RNF216

ring finger protein 216, the group of MicroRNA protein coding host genes|Ring finger proteins|RBR E3 ubiquitin ligases

Basic information

Region (hg38): 7:5620047-5781696

Links

ENSG00000011275NCBI:54476OMIM:609948HGNC:21698Uniprot:Q9NWF9AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • cerebellar ataxia-hypogonadism syndrome (Strong), mode of inheritance: AR
  • cerebellar ataxia-hypogonadism syndrome (Supportive), mode of inheritance: AR
  • cerebellar ataxia-hypogonadism syndrome (Moderate), mode of inheritance: AR
  • cerebellar ataxia-hypogonadism syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Cerebellar ataxia and hypogonadotropic hypogonadism (Gordon Holmes syndrome)AREndocrineIndividuals have been described with response to medical treatment (eg, exogenous GnRH therapy), though with progressive loss of pituitary function such that response to treatment decreased and was lost later in the course of diseaseEndocrine; Neurologic11932290; 23656588

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RNF216 gene.

  • not_provided (202 variants)
  • Inborn_genetic_diseases (132 variants)
  • Cerebellar_ataxia-hypogonadism_syndrome (27 variants)
  • RNF216-related_disorder (13 variants)
  • Hypogonadotropic_hypogonadism_7_with_or_without_anosmia (1 variants)
  • Leukodystrophy (1 variants)
  • not_specified (1 variants)
  • Rosette-forming_glioneuronal_tumor (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNF216 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000207111.4. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
1
clinvar
76
clinvar
7
clinvar
85
missense
3
clinvar
2
clinvar
189
clinvar
16
clinvar
1
clinvar
211
nonsense
8
clinvar
8
start loss
1
1
frameshift
3
clinvar
1
clinvar
1
clinvar
5
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
2
Total 15 5 192 92 8

Highest pathogenic variant AF is 0.000164245

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
RNF216protein_codingprotein_codingENST00000389902 16161693
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.000002261.001257161311257480.000127
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-1.235985191.150.00002876128
Missense in Polyphen208224.480.92662635
Synonymous-3.252521941.300.00001161678
Loss of Function4.111950.60.3760.00000285575

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0002370.000236
Ashkenazi Jewish0.00009990.0000992
East Asian0.0002720.000272
Finnish0.00004620.0000462
European (Non-Finnish)0.0001340.000123
Middle Eastern0.0002720.000272
South Asian0.0001630.000131
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Isoform 1 acts as an E3 ubiquitin ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Promotes degradation of TRAF3, TLR4 and TLR9. Contributes to the regulation of antiviral responses. Down- regulates activation of NF-kappa-B, IRF3 activation and IFNB production. Isoform 3 inhibits TNF and IL-1 mediated activation of NF-kappa-B. Promotes TNF and RIP mediated apoptosis. {ECO:0000269|PubMed:15107846, ECO:0000269|PubMed:19893624}.;
Disease
DISEASE: Gordon Holmes syndrome (GDHS) [MIM:212840]: A disease characterized by cerebellar symptoms and signs of sex steroid deficiency. Clinical features include cerebellar and brain stem atrophy, cerebellar ataxia, hypothalamic LHRH deficiency, hypogonadotrophic hypogonadism, lack of secondary sexual characteristics, and infertility. {ECO:0000269|PubMed:23656588}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Regulation of toll-like receptor signaling pathway;Gastric Cancer Network 1;protein ubiquitylation (Consensus)

Recessive Scores

pRec
0.0899

Intolerance Scores

loftool
0.596
rvis_EVS
-1.19
rvis_percentile_EVS
5.89

Haploinsufficiency Scores

pHI
0.121
hipred
Y
hipred_score
0.694
ghis
0.532

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.869

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Rnf216
Phenotype
reproductive system phenotype; hematopoietic system phenotype; immune system phenotype;

Zebrafish Information Network

Gene name
rnf216
Affected structure
head
Phenotype tag
abnormal
Phenotype quality
decreased size

Gene ontology

Biological process
apoptotic process;viral process;negative regulation of type I interferon production;regulation of interferon-beta production;proteasome-mediated ubiquitin-dependent protein catabolic process;regulation of defense response to virus by host;protein K48-linked ubiquitination;protein catabolic process, modulating synaptic transmission
Cellular component
nucleus;nucleoplasm;cytosol;Schaffer collateral - CA1 synapse;postsynaptic endocytic zone;glutamatergic synapse
Molecular function
protein binding;metal ion binding;ubiquitin protein ligase activity