DIS3L2 DIS3 like 3'-5' exoribonuclease 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DIS3L2provided by HGNC
Official Full Name: DIS3 like 3'-5' exoribonuclease 2provided by HGNC
Primary source: HGNC:HGNC:28648
See related: Ensembl:ENSG00000144535 MIM:614184; AllianceGenome:HGNC:28648
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FAM6A; PRLMNS; hDIS3L2
Summary: The protein encoded by this gene is similar in sequence to 3'/5' exonucleolytic subunits of the RNA exosome. The exosome is a large multimeric ribonucleotide complex responsible for degrading various RNA substrates. Several transcript variants, some protein-coding and some not, have been found for this gene. [provided by RefSeq, Mar 2012]
Expression: Ubiquitous expression in testis (RPKM 5.8), thyroid (RPKM 4.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q37.1

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (231961713..232344350)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (232448342..232831055)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (232826423..233209060)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

DIS3L2 knockdown impairs key oncogenic properties of colorectal cancer cells via the mTOR signaling pathway.
Title: DIS3L2 knockdown impairs key oncogenic properties of colorectal cancer cells via the mTOR signaling pathway.
DIS3L2 and LSm proteins are involved in the surveillance of Sm ring-deficient snRNAs.
Title: DIS3L2 and LSm proteins are involved in the surveillance of Sm ring-deficient snRNAs.
AGO-bound mature miRNAs are oligouridylated by TUTs and subsequently degraded by DIS3L2.
Title: AGO-bound mature miRNAs are oligouridylated by TUTs and subsequently degraded by DIS3L2.
The Perlman syndrome DIS3L2 exoribonuclease safeguards endoplasmic reticulum-targeted mRNA translation and calcium ion homeostasis.
Title: The Perlman syndrome DIS3L2 exoribonuclease safeguards endoplasmic reticulum-targeted mRNA translation and calcium ion homeostasis.
Findings indicate a role for DIS3 like 3'-5' exoribonuclease 2 (DIS3L2) and uridylation in nonsense-mediated mRNA decay (NMD).
Title: A role for DIS3L2 over natural nonsense-mediated mRNA decay targets in human cells.
our findings uncover an oncogenic role of DIS3L2, in which it promotes liver cancer progression through a previously unappreciated mechanism of regulating hnRNP U-mediated alterative splicing
Title: DIS3L2 Promotes Progression of Hepatocellular Carcinoma via hnRNP U-Mediated Alternative Splicing.
These findings suggest that sequestration of the exoribonucleases DIS3L2 and XRN1 to nuclear inclusions may be related to the pathogenesis of intranuclear inclusion body disease
Title: Immunohistochemical localization of exoribonucleases (DIS3L2 and XRN1) in intranuclear inclusion body disease.
The evidence has been presented that Dis3l2 controls miRNA-9 production.
Title: Lin28a uses distinct mechanisms of binding to RNA and affects miRNA levels positively and negatively.
Our findings establish the role of DIS3L2 and oligouridylation as the cytoplasmic quality control for highly structured ncRNAs
Title: TUT-DIS3L2 is a mammalian surveillance pathway for aberrant structured non-coding RNAs.
Studies indicate important roles of the exoribonucleases DIS3L2 and XRN1 in cellular function, viability and disease.
Title: The roles of the exoribonucleases DIS3L2 and XRN1 in human disease.

Submit: New GeneRIF Correction See all GeneRIFs (16)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Perlman syndrome MedGen: C0796113 OMIM: 267000 GeneReviews: Wilms Tumor Predisposition	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2020-10-14) ClinGen Genome Curation Page Haploinsufficency Little evidence for dosage pathogenicity (Last evaluated 2020-10-14) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study of northwestern Europeans involves the C-type natriuretic peptide signaling pathway in the etiology of human height variation. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture. EBI GWAS Catalog EBI GWAS CatalogPubMed
Many sequence variants affecting diversity of adult human height. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-80023 (e-PCR)
- UniSTS:101639

