination repair. (PMID:37155876)
• Iron deficiency-induced ferritinophagy impairs skeletal muscle regeneration through RNF20-mediated H2Bub1 modification. (PMID:37976359)
• RNF20 Regulates Oocyte Meiotic Spindle Assembly by Recruiting TPM3 to Centromeres and Spindle Poles. (PMID:38240347)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf20	ENSDARG00000016664
mus_musculus	Rnf20	ENSMUSG00000028309
rattus_norvegicus	Rnf20	ENSRNOG00000006087
drosophila_melanogaster	Bre1	FBGN0086694
caenorhabditis_elegans		WBGENE00007008

Paralogs (1): RNF40 (ENSG00000103549)

Protein

Protein identifiers

E3 ubiquitin-protein ligase BRE1A — Q5VTR2 (reviewed: Q5VTR2)

Alternative names: RING finger protein 20, RING-type E3 ubiquitin transferase BRE1A

All UniProt accessions (4): Q5VTR2, C9J0A5, C9JWJ4, C9JXC9

UniProt curated annotations — full annotation on UniProt →

Function. Component of the RNF20/40 E3 ubiquitin-protein ligase complex that mediates monoubiquitination of ‘Lys-120’ of histone H2B (H2BK120ub1). H2BK120ub1 gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 ‘Lys-4’ and ‘Lys-79’ methylation (H3K4me and H3K79me, respectively). It thereby plays a central role inb histone code and gene regulation. The RNF20/40 complex forms a H2B ubiquitin ligase complex in cooperation with the E2 enzyme UBE2A or UBE2B; reports about the cooperation with UBE2E1/UBCH are contradictory. Required for transcriptional activation of Hox genes. Recruited to the MDM2 promoter, probably by being recruited by p53/TP53, and thereby acts as a transcriptional coactivator. Mediates the polyubiquitination of isoform 2 of PA2G4 in cancer cells leading to its proteasome-mediated degradation. (Microbial infection) Promotes the human herpesvirus 8 (KSHV) lytic cycle by inducing the expression of lytic viral genes including the latency switch gene RTA/ORF50.

Subunit / interactions. Component of the RNF20/40 complex (also known as BRE1 complex) probably composed of 2 copies of RNF20/BRE1A and 2 copies of RNF40/BRE1B. Interacts with UBE2E1/UBCH6. Interacts with p53/TP53 and WAC. Interacts with PAF1; the interaction mediates the association of the PAF1 and RNF20/40 complexes which is a prerequsite for recruitment of UBE2A/B. Interacts with isoform 1 and isoform 2 of PA2G4. Interacts with FBXL19. (Microbial infection) Interacts with human herpesvirus 8 (KSHV) protein RTA/ORF50; this interaction targets the SMC5-SMC6 complex for proteasomal degradation.

Subcellular location. Nucleus.

Tissue specificity. Expressed in the normal brain and also in malignant gliomas (at protein level).

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the BRE1 family.

RefSeq proteins (1): NP_062538* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013956	E3_ubiquit_lig_Bre1	Family
IPR017907	Znf_RING_CS	Conserved_site
IPR018957	Znf_C3HC4_RING-type	Domain
IPR058642	BRE1A/B-like_dom	Domain
IPR058643	BRE1-like_CC	Domain

Pfam: PF00097, PF26052, PF26095

Enzyme classification (BRENDA):

• EC 2.3.2.27 — RING-type E3 ubiquitin transferase (BRENDA: 28 organisms, 138 substrates, 10 inhibitors, 1 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[UBE2W]-S-UBIQUITINYL-L-CYSTEINE	0.3014	1

UniProt features (35 total): modified residue 8, sequence conflict 6, compositionally biased region 4, strand 4, region of interest 3, turn 3, coiled-coil region 3, helix 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
5TRB	X-RAY DIFFRACTION	1.8
8GUJ	ELECTRON MICROSCOPY	2.8
8GUI	ELECTRON MICROSCOPY	2.81
8IEJ	ELECTRON MICROSCOPY	3.12
9KQO	ELECTRON MICROSCOPY	3.48

