XRN2

5'-3' exoribonuclease 2

Basic information

Region (hg38): 20:21303331-21389825

Links

ENSG00000088930 ∙ NCBI:22803 ∙ OMIM:608851 ∙ HGNC:12836 ∙ Uniprot:Q9H0D6 ∙ 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 XRN2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the XRN2 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						0
missense			30		1	31
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	30	0	1

Variants in XRN2

This is a list of pathogenic ClinVar variants found in the XRN2 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-21330510-G-C		not specified	Uncertain significance (Jan 20, 2023)
20-21330652-C-T		not specified	Uncertain significance (Jul 12, 2022)
20-21330671-G-A		not specified	Uncertain significance (Jun 12, 2023)
20-21331792-C-T		not specified	Uncertain significance (Dec 19, 2022)
20-21332291-A-G		not specified	Uncertain significance (Jun 27, 2022)
20-21332319-C-T		not specified	Uncertain significance (Jun 01, 2023)
20-21332379-G-A		not specified	Uncertain significance (Nov 07, 2022)
20-21332388-T-A		not specified	Uncertain significance (Jan 02, 2024)
20-21332424-G-A		not specified	Uncertain significance (Dec 01, 2022)
20-21333565-C-T		not specified	Uncertain significance (Mar 31, 2022)
20-21333572-G-T		not specified	Uncertain significance (Dec 08, 2023)
20-21333776-G-A			Benign (Aug 27, 2018)
20-21333953-C-T		not specified	Uncertain significance (Dec 01, 2022)
20-21333954-G-A		not specified	Uncertain significance (Sep 27, 2022)
20-21333967-A-G		not specified	Uncertain significance (Apr 23, 2024)
20-21334125-G-C		not specified	Uncertain significance (Jun 29, 2022)
20-21340787-C-T		not specified	Uncertain significance (Aug 23, 2021)
20-21340806-G-C		not specified	Uncertain significance (May 18, 2023)
20-21340812-C-T		not specified	Uncertain significance (Jul 06, 2021)
20-21340834-G-A		not specified	Uncertain significance (Sep 20, 2023)
20-21340840-G-A		not specified	Uncertain significance (Dec 12, 2023)
20-21340848-A-G		not specified	Uncertain significance (Feb 23, 2023)
20-21344193-C-T		not specified	Uncertain significance (Aug 26, 2022)
20-21348252-C-T		not specified	Uncertain significance (Feb 09, 2023)
20-21348410-C-T		not specified	Uncertain significance (Jan 08, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
XRN2	protein_coding	protein_coding	ENST00000377191	30	86522

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.349	0.651	125718	0	30	125748	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.50	359	519	0.691	0.0000268	6296
Missense in Polyphen		99	208.58	0.47465		2574
Synonymous	0.437	160	167	0.957	0.00000841	1697
Loss of Function	5.62	14	61.6	0.227	0.00000315	729

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000467	0.0000462
European (Non-Finnish)	0.000195	0.000193
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Possesses 5'->3' exoribonuclease activity (By similarity). May promote the termination of transcription by RNA polymerase II. During transcription termination, cleavage at the polyadenylation site liberates a 5' fragment which is subsequently processed to form the mature mRNA and a 3' fragment which remains attached to the elongating polymerase. The processive degradation of this 3' fragment by this protein may promote termination of transcription. Binds to RNA polymerase II (RNAp II) transcription termination R-loops formed by G-rich pause sites (PubMed:21700224). {ECO:0000250, ECO:0000269|PubMed:15565158, ECO:0000269|PubMed:16648491, ECO:0000269|PubMed:21700224}.
• Pathway: Ribosome biogenesis in eukaryotes - Homo sapiens (human);RNA degradation - Homo sapiens (human);mRNA Processing;Metabolism of proteins;Chaperonin-mediated protein folding;Association of TriC/CCT with target proteins during biosynthesis;Protein folding (Consensus)

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.592
• rvis_EVS: -0.57
• rvis_percentile_EVS: 18.9

Haploinsufficiency Scores

• pHI: 0.451
• hipred: Y
• hipred_score: 0.652
• ghis: 0.634

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.899

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Xrn2

Gene ontology

• Biological process: DNA catabolic process, exonucleolytic;DNA-templated transcription, termination;rRNA processing;RNA processing;mRNA processing;RNA catabolic process;spermatogenesis;RNA metabolic process;hippocampus development;neuron differentiation;retina development in camera-type eye;RNA phosphodiester bond hydrolysis, exonucleolytic
• Cellular component: nucleus;nucleoplasm;nucleolus;membrane;aggresome
• Molecular function: 3'-5'-exoribonuclease activity;transcription termination site sequence-specific DNA binding;RNA binding;nuclease activity;5'-3' exoribonuclease activity;protein binding;5'-3' exonuclease activity;metal ion binding