RNF135
Basic information
Region (hg38): 17:30970984-30999911
Links
Phenotypes
GenCC
Source:
- overgrowth-macrocephaly-facial dysmorphism syndrome (Limited), mode of inheritance: AD
- overgrowth-macrocephaly-facial dysmorphism syndrome (Supportive), mode of inheritance: AD
- overgrowth syndrome (Limited), mode of inheritance: AD
- overgrowth-macrocephaly-facial dysmorphism syndrome (Limited), mode of inheritance: AD
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Macrocephaly, macrosomia, facial dysmorphism 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 | Craniofacial; Musculoskeletal; Neurologic | 17632510 |
ClinVar
This is a list of variants' phenotypes submitted to
- Macrocephaly, macrosomia, facial dysmorphism syndrome (1 variants)
- Autism spectrum disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNF135 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 | 11 | |||||
missense | 33 | 44 | ||||
nonsense | 0 | |||||
start loss | 0 | |||||
frameshift | 3 | |||||
inframe indel | 1 | |||||
splice donor/acceptor (+/-2bp) | 1 | |||||
splice region | 2 | 2 | ||||
non coding | 12 | |||||
Total | 1 | 0 | 37 | 23 | 11 |
Highest pathogenic variant AF is 0.0000394
Variants in RNF135
This is a list of pathogenic ClinVar variants found in the RNF135 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
17-30971078-C-T | RNF135-related disorder | Uncertain significance (Oct 30, 2023) | ||
17-30971093-G-C | Uncertain significance (Jan 22, 2019) | |||
17-30971129-T-C | not specified | Uncertain significance (Jun 11, 2021) | ||
17-30971142-C-A | RNF135-related disorder | Likely benign (Sep 13, 2019) | ||
17-30971192-T-C | not specified | Uncertain significance (May 15, 2024) | ||
17-30971197-C-T | not specified | Conflicting classifications of pathogenicity (Feb 01, 2023) | ||
17-30971202-C-T | Benign/Likely benign (Mar 23, 2021) | |||
17-30971225-C-G | not specified | Uncertain significance (Jun 29, 2023) | ||
17-30971269-G-T | not specified | Uncertain significance (Sep 26, 2022) | ||
17-30971271-C-T | RNF135-related disorder | Likely benign (Mar 20, 2019) | ||
17-30971273-C-G | not specified | Uncertain significance (Aug 12, 2021) | ||
17-30971286-C-G | Benign (Jul 21, 2018) | |||
17-30971291-G-A | not specified | Uncertain significance (Jul 06, 2022) | ||
17-30971302-C-G | not specified | Uncertain significance (Mar 15, 2024) | ||
17-30971310-G-A | Likely benign (Dec 31, 2019) | |||
17-30971313-C-A | not specified | Uncertain significance (Jan 02, 2024) | ||
17-30971313-C-G | not specified | Uncertain significance (Feb 27, 2023) | ||
17-30971314-C-T | Likely benign (Mar 29, 2018) | |||
17-30971338-G-A | not specified | Uncertain significance (Sep 27, 2022) | ||
17-30971339-C-A | not specified | Uncertain significance (Sep 27, 2022) | ||
17-30971365-C-G | not specified • RNF135-related disorder | Benign/Likely benign (Mar 16, 2020) | ||
17-30971372-A-G | not specified | Benign/Likely benign (Oct 01, 2023) | ||
17-30971381-G-T | not specified | Uncertain significance (Jun 11, 2021) | ||
17-30971395-T-C | Benign (Jul 21, 2018) | |||
17-30971417-G-A | not specified • RNF135-related disorder | Benign (Jan 06, 2020) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
RNF135 | protein_coding | protein_coding | ENST00000328381 | 5 | 31127 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
2.20e-9 | 0.142 | 125643 | 0 | 105 | 125748 | 0.000418 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 0.0869 | 215 | 219 | 0.983 | 0.0000110 | 2765 |
Missense in Polyphen | 41 | 47.116 | 0.87019 | 627 | ||
Synonymous | -0.356 | 93 | 88.7 | 1.05 | 0.00000447 | 893 |
Loss of Function | 0.284 | 14 | 15.2 | 0.921 | 6.55e-7 | 173 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000152 | 0.000152 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.00141 | 0.00141 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.000644 | 0.000642 |
Middle Eastern | 0.00141 | 0.00141 |
South Asian | 0.0000983 | 0.0000980 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Acts as an E2-dependent E3 ubiquitin-protein ligase, involved in innate immune defense against viruses. Ubiquitinates DDX58 and is required for full activation of the DDX58 signaling resulting in interferon beta production. {ECO:0000269|PubMed:19017631, ECO:0000269|PubMed:19484123}.;
- Pathway
- NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10;Post-translational protein modification;TRAF6 mediated IRF7 activation;TRAF6 mediated NF-kB activation;DDX58/IFIH1-mediated induction of interferon-alpha/beta;Metabolism of proteins;Innate Immune System;Immune System;TRAF3-dependent IRF activation pathway;Negative regulators of DDX58/IFIH1 signaling;Ovarian tumor domain proteases;Deubiquitination
(Consensus)
Haploinsufficiency Scores
- pHI
- 0.428
- hipred
- N
- hipred_score
- 0.146
- ghis
- 0.403
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.833
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Rnf135
- Phenotype
Gene ontology
- Biological process
- protein ubiquitination;negative regulation of type I interferon production;positive regulation of interferon-beta production;innate immune response;regulation of innate immune response
- Cellular component
- cytoplasm;cytosol
- Molecular function
- ubiquitin-protein transferase activity;protein binding;identical protein binding;ribonucleoprotein complex binding;metal ion binding