Cone-rod dystrophy 9

Summary

Cone-rod dystrophy 9 (MONDO:0013002) is a disease caused by ADAM9 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: ADAM9 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 80

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cone-rod dystrophy 9
Mondo ID	MONDO:0013002
OMIM	612775
DOID	DOID:0111020
UMLS	C1423873
MedGen	244692
GARD	0015582
Is cancer (heuristic)	no

Also known as: ADAM9 cone-rod dystrophy · cone-rod dystrophy 9 · cone-rod dystrophy caused by mutation in ADAM9 · cone-rod dystrophy type 9 · CORD9

Data availability: 80 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › cone-rod dystrophy › cone-rod dystrophy 9

Related subtypes (27): cone-rod dystrophy 2, macular degeneration, X-linked atrophic, cone-rod dystrophy 1, cone-rod dystrophy 5, cone-rod dystrophy 6, cone dystrophy 3, cone-rod dystrophy 7, cone-rod dystrophy 3, Leber congenital amaurosis 4, cone-rod dystrophy 8, Newfoundland cone-rod dystrophy, cone-rod dystrophy 13, cone-rod dystrophy 10, cone-rod dystrophy 11, retinal cone dystrophy 4, cone-rod dystrophy 12, cone-rod dystrophy 15, cone-rod dystrophy 16, cone-rod dystrophy 17, cone-rod dystrophy 18, cone-rod dystrophy 19, cone-rod dystrophy 20, cone-rod dystrophy 21, X-linked cone-rod dystrophy, cone-rod dystrophy 22, cone-rod dystrophy 14, cone-rod dystrophy 24

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

80 retrieved; paginated sample, class counts are floors:

34 uncertain significance, 18 conflicting classifications of pathogenicity, 9 pathogenic, 6 benign, 6 benign/likely benign, 4 likely pathogenic, 2 likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1184447	NM_003816.3(ADAM9):c.1588_1591+10del	ADAM9	Pathogenic	no assertion criteria provided
1708172	NM_003816.3(ADAM9):c.1616del (p.Cys539fs)	ADAM9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
189795	NM_003816.3(ADAM9):c.1396-2A>G	ADAM9	Pathogenic	no assertion criteria provided
3068523	NM_003816.3(ADAM9):c.702del (p.Ala234_Val235insTer)	ADAM9	Pathogenic	criteria provided, single submitter
3069202	NM_003816.3(ADAM9):c.1189A>T (p.Lys397Ter)	ADAM9	Pathogenic	criteria provided, single submitter
6876	NM_003816.3(ADAM9):c.1130+1G>A	ADAM9	Pathogenic	no assertion criteria provided
6877	NM_003816.3(ADAM9):c.766C>T (p.Arg256Ter)	ADAM9	Pathogenic	no assertion criteria provided
6878	NM_003816.3(ADAM9):c.490C>T (p.Arg164Ter)	ADAM9	Pathogenic	criteria provided, single submitter
6879	NM_003816.3(ADAM9):c.411-8A>G	ADAM9	Pathogenic	no assertion criteria provided
915360	NM_003816.3(ADAM9):c.639T>G (p.Tyr213Ter)	ADAM9	Pathogenic	criteria provided, single submitter
1065690	NM_003816.3(ADAM9):c.576del (p.Glu193fs)	ADAM9	Likely pathogenic	criteria provided, single submitter
3341288	NM_003816.3(ADAM9):c.1698-1715_1881+156del	ADAM9	Likely pathogenic	criteria provided, single submitter
3382263	NM_003816.3(ADAM9):c.103C>T (p.Gln35Ter)	ADAM9	Likely pathogenic	criteria provided, single submitter
3779322	NM_003816.3(ADAM9):c.539del (p.Lys180fs)	ADAM9	Likely pathogenic	criteria provided, single submitter
362923	NM_003816.3(ADAM9):c.315T>G (p.Thr105=)	ADAM9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
362924	NM_003816.3(ADAM9):c.504C>T (p.Val168=)	ADAM9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
362930	NM_003816.3(ADAM9):c.1130+8C>G	ADAM9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
362935	NM_003816.3(ADAM9):c.1530C>G (p.Ala510=)	ADAM9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
362937	NM_003816.3(ADAM9):c.2069-4C>A	ADAM9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
362939	NM_003816.3(ADAM9):c.2210+14T>C	ADAM9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
388305	NM_003816.3(ADAM9):c.280G>A (p.Val94Ile)	ADAM9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
729582	NM_003816.3(ADAM9):c.2091C>T (p.Asp697=)	ADAM9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
908570	NM_003816.3(ADAM9):c.1269C>T (p.Asp423=)	ADAM9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
908571	NM_003816.3(ADAM9):c.1362G>A (p.Glu454=)	ADAM9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
908572	NM_003816.3(ADAM9):c.1419C>T (p.Cys473=)	ADAM9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
908573	NM_003816.3(ADAM9):c.1449A>G (p.Pro483=)	ADAM9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
909427	NM_003816.3(ADAM9):c.1560T>C (p.Tyr520=)	ADAM9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
909428	NM_003816.3(ADAM9):c.1697+15G>A	ADAM9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
909429	NM_003816.3(ADAM9):c.1698-10C>G	ADAM9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
909430	NM_003816.3(ADAM9):c.1698-10C>T	ADAM9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
ADAM9	Definitive	Autosomal recessive	cone-rod dystrophy 9	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ADAM9	Orphanet:1872	Cone rod dystrophy

