RNASEH2C

Summary

RNASEH2C (ribonuclease H2 subunit C, HGNC:24116) is a protein-coding gene on chromosome 11q13.1, encoding Ribonuclease H2 subunit C (Q8TDP1). Non catalytic subunit of RNase H2, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. It is a selective cancer dependency (DepMap: 26.2% of cell lines).

This gene encodes a ribonuclease H subunit that can cleave ribonucleotides from RNA:DNA duplexes. Mutations in this gene cause Aicardi-Goutieres syndrome-3, a disease that causes severe neurologic dysfunction. A pseudogene for this gene has been identified on chromosome Y, near the sex determining region Y (SRY) gene.

Source: NCBI Gene 84153 — RefSeq curated summary.

At a glance

• Gene–disease (curated): RNASEH2C-related type 1 interferonopathy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 21
• Clinical variants (ClinVar): 292 total — 1 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 85
• Cancer dependency (DepMap): dependent in 26.2% of screened cell lines
• MANE Select transcript: NM_032193

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24116
Approved symbol	RNASEH2C
Name	ribonuclease H2 subunit C
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	AYP1, AGS3
Ensembl gene	ENSG00000172922
Ensembl biotype	protein_coding
OMIM	610330
Entrez	84153

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 7 retained_intron, 5 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000308418, ENST00000527610, ENST00000528220, ENST00000530192, ENST00000531596, ENST00000533698, ENST00000534482, ENST00000642430, ENST00000643214, ENST00000644142, ENST00000644198, ENST00000645835, ENST00000646597, ENST00000886951, ENST00000886952, ENST00000886953

RefSeq mRNA: 1 — MANE Select: NM_032193 NM_032193

CCDS: CCDS8111

Canonical transcript exons

ENST00000308418 — 4 exons

Exon	Start	End
ENSE00001190961	65717673	65719809
ENSE00001190968	65720045	65720164
ENSE00001190975	65720242	65720417
ENSE00003901476	65720587	65720798

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 98.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.3482 / max 625.9175, expressed in 1822 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120672	33.0500	1821
120671	2.2981	1342

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	98.84	gold quality
tendon of biceps brachii	UBERON:0008188	97.62	gold quality
apex of heart	UBERON:0002098	95.49	gold quality
right atrium auricular region	UBERON:0006631	95.46	gold quality
cardiac atrium	UBERON:0002081	95.29	gold quality
left coronary artery	UBERON:0001626	94.77	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.73	gold quality
coronary artery	UBERON:0001621	94.67	gold quality
cerebellar hemisphere	UBERON:0002245	94.43	gold quality
thoracic aorta	UBERON:0001515	94.39	gold quality
right adrenal gland	UBERON:0001233	94.35	gold quality
ascending aorta	UBERON:0001496	94.35	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.34	gold quality
descending thoracic aorta	UBERON:0002345	94.30	gold quality
cerebellar cortex	UBERON:0002129	94.28	gold quality
vena cava	UBERON:0004087	94.16	gold quality
right adrenal gland cortex	UBERON:0035827	94.00	gold quality
aorta	UBERON:0000947	93.95	gold quality
left adrenal gland cortex	UBERON:0035825	93.93	gold quality
adrenal cortex	UBERON:0001235	93.90	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.89	gold quality
lower esophagus	UBERON:0013473	93.85	gold quality
left adrenal gland	UBERON:0001234	93.84	gold quality
body of uterus	UBERON:0009853	93.84	gold quality
left uterine tube	UBERON:0001303	93.77	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.77	gold quality
pericardium	UBERON:0002407	93.69	gold quality
popliteal artery	UBERON:0002250	93.66	gold quality
bone marrow	UBERON:0002371	93.65	gold quality
tibial artery	UBERON:0007610	93.64	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9467	yes	31.01
E-ANND-3	yes	10.64
E-MTAB-6142	no	160.73
E-GEOD-125970	no	3.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

98 targeting RNASEH2C, 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-4283	100.00	66.42	2097
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-515-5P	99.92	69.82	2343

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 26.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

