RNASEH1

ribonuclease H1

Basic information

Region (hg38): 2:3541430-3558333

Links

ENSG00000171865 ∙ NCBI:246243 ∙ OMIM:604123 ∙ HGNC:18466 ∙ Uniprot:O60930 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2 (Strong), mode of inheritance: AR
• adult-onset chronic progressive external ophthalmoplegia with mitochondrial myopathy (Supportive), mode of inheritance: AD
• Leigh syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive, 2	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Musculoskeletal; Neurologic	26094573

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RNASEH1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNASEH1 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			3	49	1	53
missense		1	45	3		49
nonsense		1	1			2
start loss						0
frameshift		1	1			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)			2			2
splice region			5	4	1	10
non coding			1	29	16	46
Total	0	3	54	81	17

Variants in RNASEH1

This is a list of pathogenic ClinVar variants found in the RNASEH1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-3545794-C-T		RNASEH1-related disorder	Likely benign (Apr 17, 2023)
2-3545795-G-T			Uncertain significance (Apr 08, 2022)
2-3545816-G-A			Uncertain significance (Apr 01, 2020)
2-3545822-C-A			Uncertain significance (May 09, 2024)
2-3545829-C-T			Uncertain significance (Apr 25, 2022)
2-3545833-T-C			Likely benign (Jul 28, 2022)
2-3545844-T-C			Uncertain significance (Feb 09, 2022)
2-3545851-C-T			Uncertain significance (Jan 21, 2022)
2-3545886-GTTTTCC-G			Likely benign (Dec 09, 2022)
2-3545888-T-C			Uncertain significance (Apr 06, 2022)
2-3545890-T-C			Likely benign (Jan 29, 2024)
2-3546023-C-T			Likely benign (Jan 28, 2019)
2-3547741-C-A			Likely benign (Jul 15, 2018)
2-3547926-C-T			Uncertain significance (May 11, 2022)
2-3547941-T-C			Uncertain significance (Nov 01, 2022)
2-3547946-C-A			Uncertain significance (May 03, 2022)
2-3547976-G-A			Likely benign (Jan 15, 2024)
2-3547985-G-A			Likely benign (Jan 29, 2024)
2-3547992-A-C		Inborn genetic diseases	Uncertain significance (Jun 23, 2023)
2-3548000-C-G			Likely benign (Apr 09, 2023)
2-3548002-C-T			Uncertain significance (Jul 26, 2022)
2-3548003-T-C		RNASEH1-related disorder	Benign/Likely benign (Mar 01, 2024)
2-3548004-G-C			Uncertain significance (Apr 11, 2023)
2-3548006-A-C			Uncertain significance (Aug 19, 2022)
2-3548034-C-T			Uncertain significance (Jul 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RNASEH1	protein_coding	protein_coding	ENST00000315212	8	13824

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0112	0.981	125726	0	22	125748	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.107	167	171	0.977	0.00000975	1874
Missense in Polyphen		44	67.619	0.6507		775
Synonymous	-2.44	94	68.3	1.38	0.00000457	530
Loss of Function	2.32	6	16.0	0.374	8.50e-7	175

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000185	0.000185
Ashkenazi Jewish	0.00	0.00
East Asian	0.000503	0.000489
Finnish	0.00	0.00
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.000503	0.000489
South Asian	0.000103	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Endonuclease that specifically degrades the RNA of RNA- DNA hybrids (PubMed:10497183). Plays a role in RNA polymerase II (RNAp II) transcription termination by degrading R-loop RNA-DNA hybrid formation at G-rich pause sites located downstream of the poly(A) site and behind the elongating RNAp II (PubMed:21700224). {ECO:0000269|PubMed:10497183, ECO:0000269|PubMed:21700224}.
• Pathway: DNA replication - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.117

Intolerance Scores

• loftool: 0.434
• rvis_EVS: -0.74
• rvis_percentile_EVS: 13.94

Haploinsufficiency Scores

• pHI: 0.107
• hipred: N
• hipred_score: 0.285
• ghis: 0.659

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: N
• gene_indispensability_score: 0.151

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rnaseh1
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; growth/size/body region phenotype; cellular phenotype

Gene ontology

• Biological process: RNA catabolic process;DNA replication, removal of RNA primer;RNA phosphodiester bond hydrolysis, endonucleolytic
• Cellular component: cytoplasm
• Molecular function: magnesium ion binding;nucleic acid binding;RNA binding;RNA-DNA hybrid ribonuclease activity;ribonuclease activity