RNASEH2B

Summary

RNASEH2B (ribonuclease H2 subunit B, HGNC:25671) is a protein-coding gene on chromosome 13q14.3, encoding Ribonuclease H2 subunit B (Q5TBB1). Non catalytic subunit of RNase H2, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids.

RNase H2 is composed of a single catalytic subunit (A) and two non-catalytic subunits (B and C) and specifically degrades the RNA of RNA:DNA hybrids. The protein encoded by this gene is the non-catalytic B subunit of RNase H2, which is thought to play a role in DNA replication. Multiple transcript variants encoding different isoforms have been found for this gene. Defects in this gene are a cause of Aicardi-Goutieres syndrome type 2 (AGS2).

Source: NCBI Gene 79621 — RefSeq curated summary.

At a glance

• Gene–disease (curated): RNASEH2B-related type 1 interferonopathy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 498 total — 27 pathogenic, 19 likely-pathogenic
• Phenotypes (HPO): 79
• MANE Select transcript: NM_024570

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25671
Approved symbol	RNASEH2B
Name	ribonuclease H2 subunit B
Location	13q14.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11712
Ensembl gene	ENSG00000136104
Ensembl biotype	protein_coding
OMIM	610326
Entrez	79621

Gene structure

Transcript identifiers

Ensembl transcripts: 65 — 37 protein_coding, 14 nonsense_mediated_decay, 10 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000336617, ENST00000422660, ENST00000459681, ENST00000465541, ENST00000495244, ENST00000611510, ENST00000613449, ENST00000616907, ENST00000621641, ENST00000636524, ENST00000637648, ENST00000642207, ENST00000642454, ENST00000642721, ENST00000642995, ENST00000643159, ENST00000643215, ENST00000643405, ENST00000643462, ENST00000643529, ENST00000643682, ENST00000643774, ENST00000644034, ENST00000644183, ENST00000644297, ENST00000644420, ENST00000644425, ENST00000644518, ENST00000645188, ENST00000645201, ENST00000645333, ENST00000645370, ENST00000645549, ENST00000645618, ENST00000645712, ENST00000645912, ENST00000645955, ENST00000645990, ENST00000646092, ENST00000646279, ENST00000646339, ENST00000646709, ENST00000646731, ENST00000646960, ENST00000646964, ENST00000647387, ENST00000713853, ENST00000713967, ENST00000713968, ENST00000713969, ENST00000713970, ENST00000713971, ENST00000713972, ENST00000713973, ENST00000713974, ENST00000713975, ENST00000713976, ENST00000714507, ENST00000913788, ENST00000913789, ENST00000913790, ENST00000951840, ENST00000951841, ENST00000951842, ENST00000951843

RefSeq mRNA: 3 — MANE Select: NM_024570 NM_001142279, NM_001411023, NM_024570

CCDS: CCDS45047, CCDS91806, CCDS9425

Canonical transcript exons

ENST00000336617 — 11 exons

Exon	Start	End
ENSE00000923503	50909791	50910140
ENSE00001342144	50956358	50956762
ENSE00003458439	50947987	50948068
ENSE00003467959	50945427	50945532
ENSE00003492935	50953905	50953985
ENSE00003579010	50929475	50929582
ENSE00003580818	50949463	50949505
ENSE00003599513	50943321	50943394
ENSE00003667287	50930683	50930759
ENSE00003686481	50934885	50934999
ENSE00003687422	50927407	50927478

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 96.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.4902 / max 473.1976, expressed in 1816 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
135174	16.7421	1808
135179	4.9165	1550
135178	3.2802	1375
135175	1.8033	893
135176	0.6609	285
135177	0.0873	30