• Examination of the effect of several Aicardi-Goutieres Syndrome-related mutations in the C subunit of RNase H2. (PMID:19015152)
• RNase H2 complex is assembled in the cytosol and imported into the nucleus in an RNase H2B-dependent manner. (PMID:24986920)
• This study reviewed that Neurologic Phenotypes Associated with Mutations in RNASEH2C in patients with Aicardi-Goutieres Syndrome. (PMID:27643693)
• The anti-inflammatory molecular make-up of centenarian’s fibroblasts (low levels of IL-6, type 1 interferon beta, and pro-inflammatory microRNAs), which is coupled with low level of DNA damage (measured by comet assay and histone-2AX activation) and preserved telomere length. In the same cells, high levels of the RNAseH2C enzyme subunit and low amounts of RNAseH2 substrates, i.e. cytoplasmic RNA:DNA hybrids are present. (PMID:30622304)
• Aicardi-Goutieres syndrome gene Rnaseh2c is a metastasis susceptibility gene in breast cancer. (PMID:31125342)
• Germline variation of Ribonuclease H2 genes in ovarian cancer patients. (PMID:33353557)
• RNASEH2C c.194G>A is a Chinese-specific founder mutation in three unrelated patients with Aicardi-Goutieres syndrome 3. (PMID:37092250)
• Describes an RNASEH2C pseudogene that is located close to the SRY gene on chromosome Y. (PMID:8244390)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rnaseh2c	ENSMUSG00000024925
rattus_norvegicus	Rnaseh2c	ENSRNOG00000020700

Protein

Protein identifiers

Ribonuclease H2 subunit C — Q8TDP1 (reviewed: Q8TDP1)

Alternative names: Aicardi-Goutieres syndrome 3 protein, RNase H1 small subunit, Ribonuclease HI subunit C

All UniProt accessions (2): Q8TDP1, E9PN81

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 3 (AGS3) [MIM:610329] 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.

Miscellaneous. The T6 pseudogene located upstream of SRY on chromosome Y is derived from the transcript of this gene.

Similarity. Belongs to the RNase H2 subunit C family.

RefSeq proteins (1): NP_115569* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013924	RNase_H2_suC	Family
IPR052863	RNase_H2_subunit_C	Family

Pfam: PF08615

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 (27 total): strand 9, sequence variant 7, helix 6, modified residue 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
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-Q8TDP1-F1	85.30	0.65

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 (2): 1, 3

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 289 (showing top): MODULE_151, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, chr11q13, MODULE_503, GOBP_DNA_DAMAGE_RESPONSE, GOBP_MISMATCH_REPAIR, BURTON_ADIPOGENESIS_3, CUI_TCF21_TARGETS_2_UP, BERENJENO_TRANSFORMED_BY_RHOA_UP, MODULE_356, MODULE_114, KEGG_DNA_REPLICATION, SANSOM_APC_TARGETS_REQUIRE_MYC

GO Biological Process (2): mismatch repair (GO:0006298), RNA catabolic process (GO:0006401)

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

GO Cellular Component (2): nucleus (GO:0005634), ribonuclease H2 complex (GO:0032299)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA repair	1
RNA metabolic process	1
nucleic acid catabolic process	1
binding	1
intracellular membrane-bounded organelle	1
intracellular protein-containing complex	1
catalytic complex	1

Protein interactions and networks

STRING

748 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNASEH2C	RNASEH2A	O75792	999
RNASEH2C	RNASEH2B	Q5TBB1	999
RNASEH2C	SAMHD1	Q9Y3Z3	965
RNASEH2C	TREX1	Q9NSU2	882
RNASEH2C	ADAR	P55265	720
RNASEH2C	IFNA13	P01562	623
RNASEH2C	IFIH1	Q9BYX4	623
RNASEH2C	DNASE2	O00115	568
RNASEH2C	IFNA8	P01565	545
RNASEH2C	IFNA10	P01566	538
RNASEH2C	IFNA14	P01570	538
RNASEH2C	IFNA5	P01569	537
RNASEH2C	IFNA7	P01567	536
RNASEH2C	IFNA21	P01568	536
RNASEH2C	IFNA16	P05015	536

IntAct

27 interactions, top by confidence:

