Aicardi-Goutieres syndrome 6

Summary

Aicardi-Goutieres syndrome 6 (MONDO:0014007) is a disease caused by ADAR (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: ADAR (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 1,480

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Aicardi-Goutieres syndrome 6
Mondo ID	MONDO:0014007
OMIM	615010
UMLS	C3539013
MedGen	761287
GARD	0015894
Is cancer (heuristic)	no

Also known as: ADAR Aicardi-Goutieres syndrome · Adar Aicardi-Goutieres syndrome · AGS6 · Aicardi-Goutieres syndrome 6 · Aicardi-Goutieres syndrome caused by mutation in ADAR · Aicardi-Goutieres syndrome caused by mutation in Adar · Aicardi-Goutieres syndrome type 6

Data availability: 1,480 ClinVar variants · 5 GenCC gene-disease records · 3 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › Aicardi-Goutieres syndrome › Aicardi-Goutieres syndrome 6

Related subtypes (9): basal ganglia calcification, idiopathic, childhood-onset, Aicardi-Goutieres syndrome 1, Aicardi-Goutieres syndrome 2, Aicardi-Goutieres syndrome 3, Aicardi-Goutieres syndrome 4, Aicardi-Goutieres syndrome 5, Aicardi-Goutieres syndrome 7, Aicardi-Goutieres syndrome 8, Aicardi-Goutieres syndrome 9

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

301 uncertain significance, 258 likely benign, 19 pathogenic, 10 conflicting classifications of pathogenicity, 6 benign, 5 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1073320	NM_001111.5(ADAR):c.2344C>T (p.Gln782Ter)	ADAR	Pathogenic	criteria provided, single submitter
1073687	NM_001111.5(ADAR):c.2929_2939dup (p.Met981fs)	ADAR	Pathogenic	criteria provided, single submitter
1184494	NM_001111.5(ADAR):c.3202+1G>A	ADAR	Pathogenic	no assertion criteria provided
126560	NM_001111.5(ADAR):c.1630C>T (p.Arg544Ter)	ADAR	Pathogenic	no assertion criteria provided
1356340	NM_001111.5(ADAR):c.85C>T (p.Gln29Ter)	ADAR	Pathogenic	criteria provided, single submitter
1437688	NM_001111.5(ADAR):c.2309del (p.Pro770fs)	ADAR	Pathogenic	criteria provided, single submitter
1451454	NM_001111.5(ADAR):c.763C>T (p.Gln255Ter)	ADAR	Pathogenic	criteria provided, single submitter
1452076	NM_001111.5(ADAR):c.2128_2131dup (p.Asn711fs)	ADAR	Pathogenic	criteria provided, single submitter
1454211	NM_001111.5(ADAR):c.344del (p.Gly115fs)	ADAR	Pathogenic	criteria provided, single submitter
1456115	NM_001111.5(ADAR):c.982C>T (p.Arg328Ter)	ADAR	Pathogenic	criteria provided, multiple submitters, no conflicts
1458191	NM_001111.5(ADAR):c.929dup (p.Ser311fs)	ADAR	Pathogenic	criteria provided, single submitter
14817	NM_001111.5(ADAR):c.1420C>T (p.Arg474Ter)	ADAR	Pathogenic	criteria provided, single submitter
1973592	NM_001111.5(ADAR):c.520C>T (p.Arg174Ter)	ADAR	Pathogenic	criteria provided, single submitter
1993678	NM_001111.5(ADAR):c.649dup (p.Ser217fs)	ADAR	Pathogenic	criteria provided, single submitter
1993820	NM_001111.5(ADAR):c.1000del (p.Val333_Leu334insTer)	ADAR	Pathogenic	criteria provided, single submitter
2016140	NM_001111.5(ADAR):c.133G>T (p.Glu45Ter)	ADAR	Pathogenic	criteria provided, single submitter
2019241	NM_001111.5(ADAR):c.2583del (p.Ser862fs)	ADAR	Pathogenic	criteria provided, single submitter
2023208	NM_001111.5(ADAR):c.3402T>A (p.Tyr1134Ter)	ADAR	Pathogenic	criteria provided, single submitter
1459168	NC_000001.10:g.(?154422067)(154580482_?)del	UBE2Q1	Pathogenic	criteria provided, single submitter
1184493	NM_001111.5(ADAR):c.3254_3255del (p.Thr1085fs)	ADAR	Likely pathogenic	no assertion criteria provided
1184495	NM_001111.5(ADAR):c.2763-2A>G	ADAR	Likely pathogenic	no assertion criteria provided
1184496	NM_001111.5(ADAR):c.758G>A (p.Trp253Ter)	ADAR	Likely pathogenic	no assertion criteria provided
1993205	NM_001111.5(ADAR):c.1602-2A>G	ADAR	Likely pathogenic	criteria provided, single submitter
2006136	NM_001111.5(ADAR):c.1786-1G>C	ADAR	Likely pathogenic	criteria provided, single submitter
1011218	NM_001111.5(ADAR):c.3331A>G (p.Ile1111Val)	ADAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1018760	NM_001111.5(ADAR):c.625G>A (p.Gly209Arg)	ADAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1047342	NM_001111.5(ADAR):c.2762+6C>T	ADAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1135015	NM_001111.5(ADAR):c.1542C>T (p.Phe514=)	ADAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1207421	NM_001111.5(ADAR):c.3463C>T (p.Arg1155Trp)	ADAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
126395	NM_001111.5(ADAR):c.577C>G (p.Pro193Ala)	ADAR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ADAR	Definitive	Autosomal recessive	Aicardi-Goutieres syndrome 6	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ADAR	Orphanet:225154	Familial infantile bilateral striatal necrosis
ADAR	Orphanet:41	Dyschromatosis symmetrica hereditaria
ADAR	Orphanet:51	Aicardi-Goutières syndrome
ADAR	Orphanet:694356	ADAR-related hereditary spastic paraplegia