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	96.71	gold quality
ganglionic eminence	UBERON:0004023	96.43	gold quality
ventricular zone	UBERON:0003053	95.94	gold quality
granulocyte	CL:0000094	94.88	gold quality
body of pancreas	UBERON:0001150	94.10	gold quality
monocyte	CL:0000576	93.69	gold quality
leukocyte	CL:0000738	93.59	gold quality
mononuclear cell	CL:0000842	93.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.47	gold quality
cortical plate	UBERON:0005343	93.42	gold quality
rectum	UBERON:0001052	92.92	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.45	gold quality
lower esophagus	UBERON:0013473	92.43	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.42	gold quality
body of uterus	UBERON:0009853	92.23	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.87	gold quality
right uterine tube	UBERON:0001302	91.74	gold quality
right lobe of thyroid gland	UBERON:0001119	91.66	gold quality
left lobe of thyroid gland	UBERON:0001120	91.54	gold quality
left uterine tube	UBERON:0001303	91.48	gold quality
lymph node	UBERON:0000029	91.42	gold quality
right lung	UBERON:0002167	91.26	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.99	gold quality
endocervix	UBERON:0000458	90.80	gold quality
adrenal tissue	UBERON:0018303	90.65	gold quality
right testis	UBERON:0004534	90.63	gold quality
mucosa of stomach	UBERON:0001199	90.61	gold quality
thyroid gland	UBERON:0002046	90.59	gold quality
pancreas	UBERON:0001264	90.51	gold quality
spleen	UBERON:0002106	90.49	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	44.29
E-CURD-112	yes	39.78
E-ANND-3	yes	10.14
E-MTAB-8271	yes	6.54
E-MTAB-10042	yes	6.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting RNASEH2B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-15A-3P	97.47	65.08	527

Literature-anchored findings (GeneRIF, showing 13)

• Congenital infection is seen with preserved neurological function, most frequently due to RNASEH2B mutations. (PMID:18422679)
• Examination of the effect of several Aicardi-Goutieres Syndrome-related mutations in the B subunit of RNase H2. (PMID:19015152)
• patients with genetic deficiency develop the spontaneous inflammatory myocarditis (PMID:19120481)
• This study demonistrated that ribonuclease H2 mutation releated to Aicardi-Goutieres syndrome. (PMID:21862834)
• A genome-wide search for homozygosity in Aicardi-Goutieres syndrome patients in the Faroe Islands revealed one single 15.6 Mb region of homozygosity on chromosome 13, which included RNASEH2B, where a splice site mutation c.322-3C>G was identified. (PMID:22882256)
• RNase H2 complex is assembled in the cytosol and imported into the nucleus in an RNase H2B-dependent manner. (PMID:24986920)
• Aicardi-Goutieres syndrome 2 is caused by mutations in the ribonuclease H2 subunit B gene RNASEH2B. (PMID:25906927)
• This study reviewed that Neurologic Phenotypes Associated with Mutations in RNASEH2B in patients with Aicardi-Goutieres Syndrome. (PMID:27643693)
• Results implicate rare variants in the Aicardi-Goutieres syndrome genes ADAR and RNASEH2B and a type I interferon signature in glioma and prostate carcinoma risk and tumorigenesis, consistent with a genetic basis underlying inflammation-driven malignant transformation in glioma and prostate carcinoma development. (PMID:29030706)
• AGS mutations in this cluster impair the interaction of RNase H2 with several members of the CoREST chromatin-silencing complex that include the histone deacetylase HDAC2 and the demethylase KDM1A, the transcriptional regulators RCOR1 and GTFII-I as well as ZMYM3, an MYM-type zinc finger protein. (PMID:30889214)
• Germline variation of Ribonuclease H2 genes in ovarian cancer patients. (PMID:33353557)
• RB1 loss overrides PARP inhibitor sensitivity driven by RNASEH2B loss in prostate cancer. (PMID:35179959)
• Depletion of RNASEH2 Activity Leads to Accumulation of DNA Double-strand Breaks and Reduced Cellular Survivability in T Cell Leukemia. (PMID:35500843)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnaseh2b	ENSDARG00000005128
mus_musculus	Rnaseh2b	ENSMUSG00000021932
rattus_norvegicus	Rnaseh2b	ENSRNOG00000009192
drosophila_melanogaster	CG11164	FBGN0030507
caenorhabditis_elegans		WBGENE00009011

