RNASEH2B

ribonuclease H2 subunit B

Basic information

Region (hg38): 13:50909747-51024120

Previous symbols: [ "DLEU8", "AGS2" ]

Links

ENSG00000136104 ∙ NCBI:79621 ∙ OMIM:610326 ∙ HGNC:25671 ∙ Uniprot:Q5TBB1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Aicardi-Goutieres syndrome 2 (Definitive), mode of inheritance: AR
• Aicardi-Goutieres syndrome (Supportive), mode of inheritance: AD
• Aicardi-Goutieres syndrome 2 (Definitive), mode of inheritance: AR
• prostate cancer (Limited), mode of inheritance: AD
• Aicardi-Goutieres syndrome 2 (Strong), mode of inheritance: AR
• RNASEH2B-related type 1 interferonopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aicardi-Goutieres syndrome 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	Cardiovascular; Gastrointestinal; Dermatologic; Hematologic; Neurologic	9706629; 16845400; 20301648; 25243380

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RNASEH2B gene.

• Aicardi-Goutieres_syndrome_2 (455 variants)
• not_provided (48 variants)
• Inborn_genetic_diseases (40 variants)
• not_specified (19 variants)
• RNASEH2B-related_disorder (7 variants)
• Aicardi_Goutieres_syndrome (6 variants)
• Hereditary_spastic_paraplegia (2 variants)
• Autism_spectrum_disorder (2 variants)
• Abnormality_of_the_nervous_system (1 variants)
• Cerebral_palsy (1 variants)
• Aicardi-Goutieres_syndrome_1 (1 variants)
• Global_developmental_delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNASEH2B gene is commonly pathogenic or not. These statistics are base on transcript: NM_000024570.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	3	99	1	104
missense		11	141	5	1	158
nonsense	8	3	1			12
start loss	1	2				3
frameshift	11	3	7	1		22
splice donor/acceptor (+/-2bp)	2	16	6			24
Total	22	36	158	105	2

Highest pathogenic variant AF is 0.002016424

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RNASEH2B	protein_coding	protein_coding	ENST00000336617	11	60779

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.239	154	146	1.06	0.00000666	2039
Missense in Polyphen		46	43.356	1.061		644
Synonymous	-0.228	53	50.9	1.04	0.00000231	545
Loss of Function	0.760	15	18.5	0.810	7.76e-7	266

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000483	0.000483
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000220	0.000202
Middle Eastern	0.000109	0.000109
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Non catalytic subunit of RNase H2, 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}.
• Pathway: DNA replication - Homo sapiens (human) (Consensus)

Intolerance Scores

• loftool: 0.193
• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.92

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.275

Gene Damage Prediction

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

Gene ontology

• Biological process: in utero embryonic development;RNA catabolic process;ribonucleotide metabolic process;regulation of G2/M transition of mitotic cell cycle;negative regulation of gene expression;positive regulation of fibroblast proliferation;RNA phosphodiester bond hydrolysis, endonucleolytic;regulation of DNA damage checkpoint
• Cellular component: nucleus;nucleoplasm;ribonuclease H2 complex
• Molecular function: RNA-DNA hybrid ribonuclease activity