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VTR2-F1	76.11	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 (8): 21, 41, 136, 138, 348, 510, 522, 562

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-8866654	E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-9013422	RHOBTB1 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-8852135	Protein ubiquitination
R-HSA-9012999	RHO GTPase cycle
R-HSA-9706574	RHOBTB GTPase Cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 147 (showing top): GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM6, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_PROTEIN_POLYUBIQUITINATION, GARY_CD5_TARGETS_DN, GOBP_MITOTIC_CELL_CYCLE, NOUZOVA_TRETINOIN_AND_H4_ACETYLATION, GOBP_CHROMATIN_REMODELING, GOBP_PROTEIN_CATABOLIC_PROCESS, ATGTTTC_MIR494, GOMF_CHROMATIN_BINDING, GOCC_TRANSFERASE_COMPLEX, GOBP_PROTEOLYSIS

GO Biological Process (9): protein polyubiquitination (GO:0000209), regulation of DNA-templated transcription (GO:0006355), ubiquitin-dependent protein catabolic process (GO:0006511), negative regulation of cell migration (GO:0030336), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), protein ubiquitination (GO:0016567)

GO Molecular Function (14): p53 binding (GO:0002039), chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), mRNA 3’-UTR binding (GO:0003730), ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), ubiquitin protein ligase binding (GO:0031625), histone binding (GO:0042393), identical protein binding (GO:0042802), ubiquitin protein ligase activity (GO:0061630), histone H2B C-terminal K residue ubiquitin ligase activity (GO:0140850), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (5): ubiquitin ligase complex (GO:0000151), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), HULC complex (GO:0033503)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Protein ubiquitination	1
RHOBTB GTPase Cycle	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Metabolism of proteins	1
Post-translational protein modification	1
Signaling by Rho GTPases	1
RHO GTPase cycle	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	3
protein ubiquitination	2
DNA-templated transcription	2
positive regulation of DNA-templated transcription	2
binding	2
nuclear lumen	2
regulation of gene expression	1
regulation of RNA biosynthetic process	1
modification-dependent protein catabolic process	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
cellular component organization	1
chromatin organization	1
protein modification by small protein conjugation	1
transcription coregulator activity	1
mRNA binding	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
ubiquitin-like protein ligase binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
histone H2B ubiquitin ligase activity	1
catalytic activity	1
cation binding	1
intracellular protein-containing complex	1
transferase complex	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
intracellular membraneless organelle	1
ubiquitin ligase complex	1
chromatin	1
ubiquitin conjugating enzyme complex	1

Protein interactions and networks

STRING

2936 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF20	RNF40	O75150	983
RNF20	H2BC21	Q16778	934
RNF20	WDR82	Q6UXN9	901
RNF20	PAF1	Q8N7H5	900
RNF20	CDC73	Q6P1J9	862
RNF20	H2BW2	P0C1H6	843
RNF20	H2BW1	Q7Z2G1	843
RNF20	H2BK1	A0A2R8Y619	843
RNF20	H2BC17	P23527	843
RNF20	H2BC12L	P57053	843
RNF20	H2BC18	Q5QNW6	843
RNF20	H2BC26	Q8N257	843
RNF20	H2BC9	Q93079	843
RNF20	H2BC14	Q99879	843
RNF20	H2BC13	Q99880	842
RNF20	H2BC3	P33778	842

IntAct

194 interactions, top by confidence:

A	B	Type	Score
MED21	MED19	psi-mi:“MI:0914”(association)	0.880
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
RNF20	RNF40	psi-mi:“MI:0915”(physical association)	0.820
RNF40	RNF20	psi-mi:“MI:0915”(physical association)	0.820
RNF20	RNF40	psi-mi:“MI:0220”(ubiquitination reaction)	0.820
RNF40	RNF20	psi-mi:“MI:0914”(association)	0.820
PRPF19	PLRG1	psi-mi:“MI:0914”(association)	0.770
BRK1	RNF20	psi-mi:“MI:0915”(physical association)	0.740
HTT	RNF20	psi-mi:“MI:0915”(physical association)	0.740

