XRN2

protein-coding

5'-3' exoribonuclease 2

Gene summary

This gene encodes a 5'-3' exonuclease that promotes transcription termination at cotranscriptional cleavage sites. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

MANE transcript

NM_012255.5

Inheritance

—

ClinVar variants

U:112B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr20:21,303,331-21,389,825

External References & Databases

Ensembl (ENSG00000088930)

Transcript & Mutation Effects

hg38 • Region Span ~86.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to XRN2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 88

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012255.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar			3
missense			94 clinvar	2 clinvar	1 clinvar	97
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			13 clinvar			13
Total	0	0	112	2	1	115

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012255.5	RefSeq	NP_036387.2	30	MANE Select
ENST00000377191.5	Ensembl	ENSP00000366396.3	30	MANE Select
NM_001317960.1	RefSeq	NP_001304889.1	30	Standard
ENST00000903939.1	Ensembl	ENSP00000573998.1	28	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ribosome biogenesis in eukaryotes - Homo sapiens (human)
RNA degradation - Homo sapiens (human)
mRNA Processing
Metabolism of proteins
Chaperonin-mediated protein folding

Biological Process

DNA catabolic process, exonucleolytic
DNA-templated transcription, termination
rRNA processing
RNA processing
mRNA processing

Molecular Function

3'-5'-exoribonuclease activity
transcription termination site sequence-specific DNA binding
RNA binding
nuclease activity
5'-3' exoribonuclease activity

Cellular Component

nucleus
nucleoplasm
nucleolus
membrane
aggresome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377191
Coding exons: 30
Length: 86522
Individuals with no LoFs: 125718
Homozygous LoFs: 0
Heterozygous LoFs: 30
Defined: 125748
p: 0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.50	359	519	0.691	0.0000268	6296
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000061	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00019	0.00019	rare
South Asian	0	0.0	absent
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.112

Intolerance Scores

LoFtool: 0.592
RVIS EVS: -0.57
RVIS percentile EVS: 18.9

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.899

Gene Damage Prediction

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