A	B	Type	Score
PKMYT1	CCNB2	psi-mi:“MI:0914”(association)	0.730
RNASEH2B	RNASEH2A	psi-mi:“MI:0914”(association)	0.640
RNASEH2C	RNASEH2A	psi-mi:“MI:0914”(association)	0.640
VAC14	RNASEH2C	psi-mi:“MI:0915”(physical association)	0.560
RNASEH2C		psi-mi:“MI:0915”(physical association)	0.560
RNASEH2C	HSPB1	psi-mi:“MI:0915”(physical association)	0.560
RNASEH2C	KIF1B	psi-mi:“MI:0915”(physical association)	0.560
Gorasp1	GOLGA2	psi-mi:“MI:0914”(association)	0.350
RNASEH2B	SAP18	psi-mi:“MI:0914”(association)	0.350
RNASEH2A	PHF20L1	psi-mi:“MI:0914”(association)	0.350
PSMC3		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
DLX6	SCGB2A1	psi-mi:“MI:0914”(association)	0.350
HSPA8	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
INSR	BLTP3B	psi-mi:“MI:0914”(association)	0.350
RNASEH2C	VAC14	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (31): RNASEH2C (Affinity Capture-MS), RNASEH2C (Co-fractionation), RNASEH2C (Co-fractionation), RNASEH2C (Co-fractionation), RNASEH2C (Co-fractionation), RNASEH2C (Co-fractionation), RNASEH2C (Affinity Capture-MS), RNASEH2C (Affinity Capture-MS), RNASEH2C (Affinity Capture-MS), RNASEH2C (Affinity Capture-MS), RNASEH2C (Affinity Capture-MS), RNASEH2C (Two-hybrid), RNASEH2C (Affinity Capture-RNA), RNASEH2C (Affinity Capture-MS), RNASEH2B (Affinity Capture-MS)

ESM2 similar proteins: A5DBC9, A6X980, O13745, O14045, O14086, O14229, O43038, O74516, O74883, P25559, P33755, P38877, P41814, P53893, Q01080, Q0E7J8, Q10448, Q12824, Q1SGF1, Q22006, Q2M2U4, Q3ECP0, Q54FE8, Q54KT7, Q5A5N5, Q5A6Q4, Q5BIN2, Q65ZA6, Q6BKK7, Q6C710, Q6CF35, Q6CLF6, Q6CLY1, Q6DFM1, Q6FJI2, Q6FNP9, Q6GQ82, Q75AQ4, Q75B32, Q8LPU4

Diamond homologs: Q2M2U4, Q8TDP1, Q9CQ18

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RNASEH2C	“form complex”	“RNase H2 complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	4
Uncertain significance	125
Likely benign	136
Benign	6

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
4847627	NM_032193.4(RNASEH2C):c.215_218delinsTGGC (p.Glu72_Val73delinsValAla)	Pathogenic
1299509	NM_032193.4(RNASEH2C):c.412C>T (p.Pro138Ser)	Likely pathogenic
191022	NM_032193.4(RNASEH2C):c.478C>T (p.Gln160Ter)	Likely pathogenic
419542	NM_032193.4(RNASEH2C):c.450G>A (p.Trp150Ter)	Likely pathogenic
983437	NM_032193.4(RNASEH2C):c.450G>T (p.Trp150Cys)	Likely pathogenic

SpliceAI

1698 predictions. Top by Δscore:

Variant	Effect	Δscore
11:65714480:A:AG	acceptor_gain	1.0000
11:65714480:ACT:A	acceptor_gain	1.0000
11:65714480:ACTG:A	acceptor_gain	1.0000
11:65714482:T:TA	acceptor_gain	1.0000
11:65714483:G:A	acceptor_gain	1.0000
11:65714488:T:TA	acceptor_gain	1.0000
11:65714489:G:A	acceptor_gain	1.0000
11:65714490:GGCA:G	acceptor_loss	1.0000
11:65714492:CAGG:C	acceptor_loss	1.0000
11:65714493:A:G	acceptor_loss	1.0000
11:65714494:G:T	acceptor_loss	1.0000
11:65714660:G:GT	donor_gain	1.0000
11:65714707:G:GG	donor_gain	1.0000
11:65714719:TCTC:T	donor_gain	1.0000
11:65714819:A:AG	acceptor_gain	1.0000
11:65714820:G:GG	acceptor_gain	1.0000
11:65714897:G:GT	donor_gain	1.0000
11:65714908:AAG:A	donor_loss	1.0000
11:65714909:AGGTT:A	donor_loss	1.0000
11:65714910:GGT:G	donor_loss	1.0000
11:65714911:G:C	donor_loss	1.0000
11:65714912:T:A	donor_loss	1.0000
11:65716665:A:AG	acceptor_gain	1.0000
11:65716666:G:GG	acceptor_gain	1.0000
11:65716666:GA:G	acceptor_gain	1.0000
11:65716666:GAGT:G	acceptor_gain	1.0000
11:65716666:GAGTT:G	acceptor_gain	1.0000
11:65716804:CAAG:C	donor_loss	1.0000
11:65716806:AGGT:A	donor_loss	1.0000
11:65716807:GGTC:G	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000415536 (11:65718789 C>CT), RS1001530239 (11:65717790 A>G), RS1001622169 (11:65719267 A>C,G), RS1002184159 (11:65718371 C>A), RS1002252797 (11:65718130 C>G,T), RS1002855248 (11:65721277 C>T), RS1002907735 (11:65720840 C>A,T), RS1003237993 (11:65719579 C>A,T), RS1003645713 (11:65722005 T>A), RS1003697425 (11:65722432 C>T), RS1005273121 (11:65722722 G>C), RS1005697887 (11:65719979 C>A), RS1005711264 (11:65721015 T>A,C,G), RS1005975542 (11:65717876 A>G), RS1006028087 (11:65718100 C>A,G)

