RNF135 |
- 0
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- RNF135 (HGNC:21158) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- ring finger protein 135
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- No previous names found
- Alias symbols
- MGC13061
- %HI
- 90.13(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0(Read more about gnomAD pLI score)
- LOEUF
- 1.44(Read more about gnomAD LOEUF score)
- Cytoband
- 17q11.2
- Genomic Coordinates
-
GRCh37/hg19: chr17:29298057-29326929 NCBI Ensembl UCSC GRCh38/hg38: chr17:30958921-30999911 NCBI Ensembl UCSC - MANE Select Transcript
- NM_032322.4 ENST00000328381.10 (Read more about MANE Select)
- Function
- E2-dependent E3 ubiquitin-protein ligase that functions as a RIGI coreceptor in the sensing of viral RNAs in cell cytoplasm and the activation of the antiviral innate immune response (PubMed:19017631, PubMed:19484123, PubMed:21147464, PubMed:23950712, PubMed:28469175, PubMed:31006531). Together with the UBE2D3, UBE2N and UB2V1 E2 ligases, catalyzes the 'Lys-63'-linked polyubiquitination of RIGI oligomerized on viral RNAs, an essential step in the activation of the RIG-I signaling pathway (PubMed... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-26689
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
No Evidence for Haploinsufficiency
(0)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Last Evaluated:
09/22/2021
Haploinsufficiency (HI) Score Details
HI Score:
0
HI Evidence Strength:
No Evidence for Haploinsufficiency
(Disclaimer)
HI Evidence:
-
PUBMED:
17632510
Douglas et al. 2007 screened 12 of 14 genes in the NF1 microdeletion interval for mutations in 245 individuals with overgrowth and learning disability phenotypes. NF1 gene was not analyzed by the authors. They found 4 truncating mutations in RNF135 gene (Q243X, L248fs, and V339fs-observed in 2 patients), but no truncating mutations in 510 normal individuals. No other mutations were identified in the other sequenced genes. All RNF135 variants were inherited, and some carriers did not have learning disability, but did show apparent macrocephaly. The Q243X and V339fs variants are also observed in individuals in the general population per gnomAD (v.2.1.1.).
-
PUBMED:
19291764
Visser et al. 2009 described a patient cohort of 160 individuals on suspicion of Sotos syndrome but negative for NSD1 gene mutations. None of those patients had RNF135 genetic variations which could be attributed exclusively to loss of function and disease causing. One female patient had the classic 1.4Mb NF1 gene microdeletion including RNF135 gene. She was diagnosed with neurofibromatosis type 1 at age of 8 years old and clinical phenotype similar to Weaver syndrome.
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PUBMED:
30665703
Wright et al. 2019 used the data of 379,768 UK Biobank participants to assess the pathogencity and disease penetrance based on allele frequency, MAF and clinical data. The authors refuted RNF135 gene disease association due to haploinsufficiency mechanism. They suggested that loss of function mutations in RNF135 are not a cause of developmental disorder given the high-quality genotyping of LoF variants, lack of association with any clinically relevant traits previously described and lack of enrichment of de novo mutations within the Deciphering Developmental Disorders Study (DDD study, published in 2017, PMID: 28135719).
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
Genomic View
Select assembly:
(NC_000017.10)
(NC_000017.11)