RNASEH2A

ribonuclease H2 subunit A

Basic information

Region (hg38): 19:12806584-12813640

Links

ENSG00000104889

∙ NCBI:10535 ∙ OMIM:606034 ∙ HGNC:18518 ∙ Uniprot:O75792 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Aicardi-Goutieres syndrome 4 (Definitive), mode of inheritance: AR
Aicardi-Goutieres syndrome 4 (Strong), mode of inheritance: AR
Aicardi-Goutieres syndrome 4 (Strong), mode of inheritance: AR
Aicardi-Goutieres syndrome (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aicardi-Goutieres syndrome 4	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	Cardiovascular; Gastrointestinal; Dermatologic; Cardiovascular; Hematologic; Neurologic	16845400; 17846997; 20301648

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RNASEH2A gene.

Aicardi-Goutieres_syndrome_4 (474 variants)
Inborn_genetic_diseases (49 variants)
not_provided (32 variants)
RNASEH2A-related_disorder (16 variants)
not_specified (9 variants)
Aicardi_Goutieres_syndrome (7 variants)
RNASEH2A-related_type_1_interferonopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNASEH2A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006397.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar	1 clinvar	3 clinvar	133 clinvar		138
missense	2 clinvar	11 clinvar	178 clinvar	8 clinvar	1 clinvar	200
nonsense	6 clinvar	2 clinvar	1 clinvar			9
start loss		1				1
frameshift	9 clinvar	4 clinvar	6 clinvar			19
splice donor/acceptor (+/-2bp)		9 clinvar				9
Total	18	28	188	141	1

Highest pathogenic variant AF is 0.0000712467

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RNASEH2A	protein_coding	protein_coding	ENST00000221486	8	7059

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00418	0.965	125700	0	48	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.193	171	178	0.959	0.0000116	1920
Missense in Polyphen		60	74.049	0.81027		831
Synonymous	-0.591	84	77.4	1.09	0.00000527	601
Loss of Function	1.88	6	13.5	0.446	5.92e-7	161

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00166	0.00166
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000508	0.000508
European (Non-Finnish)	0.0000527	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: Catalytic subunit of RNase HII, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging- strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes. {ECO:0000269|PubMed:16845400, ECO:0000269|PubMed:21177858}.;
Disease: DISEASE: Aicardi-Goutieres syndrome 4 (AGS4) [MIM:610333]: A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood. {ECO:0000269|PubMed:16845400, ECO:0000269|PubMed:17846997, ECO:0000269|PubMed:20131292}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: DNA replication - Homo sapiens (human) (Consensus)

Recessive Scores

pRec: 0.484

Intolerance Scores

loftool: 0.254
rvis_EVS: -0.05
rvis_percentile_EVS: 50.01

Haploinsufficiency Scores

pHI: 0.815
hipred: Y
hipred_score: 0.723
ghis: 0.654

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.896

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Rnaseh2a
Phenotype

Gene ontology

Biological process: DNA replication;mismatch repair;RNA catabolic process;DNA replication, removal of RNA primer;RNA phosphodiester bond hydrolysis, endonucleolytic
Cellular component: nucleoplasm;cytosol;ribonuclease H2 complex
Molecular function: RNA binding;RNA-DNA hybrid ribonuclease activity;ribonuclease activity;metal ion binding