Protein

Protein identifiers

Ribonuclease H2 subunit B — Q5TBB1 (reviewed: Q5TBB1)

Alternative names: Aicardi-Goutieres syndrome 2 protein, Deleted in lymphocytic leukemia 8, Ribonuclease HI subunit B

All UniProt accessions (35): A0A087WXR7, A0A087WZJ6, A0A2R8Y459, A0A2R8Y4S2, A0A2R8Y4Y9, A0A2R8Y687, A0A2R8Y6M7, A0A2R8Y6Q6, A0A2R8Y6U1, A0A2R8Y6Y1, A0A2R8Y761, A0A2R8Y7A3, A0A2R8Y7M7, A0A2R8Y7Q3, A0A2R8Y7R8, A0A2R8Y883, A0A2R8YCJ4, A0A2R8YCP1, A0A2R8YCX2, A0A2R8YE60, Q5TBB1, A0A2R8YEB4, A0A2R8YEC1, A0A2R8YEH2, A0A2R8YEK5, A0A2R8YEQ4, A0A2R8YEU9, A0A2R8YGP2, A0AAQ5BH34, A0AAQ5BH45, A0AAQ5BH61, A0AAQ5BH87, A0AAQ5BHA0, A0AAQ5BHA8, A0AAQ5BI53

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. The RNase H2 complex is a heterotrimer composed of the catalytic subunit RNASEH2A and the non-catalytic subunits RNASEH2B and RNASEH2C.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed.

Disease relevance. Aicardi-Goutieres syndrome 2 (AGS2) [MIM:610181] 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the RNase H2 subunit B family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5TBB1-1	1	yes
Q5TBB1-2	2

RefSeq proteins (3): NP_001135751, NP_001397952, NP_078846* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019024	RNase_H2_suB_wHTH	Domain
IPR040456	RNase_H2_suB	Family
IPR041195	Rnh202_N	Domain

Pfam: PF09468, PF17745

Enzyme classification (BRENDA):

• EC 3.1.26.4 — ribonuclease H (BRENDA: 55 organisms, 293 substrates, 156 inhibitors, 81 Km, 43 kcat entries)

Substrate kinetics (BRENDA)

24 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
RNA*DNA HYBRID	0.0001–0.0084	9
DNA-RNA-DNA HYBRID	0.0011–0.0078	7
RNA-DNA HETERODUPLEX	0.0001–0.2	7
RNA-DNA*DNA HYBRID	0.0001–0.0036	5
M13 DNA/RNA HYBRID	0.0004–0.0014	4
RNA-DNA HYBRID	0.0011–0.0028	4
D14R1D3:DNA18	—	3
M13 DNA-RNA HYBRID	0.071–0.26	3
POLY(RADT)	0.0005–0.0019	3
RNA18:DNA18	0.0001–0.0002	3
DNA-RNA HYBRID DUPLEX	—	2
M13 DNA/RNA	0.0005–0.0011	2
5’-(6-CARBOXY-FLUORESCEIN)-CGGAGAUGACGG-3’/5’-CC	0.0004	1
DNA-(1’,2’-METHYLENE-BRIDGED AZETIDINE-T)-ANTISE	0.0001	1
DNA-(2’-ALKOXY-1’,2’-METHYLENE-BRIDGED AZETIDINE	0.0002	1

UniProt features (45 total): sequence variant 14, strand 9, helix 8, turn 4, modified residue 3, sequence conflict 2, splice variant 2, initiator methionine 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3P87	X-RAY DIFFRACTION	2.99
3PUF	X-RAY DIFFRACTION	3.1
3P56	X-RAY DIFFRACTION	4.06
8YJZ	ELECTRON MICROSCOPY	5.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TBB1-F1	77.22	0.31

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 2, 295, 296

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 378 (showing top): GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_POSITIVE_REGULATION_OF_FIBROBLAST_PROLIFERATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOLDRATH_ANTIGEN_RESPONSE, PUJANA_CHEK2_PCC_NETWORK, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS