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
ADAM9	HGNC:216	ENSG00000168615	Q13443	Disintegrin and metalloproteinase domain-containing protein 9	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ADAM9	Disintegrin and metalloproteinase domain-containing protein 9	Metalloprotease that cleaves and releases a number of molecules with important roles in tumorigenesis and angiogenesis, such as TEK, KDR, EPHB4, CD40, VCAM1 and CDH5.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ADAM9	Protease	yes	3.4.24.B9	EGF, Peptidase_M12B, Disintegrin_dom

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
gall bladder	1
islet of Langerhans	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ADAM9	215	ubiquitous	marker	stromal cell of endometrium, islet of Langerhans, gall bladder

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ADAM9	1,555

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ADAM9	Q13443	76.14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Collagen degradation	1	175.7×	0.013	ADAM9
Degradation of the extracellular matrix	1	117.7×	0.013	ADAM9
Extracellular matrix organization	1	63.1×	0.016	ADAM9

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 macrophage fusion	1	3370.4×	0.003	ADAM9
response to manganese ion	1	2808.7×	0.003	ADAM9
monocyte activation	1	1872.4×	0.003	ADAM9
cell-cell adhesion mediated by integrin	1	1532.0×	0.003	ADAM9
positive regulation of keratinocyte migration	1	1296.3×	0.003	ADAM9
membrane protein intracellular domain proteolysis	1	1203.7×	0.003	ADAM9
amyloid precursor protein catabolic process	1	1203.7×	0.003	ADAM9
positive regulation of cell adhesion mediated by integrin	1	1053.2×	0.003	ADAM9
positive regulation of membrane protein ectodomain proteolysis	1	936.2×	0.003	ADAM9
cell adhesion mediated by integrin	1	674.1×	0.003	ADAM9
membrane protein ectodomain proteolysis	1	648.1×	0.003	ADAM9
response to tumor necrosis factor	1	624.1×	0.003	ADAM9
response to hydrogen peroxide	1	468.1×	0.004	ADAM9
positive regulation of protein secretion	1	343.9×	0.005	ADAM9
response to glucocorticoid	1	324.1×	0.005	ADAM9
response to calcium ion	1	318.0×	0.005	ADAM9
keratinocyte differentiation	1	247.8×	0.006	ADAM9
protein processing	1	170.2×	0.008	ADAM9
cell-matrix adhesion	1	163.6×	0.008	ADAM9
integrin-mediated signaling pathway	1	160.5×	0.008	ADAM9
transforming growth factor beta receptor signaling pathway	1	159.0×	0.008	ADAM9
cellular response to lipopolysaccharide	1	98.0×	0.012	ADAM9
positive regulation of MAPK cascade	1	80.6×	0.014	ADAM9
positive regulation of cell migration	1	61.7×	0.017	ADAM9
cell migration	1	61.5×	0.017	ADAM9
cell adhesion	1	37.5×	0.027	ADAM9

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ADAM9	3	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ILOMASTAT	2	ADAM9
APRATASTAT	2	ADAM9
PEPSTATIN	2	ADAM9

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ADAM9	19	Binding:18, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ADAM9	3.4.24.B9

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

3 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.

Compound	Max phase	Cohort target (bioactivity)
ILOMASTAT	2	ADAM9
APRATASTAT	2	ADAM9
PEPSTATIN	2	ADAM9

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	1	ADAM9
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.