RNF125

ring finger protein 125, the group of Ring finger proteins

Basic information

Region (hg38): 18:32018825-32088144

Links

ENSG00000101695

∙ NCBI:54941 ∙ OMIM:610432 ∙ HGNC:21150 ∙ Uniprot:Q96EQ8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Tenorio syndrome (Strong), mode of inheritance: AD
Tenorio syndrome (Limited), mode of inheritance: AD
Tenorio syndrome (Limited), mode of inheritance: AD
Tenorio syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Tenorio syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Allergy/Immunology/Infectious; Musculoskeletal; Neurologic	25196541

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RNF125 gene.

Tenorio_syndrome (48 variants)
Inborn_genetic_diseases (24 variants)
not_provided (14 variants)
RNF125-related_disorder (9 variants)
not_specified (6 variants)
Hypertrophic_cardiomyopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNF125 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000017831.4. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				7 clinvar	5 clinvar	12
missense	1 clinvar	2 clinvar	39 clinvar	8 clinvar	2 clinvar	52
nonsense						0
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	2	43	15	7

Highest pathogenic variant AF is 0.00000806739

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RNF125	protein_coding	protein_coding	ENST00000217740	6	54842

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000464	0.667	125718	0	30	125748	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.783	109	135	0.810	0.00000713	1506
Missense in Polyphen		30	39.584	0.75788		479
Synonymous	0.354	46	49.2	0.936	0.00000238	438
Loss of Function	0.893	8	11.2	0.713	5.56e-7	145

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000235	0.000235
Ashkenazi Jewish	0.00	0.00
East Asian	0.000491	0.000489
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000798	0.0000791
Middle Eastern	0.000491	0.000489
South Asian	0.0000986	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins, such as DDX58/RIG-I, MAVS/IPS1, IFIH1/MDA5, JAK1 and p53/TP53 (PubMed:15843525, PubMed:17460044, PubMed:17643463, PubMed:26027934, PubMed:26471729, PubMed:25591766, PubMed:27411375). Acts as a negative regulator of type I interferon production by mediating ubiquitination of DDX58/RIG-I at 'Lys-181', leading to DDX58/RIG-I degradation (PubMed:17460044, PubMed:26471729). Mediates ubiquitination and subsequent degradation of p53/TP53 (PubMed:25591766). Mediates ubiquitination and subsequent degradation of JAK1 (PubMed:26027934). Acts as a positive regulator of T-cell activation (PubMed:15843525). {ECO:0000269|PubMed:15843525, ECO:0000269|PubMed:17460044, ECO:0000269|PubMed:17643463, ECO:0000269|PubMed:25591766, ECO:0000269|PubMed:26027934, ECO:0000269|PubMed:26471729, ECO:0000269|PubMed:27411375}.;
Disease: DISEASE: Tenorio syndrome (TNORS) [MIM:616260]: A disease characterized by overgrowth, macrocephaly, and intellectual disability. Some patients may have mild hydrocephaly, hypoglycemia, and inflammatory diseases resembling Sjogren syndrome. {ECO:0000269|PubMed:25196541}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: RIG-I-like receptor signaling pathway - Homo sapiens (human);RIG-I-like Receptor Signaling (Consensus)

Recessive Scores

pRec: 0.102

Intolerance Scores

loftool: 0.309
rvis_EVS: 0.55
rvis_percentile_EVS: 81.38

Haploinsufficiency Scores

pHI: 0.600
hipred: N
hipred_score: 0.459
ghis: 0.390

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.449

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Rnf125
Phenotype: hematopoietic system phenotype; immune system phenotype;

Gene ontology

Biological process: protein polyubiquitination;adaptive immune response;ubiquitin-dependent protein catabolic process;negative regulation of type I interferon production;negative regulation of RIG-I signaling pathway
Cellular component: Golgi membrane;VCP-NPL4-UFD1 AAA ATPase complex;intracellular membrane-bounded organelle
Molecular function: p53 binding;protein binding;zinc ion binding;ubiquitin conjugating enzyme binding;ubiquitin protein ligase activity