GO Biological Process (11): in utero embryonic development (GO:0001701), mismatch repair (GO:0006298), RNA catabolic process (GO:0006401), ribonucleotide metabolic process (GO:0009259), regulation of G2/M transition of mitotic cell cycle (GO:0010389), gene expression (GO:0010467), negative regulation of gene expression (GO:0010629), fibroblast proliferation (GO:0048144), positive regulation of fibroblast proliferation (GO:0048146), regulation of DNA damage checkpoint (GO:2000001), nucleobase-containing compound metabolic process (GO:0006139)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): nucleoplasm (GO:0005654), ribonuclease H2 complex (GO:0032299), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chordate embryonic development	1
DNA repair	1
RNA metabolic process	1
nucleic acid catabolic process	1
nucleotide metabolic process	1
ribose phosphate metabolic process	1
G2/M transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of cell cycle G2/M phase transition	1
macromolecule biosynthetic process	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
cell population proliferation	1
positive regulation of cell population proliferation	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
DNA damage checkpoint signaling	1
regulation of cellular response to stress	1
regulation of cell cycle checkpoint	1
primary metabolic process	1
binding	1
nuclear lumen	1
cellular anatomical structure	1
intracellular protein-containing complex	1
catalytic complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1218 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNASEH2B	RNASEH2A	O75792	999
RNASEH2B	RNASEH2C	Q8TDP1	999
RNASEH2B	SAMHD1	Q9Y3Z3	950
RNASEH2B	TREX1	Q9NSU2	873
RNASEH2B	ADAR	P55265	724
RNASEH2B	FEN1	P39748	717
RNASEH2B	IFIH1	Q9BYX4	635
RNASEH2B	IFNA13	P01562	626
RNASEH2B	IFNA8	P01565	562
RNASEH2B	IFNA5	P01569	558
RNASEH2B	IFNA14	P01570	558
RNASEH2B	IFNA10	P01566	557
RNASEH2B	IFNA7	P01567	555
RNASEH2B	IFNA21	P01568	555
RNASEH2B	IFNA16	P05015	555

IntAct

20 interactions, top by confidence:

A	B	Type	Score
RNASEH2B	RNASEH2A	psi-mi:“MI:0914”(association)	0.640
RNASEH2C	RNASEH2A	psi-mi:“MI:0914”(association)	0.640
RNASEH2B	ZMYM3	psi-mi:“MI:0915”(physical association)	0.580
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
ZMYM2	RNASEH2B	psi-mi:“MI:0915”(physical association)	0.400
ZMYM4	RNASEH2B	psi-mi:“MI:0915”(physical association)	0.400
RNASEH2B	WT1	psi-mi:“MI:0915”(physical association)	0.370
RNASEH2B	SAP18	psi-mi:“MI:0914”(association)	0.350
RNASEH2A	PHF20L1	psi-mi:“MI:0914”(association)	0.350
ENG	IGKV2-28	psi-mi:“MI:0914”(association)	0.350
RNASEH2B	KDM1A	psi-mi:“MI:0914”(association)	0.350
RNASEH2B	PCNA	psi-mi:“MI:0914”(association)	0.350
RNASEH2A	NDUFA3	psi-mi:“MI:0914”(association)	0.350
NUBP2	POTEF	psi-mi:“MI:0914”(association)	0.350
HSPA2	HGS	psi-mi:“MI:0914”(association)	0.350
INSR	UBXN8	psi-mi:“MI:0914”(association)	0.350
H2BC10	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (68): RNASEH2A (Co-fractionation), RNASEH2B (Co-fractionation), RNASEH2B (Co-fractionation), VBP1 (Co-fractionation), RNASEH2B (Proximity Label-MS), ABCA2 (Affinity Capture-MS), CLPTM1 (Affinity Capture-MS), FOXM1 (Affinity Capture-MS), HIVEP1 (Affinity Capture-MS), PSMD5 (Affinity Capture-MS), RRM1 (Affinity Capture-MS), MKNK1 (Affinity Capture-MS), RABGAP1L (Affinity Capture-MS), ARPC5 (Affinity Capture-MS), SAP18 (Affinity Capture-MS)

