Blue cone monochromacy

Summary

Blue cone monochromacy (MONDO:0010563) is a disease caused by variants in OPN1LW and OPN1MW, with 2 cohort genes and 2 clinical trials.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Causal genes: OPN1LW (GenCC Definitive), OPN1MW (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 10
• Phenotypes (HPO): 12
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	1	Worldwide	Validated
Prevalence at birth	1-9 / 100 000	1	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

12 HPO clinical features (Orphanet curated; top 12 by frequency):

HPO ID	Term	Frequency
HP:0007939	Blue cone monochromacy	Very frequent (80-99%)
HP:0000545	Myopia	Frequent (30-79%)
HP:0000551	Color vision defect	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0025549	Eccentric visual fixation	Frequent (30-79%)
HP:0030619	Reduced OCT-measured foveal thickness	Frequent (30-79%)
HP:0000505	Visual impairment	Occasional (5-29%)
HP:0000512	Abnormal electroretinogram	Occasional (5-29%)
HP:0000540	Hypermetropia	Occasional (5-29%)
HP:0000613	Photophobia	Occasional (5-29%)
HP:0001131	Corneal dystrophy	Occasional (5-29%)
HP:0007703	Abnormality of retinal pigmentation	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	blue cone monochromacy
Mondo ID	MONDO:0010563
MeSH	C536238
OMIM	303700
Orphanet	16
DOID	DOID:0050679
SNOMED CT	24704003
UMLS	C0339537
MedGen	87386
GARD	0000917
Is cancer (heuristic)	no

Also known as: achromatopsia incomplete X-linked · atypical X-linked achromatopsia · BCM · blue cone monochromacy · blue cone monochromacy, X-linked recessive · blue cone monochromatism · CBBM · color blindness blue mono cone monochromatic type · color blindness, blue monocone monochromatic type · colour blindness blue mono cone monochromatic type · colour blindness, blue monocone monochromatic type · incomplete achromatopsia X-linked · S cone monochromacy · S cone monochromatism · X-chromosome-linked achromatopsia · X-linked achromatopsia incomplete · X-linked incomplete achromatopsia

Data availability: 10 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › perceptual disorders › vision disorder › color vision disorder › achromatopsia › blue cone monochromacy

Related subtypes (5): achromatopsia 2, achromatopsia 3, achromatopsia 6, achromatopsia 4, achromatopsia 7

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:

6 pathogenic, 2 benign, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
448956	Single allele	LOC125467793	Pathogenic	no assertion criteria provided
10503	NM_020061.6(OPN1LW):c.739C>T (p.Arg247Ter)	OPN1LW	Pathogenic	no assertion criteria provided
10505	NM_020061.6(OPN1LW):c.607T>C (p.Cys203Arg)	OPN1LW	Pathogenic	criteria provided, multiple submitters, no conflicts
10507	NC_000023.11:g.(154153459_154153462)_(154154925_154154928)del	OPN1LW	Pathogenic	no assertion criteria provided
1299568	NM_020061.6(OPN1LW):c.269G>A (p.Trp90Ter)	OPN1LW	Pathogenic	criteria provided, single submitter
10508	NM_000513.2(OPN1MW):c.607T>C (p.Cys203Arg)	OPN1MW	Pathogenic	no assertion criteria provided
1700833	NM_020061.6(OPN1LW):c.920C>T (p.Pro307Leu)	OPN1LW	Uncertain significance	criteria provided, multiple submitters, no conflicts
2584668	NM_020061.6(OPN1LW):c.843G>T (p.Trp281Cys)	OPN1LW	Uncertain significance	criteria provided, single submitter
1326975	NM_020061.6(OPN1LW):c.511G>A (p.Val171Met)	OPN1LW	Benign	criteria provided, multiple submitters, no conflicts
1326976	NM_020061.6(OPN1LW):c.513G>T (p.Val171=)	OPN1LW	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 6 · 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
OPN1LW	Definitive	X-linked	blue cone monochromacy	5
OPN1MW	Definitive	X-linked	blue cone monochromacy	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
OPN1MW	Orphanet:16	Blue cone monochromatism
OPN1MW	Orphanet:1872	Cone rod dystrophy
OPN1MW	Orphanet:90001	X-linked cone dysfunction syndrome with myopia
OPN1LW	Orphanet:16	Blue cone monochromatism
OPN1LW	Orphanet:1872	Cone rod dystrophy
OPN1LW	Orphanet:90001	X-linked cone dysfunction syndrome with myopia

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
OPN1MW	HGNC:4206	ENSG00000268221	P04001	Medium-wave-sensitive opsin 1	gencc,clinvar
OPN1LW	HGNC:9936	ENSG00000102076	P04000	Long-wave-sensitive opsin 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
OPN1MW	Medium-wave-sensitive opsin 1	Visual pigments are the light-absorbing molecules that mediate vision.
OPN1LW	Long-wave-sensitive opsin 1	Visual pigments are the light-absorbing molecules that mediate vision.

Protein-family classification

Druggable: 2 · 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
GPCR	2	23.9×	0.002

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
OPN1MW	GPCR	yes		GPCR_Rhodpsn, Opsin_red/grn, Opsin
OPN1LW	GPCR	yes		GPCR_Rhodpsn, Opsin_red/grn, Opsin

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)	2
broad (>20)	0
unknown	0

Top tissues across cohort

Tissue	Cohort genes
colonic epithelium	2
sural nerve	2
male germ line stem cell (sensu Vertebrata) in testis	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
OPN1MW	16		yes	male germ line stem cell (sensu Vertebrata) in testis, colonic epithelium, sural nerve
OPN1LW	16	tissue_specific	marker	ganglionic eminence, sural nerve, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
OPN1LW	612
OPN1MW	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
OPN1MW	P04001	3
OPN1LW	P04000	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 2 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
The retinoid cycle in cones (daylight vision)	2	1631.4×	1e-06	OPN1MW, OPN1LW
Opsins	2	1268.9×	1e-06	OPN1MW, OPN1LW
Defective visual phototransduction due to OPN1MW loss of function	1	5710.0×	2e-04	OPN1MW
Defective visual phototransduction due to OPN1LW loss of function	1	5710.0×	2e-04	OPN1LW
G alpha (i) signalling events	2	39.0×	7e-04	OPN1MW, OPN1LW

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
absorption of visible light	2	2808.7×	7e-07	OPN1MW, OPN1LW
cellular response to light stimulus	2	1053.2×	3e-06	OPN1MW, OPN1LW
phototransduction	2	495.6×	9e-06	OPN1MW, OPN1LW
positive regulation of cytokinesis	2	401.2×	1e-05	OPN1MW, OPN1LW
visual perception	2	79.5×	2e-04	OPN1MW, OPN1LW
G protein-coupled receptor signaling pathway	2	36.2×	9e-04	OPN1MW, OPN1LW
signal transduction	1	8.0×	0.121	OPN1LW

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
OPN1MW	0	0
OPN1LW	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
OPN1LW	4	Binding:4

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	2	OPN1MW, OPN1LW
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
OPN1MW	0	—
OPN1LW	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06491615	Not specified	RECRUITING	National Ophthalmic Genotyping and Phenotyping Network (eyeGENE (Registered Trademark)), Stage 3 - Expansion of DNA and Data Repositories for Rare Inherited Ophthalmic Diseases
NCT04034940	Not specified	UNKNOWN	Correlations Between Oxidative Stress Biomarkers, h-FABP and Left Ventricular Dysfunction in Patients With Acute Myocardial Infarction Undergoing Primary PCI