RNF135

ring finger protein 135, the group of Ring finger proteins

Basic information

Region (hg38): 17:30970983-30999911

Links

ENSG00000181481 ∙ NCBI:84282 ∙ OMIM:611358 ∙ HGNC:21158 ∙ Uniprot:Q8IUD6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the RNF135 gene.

• not provided (44 variants)
• Inborn genetic diseases (17 variants)
• not specified (5 variants)
• Macrocephaly, macrosomia, facial dysmorphism syndrome (1 variants)
• Chromosome 17q11.2 deletion syndrome, 1.4Mb (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				6	3	9
missense			23	6	4	33
nonsense						0
start loss						0
frameshift	1		2			3
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			2			2
non coding				7	5	12
Total	1	0	27	19	12

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)
17-30971197-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)
17-30971310-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)
17-30971419-C-T		not specified	Uncertain significance (Jan 04, 2024)
17-30971429-G-A		not specified	Uncertain significance (Jan 02, 2024)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

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