BioGRID (382): PA2G4 (Biochemical Activity), RNF20 (Affinity Capture-Western), RNF20 (Co-localization), RNF40 (Affinity Capture-Western), UBE2A (Reconstituted Complex), UBE2B (Reconstituted Complex), UBE2A (Affinity Capture-Western), UBE2B (Affinity Capture-Western), RNF20 (Biochemical Activity), HIST1H2BB (Biochemical Activity), UBE2A (Biochemical Activity), UBE2B (Biochemical Activity), RNF20 (Two-hybrid), USHBP1 (Two-hybrid), RNF20 (Two-hybrid)

ESM2 similar proteins: A0PJP4, A0PJT0, A2VDP1, A4IFK7, D3ZUQ0, E9PSL7, O14578, O75665, P0C219, P49025, P97817, Q01850, Q0IHE5, Q14BN4, Q17QG3, Q28623, Q3LGD4, Q3SYW5, Q3URD3, Q3V079, Q4R3X1, Q4R7Y8, Q58A65, Q5DTM8, Q5EBL4, Q5R5R4, Q5VTR2, Q5ZJA3, Q5ZLS3, Q62172, Q62796, Q68CZ1, Q6AYA0, Q6DFC2, Q6DH86, Q6NRH3, Q6ZUS6, Q7Z3E2, Q86VS8, Q8BR07

Diamond homologs: A2VDP1, A2XW69, O74563, O75150, P34537, Q09463, Q3U319, Q4P3X7, Q4R7K7, Q5DTM8, Q5RAU7, Q5VTR2, Q5ZLS3, Q60YN5, Q6LFN2, Q7XU27, Q8CJB9, Q9R1A8, Q9VRP9, A2ZAC2, O35445, Q336R3, Q568Y3, Q5M807, Q5RFK9, Q5ZIR9, Q6BWW6, Q6PC78, Q86KL1, Q91YT2, Q96GF1, Q99942, Q9C895, Q4WDD7, Q6FWF3, Q7S304, A0A1L8FG46, A0A1L8FM16, B1AUE5, B6VQ60

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ATM	up-regulates	RNF20	phosphorylation
Ub:E2	“up-regulates activity”	RNF20	ubiquitination
ATM	“up-regulates activity”	RNF20	phosphorylation
RNF20	“down-regulates activity”	SREBF1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 157 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
E3 ubiquitin ligases ubiquitinate target proteins	8	14.9×	3e-05
Association of TriC/CCT with target proteins during biosynthesis	5	14.1×	5e-03
Regulation of ornithine decarboxylase (ODC)	5	13.1×	6e-03
Respiratory Syncytial Virus Infection Pathway	6	11.4×	4e-03
RSV-host interactions	6	9.0×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription elongation by RNA polymerase II	6	13.0×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	98
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2729 predictions. Top by Δscore:

