XRN1

5'-3' exoribonuclease 1

Basic information

Region (hg38): 3:142306606-142448062

Links

ENSG00000114127 ∙ NCBI:54464 ∙ OMIM:607994 ∙ HGNC:30654 ∙ Uniprot:Q8IZH2 ∙ 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 XRN1 gene.

• Inborn genetic diseases (50 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the XRN1 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	2
missense			49	2		51
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	49	4	1

Variants in XRN1

This is a list of pathogenic ClinVar variants found in the XRN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-142311528-A-C		not specified	Uncertain significance (Mar 01, 2023)
3-142311632-T-G		not specified	Uncertain significance (Jan 03, 2024)
3-142311647-G-A		not specified	Uncertain significance (Jan 06, 2023)
3-142311648-G-A		not specified	Uncertain significance (Feb 06, 2024)
3-142311693-G-A		not specified	Uncertain significance (Dec 12, 2023)
3-142311795-C-T		not specified	Uncertain significance (Jan 06, 2023)
3-142312645-C-T		not specified	Uncertain significance (Dec 15, 2023)
3-142312657-T-C		not specified	Uncertain significance (Jan 06, 2023)
3-142312704-G-A		not specified	Uncertain significance (Oct 05, 2022)
3-142312722-G-A		not specified	Uncertain significance (Jun 27, 2022)
3-142312732-G-T		not specified	Uncertain significance (Jun 09, 2022)
3-142312747-G-C		not specified	Uncertain significance (Dec 11, 2023)
3-142313143-C-G		not specified	Uncertain significance (Apr 19, 2023)
3-142318603-G-A		not specified	Uncertain significance (Jun 18, 2021)
3-142318628-G-A		not specified	Uncertain significance (Mar 20, 2023)
3-142318894-C-T		not specified	Uncertain significance (Sep 27, 2021)
3-142329561-A-G			Uncertain significance (Oct 16, 2023)
3-142329608-A-G			Benign (Nov 18, 2017)
3-142332524-C-T		not specified	Uncertain significance (Feb 06, 2024)
3-142332972-C-T		not specified	Uncertain significance (Aug 15, 2023)
3-142333011-C-T		not specified	Uncertain significance (Jul 13, 2021)
3-142333040-T-G		not specified	Uncertain significance (Oct 27, 2022)
3-142335460-C-A		not specified	Uncertain significance (Jun 29, 2023)
3-142335468-G-C		not specified	Uncertain significance (Feb 05, 2024)
3-142347276-T-C		not specified	Uncertain significance (May 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
XRN1	protein_coding	protein_coding	ENST00000264951	42	141456

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	6.79e-8	125714	0	33	125747	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.11	693	868	0.799	0.0000426	11251
Missense in Polyphen		83	173.71	0.4778		2202
Synonymous	0.738	273	289	0.945	0.0000138	3088
Loss of Function	8.08	12	98.6	0.122	0.00000489	1272

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000549	0.000543
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000151	0.000141
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000664	0.0000653
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Major 5'-3' exoribonuclease involved in mRNA decay. Required for the 5'-3'-processing of the G4 tetraplex-containing DNA and RNA substrates. The kinetic of hydrolysis is faster for G4 RNA tetraplex than for G4 DNA tetraplex and monomeric RNA tetraplex. Binds to RNA and DNA (By similarity). Plays a role in replication-dependent histone mRNA degradation. May act as a tumor suppressor protein in osteogenic sarcoma (OGS). {ECO:0000250|UniProtKB:P97789, ECO:0000269|PubMed:18172165}.
• Pathway: Ribosome biogenesis in eukaryotes - Homo sapiens (human);RNA degradation - Homo sapiens (human);Butyrate Response Factor 1 (BRF1) 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 5, to 3, exoribonuclease;Deadenylation-dependent mRNA decay (Consensus)

Recessive Scores

• pRec: 0.321

Intolerance Scores

• loftool: 0.675
• rvis_EVS: -0.32
• rvis_percentile_EVS: 30.96

Haploinsufficiency Scores

• pHI: 0.627
• hipred: Y
• hipred_score: 0.706
• ghis: 0.580

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.296

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Xrn1

Gene ontology

• Biological process: nuclear-transcribed mRNA catabolic process;rRNA catabolic process;negative regulation of translation;negative regulation of telomere maintenance via telomerase;response to testosterone;regulation of mRNA stability;nuclear mRNA surveillance;histone mRNA catabolic process;cellular response to cycloheximide;RNA phosphodiester bond hydrolysis, exonucleolytic;cellular response to puromycin
• Cellular component: P-body;nucleus;cytosol;plasma membrane;membrane;dendrite;neuronal cell body;synapse
• Molecular function: G-quadruplex RNA binding;RNA binding;5'-3' exoribonuclease activity;protein binding;G-quadruplex DNA binding;telomerase RNA binding