DIS3

DIS3 homolog, exosome endoribonuclease and 3'-5' exoribonuclease, the group of Exosome complex|Endoribonucleases

Basic information

Region (hg38): 13:72752169-72782096

Previous symbols: [ "KIAA1008" ]

Links

ENSG00000083520 ∙ NCBI:22894 ∙ OMIM:607533 ∙ HGNC:20604 ∙ Uniprot:Q9Y2L1 ∙ 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 DIS3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DIS3 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			1			1
missense			37	5	1	43
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1		1	2
non coding			8			8
Total	0	0	46	5	1

Variants in DIS3

This is a list of pathogenic ClinVar variants found in the DIS3 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-72753783-T-C		not specified	Uncertain significance (Feb 27, 2023)
13-72753786-G-C		not specified	Uncertain significance (Nov 08, 2022)
13-72755194-C-T		not specified	Uncertain significance (Dec 07, 2021)
13-72755200-A-T		not specified	Uncertain significance (Feb 07, 2023)
13-72755208-A-G		not specified	Uncertain significance (Jan 17, 2024)
13-72755211-C-A		not specified	Uncertain significance (Jan 26, 2023)
13-72759797-A-G		not specified	Likely benign (Nov 12, 2021)
13-72759806-G-A		not specified	Uncertain significance (Aug 17, 2022)
13-72759853-T-C		not specified	Uncertain significance (Jan 09, 2024)
13-72760539-A-G		not specified	Uncertain significance (Dec 16, 2022)
13-72760623-A-G		not specified	Uncertain significance (Jul 14, 2021)
13-72761401-T-G		not specified	Uncertain significance (Jun 07, 2024)
13-72761421-C-T		not specified	Uncertain significance (Jan 26, 2022)
13-72761466-C-A		not specified	Uncertain significance (Apr 22, 2024)
13-72761481-T-C		not specified	Uncertain significance (Nov 12, 2021)
13-72761500-T-C		not specified	Benign (Jul 19, 2022)
13-72761513-G-C		not specified	Uncertain significance (Dec 02, 2024)
13-72761773-A-G		not specified	Uncertain significance (Jan 23, 2024)
13-72761930-T-A		Multiple myeloma	Likely pathogenic (Aug 31, 2019)
13-72761953-A-G		not specified	Uncertain significance (Sep 26, 2024)
13-72762016-T-C		not specified	Uncertain significance (Jan 17, 2023)
13-72762029-G-A		not specified	Uncertain significance (May 27, 2022)
13-72762029-G-T		not specified	Uncertain significance (Feb 26, 2024)
13-72762089-C-G		not specified	Uncertain significance (Aug 05, 2024)
13-72763505-A-G		not specified	Uncertain significance (Jul 21, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DIS3	protein_coding	protein_coding	ENST00000377767	21	26695

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.27e-21	0.116	125493	0	254	125747	0.00101

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.693	459	503	0.913	0.0000249	6295
Missense in Polyphen		141	177.47	0.79448		2176
Synonymous	-0.469	181	173	1.05	0.00000882	1772
Loss of Function	1.51	39	50.6	0.771	0.00000282	628

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00256	0.00255
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00109	0.00109
Finnish	0.000139	0.000139
European (Non-Finnish)	0.00105	0.00104
Middle Eastern	0.00109	0.00109
South Asian	0.00114	0.00111
Other	0.00198	0.00196

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Putative catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. DIS3 has both 3'-5' exonuclease and endonuclease activities. {ECO:0000269|PubMed:19056938, ECO:0000269|PubMed:20531386}.
• Pathway: RNA degradation - Homo sapiens (human);Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA;KSRP (KHSRP) binds and destabilizes mRNA;Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA;Metabolism of RNA;Regulation of mRNA stability by proteins that bind AU-rich elements;mRNA decay by 3, to 5, exoribonuclease;Deadenylation-dependent mRNA decay (Consensus)

Recessive Scores

• pRec: 0.114

Intolerance Scores

• loftool: 0.962
• rvis_EVS: -0.02
• rvis_percentile_EVS: 52.32

Haploinsufficiency Scores

• pHI: 0.427
• hipred: Y
• hipred_score: 0.714
• ghis: 0.623

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.485

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dis3
• Phenotype: vision/eye 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)

Gene ontology

• Biological process: rRNA processing;RNA catabolic process;rRNA catabolic process;regulation of mRNA stability;exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay;CUT catabolic process;RNA phosphodiester bond hydrolysis, exonucleolytic
• Cellular component: nuclear exosome (RNase complex);cytoplasmic exosome (RNase complex);exosome (RNase complex);nucleus;nucleoplasm;nucleolus;cytosol;membrane
• Molecular function: 3'-5'-exoribonuclease activity;RNA binding;endonuclease activity;guanyl-nucleotide exchange factor activity;protein binding