Disease associations

OMIM: gene MIM:610330 | disease phenotypes: MIM:610329, MIM:225750

GenCC curated gene-disease

Disease	Classification	Inheritance
Aicardi-Goutieres syndrome 3	Definitive	Autosomal recessive
Aicardi-Goutieres syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
RNASEH2C-related type 1 interferonopathy	Definitive	AR

Mondo (3): Aicardi-Goutieres syndrome 3 (MONDO:0012471), congenital nervous system disorder (MONDO:0002320), Aicardi-Goutieres syndrome (MONDO:0018866)

Orphanet (1): Aicardi-Goutières syndrome (Orphanet:51)

HPO phenotypes

85 total (30 of 85 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000054	Micropenis
HP:0000252	Microcephaly
HP:0000253	Progressive 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:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001357	Plagiocephaly

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST000649_13	Chronic kidney disease	1.000000e-07
GCST002481_8	Acne (severe)	3.000000e-11
GCST003622_1	Systemic lupus erythematosus	2.000000e-06
GCST003622_20	Systemic lupus erythematosus	6.000000e-09
GCST004292_2	Glomerular filtration rate (creatinine)	2.000000e-09
GCST005752_164	Systemic lupus erythematosus	7.000000e-06
GCST005985_53	Creatinine levels	2.000000e-09
GCST005987_47	Albumin-globulin ratio	1.000000e-08
GCST006190_11	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	6.000000e-09
GCST006190_80	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-11
GCST006192_55	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-08
GCST006192_82	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	9.000000e-06
GCST006193_44	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	6.000000e-08
GCST006193_82	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-10
GCST006195_74	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-07
GCST006291_81	Spherical equivalent or myopia (age of diagnosis)	1.000000e-09
GCST006697_6	Parental longevity (combined parental attained age, Martingale residuals)	4.000000e-06
GCST007344_110	Estimated glomerular filtration rate	6.000000e-13
GCST008916_61	Asthma	4.000000e-11
GCST008972_178	Urate levels	7.000000e-52
GCST010002_240	Refractive error	3.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0005128	albumin:globulin ratio measurement
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure
EFO:0004847	age at onset
EFO:0007796	parental longevity
EFO:0004531	urate measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C563683	Aicardi-Goutieres Syndrome 3 (supp.)
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

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
beta-lapachone	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Air Pollutants	increases expression, affects cotreatment, increases abundance	1
Atrazine	increases expression	1
Carbamazepine	affects expression	1
Ethyl Methanesulfonate	decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Ozone	affects cotreatment, increases expression, increases abundance	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Cyclosporine	decreases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	decreases expression	1
Volatile Organic Compounds	increases expression, affects cotreatment	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TJ15	HAP1 RNASEH2C (-) 1	Cancer cell line	Male
CVCL_TJ16	HAP1 RNASEH2C (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02363452	PHASE2	COMPLETED	Reverse Transcriptase Inhibitors in AGS
NCT03921554	PHASE2	COMPLETED	JAK Inhibitor Treatment in AGS
NCT04731103	PHASE2	COMPLETED	Inhibition of Reverse Transcription in Aicardi-Goutières Syndrome
NCT05613868	PHASE2	TERMINATED	TPN-101 in Aicardi-Goutières Syndrome (AGS)
NCT04517253	PHASE2/PHASE3	TERMINATED	A Study of Baricitinib (LY3009104) in Adult and Pediatric Japanese Participants With NNS/CANDLE, SAVI, and AGS
NCT03304717	PHASE1/PHASE2	WITHDRAWN	Reverse Transcriptase Inhibitors in Aicardi Goutières Syndrome
NCT01724580	Not specified	APPROVED_FOR_MARKETING	Compassionate Use Protocol for the Treatment of Autoinflammatory Syndromes
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT06898372	Not specified	COMPLETED	Evaluate the Efficacy of Anti-Jak1 Inhibitors as Treatment for Patients With Aicardi-Goutières Syndrome