RNF43

ring finger protein 43, the group of Ring finger proteins

Basic information

Region (hg38): 17:58353676-58417595

Links

ENSG00000108375 ∙ NCBI:54894 ∙ OMIM:612482 ∙ HGNC:18505 ∙ Uniprot:Q68DV7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• sessile serrated polyposis cancer syndrome (Moderate), mode of inheritance: AD
• hyperplastic polyposis syndrome (Supportive), mode of inheritance: AD
• sessile serrated polyposis cancer syndrome (Limited), mode of inheritance: AD
• sessile serrated polyposis cancer syndrome (Limited), mode of inheritance: AD
• sessile serrated polyposis cancer syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Sessile serrated polyposis cancer syndrome	AD	Oncologic	Individuals are at high risk of developing colorectal cancer (and possibly additional neoplasms), and awareness may allow surveillance and early surgical and medical management of neoplasms	Oncologic	24512911; 27081527

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RNF43 gene.

• Sessile serrated polyposis cancer syndrome (2 variants)
• Colon serrated polyposis (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNF43 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			2	122	4	128
missense			367	2	12	381
nonsense	1	3	10			14
start loss						0
frameshift	2	1	14			17
inframe indel			8			8
splice donor/acceptor (+/-2bp)			4			4
splice region			9	9		18
non coding			3	56	10	69
Total	3	4	408	180	26

Variants in RNF43

This is a list of pathogenic ClinVar variants found in the RNF43 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-58354727-G-A			Likely benign (Jun 15, 2019)
17-58354935-T-C			Uncertain significance (Dec 22, 2023)
17-58354944-C-T			Likely benign (Jun 21, 2021)
17-58354949-A-G			Likely benign (Apr 29, 2020)
17-58354952-C-T			Likely benign (Aug 02, 2023)
17-58354957-C-G		Sessile serrated polyposis cancer syndrome	Uncertain significance (Oct 09, 2023)
17-58354961-C-G			Likely benign (Dec 30, 2022)
17-58354963-GCTC-G			Uncertain significance (Dec 06, 2023)
17-58354969-C-T		Sessile serrated polyposis cancer syndrome	Uncertain significance (Mar 12, 2024)
17-58354970-G-A			Likely benign (Dec 19, 2023)
17-58354973-TTCC-T			Uncertain significance (Mar 07, 2022)
17-58354976-C-G			Uncertain significance (Nov 20, 2020)
17-58354982-T-G			Likely benign (Sep 24, 2020)
17-58354990-T-A			Likely benign (Dec 03, 2020)
17-58354994-TAG-T			Conflicting classifications of pathogenicity (Mar 29, 2024)
17-58354998-G-A			Likely benign (Jan 28, 2024)
17-58355001-C-G		not specified	Benign (Jul 31, 2024)
17-58355001-C-T		not specified	Likely benign (Jul 31, 2024)
17-58355015-G-A		not specified	Benign (Aug 15, 2023)
17-58357446-CCA-C			Likely benign (Jul 09, 2021)
17-58357467-C-A		Sessile serrated polyposis cancer syndrome	Likely pathogenic (Dec 05, 2022)
17-58357471-G-A			Uncertain significance (Sep 24, 2020)
17-58357471-G-C			Uncertain significance (Mar 07, 2022)
17-58357478-C-T		RNF43-related disorder • not specified	Likely benign (Jul 31, 2024)
17-58357479-G-A		not specified	Uncertain significance (Jun 11, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RNF43	protein_coding	protein_coding	ENST00000584437	9	65096

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.735	0.265	125726	0	21	125747	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.85	339	449	0.754	0.0000261	4982
Missense in Polyphen		87	150.41	0.5784		1773
Synonymous	1.08	156	174	0.896	0.00000915	1678
Loss of Function	4.40	7	35.1	0.199	0.00000206	339

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000244	0.000244
Ashkenazi Jewish	0.000106	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000883	0.0000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000691	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination, endocytosis and subsequent degradation of Wnt receptor complex components Frizzled. Acts on both canonical and non-canonical Wnt signaling pathway. Acts as a tumor suppressor in the intestinal stem cell zone by inhibiting the Wnt signaling pathway, thereby resticting the size of the intestinal stem cell zone. {ECO:0000269|PubMed:18313049, ECO:0000269|PubMed:22575959, ECO:0000269|PubMed:22895187}.
• Disease: DISEASE: Sessile serrated polyposis cancer syndrome (SSPCS) [MIM:617108]: A rare disease characterized by multiple and/or large serrated polyps developing in the colon, and an increased personal and familial risk of colorectal cancer. A patient is diagnosed with SSPCS if at least one of the following criteria is met: the presence of at least five sessile serrated polyps proximal to the sigmoid colon, two of which are greater than 10 mm in diameter; the presence of any number of serrated polyps occurring proximal to the sigmoid colon in an individual who has a first-degree relative with serrated polyposis; the presence of more than 20 serrated polyps of any size distributed throughout the colon. Sessile serrated polyps are also known as sessile serrated adenomas (SSA) and are estimated to be responsible for 20 to 35% of all colon cancers. Individuals with SSPCS may have a strong personal or family history of extracolonic cancers. {ECO:0000269|PubMed:24512911, ECO:0000269|PubMed:27081527}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.
• Pathway: Signaling by WNT;Signal Transduction;p73 transcription factor network;Regulation of FZD by ubiquitination;TCF dependent signaling in response to WNT (Consensus)

Recessive Scores

• pRec: 0.0897

Intolerance Scores

• loftool: 0.632
• rvis_EVS: 0.74
• rvis_percentile_EVS: 86.33

Haploinsufficiency Scores

• pHI: 0.0529
• hipred: Y
• hipred_score: 0.609
• ghis: 0.453

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.910

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Rnf43
• Phenotype: digestive/alimentary phenotype; neoplasm; cellular phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;multicellular organism development;Wnt signaling pathway;protein ubiquitination;negative regulation of Wnt signaling pathway;Wnt receptor catabolic process;stem cell proliferation
• Cellular component: nuclear envelope;endoplasmic reticulum membrane;plasma membrane;integral component of plasma membrane
• Molecular function: ubiquitin-protein transferase activity;frizzled binding;protein binding;metal ion binding;ubiquitin protein ligase activity