ESM2 similar proteins: A0JMD0, A1L2I9, E1C760, E7EXT2, F6RRD7, F7AEX0, O60566, O94627, O95905, P58501, Q03701, Q05B18, Q0IHW8, Q0VBD2, Q1L987, Q1LWH4, Q28E45, Q28GD9, Q32NQ8, Q3ZBI3, Q5EAW4, Q5HZP1, Q5I0E6, Q5R789, Q5RA37, Q5RHY1, Q5SW19, Q5TBB1, Q5XI96, Q5XID1, Q66JD1, Q68Y81, Q6DGB6, Q6GLI9, Q6IV68, Q6NZY4, Q6XV80, Q7L590, Q7SYB2, Q80V62

Diamond homologs: Q28GD9, Q3ZBI3, Q5HZP1, Q5TBB1, Q5XI96, Q80ZV0, O94627

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RNASEH2B	“form complex”	“RNase H2 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Negative Regulation of CDH1 Gene Transcription	5	46.2×	7e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

498 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	27
Likely pathogenic	19
Uncertain significance	171
Likely benign	224
Benign	16

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071567	NM_024570.4(RNASEH2B):c.132T>A (p.Cys44Ter)	Pathogenic
1353481	NM_024570.4(RNASEH2B):c.129dup (p.Cys44fs)	Pathogenic
1451439	NM_024570.4(RNASEH2B):c.4del (p.Ala2fs)	Pathogenic
1451862	NM_024570.4(RNASEH2B):c.476del (p.Ser159fs)	Pathogenic
1456507	NM_024570.4(RNASEH2B):c.331C>T (p.Gln111Ter)	Pathogenic
2426831	NC_000013.10:g.(?51484213)(51484296_?)del	Pathogenic
2426832	NC_000013.10:g.(?51501523)(51530610_?)del	Pathogenic
2691643	NM_024570.4(RNASEH2B):c.737C>A (p.Ser246Ter)	Pathogenic
2764119	NM_024570.4(RNASEH2B):c.648del (p.Ser217fs)	Pathogenic
2820897	NM_024570.4(RNASEH2B):c.509dup (p.Val171fs)	Pathogenic
2842511	NM_024570.4(RNASEH2B):c.69T>A (p.Tyr23Ter)	Pathogenic
2859739	NM_024570.4(RNASEH2B):c.83C>G (p.Ser28Ter)	Pathogenic
3244196	NC_000013.10:g.(?51484213)(51530610_?)del	Pathogenic
3244197	NC_000013.10:g.(?51484213)(51528141_?)del	Pathogenic
3244198	NC_000013.10:g.(?51503591)(51530610_?)del	Pathogenic
3366699	NC_000013.10:g.(51519669_51522122)_(51523642_51528040)del	Pathogenic
3720083	NM_024570.4(RNASEH2B):c.98dup (p.Asn33fs)	Pathogenic
3769137	NC_000013.10:g.(?51483926)(51484277_51501542)del	Pathogenic
4074891	NM_024570.4(RNASEH2B):c.311_319del (p.Ala104_Lys106del)	Pathogenic
4687841	NM_024570.4(RNASEH2B):c.281dup (p.Phe95fs)	Pathogenic
4727551	NM_024570.4(RNASEH2B):c.693C>G (p.Tyr231Ter)	Pathogenic
4735463	NM_024570.4(RNASEH2B):c.737C>G (p.Ser246Ter)	Pathogenic
540251	NM_024570.4(RNASEH2B):c.667G>T (p.Glu223Ter)	Pathogenic
566198	NM_024570.4(RNASEH2B):c.136+1del	Pathogenic
567225	NM_024570.4(RNASEH2B):c.121del (p.Val41fs)	Pathogenic
650490	NM_024570.4(RNASEH2B):c.510+1G>A	Pathogenic
870598	NM_024570.4(RNASEH2B):c.491dup (p.Leu164fs)	Pathogenic
1513798	NM_024570.4(RNASEH2B):c.436+1G>A	Likely pathogenic
1933332	NM_024570.4(RNASEH2B):c.322-2A>T	Likely pathogenic
1999890	NM_024570.4(RNASEH2B):c.698+1G>C	Likely pathogenic