Variant	Effect	Δscore
9:101535532:C:G	donor_gain	1.0000
9:101535536:G:GT	donor_gain	1.0000
9:101540172:T:TA	acceptor_gain	1.0000
9:101540173:G:A	acceptor_gain	1.0000
9:101540366:GTCAG:G	donor_gain	1.0000
9:101540367:TCAGG:T	donor_loss	1.0000
9:101540368:CAG:C	donor_loss	1.0000
9:101540371:G:C	donor_loss	1.0000
9:101540372:T:G	donor_loss	1.0000
9:101540467:T:G	acceptor_gain	1.0000
9:101540468:A:AG	acceptor_gain	1.0000
9:101540468:AATT:A	acceptor_gain	1.0000
9:101540469:A:G	acceptor_gain	1.0000
9:101540488:A:AG	acceptor_gain	1.0000
9:101540489:G:GA	acceptor_gain	1.0000
9:101540489:GTTT:G	acceptor_gain	1.0000
9:101540614:A:T	donor_gain	1.0000
9:101540642:GT:G	donor_gain	1.0000
9:101540971:TGGAG:T	donor_loss	1.0000
9:101540974:AGGTG:A	donor_loss	1.0000
9:101540975:GGTG:G	donor_loss	1.0000
9:101540976:G:GC	donor_loss	1.0000
9:101540977:T:A	donor_loss	1.0000
9:101541014:GAA:G	donor_gain	1.0000
9:101544883:G:GT	donor_gain	1.0000
9:101546811:G:A	acceptor_gain	1.0000
9:101546816:GTAGT:G	acceptor_loss	1.0000
9:101546818:A:AG	acceptor_gain	1.0000
9:101546819:G:A	acceptor_loss	1.0000
9:101546819:G:GT	acceptor_gain	1.0000

AlphaMissense

6466 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:101540267:G:C	R65P	1.000
9:101551733:T:C	L441P	1.000
9:101551775:T:C	L455P	1.000
9:101551786:T:C	F459L	1.000
9:101551788:T:A	F459L	1.000
9:101551788:T:G	F459L	1.000
9:101551793:A:C	Q461P	1.000
9:101551799:T:C	L463P	1.000
9:101551801:G:C	A464P	1.000
9:101551802:C:A	A464D	1.000
9:101551804:G:C	A465P	1.000
9:101551805:C:A	A465D	1.000
9:101552147:T:A	I472K	1.000
9:101552159:T:C	M476T	1.000
9:101552159:T:G	M476R	1.000
9:101552162:G:C	R477P	1.000
9:101552168:T:C	L479P	1.000
9:101552180:T:C	L483P	1.000
9:101554020:T:C	L645P	1.000
9:101554026:T:C	L647P	1.000
9:101554060:A:C	R658S	1.000
9:101554060:A:T	R658S	1.000
9:101554074:T:C	L663P	1.000
9:101557397:T:C	L728P	1.000
9:101557400:T:C	L729P	1.000
9:101557420:G:C	G736R	1.000
9:101557421:G:A	G736D	1.000
9:101557424:A:C	Q737P	1.000
9:101557426:G:C	A738P	1.000
9:101557427:C:A	A738D	1.000

dbSNP variants (sampled 300 via entrez): RS1000044108 (9:101553387 G>A,C), RS1000082759 (9:101546932 G>A), RS1000111027 (9:101554898 A>T), RS1000435042 (9:101546686 A>G,T), RS1000491562 (9:101561173 G>C,T), RS1000517682 (9:101541896 G>A), RS1000542750 (9:101553087 G>A), RS1000569840 (9:101542244 A>G), RS1000830573 (9:101554923 T>C), RS1000882757 (9:101555342 C>T), RS1001038543 (9:101548353 A>G), RS1001071771 (9:101535314 G>A), RS1001196711 (9:101538046 G>A), RS1001217882 (9:101545245 T>C), RS1001264850 (9:101539596 GTT>G)

Disease associations

OMIM: gene MIM:607699 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	3
bisphenol A	decreases expression, increases expression	2
Arsenic	increases expression, increases methylation, increases abundance	2
Cyclosporine	increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
tetrabromobisphenol A	decreases expression	1
coumarin	increases phosphorylation	1
isobutyl alcohol	increases expression, affects cotreatment, increases abundance	1
beta-methylcholine	affects expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Clozapine	increases expression, affects cotreatment	1
Cuprizone	affects cotreatment, increases expression	1
Gasoline	increases abundance, increases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Phthalic Acids	decreases methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Rotenone	decreases expression	1
Tretinoin	affects cotreatment, decreases expression	1
Valproic Acid	increases expression	1
Vanadates	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1FB	Ubigene ZR-75-1 RNF20 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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