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 (Strong), mode of inheritance: AR
• cerebellar ataxia-hypogonadism syndrome (Supportive), mode of inheritance: AR
• cerebellar ataxia-hypogonadism syndrome (Moderate), 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 (5 variants)
• Cerebellar ataxia-hypogonadism syndrome (4 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.

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				67	8	75
missense	1	1	120	11		133
nonsense	5					5
start loss			1			1
frameshift	2	1				3
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region		1	3	6		10
non coding				15	2	17
Total	9	2	121	93	10

Variants in RNF216

This is a list of pathogenic ClinVar variants found in the RNF216 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-5622873-C-T			Uncertain significance (Dec 16, 2021)
7-5622875-C-T			Likely benign (Jan 29, 2024)
7-5622876-G-A		Inborn genetic diseases	Uncertain significance (Feb 23, 2023)
7-5622896-G-C			Likely benign (Dec 02, 2021)
7-5622901-G-A			Likely benign (Jan 19, 2023)
7-5622902-G-A			Likely benign (Jul 21, 2023)
7-5622913-G-C			Likely benign (Aug 16, 2022)
7-5622917-C-T		Inborn genetic diseases	Uncertain significance (May 12, 2024)
7-5622939-TA-T			Uncertain significance (Nov 09, 2021)
7-5622942-T-C		Inborn genetic diseases	Uncertain significance (Jul 17, 2023)
7-5622946-C-A		Cerebellar ataxia-hypogonadism syndrome	Uncertain significance (May 28, 2019)
7-5622946-C-T		RNF216-related disorder	Likely benign (Dec 10, 2023)
7-5622948-C-T		Inborn genetic diseases	Uncertain significance (Jun 07, 2023)
7-5622949-G-A			Uncertain significance (Jul 07, 2023)
7-5622952-C-G		Inborn genetic diseases	Uncertain significance (Jul 26, 2021)
7-5622959-C-T			Likely benign (Feb 10, 2023)
7-5622965-G-C			Likely benign (Jan 02, 2022)
7-5622969-A-T		Cerebellar ataxia-hypogonadism syndrome	Uncertain significance (Sep 26, 2019)
7-5622970-C-T		Inborn genetic diseases	Uncertain significance (Apr 21, 2023)
7-5622971-G-A		Inborn genetic diseases	Likely benign (May 15, 2024)
7-5622989-C-T			Likely benign (Feb 25, 2018)
7-5623001-T-C			Likely benign (Dec 02, 2021)
7-5623018-C-T		RNF216-related disorder	Likely benign (Sep 27, 2023)
7-5623027-C-T		Inborn genetic diseases	Uncertain significance (Nov 14, 2023)
7-5623040-G-A			Benign (Dec 19, 2023)

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