SpliceAI

1826 predictions. Top by Δscore:

Variant	Effect	Δscore
13:50927475:TCAGG:T	donor_loss	1.0000
13:50927476:CAGGT:C	donor_loss	1.0000
13:50927478:GGTA:G	donor_loss	1.0000
13:50927479:G:C	donor_loss	1.0000
13:50927480:T:A	donor_loss	1.0000
13:50934998:AGGTA:A	donor_loss	1.0000
13:50935000:G:GA	donor_loss	1.0000
13:50935001:T:A	donor_loss	1.0000
13:50945528:GGAAG:G	donor_gain	1.0000
13:50945529:GAAG:G	donor_gain	1.0000
13:50945529:GAAGG:G	donor_gain	1.0000
13:50945530:AAGGT:A	donor_loss	1.0000
13:50945533:G:GG	donor_gain	1.0000
13:50945533:GTAA:G	donor_loss	1.0000
13:50945534:T:A	donor_loss	1.0000
13:50947985:A:AG	acceptor_gain	1.0000
13:50947985:AGAG:A	acceptor_gain	1.0000
13:50947986:G:GG	acceptor_gain	1.0000
13:50947986:GA:G	acceptor_gain	1.0000
13:50947986:GAGG:G	acceptor_gain	1.0000
13:50948069:G:GG	donor_gain	1.0000
13:50949461:A:AG	acceptor_gain	1.0000
13:50949462:G:GG	acceptor_gain	1.0000
13:50949502:AAAGG:A	donor_loss	1.0000
13:50949504:AGGTA:A	donor_loss	1.0000
13:50949506:GTAAG:G	donor_loss	1.0000
13:50949507:T:G	donor_loss	1.0000
13:50950151:A:G	donor_gain	1.0000
13:50910135:TTTC:T	donor_gain	0.9900
13:50927405:A:AG	acceptor_gain	0.9900

AlphaMissense

2056 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:50943380:T:A	W166R	0.989
13:50943380:T:C	W166R	0.989
13:50929555:T:A	W73R	0.986
13:50929555:T:C	W73R	0.986
13:50943384:T:C	L167P	0.986
13:50956394:G:C	A287P	0.985
13:50929574:T:A	V79D	0.983
13:50934891:T:C	F110L	0.980
13:50934893:T:A	F110L	0.980
13:50934893:T:G	F110L	0.980
13:50956436:T:C	F301L	0.979
13:50956438:T:A	F301L	0.979
13:50956438:T:G	F301L	0.979
13:50948014:T:C	L215P	0.978
13:50956433:T:C	F300L	0.977
13:50956435:T:A	F300L	0.977
13:50956435:T:G	F300L	0.977
13:50948005:C:A	A212D	0.976
13:50956392:T:C	L286S	0.976
13:50956387:G:C	K284N	0.973
13:50956387:G:T	K284N	0.973
13:50956388:G:C	A285P	0.972
13:50948004:G:C	A212P	0.968
13:50956380:C:A	A282D	0.966
13:50956384:G:C	Q283H	0.966
13:50956384:G:T	Q283H	0.966
13:50953944:G:C	D261H	0.965
13:50943382:G:C	W166C	0.963
13:50943382:G:T	W166C	0.963
13:50948017:T:A	I216K	0.963

dbSNP variants (sampled 300 via entrez): RS1000018885 (13:50939865 T>C), RS1000128360 (13:50946852 G>C), RS1000135580 (13:50946971 C>T), RS1000145800 (13:50941746 G>C), RS1000155275 (13:50946347 G>A), RS1000189962 (13:50967695 A>G), RS1000194528 (13:50948896 A>G), RS1000221789 (13:50919997 T>C), RS1000252644 (13:50954337 A>C), RS1000305205 (13:50908212 T>G), RS1000458487 (13:50914475 A>G,T), RS1000474172 (13:50969504 T>A), RS1000535035 (13:50945009 C>T), RS1000573737 (13:50952593 G>T), RS1000581165 (13:50940671 C>T)

