Joubert syndrome 30

Summary

Joubert syndrome 30 (MONDO:0033308) is a disease caused by ARMC9 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: ARMC9 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 34

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Joubert syndrome 30
Mondo ID	MONDO:0033308
OMIM	617622
DOID	DOID:0080275
UMLS	C4539937
MedGen	1613861
GARD	0016243
Is cancer (heuristic)	no

Also known as: JBTS30 · Joubert syndrome 30

Data availability: 34 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Joubert syndrome › Joubert syndrome 30

Related subtypes (38): Joubert syndrome 1, Joubert syndrome 10, Joubert syndrome 2, Joubert syndrome 3, Joubert syndrome with renal defect, Joubert syndrome 5, Joubert syndrome 6, Joubert syndrome 7, Joubert syndrome 9, Joubert syndrome 8, Joubert syndrome 13, Joubert syndrome 14, Joubert syndrome 15, Joubert syndrome 16, Joubert syndrome 17, Joubert syndrome 18, Joubert syndrome 20, Joubert syndrome 21, Joubert syndrome 22, Joubert syndrome 23, Joubert syndrome 24, Joubert syndrome 25, Joubert syndrome 26, Joubert syndrome 27, Joubert syndrome 28, Joubert syndrome 38, Joubert syndrome 39, Joubert syndrome 40, Joubert syndrome 37, Joubert syndrome 35, Joubert syndrome 36, Joubert syndrome 32, Joubert syndrome 31, Joubert syndrome 33, Joubert syndrome 19, Joubert syndrome 29, Joubert syndrome 11, Joubert syndrome 34

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

34 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 6 pathogenic, 6 pathogenic/likely pathogenic, 5 likely pathogenic, 4 conflicting classifications of pathogenicity, 3 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1034090	NM_001352754.2(ARMC9):c.100G>T (p.Glu34Ter)	ARMC9	Pathogenic	criteria provided, single submitter
1453533	NM_001352754.2(ARMC9):c.895C>T (p.Arg299Ter)	ARMC9	Pathogenic	criteria provided, multiple submitters, no conflicts
1909040	NM_001352754.2(ARMC9):c.1423dup (p.Thr475fs)	ARMC9	Pathogenic	criteria provided, multiple submitters, no conflicts
3699584	NM_001352754.2(ARMC9):c.788_789del (p.Pro263fs)	ARMC9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
427932	NM_001352754.2(ARMC9):c.1027C>T (p.Arg343Cys)	ARMC9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
427933	NM_001352754.2(ARMC9):c.259C>T (p.Arg87Ter)	ARMC9	Pathogenic	criteria provided, single submitter
427934	NM_001352754.2(ARMC9):c.1474+1G>C	ARMC9	Pathogenic/Likely pathogenic	no assertion criteria provided
427936	NM_001352754.2(ARMC9):c.1559C>T (p.Pro520Leu)	ARMC9	Pathogenic/Likely pathogenic	no assertion criteria provided
427938	NM_001352754.2(ARMC9):c.1211-434_1335-1595delinsGTTTGTTTGTTTGTTTGCATTA	ARMC9	Pathogenic	no assertion criteria provided
427939	NM_001352754.2(ARMC9):c.1336C>T (p.Arg446Cys)	ARMC9	Pathogenic/Likely pathogenic	no assertion criteria provided
4292717	NM_001352754.2(ARMC9):c.1878+1G>A	ARMC9	Pathogenic	criteria provided, single submitter
522606	NM_001352754.2(ARMC9):c.879G>A (p.Thr293=)	ARMC9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1323929	NM_001352754.2(ARMC9):c.178-2A>C	ARMC9	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3381962	NM_001352754.2(ARMC9):c.780+1G>A	ARMC9	Likely pathogenic	criteria provided, single submitter
427935	NM_001352754.2(ARMC9):c.1474G>A (p.Gly492Arg)	ARMC9	Likely pathogenic	criteria provided, single submitter
4845592	NM_001352754.2(ARMC9):c.1194del (p.Phe398fs)	ARMC9	Likely pathogenic	criteria provided, single submitter
4849440	NM_001352754.2(ARMC9):c.2201dup (p.Thr736fs)	ARMC9	Likely pathogenic	criteria provided, single submitter
1497937	NM_001352754.2(ARMC9):c.2160G>A (p.Trp720Ter)	ARMC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1727003	NM_001352754.2(ARMC9):c.2261+1G>A	ARMC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
427930	NM_001352754.2(ARMC9):c.205G>A (p.Gly69Arg)	ARMC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
427931	NM_001352754.2(ARMC9):c.51+5G>T	ARMC9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1021466	NM_001352754.2(ARMC9):c.2411C>T (p.Ala804Val)	ARMC9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1030903	NM_001352754.2(ARMC9):c.1213C>T (p.Arg405Cys)	ARMC9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1061811	NM_001352754.2(ARMC9):c.1907G>A (p.Arg636Gln)	ARMC9	Uncertain significance	criteria provided, multiple submitters, no conflicts
1679837	NM_001352754.2(ARMC9):c.1307T>C (p.Leu436Pro)	ARMC9	Uncertain significance	criteria provided, single submitter
427937	NM_001352754.2(ARMC9):c.1027C>A (p.Arg343Ser)	ARMC9	Uncertain significance	criteria provided, single submitter
636241	NM_001352754.2(ARMC9):c.725T>A (p.Ile242Asn)	ARMC9	Uncertain significance	criteria provided, multiple submitters, no conflicts
636278	NM_001352754.2(ARMC9):c.-41-2521_177+2986del	ARMC9	Uncertain significance	criteria provided, single submitter
955956	NM_001352754.2(ARMC9):c.1028G>A (p.Arg343His)	ARMC9	Uncertain significance	criteria provided, multiple submitters, no conflicts
963914	NM_001352754.2(ARMC9):c.1196C>T (p.Ala399Val)	ARMC9	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
ARMC9	Definitive	Autosomal recessive	Joubert syndrome 30	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ARMC9	Orphanet:475	Isolated Joubert syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ARMC9	HGNC:20730	ENSG00000135931	Q7Z3E5	LisH domain-containing protein ARMC9	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ARMC9	LisH domain-containing protein ARMC9	Involved in ciliogenesis.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ARMC9	Other/Unknown	no		LisH, ARM-like, ARM-type_fold

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	1
secondary oocyte	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ARMC9	244	ubiquitous	marker	stromal cell of endometrium, secondary oocyte, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ARMC9	850

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ARMC9	Q7Z3E5	71.71

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 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
positive regulation of smoothened signaling pathway	1	421.3×	0.005	ARMC9
cilium assembly	1	73.6×	0.014	ARMC9

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
ARMC9	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	ARMC9

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ARMC9	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.