RNF4

ring finger protein 4, the group of Ring finger proteins

Basic information

Region (hg38): 4:2462220-2515857

Links

ENSG00000063978 ∙ NCBI:6047 ∙ OMIM:602850 ∙ HGNC:10067 ∙ Uniprot:P78317 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RNF4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNF4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			15	1		16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	15	1	0

Variants in RNF4

This is a list of pathogenic ClinVar variants found in the RNF4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-2462456-A-G		not specified	Uncertain significance (Aug 17, 2022)
4-2462457-A-C		not specified	Uncertain significance (Aug 17, 2022)
4-2462465-G-A		not specified	Uncertain significance (Feb 28, 2023)
4-2462498-C-A		not specified	Uncertain significance (Jul 27, 2024)
4-2462540-G-A		not specified	Uncertain significance (Jul 08, 2022)
4-2462540-G-C		not specified	Uncertain significance (Feb 22, 2023)
4-2462544-G-A		not specified	Uncertain significance (May 01, 2024)
4-2462546-A-G		not specified	Uncertain significance (Feb 15, 2023)
4-2462583-G-A		not specified	Uncertain significance (Dec 19, 2022)
4-2462603-C-G		not specified	Uncertain significance (Sep 14, 2023)
4-2462837-G-A		not specified	Uncertain significance (Jul 26, 2024)
4-2462871-C-T		not specified	Uncertain significance (Apr 01, 2024)
4-2462880-A-C		not specified	Uncertain significance (Jun 06, 2023)
4-2462898-G-A		not specified	Uncertain significance (Jun 03, 2024)
4-2462918-G-A		not specified	Uncertain significance (Jun 29, 2023)
4-2497014-G-A		not specified	Uncertain significance (Oct 06, 2024)
4-2497044-C-T		not specified	Uncertain significance (Jul 14, 2021)
4-2497067-A-C		not specified	Uncertain significance (Apr 04, 2023)
4-2497071-C-T		not specified	Uncertain significance (Aug 02, 2022)
4-2497088-T-G		not specified	Uncertain significance (May 06, 2024)
4-2497103-A-G		not specified	Uncertain significance (Jan 18, 2025)
4-2500695-T-C		not specified	Uncertain significance (Jun 30, 2024)
4-2512457-G-T		not specified	Uncertain significance (Jul 13, 2021)
4-2512512-G-A		not specified	Uncertain significance (Apr 15, 2024)
4-2512519-A-T		not specified	Uncertain significance (Jul 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RNF4	protein_coding	protein_coding	ENST00000511600	7	163101

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.800	0.199	124589	0	1	124590	0.00000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.07	83	115	0.719	0.00000691	1234
Missense in Polyphen		11	29.134	0.37756		345
Synonymous	0.105	40	40.9	0.979	0.00000243	363
Loss of Function	2.58	1	9.68	0.103	4.08e-7	128

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000885	0.00000885
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3 ubiquitin-protein ligase which binds polysumoylated chains covalently attached to proteins and mediates 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination of those substrates and their subsequent targeting to the proteasome for degradation. Regulates the degradation of several proteins including PML and the transcriptional activator PEA3. Involved in chromosome alignment and spindle assembly, it regulates the kinetochore CENPH-CENPI-CENPK complex by targeting polysumoylated CENPI to proteasomal degradation. Regulates the cellular responses to hypoxia and heat shock through degradation of respectively EPAS1 and PARP1. Alternatively, it may also bind DNA/nucleosomes and have a more direct role in the regulation of transcription for instance enhancing basal transcription and steroid receptor- mediated transcriptional activation. {ECO:0000269|PubMed:12885770, ECO:0000269|PubMed:18408734, ECO:0000269|PubMed:19307308, ECO:0000269|PubMed:20026589, ECO:0000269|PubMed:20212317, ECO:0000269|PubMed:20943951}.
• Pathway: Androgen receptor signaling pathway;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;DNA Double-Strand Break Repair;Homology Directed Repair;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;AndrogenReceptor;Processing of DNA double-strand break ends (Consensus)

Recessive Scores

• pRec: 0.123

Intolerance Scores

• loftool: 0.167
• rvis_EVS: 0.55
• rvis_percentile_EVS: 81.22

Haploinsufficiency Scores

• pHI: 0.155
• hipred: Y
• hipred_score: 0.798
• ghis: 0.608

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.920

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rnf4
• Phenotype: cellular phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: androgen receptor signaling pathway;proteasome-mediated ubiquitin-dependent protein catabolic process;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;response to arsenic-containing substance;protein autoubiquitination;protein K63-linked ubiquitination;protein K48-linked ubiquitination;protein K11-linked ubiquitination;protein K6-linked ubiquitination;regulation of spindle assembly;regulation of kinetochore assembly
• Cellular component: nucleus;nucleoplasm;cytoplasm;PML body
• Molecular function: DNA binding;transcription coactivator activity;ubiquitin-protein transferase activity;protein binding;transcription factor binding;zinc ion binding;nuclear receptor transcription coactivator activity;nucleosome binding;SUMO polymer binding;identical protein binding;androgen receptor binding;ubiquitin protein ligase activity