Disease associations

OMIM: gene MIM:610326 | disease phenotypes: MIM:610181, MIM:225750, MIM:303350

GenCC curated gene-disease

Disease	Classification	Inheritance
Aicardi-Goutieres syndrome 2	Definitive	Autosomal recessive
Aicardi-Goutieres syndrome	Supportive	Autosomal dominant
prostate cancer	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
RNASEH2B-related type 1 interferonopathy	Definitive	AR

Mondo (8): Aicardi-Goutieres syndrome 2 (MONDO:0012429), congenital nervous system disorder (MONDO:0002320), autism spectrum disorder (MONDO:0005258), cerebral palsy (MONDO:0006497), Aicardi-Goutieres syndrome (MONDO:0018866), hereditary spastic paraplegia (MONDO:0019064), Aicardi-Goutieres syndrome 1 (MONDO:0009165), prostate cancer (MONDO:0008315)

Orphanet (3): Aicardi-Goutières syndrome (Orphanet:51), Hereditary spastic paraplegia (Orphanet:685), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

79 total (30 of 79 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000054	Micropenis
HP:0000252	Microcephaly
HP:0000369	Low-set ears
HP:0000444	Convex nasal ridge
HP:0000496	Abnormality of eye movement
HP:0000501	Glaucoma
HP:0000508	Ptosis
HP:0000625	Eyelid coloboma
HP:0000639	Nystagmus
HP:0000737	Irritability
HP:0000819	Diabetes mellitus
HP:0000821	Hypothyroidism
HP:0000958	Dry skin
HP:0000965	Cutis marmorata
HP:0001063	Acrocyanosis
HP:0001087	Developmental glaucoma
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001258	Spastic paraplegia
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001298	Encephalopathy
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001357	Plagiocephaly
HP:0001369	Arthritis
HP:0001433	Hepatosplenomegaly
HP:0001609	Hoarse voice

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002357_3	Rheumatoid arthritis (ACPA-negative)	1.000000e-06
GCST006624_49	Systolic blood pressure	2.000000e-13
GCST007507_18	Benign prostatic hyperplasia and lower urinary tract symptoms	1.000000e-08
GCST009391_192	Metabolite levels	7.000000e-06
GCST009391_792	Metabolite levels	3.000000e-06
GCST90002390_190	Mean corpuscular hemoglobin	4.000000e-11
GCST90002392_411	Mean corpuscular volume	9.000000e-14

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0008008	lower urinary tract symptom
EFO:0010482	gamma-aminoisobutyric acid measurement
EFO:0010395	sphingomyelin 22:0 measurement
EFO:0004527	mean corpuscular hemoglobin

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D002547	Cerebral Palsy	C10.228.140.140.254
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820
C535607	Aicardi-Goutieres syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	affects expression, decreases expression	3
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	increases abundance, affects cotreatment, affects expression	1
sodium arsenate	increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
methacrylaldehyde	affects cotreatment, affects expression, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Acrolein	affects cotreatment, affects expression, increases abundance	1
Air Pollutants	affects cotreatment, affects expression, increases abundance	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Cannabidiol	decreases expression	1
Cisplatin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Formaldehyde	decreases expression	1
Gallic Acid	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ozone	increases abundance, affects cotreatment, affects expression	1

Cellosaurus cell lines

3 cell lines: 3 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_YB48	UNIBSi007-A	Induced pluripotent stem cell	Female
CVCL_YB49	UNIBSi007-B	Induced pluripotent stem cell	Female
CVCL_YB50	UNIBSi007-C	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

600 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer