RNF146

ring finger protein 146, the group of Ring finger proteins

Basic information

Region (hg38): 6:127266726-127288567

Links

ENSG00000118518 ∙ NCBI:81847 ∙ OMIM:612137 ∙ HGNC:21336 ∙ Uniprot:Q9NTX7 ∙ 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 RNF146 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNF146 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				1		1
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	1

Variants in RNF146

This is a list of pathogenic ClinVar variants found in the RNF146 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-127286633-A-T		not specified	Uncertain significance (Aug 11, 2022)
6-127286675-C-T		not specified	Uncertain significance (Dec 16, 2023)
6-127286713-G-A		not specified	Uncertain significance (Dec 01, 2022)
6-127286759-G-T		not specified	Uncertain significance (Mar 29, 2023)
6-127286978-G-C		not specified	Uncertain significance (Sep 29, 2023)
6-127287125-T-C		not specified	Uncertain significance (May 13, 2024)
6-127287133-C-A		not specified	Uncertain significance (Sep 22, 2022)
6-127287180-C-T			Likely benign (Jan 01, 2023)
6-127287181-G-A		not specified	Uncertain significance (Nov 13, 2023)
6-127287199-A-G		not specified	Uncertain significance (Nov 14, 2023)
6-127287289-G-T		not specified	Uncertain significance (Oct 12, 2022)
6-127287290-A-G		not specified	Uncertain significance (Jan 09, 2024)
6-127287305-G-C		not specified	Uncertain significance (Mar 01, 2024)
6-127287320-C-T		not specified	Uncertain significance (Jan 17, 2023)
6-127287583-G-A			Benign (Mar 29, 2018)
6-127287587-G-A		not specified	Uncertain significance (Dec 28, 2022)
6-127287653-C-A		not specified	Uncertain significance (Apr 07, 2022)
6-127287680-T-G		not specified	Uncertain significance (May 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RNF146	protein_coding	protein_coding	ENST00000368314	2	21958

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.820	0.180	125505	0	9	125514	0.0000359

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.33	148	201	0.736	0.0000106	2311
Missense in Polyphen		32	74.975	0.42681		856
Synonymous	0.384	71	75.2	0.944	0.00000421	750
Loss of Function	3.03	2	14.4	0.139	9.61e-7	155

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000627	0.0000616
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000356	0.0000353
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3 ubiquitin-protein ligase that specifically binds poly-ADP-ribosylated (PARsylated) proteins and mediates their ubiquitination and subsequent degradation. May regulate many important biological processes, such as cell survival and DNA damage response. Acts as an activator of the Wnt signaling pathway by mediating the ubiquitination of PARsylated AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex. Acts in cooperation with tankyrase proteins (TNKS and TNKS2), which mediate PARsylation of target proteins AXIN1, AXIN2, BLZF1, CASC3, TNKS and TNKS2. Recognizes and binds tankyrase-dependent PARsylated proteins via its WWE domain and mediates their ubiquitination, leading to their degradation. Different ubiquitin linkage types have been observed: TNKS2 undergoes ubiquitination at 'Lys-48' and 'Lys-63', while AXIN1 is only ubiquitinated at 'Lys-48'. May regulate TNKS and TNKS2 subcellular location, preventing aggregation at a centrosomal location. Neuroprotective protein. Protects the brain against N-methyl-D-aspartate (NMDA) receptor-mediated glutamate excitotoxicity and ischemia, by interfering with PAR-induced cell death, called parthanatos. Prevents nuclear translocation of AIFM1 in a PAR-binding dependent manner. Does not affect PARP1 activation (By similarity). Protects against cell death induced by DNA damaging agents, such as N- methyl-N-nitro-N-nitrosoguanidine (MNNG) and rescues cells from G1 arrest. Promotes cell survival after gamma-irradiation. Facilitates DNA repair. {ECO:0000250, ECO:0000269|PubMed:21478859, ECO:0000269|PubMed:21602803, ECO:0000269|PubMed:21799911, ECO:0000269|PubMed:21825151, ECO:0000269|PubMed:22267412}.
• Disease: DISEASE: Note=Defects in RNF146 are a cause of susceptibility to breast cancer.
• Pathway: Signaling by WNT;Signal Transduction;Regulation of PTEN stability and activity;Post-translational protein modification;Metabolism of proteins;Ub-specific processing proteases;PTEN Regulation;PIP3 activates AKT signaling;Deubiquitination;Intracellular signaling by second messengers;TCF dependent signaling in response to WNT;Degradation of AXIN (Consensus)

Recessive Scores

• pRec: 0.0731

Intolerance Scores

• loftool: 0.402
• rvis_EVS: 0.15
• rvis_percentile_EVS: 64.51

Haploinsufficiency Scores

• pHI: 0.0571
• hipred: Y
• hipred_score: 0.591
• ghis: 0.520

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rnf146
• Phenotype: craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); hematopoietic system phenotype; growth/size/body region phenotype; 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); limbs/digits/tail phenotype; skeleton phenotype; immune system phenotype; respiratory system phenotype

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;Wnt signaling pathway;protein autoubiquitination;protein K48-linked ubiquitination;positive regulation of canonical Wnt signaling pathway
• Cellular component: nucleoplasm;cytosol;plasma membrane
• Molecular function: ubiquitin-protein transferase activity;protein binding;zinc ion binding;ubiquitin protein ligase activity;poly-ADP-D-ribose binding