RNF31

ring finger protein 31, the group of Linear ubiquitin chain assembly complex |RBR E3 ubiquitin ligases|Ring finger proteins|Zinc fingers RANBP2-type

Basic information

Region (hg38): 14:24146683-24160660

Links

ENSG00000092098 ∙ NCBI:55072 ∙ OMIM:612487 ∙ HGNC:16031 ∙ Uniprot:Q96EP0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis (Supportive), mode of inheritance: AR
• immunodeficiency 115 with autoinflammation (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 115 with autoinflammation	AR	Allergy/Immunology/Infectious	The condition involves susceptibility to infections, and and prophylactic measures, as well as early and aggressive treatment of infections with consideration of vaccine regimen, may be beneficial; For autoimmune sequelae, medical management (eg, with TNF antagonists), has been reported to be beneficial	Allergy/Immunology/Infectious	26008899; 30936877

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RNF31 gene.

• not_provided (730 variants)
• not_specified (115 variants)
• RNF31-related_disorder (16 variants)
• Immunodeficiency_115_with_autoinflammation (4 variants)
• Short_stature (2 variants)
• Polyglucosan_body_myopathy_type_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNF31 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000017999.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	189	7	199
missense	2	1	384	10	3	400
nonsense			6			6
start loss						0
frameshift			6			6
splice donor/acceptor (+/-2bp)			2			2
Total	2	1	401	199	10

Highest pathogenic variant AF is 0.0000020521325

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RNF31	protein_coding	protein_coding	ENST00000324103	21	13979

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000283	124805	0	13	124818	0.0000521

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.14	493	646	0.764	0.0000389	6883
Missense in Polyphen		122	225.01	0.5422		2416
Synonymous	-0.970	273	253	1.08	0.0000137	2235
Loss of Function	6.60	6	62.2	0.0965	0.00000353	618

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000584	0.0000584
Ashkenazi Jewish	0.00	0.00
East Asian	0.000111	0.000111
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.0000710	0.0000706
Middle Eastern	0.000111	0.000111
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3 ubiquitin-protein ligase component of the LUBAC complex which conjugates linear ('Met-1'-linked) polyubiquitin chains to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation (PubMed:17006537, PubMed:19136968, PubMed:20005846, PubMed:21455173, PubMed:21455180, PubMed:21455181, PubMed:22863777, PubMed:28189684). LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways (PubMed:17006537, PubMed:19136968, PubMed:20005846, PubMed:21455173, PubMed:21455180, PubMed:21455181, PubMed:22863777, PubMed:28189684). Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation (PubMed:21455173, PubMed:28189684). LUBAC is recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex (PubMed:20005846, PubMed:27458237). Together with OTULIN, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis (PubMed:23708998). Binds polyubiquitin of different linkage types (PubMed:23708998). {ECO:0000269|PubMed:17006537, ECO:0000269|PubMed:19136968, ECO:0000269|PubMed:20005846, ECO:0000269|PubMed:21455173, ECO:0000269|PubMed:21455180, ECO:0000269|PubMed:21455181, ECO:0000269|PubMed:22863777, ECO:0000269|PubMed:23708998, ECO:0000269|PubMed:27458237, ECO:0000269|PubMed:28189684}.
• Pathway: Necroptosis - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Regulation of toll-like receptor signaling pathway;Signal Transduction;TNFR1-induced NFkappaB signaling pathway;TNF signaling;Death Receptor Signalling;Regulation of TNFR1 signaling (Consensus)

Recessive Scores

• pRec: 0.387

Intolerance Scores

• loftool: 0.427
• rvis_EVS: -0.57
• rvis_percentile_EVS: 19.01

Haploinsufficiency Scores

• pHI: 0.168
• hipred: Y
• hipred_score: 0.542
• ghis: 0.585

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.964

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rnf31
• 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); hematopoietic system phenotype; immune system phenotype

Gene ontology

• Biological process: protein polyubiquitination;I-kappaB kinase/NF-kappaB signaling;regulation of tumor necrosis factor-mediated signaling pathway;CD40 signaling pathway;positive regulation of I-kappaB kinase/NF-kappaB signaling;T cell receptor signaling pathway;positive regulation of NF-kappaB transcription factor activity;protein linear polyubiquitination;positive regulation of protein targeting to mitochondrion
• Cellular component: cytosol;cytoplasmic side of plasma membrane;CD40 receptor complex;LUBAC complex
• Molecular function: ubiquitin-protein transferase activity;protein binding;ubiquitin protein ligase binding;ubiquitin binding;metal ion binding