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

ENSG00000011275

∙ NCBI:54476 ∙ OMIM:609948 ∙ HGNC:21698 ∙ Uniprot:Q9NWF9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cerebellar ataxia and hypogonadotropic hypogonadism (Gordon Holmes syndrome)	AR	Endocrine	Individuals 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 disease	Endocrine; Neurologic	11932290; 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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
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

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RNF216	protein_coding	protein_coding	ENST00000389902	16	161693

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000226	1.00	125716	1	31	125748	0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.23	598	519	1.15	0.0000287	6128
Missense in Polyphen		208	224.48	0.9266		2635
Synonymous	-3.25	252	194	1.30	0.0000116	1678
Loss of Function	4.11	19	50.6	0.376	0.00000285	575

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000237	0.000236
Ashkenazi Jewish	0.0000999	0.0000992
East Asian	0.000272	0.000272
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000134	0.000123
Middle Eastern	0.000272	0.000272
South Asian	0.000163	0.000131
Other	0.00	0.00

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

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

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