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ADAR	HGNC:225	ENSG00000160710	P55265	Double-stranded RNA-specific adenosine deaminase	gencc,clinvar
UBE2Q1	HGNC:15698	ENSG00000160714	Q7Z7E8	Ubiquitin-conjugating enzyme E2 Q1	clinvar
NUP210L	HGNC:29915	ENSG00000143552	Q5VU65	Nuclear pore membrane glycoprotein 210-like	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ADAR	Double-stranded RNA-specific adenosine deaminase	Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing.
UBE2Q1	Ubiquitin-conjugating enzyme E2 Q1	Catalyzes the covalent attachment of ubiquitin to other proteins.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	2	8.0×	0.039
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ADAR	Enzyme (other)	yes	3.5.4.37	A_deamin, dsRBD_dom, WH-like_DNA-bd_sf
UBE2Q1	Enzyme (other)	yes	2.3.2.23	UBC, UBQ-conjugating_enzyme/RWD
NUP210L	Other/Unknown	no		Big_2, Invasin/intimin_cell_adhesion, NUP210-like

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	2
right testis	2
endothelial cell	1
middle temporal gyrus	1
visceral pleura	1
granulocyte	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ADAR	295	ubiquitous	marker	endothelial cell, middle temporal gyrus, visceral pleura
UBE2Q1	293	ubiquitous	marker	left testis, right testis, granulocyte
NUP210L	120	tissue_specific	marker	sperm, left testis, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ADAR	3,166
UBE2Q1	905
NUP210L	702

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ADAR	P55265	24
UBE2Q1	Q7Z7E8	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NUP210L	Q5VU65	79.54

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 3 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
C6 deamination of adenosine	1	2855.0×	9e-04	ADAR
Formation of editosomes by ADAR proteins	1	2855.0×	9e-04	ADAR
Interferon alpha/beta signaling	1	76.1×	0.018	ADAR
PKR-mediated signaling	1	70.5×	0.018	ADAR
Antigen processing: Ubiquitination & Proteasome degradation	1	18.6×	0.053	UBE2Q1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
somatic diversification of immune receptors via somatic mutation	1	5617.3×	0.003	ADAR
negative regulation of post-transcriptional gene silencing by regulatory ncRNA	1	5617.3×	0.003	ADAR
prolactin secretion	1	1872.4×	0.005	UBE2Q1
base conversion or substitution editing	1	1404.3×	0.005	ADAR
adenosine to inosine editing	1	1123.5×	0.005	ADAR
negative regulation of protein kinase activity by regulation of protein phosphorylation	1	1123.5×	0.005	ADAR
mating behavior	1	936.2×	0.005	UBE2Q1
negative regulation of hepatocyte apoptotic process	1	936.2×	0.005	ADAR
reproductive system development	1	802.5×	0.005	UBE2Q1
suckling behavior	1	561.7×	0.006	UBE2Q1
response to interferon-alpha	1	561.7×	0.006	ADAR
RISC complex assembly	1	510.7×	0.006	ADAR
mRNA modification	1	432.1×	0.006	ADAR
pre-miRNA processing	1	374.5×	0.006	ADAR
Sertoli cell development	1	374.5×	0.006	NUP210L
hepatocyte apoptotic process	1	351.1×	0.006	ADAR
definitive hemopoiesis	1	312.1×	0.007	ADAR
negative regulation of type I interferon-mediated signaling pathway	1	255.3×	0.008	ADAR
positive regulation of viral genome replication	1	193.7×	0.009	ADAR
hematopoietic stem cell homeostasis	1	187.2×	0.009	ADAR
protein export from nucleus	1	170.2×	0.010	ADAR
embryo implantation	1	117.0×	0.014	UBE2Q1
fertilization	1	104.0×	0.015	UBE2Q1
erythrocyte differentiation	1	89.2×	0.016	ADAR
hematopoietic progenitor cell differentiation	1	79.1×	0.018	ADAR
RNA processing	1	73.0×	0.018	ADAR
cellular response to virus	1	66.9×	0.019	ADAR
spermatid development	1	48.4×	0.024	NUP210L
protein import into nucleus	1	48.0×	0.024	ADAR
response to virus	1	48.0×	0.024	ADAR

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ADAR	0	0
UBE2Q1	0	0
NUP210L	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ADAR	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ADAR	3.5.4.37	double-stranded RNA adenine deaminase
UBE2Q1	2.3.2.23	E2 ubiquitin-conjugating enzyme

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	ADAR, UBE2Q1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	NUP210L

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ADAR	2	—
UBE2Q1	0	—
NUP210L	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.