Cone-rod dystrophy 15

Summary

Cone-rod dystrophy 15 (MONDO:0013348) is a disease caused by CDHR1 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: CDHR1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 181

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cone-rod dystrophy 15
Mondo ID	MONDO:0013348
OMIM	613660
DOID	DOID:0111021
UMLS	C3150912
MedGen	462262
GARD	0015686
Is cancer (heuristic)	no

Also known as: CDHR1 cone-rod dystrophy · cone-rod dystrophy 15 · cone-rod dystrophy caused by mutation in CDHR1 · cone-rod dystrophy type 15 · CORD15

Data availability: 181 ClinVar variants · 3 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 15

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 9, 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

181 retrieved; paginated sample, class counts are floors:

100 uncertain significance, 43 conflicting classifications of pathogenicity, 11 benign, 10 pathogenic, 6 likely benign, 4 likely pathogenic, 4 pathogenic/likely pathogenic, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1213966	NM_033100.4(CDHR1):c.1219C>T (p.Arg407Ter)	CDHR1	Pathogenic	criteria provided, multiple submitters, no conflicts
1361262	NM_033100.4(CDHR1):c.1503_1507del (p.Gly502fs)	CDHR1	Pathogenic	criteria provided, multiple submitters, no conflicts
1481629	NM_033100.4(CDHR1):c.56-1G>A	CDHR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
18416	NM_033100.4(CDHR1):c.524dup (p.Asn176fs)	CDHR1	Pathogenic	criteria provided, multiple submitters, no conflicts
194793	NM_033100.4(CDHR1):c.2522_2528del (p.Ile841fs)	CDHR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2136903	NM_033100.4(CDHR1):c.2087_2090del (p.Asp696fs)	CDHR1	Pathogenic	criteria provided, multiple submitters, no conflicts
2699135	NM_033100.4(CDHR1):c.713del (p.Asp238fs)	CDHR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280752	NM_033100.4(CDHR1):c.863-1G>A	CDHR1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
37292	NM_033100.4(CDHR1):c.338del (p.Gly113fs)	CDHR1	Pathogenic	criteria provided, multiple submitters, no conflicts
438116	NM_033100.4(CDHR1):c.1463del (p.Gly488fs)	CDHR1	Pathogenic	criteria provided, multiple submitters, no conflicts
802596	NM_033100.4(CDHR1):c.1782+1del	CDHR1	Pathogenic	criteria provided, single submitter
812262	NM_033100.4(CDHR1):c.1485+2T>G	CDHR1	Pathogenic	criteria provided, single submitter
838681	NM_033100.4(CDHR1):c.525+1G>A	CDHR1	Pathogenic	criteria provided, multiple submitters, no conflicts
931851	NM_033100.4(CDHR1):c.616del (p.His206fs)	CDHR1	Pathogenic	criteria provided, multiple submitters, no conflicts
1213967	NM_033100.4(CDHR1):c.10del (p.Cys4fs)	CDHR1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1297147	NM_033100.4(CDHR1):c.928C>T (p.Gln310Ter)	CDHR1	Likely pathogenic	criteria provided, single submitter
2920613	NM_033100.4(CDHR1):c.1729G>T (p.Gly577Ter)	CDHR1	Likely pathogenic	no assertion criteria provided
3600268	NM_033100.4(CDHR1):c.152-2A>G	CDHR1	Likely pathogenic	criteria provided, single submitter
1456736	NM_033100.4(CDHR1):c.1720C>G (p.Pro574Ala)	CDHR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
193474	NM_033100.4(CDHR1):c.1A>G (p.Met1Val)	CDHR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
198604	NM_033100.4(CDHR1):c.526-7C>G	CDHR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
252762	NM_033100.4(CDHR1):c.1868A>G (p.Asn623Ser)	CDHR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
285030	NM_033100.4(CDHR1):c.2176C>T (p.Arg726Cys)	CDHR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
286108	NM_033100.4(CDHR1):c.2229G>A (p.Arg743=)	CDHR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
301208	NM_033100.4(CDHR1):c.118G>A (p.Ala40Thr)	CDHR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
301211	NM_033100.4(CDHR1):c.152-9T>C	CDHR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
301217	NM_033100.4(CDHR1):c.526-14C>A	CDHR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
301219	NM_033100.4(CDHR1):c.547G>A (p.Val183Met)	CDHR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
301221	NM_033100.4(CDHR1):c.640-14C>T	CDHR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
301222	NM_033100.4(CDHR1):c.700G>A (p.Val234Ile)	CDHR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 5 · 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
CDHR1	Definitive	Autosomal recessive	cone-rod dystrophy 15	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDHR1	Orphanet:1872	Cone rod dystrophy
CDHR1	Orphanet:791	Retinitis pigmentosa
RPE65	Orphanet:364055	Severe early-childhood-onset retinal dystrophy
RPE65	Orphanet:65	Leber congenital amaurosis
RPE65	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CDHR1	HGNC:14550	ENSG00000148600	Q96JP9	Cadherin-related family member 1	gencc,clinvar
RPE65	HGNC:10294	ENSG00000116745	Q16518	Retinoid isomerohydrolase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDHR1	Cadherin-related family member 1	Potential calcium-dependent cell-adhesion protein.
RPE65	Retinoid isomerohydrolase	Critical isomerohydrolase in the retinoid cycle involved in regeneration of 11-cis-retinal, the chromophore of rod and cone opsins.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CDHR1	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS
RPE65	Enzyme (other)	yes	3.1.1.64	Carotenoid_Oase

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
skin of abdomen	1
skin of leg	1
upper arm skin	1
male germ line stem cell (sensu Vertebrata) in testis	1
pigmented layer of retina	1
retina	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDHR1	186	broad	marker	upper arm skin, skin of leg, skin of abdomen
RPE65	92	tissue_specific	marker	pigmented layer of retina, retina, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPE65	1,414
CDHR1	1,020

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RPE65	Q16518	95.34
CDHR1	Q96JP9	78.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 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
The canonical retinoid cycle in rods (twilight vision)	1	519.1×	0.006	RPE65
Visual phototransduction	1	259.6×	0.006	RPE65
Sensory Perception	1	95.2×	0.011	RPE65

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
zeaxanthin biosynthetic process	1	8426.0×	0.002	RPE65
photoreceptor cell morphogenesis	1	1404.3×	0.004	CDHR1
vitamin A metabolic process	1	1203.7×	0.004	RPE65
retina homeostasis	1	561.7×	0.004	RPE65
photoreceptor cell outer segment organization	1	526.6×	0.004	CDHR1
neural retina development	1	468.1×	0.004	RPE65
retinal metabolic process	1	468.1×	0.004	RPE65
detection of light stimulus involved in visual perception	1	324.1×	0.005	RPE65
retinoid metabolic process	1	247.8×	0.006	RPE65
photoreceptor cell maintenance	1	179.3×	0.008	CDHR1
circadian rhythm	1	122.1×	0.010	RPE65
homophilic cell-cell adhesion	1	70.2×	0.017	CDHR1
visual perception	1	39.8×	0.027	RPE65
cell adhesion	1	18.7×	0.053	CDHR1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CDHR1	0	0
RPE65	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RPE65	3.1.1.64, 5.3.3.22	retinoid isomerohydrolase, lutein isomerase

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	1	RPE65
E	Difficult family or no structure, no drug	1	CDHR1

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)
CDHR1	0	—
RPE65	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.