RNF20

protein-coding

ring finger protein 20, the group of Ring finger proteins

Gene summary

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). [provided by RefSeq, Feb 2012]

MANE transcript

NM_019592.7

Inheritance

—

ClinVar variants

U:113B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.45

Max pathogenic AF

—

Genomic locus

chr9:101,533,853-101,563,344

External References & Databases

Ensembl (ENSG00000155827)

Transcript & Mutation Effects

hg38 • Region Span ~29.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RNF20 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 100

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_019592.7. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	2 clinvar	1 clinvar	4
missense			104 clinvar	2 clinvar		106
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	113	4	1	118

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_019592.7	RefSeq	NP_062538.5	19	MANE Select
ENST00000389120.8	Ensembl	ENSP00000373772.3	19	MANE Select
ENST00000374819.6	Ensembl	ENSP00000363952.2	4	Standard
ENST00000466817.1	Ensembl	ENSP00000418924.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

ATM Signaling Network in Development and Disease
Post-translational protein modification
Metabolism of proteins
Protein ubiquitination
E3 ubiquitin ligases ubiquitinate target proteins

Biological Process

protein polyubiquitination
regulation of transcription, DNA-templated
ubiquitin-dependent protein catabolic process
regulation of mitotic cell cycle
histone monoubiquitination

Molecular Function

p53 binding
chromatin binding
transcription coactivator activity
mRNA 3'-UTR binding
ubiquitin-protein transferase activity

Cellular Component

ubiquitin ligase complex
nucleus
nucleoplasm
nucleolus
HULC complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000389120
Coding exons: 19
Length: 29490
Individuals with no LoFs: 125680
Homozygous LoFs: 0
Heterozygous LoFs: 68
Defined: 125748
p: 0.000270

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.11	343	548	0.626	0.0000323	6453
Missense (PolyPhen)		23	68.024	0.33811		683
Synonymous	0.703	176	188	0.935	0.00000900	1776
Loss of Function	3.99	27	60.5	0.446	0.00000398	657

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00068	0.00068	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00027	0.00027	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00029	0.00028	rare
South Asian	0.00023	0.00023	rare
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. {ECO:0000269|PubMed:16307923, ECO:0000269|PubMed:16337599, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19410543}.;

Recessive Scores

pRec: 0.130

Intolerance Scores

LoFtool: 0.764
RVIS EVS: -0.6
RVIS percentile EVS: 18.14

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.912

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium