Aicardi-Goutieres syndrome 9

Summary

Aicardi-Goutieres syndrome 9 (MONDO:0030362) is a disease caused by RNU7-1 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: RNU7-1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Aicardi-Goutieres syndrome 9
Mondo ID	MONDO:0030362
OMIM	619487
UMLS	C5561966
MedGen	1794176
GARD	0025553
Is cancer (heuristic)	no

Also known as: AGS9 · Aicardi-Goutieres syndrome 9

Data availability: 10 ClinVar variants · 3 GenCC gene-disease records.

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 9

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 6, Aicardi-Goutieres syndrome 7, Aicardi-Goutieres syndrome 8

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

10 retrieved; paginated sample, class counts are floors:

4 likely pathogenic, 3 uncertain significance, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1202611	NR_023317.1(RNU7-1):n.28C>T	C12orf57	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1202616	NR_023317.1:n.34_50delins25	RNU7-1	Pathogenic	no assertion criteria provided
1202612	NR_023317.1(RNU7-1):n.40_47del	C12orf57	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1202615	NR_023317.1(RNU7-1):n.35G>A	C12orf57	Likely pathogenic	criteria provided, single submitter
1328141	NR_023317.1(RNU7-1):n.28C>G	C12orf57	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1328524	NR_023317.1(RNU7-1):n.30A>G	C12orf57	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1202613	NR_023317.1(RNU7-1):n.51C>T	C12orf57	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1202614	NR_023317.1(RNU7-1):n.41T>G	C12orf57	Uncertain significance	criteria provided, single submitter
1810412	NR_023317.1(RNU7-1):n.23T>G	C12orf57	Uncertain significance	criteria provided, single submitter
4293682	NR_023317.1(RNU7-1):n.58G>C	C12orf57	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 2 · 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
RNU7-1	Strong	Autosomal recessive	Aicardi-Goutieres syndrome 9	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RNU7-1	Orphanet:51	Aicardi-Goutières syndrome
C12orf57	Orphanet:1777	Temtamy syndrome

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RNU7-1	HGNC:34033	ENSG00000238923		RNA, U7 small nuclear 1	gencc,clinvar
C12orf57	HGNC:29521	ENSG00000111678	Q99622	Protein C10	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
C12orf57	Protein C10	In brain, may be required for corpus callosum development.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RNU7-1	Other/Unknown	no
C12orf57	Other/Unknown	no		Grcc10

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
liver	1
skeletal muscle tissue	1
sural nerve	1
endocervix	1
left ovary	1
thymus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNU7-1	23	broad	yes	sural nerve, liver, skeletal muscle tissue
C12orf57	145	ubiquitous	marker	thymus, left ovary, endocervix

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
C12orf57	843
RNU7-1	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
C12orf57	Q99622	81.41

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
third ventricle development	1	3370.4×	7e-04	C12orf57
psychomotor behavior	1	3370.4×	7e-04	C12orf57
regulation of skeletal muscle contraction	1	2808.7×	7e-04	C12orf57
corpus callosum morphogenesis	1	2407.4×	7e-04	C12orf57
camera-type eye morphogenesis	1	766.0×	0.002	C12orf57
cognition	1	285.6×	0.004	C12orf57
post-embryonic development	1	205.5×	0.005	C12orf57

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RNU7-1	0	0
C12orf57	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	RNU7-1, C12orf57

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RNU7-1	0	—
C12orf57	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.