RH78132 (e-PCR)
- UniSTS:38990

G33007 (e-PCR)
- UniSTS:117584

D2S2801 (e-PCR)
- UniSTS:52876

D2S1819 (e-PCR)
- UniSTS:2459

A009Z08 (e-PCR)
- UniSTS:40876

SHGC-147151 (e-PCR)
- UniSTS:172756

SHGC-112113 (e-PCR)
- UniSTS:183281

RH68821 (e-PCR)
- UniSTS:9210

RH70119 (e-PCR)
- UniSTS:81661

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 3'-5'-RNA exonuclease activity	IBA Inferred from Biological aspect of Ancestor more info
enables 3'-5'-RNA exonuclease activity	IDA Inferred from Direct Assay more info	PubMed
enables RNA nuclease activity	IDA Inferred from Direct Assay more info	PubMed
enables magnesium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables poly(U) RNA binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in cell division	IEA Inferred from Electronic Annotation more info
involved_in mRNA catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in miRNA catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in miRNA catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in miRNA catabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in mitotic cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitotic sister chromatid separation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nuclear-transcribed mRNA catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in polyuridylation-dependent mRNA catabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in stem cell population maintenance	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
is_active_in P-body	IBA Inferred from Biological aspect of Ancestor more info
located_in P-body	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: DIS3-like exonuclease 2

Names: DIS3 mitotic control homolog-like 2; family with sequence similarity 6, member A

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_032572.1 RefSeqGene

Range

5001..387386

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_534

mRNA and Protein(s)

NM_001257281.2 → NP_001244210.1 DIS3-like exonuclease 2 isoform 2

See identical proteins and their annotated locations for NP_001244210.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks several exons and includes an alternate 3' terminal exon compared to variant 1. It encodes isoform 2, which is shorter and has a distinct C-terminus compared to isoform 1.

Source sequence(s)

AC068134, AK094293

Consensus CDS

CCDS58752.1

UniProtKB/Swiss-Prot

Q8IYB7

Related

ENSP00000273009.6, ENST00000273009.10

Conserved Domains (2) summary

pfam00773
Location:371 → 512

RNB; RNB domain

pfam08961
Location:527 → 601

DUF1875; Domain of unknown function (DUF1875)
NM_001257282.2 → NP_001244211.1 DIS3-like exonuclease 2 isoform 3

See identical proteins and their annotated locations for NP_001244211.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks several exons and its transcription extends past a splice site that is used in variant 1, resulting in a novel 3' coding region and 3' UTR compared to variant 1. It encodes isoform 3, which is shorter and has a distinct C-terminus compared to isoform 1.

Source sequence(s)

AC019130, AC138658, AF443854

Consensus CDS

CCDS58753.1

UniProtKB/Swiss-Prot

Q8IYB7

Related

ENSP00000386594.3, ENST00000409401.7

Conserved Domains (1) summary

COG0557
Location:68 → 122

VacB; Exoribonuclease R [Transcription]
NM_152383.5 → NP_689596.4 DIS3-like exonuclease 2 isoform 1

See identical proteins and their annotated locations for NP_689596.4

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

BC036113, BG746662, BM128478, DA058505

Consensus CDS

CCDS42834.1

UniProtKB/Swiss-Prot

Q53S79, Q580W6, Q5XKH0, Q69YG5, Q6AW99, Q7Z4T6, Q8IYB7, Q8N9K9

Related

ENSP00000315569.7, ENST00000325385.12

Conserved Domains (2) summary

COG0557
Location:226 → 812

VacB; Exoribonuclease R [Transcription]

pfam00773
Location:371 → 719

RNB; RNB domain

RNA

NR_046476.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate splice site in an internal exon compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region found in variant 1.

Source sequence(s)

AA781347, AK094293, AW589919, BC026166, BX648325

Related

ENST00000390005.9
NR_046477.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) has a longer internal exon and lacks a 3' intron compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region found in variant 1.

Source sequence(s)

AA781347, AC068134, AC138658, AK094293, AW589919, BC026166, BX648325