ENDOU

protein-coding

endonuclease, poly(U) specific, the group of Serine proteases|Endoribonucleases

Gene summary

This gene encodes a protein with endoribonuclease activity that binds polyuridine-enriched single-stranded RNA. This gene was initially characterized based on its high expression in placenta but was mischaracterized as a serine protease. In mouse, this gene promotes tolerance to self-antigens by regulating B cell activation-induced cell death (AICD). The protein may be useful as a tumor marker. Multiple alternatively spliced transcript variants encoding distinct protein isoforms have been found for this gene. [provided by RefSeq, Jul 2020]

MANE transcript

NM_001172439.2

Inheritance

—

ClinVar variants

U:53B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.91

Max pathogenic AF

—

Genomic locus

chr12:47,709,734-47,725,567

External References & Databases

Ensembl (ENSG00000111405)

Transcript & Mutation Effects

hg38 • Region Span ~15.8 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 ENDOU variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 52

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001172439.2. 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					2 clinvar	2
missense			50 clinvar	3 clinvar	1 clinvar	54
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	53	3	3	59

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001172439.2	RefSeq	NP_001165910.1	10	MANE Select
ENST00000422538.8	Ensembl	ENSP00000397679.3	10	MANE Select
NM_001172440.2	RefSeq	NP_001165911.1	8	Standard
NM_006025.4	RefSeq	NP_006016.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis
receptor-mediated endocytosis
immune response
female pregnancy
regulation of signaling receptor activity

Molecular Function

RNA binding
endoribonuclease activity
scavenger receptor activity
growth factor activity
serine-type peptidase activity

Cellular Component

extracellular region
extracellular space
cytoplasm
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000422538
Coding exons: 10
Length: 15834
Individuals with no LoFs: 125223
Homozygous LoFs: 0
Heterozygous LoFs: 525
Defined: 125748
p: 0.00209

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.653	207	235	0.880	0.0000128	2725
Missense (PolyPhen)		67	83.619	0.80125		1066
Synonymous	0.797	82	91.7	0.894	0.00000516	715
Loss of Function	0.397	22	24.1	0.913	0.00000119	287

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0020	0.0020	notable
Latino/Admixed American	0.0022	0.0022	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00044	0.00044	rare
Finnish	0.0028	0.0028	notable
European (Non-Finnish)	0.0027	0.0027	notable
South Asian	0.00085	0.00085	rare
Other	0.0024	0.0024	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Endoribonuclease that cleaves single-stranded RNAs at uridylates and releases products that have 2'-3'-cyclic phosphate termini. {ECO:0000269|PubMed:18936097}.;

Intolerance Scores

LoFtool: 0.415
RVIS EVS: -0.18
RVIS percentile EVS: 40.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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