RC3H2

ring finger and CCCH-type domains 2, the group of Zinc fingers CCCH-type|Small nucleolar RNA protein coding host genes|Ring finger proteins

Basic information

Region (hg38): 9:122844555-122905359

Previous symbols: [ "MNAB" ]

Links

ENSG00000056586 ∙ NCBI:54542 ∙ OMIM:615231 ∙ HGNC:21461 ∙ Uniprot:Q9HBD1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RC3H2 gene.

• Inborn genetic diseases (26 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RC3H2 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				2		2
missense			26			26
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	27	2	0

Variants in RC3H2

This is a list of pathogenic ClinVar variants found in the RC3H2 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-122849691-A-C		not specified	Uncertain significance (Jan 24, 2024)
9-122849694-T-A		not specified	Uncertain significance (Jan 04, 2022)
9-122849694-T-G		not specified	Uncertain significance (Sep 16, 2021)
9-122849794-T-C		not specified	Uncertain significance (Dec 03, 2021)
9-122849799-G-C		not specified	Uncertain significance (Oct 25, 2022)
9-122851153-T-G		not specified	Uncertain significance (Aug 04, 2023)
9-122851405-T-C		not specified	Uncertain significance (Dec 28, 2022)
9-122854056-C-T		not specified	Uncertain significance (Oct 10, 2023)
9-122854261-C-T		not specified	Uncertain significance (Feb 28, 2024)
9-122855389-G-C		not specified	Uncertain significance (Sep 17, 2021)
9-122855773-C-T		not specified	Uncertain significance (Dec 01, 2023)
9-122855866-C-T		not specified	Uncertain significance (Apr 22, 2022)
9-122857930-C-A		not specified	Uncertain significance (Feb 16, 2023)
9-122857930-C-T		not specified	Uncertain significance (Jan 23, 2024)
9-122857942-C-T		not specified	Uncertain significance (Jan 19, 2022)
9-122858026-T-C		not specified	Uncertain significance (Jul 06, 2021)
9-122858712-C-T		not specified	Uncertain significance (Dec 13, 2022)
9-122858721-G-A		not specified	Uncertain significance (Nov 13, 2023)
9-122858755-G-A		not specified	Uncertain significance (May 13, 2022)
9-122858788-C-A		not specified	Uncertain significance (Sep 27, 2022)
9-122858922-G-A		not specified	Uncertain significance (Dec 13, 2022)
9-122858956-G-C		not specified	Uncertain significance (Jun 02, 2023)
9-122859083-T-TG			Uncertain significance (Mar 12, 2021)
9-122859087-G-A		not specified	Uncertain significance (Dec 13, 2023)
9-122859951-C-G		not specified	Uncertain significance (Dec 21, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RC3H2	protein_coding	protein_coding	ENST00000373670	20	60786

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	5.27e-7	124789	0	10	124799	0.0000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.45	463	637	0.727	0.0000328	7761
Missense in Polyphen		233	362.9	0.64205		4485
Synonymous	0.645	217	229	0.946	0.0000121	2375
Loss of Function	6.72	5	62.2	0.0803	0.00000354	706

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000646	0.0000646
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000558	0.0000556
Finnish	0.00	0.00
European (Non-Finnish)	0.0000629	0.0000618
Middle Eastern	0.0000558	0.0000556
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Post-transcriptional repressor of mRNAs containing a conserved stem loop motif, called constitutive decay element (CDE), which is often located in the 3'-UTR, as in HMGXB3, ICOS, IER3, NFKBID, NFKBIZ, PPP1R10, TNF and in many more mRNAs. Binds to CDE and promotes mRNA deadenylation and degradation. This process does not involve miRNAs. In follicular helper T (Tfh) cells, represses of ICOS and TNFRSF4 expression, thus preventing spontaneous Tfh cell differentiation, germinal center B-cell differentiation in the absence of immunization and autoimmunity. In resting or LPS-stimulated macrophages, controls inflammation by suppressing TNF expression. Also recognizes CDE in its own mRNA and in that of paralogous RC3H1, possibly leading to feedback loop regulation (By similarity). miRNA-binding protein that regulates microRNA homeostasis. Enhances DICER-mediated processing of pre- MIR146a but reduces mature MIR146a levels through an increase of 3' end uridylation. Both inhibits ICOS mRNA expression and they may act together to exert the suppression (PubMed:25697406). Acts as a ubiquitin E3 ligase. Pairs with E2 enzymes UBE2B, UBE2D2, UBE2E2, UBE2E3, UBE2G2, UBE2K and UBE2Q2 and produces polyubiquitin chains (PubMed:26489670). Show the strongest activity when paired with UBE2N:UBE2V1 or UBE2N:UBE2V2 E2 complexes and generate both short and long polyubiquitin chains (PubMed:26489670). Involved in the ubiquitination of MAP3K5 (PubMed:24448648, PubMed:26489670) (By similarity). Able to interact with double-stranded RNA (dsRNA) (PubMed:26489670). {ECO:0000250|UniProtKB:P0C090, ECO:0000269|PubMed:24448648, ECO:0000269|PubMed:26489670}.

Intolerance Scores

• loftool: 0.0705
• rvis_EVS: -1.33
• rvis_percentile_EVS: 4.69

Haploinsufficiency Scores

• pHI: 0.465
• hipred: Y
• hipred_score: 0.707
• ghis: 0.694

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.974

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rc3h2
• Phenotype: immune system phenotype; renal/urinary system phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: protein polyubiquitination;B cell homeostasis;regulation of transcription by RNA polymerase II;post-embryonic development;posttranscriptional regulation of gene expression;multicellular organism growth;T cell proliferation;T cell homeostasis;lung alveolus development;lymph node development;spleen development;T cell receptor signaling pathway;limb development;T follicular helper cell differentiation;positive regulation of NIK/NF-kappaB signaling;negative regulation of T-helper 17 cell differentiation;regulation of miRNA metabolic process
• Cellular component: P-body;cell surface;membrane;intracellular membrane-bounded organelle
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;RNA binding;double-stranded RNA binding;mRNA binding;ubiquitin-protein transferase activity;RNA stem-loop binding;metal ion binding