ENDOG

protein-coding

endonuclease G

Gene summary

The protein encoded by this gene is a nuclear encoded endonuclease that is localized in the mitochondrion. The encoded protein is widely distributed among animals and cleaves DNA at GC tracts. This protein is capable of generating the RNA primers required by DNA polymerase gamma to initiate replication of mitochondrial DNA. [provided by RefSeq, Jul 2008]

MANE transcript

NM_004435.2

Inheritance

—

ClinVar variants

U:55B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr9:128,818,500-128,822,676

External References & Databases

Ensembl (ENSG00000167136)

Transcript & Mutation Effects

hg38 • Region Span ~4.2 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 ENDOG variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 52

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004435.2. 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				3 clinvar	1 clinvar	4
missense			54 clinvar		3 clinvar	57
nonsense						0
start loss						0
frameshift				1 clinvar		1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	55	4	4	63

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004435.2	RefSeq	NP_004426.2	3	MANE Select
ENST00000372642.5	Ensembl	ENSP00000361725.4	3	MANE Select
ENST00000854121.1	Ensembl	ENSP00000524180.1	4	Standard
ENST00000854121.2	Ensembl	ENSP00000524180.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Apoptosis - Homo sapiens (human)
Apoptosis Modulation and Signaling
Nanomaterial induced apoptosis
apoptotic dna-fragmentation and tissue homeostasis

Biological Process

DNA catabolic process, endonucleolytic
in utero embryonic development
apoptotic DNA fragmentation
DNA recombination
aging

Molecular Function

single-stranded DNA endodeoxyribonuclease activity
nucleic acid binding
endonuclease activity
endoribonuclease activity
exodeoxyribonuclease activity

Cellular Component

nucleus
mitochondrion
mitochondrial inner membrane
cytosol
perikaryon

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372642
Coding exons: 3
Length: 4204
Individuals with no LoFs: 125370
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125382
p: 0.0000479

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.12	88	123	0.715	0.00000755	1803
Missense (PolyPhen)		53	59.073	0.8972		722
Synonymous	1.69	35	50.2	0.697	0.00000297	633
Loss of Function	0.331	6	6.94	0.864	2.97e-7	98

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000061	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000037	0.000035	rare
South Asian	0.00010	0.000098	rare
Other	0.00019	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cleaves DNA at double-stranded (DG)n.(DC)n and at single-stranded (DC)n tracts. In addition to deoxyribonuclease activities, also has ribonuclease (RNase) and RNase H activities. Capable of generating the RNA primers required by DNA polymerase gamma to initiate replication of mitochondrial DNA (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.201

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.907

Gene Damage Prediction

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