Blindness (disorder)

Summary

Blindness (disorder) (MONDO:0001941) is a disease with 8 cohort genes.

At a glance

• Cohort genes: 8
• ClinVar variants: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	blindness (disorder)
Mondo ID	MONDO:0001941
MeSH	D001766
DOID	DOID:1432
ICD-10-CM	H54
NCIT	C97109
SNOMED CT	105597003
UMLS	C0456909
MedGen	99138
Is cancer (heuristic)	no

Data availability: 13 ClinVar variants.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › perceptual disorders › vision disorder › blindness (disorder)

Related subtypes (6): visual agnosia, amblyopia, binocular vision disease, color vision disorder, visual pathway disorder, Alice in Wonderland syndrome

Subtypes (4): cortical blindness, night blindness, microcephaly microphthalmos blindness, amaurosis fugax

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

13 retrieved; paginated sample, class counts are floors:

7 pathogenic, 3 likely pathogenic, 2 pathogenic/likely pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
99460	NM_000350.3(ABCA4):c.6445C>T (p.Arg2149Ter)	ABCA4	Pathogenic	reviewed by expert panel
1339	NM_025114.4(CEP290):c.4723A>T (p.Lys1575Ter)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
217635	NM_025114.4(CEP290):c.4882C>T (p.Gln1628Ter)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
286074	NM_025114.4(CEP290):c.1512_1515del (p.Arg504fs)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
373994	NM_025114.4(CEP290):c.2941C>T (p.Gln981Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
221552	NM_015160.3(PMPCA):c.1129G>A (p.Ala377Thr)	PMPCA	Pathogenic	no assertion criteria provided
221553	NM_015160.3(PMPCA):c.1066G>A (p.Gly356Ser)	PMPCA	Pathogenic	no assertion criteria provided
523376	NM_000539.3(RHO):c.891C>G (p.Ser297Arg)	RHO	Pathogenic	criteria provided, multiple submitters, no conflicts
2358	NM_206933.4(USH2A):c.949C>A (p.Arg317=)	USH2A	Pathogenic	criteria provided, multiple submitters, no conflicts
267933	46;XY;t(1;14)(p21.2;q11.2)dn;t(4;10)(p13;q11.2)dn		Likely pathogenic	criteria provided, single submitter
183341	NM_022786.3(ARV1):c.565G>A (p.Gly189Arg)	ARV1	Likely pathogenic	criteria provided, single submitter
523395	NM_001039348.3(EFEMP1):c.1189T>C (p.Tyr397His)	EFEMP1	Likely pathogenic	criteria provided, single submitter
374080	NC_012920.1(MT-ND6):m.14598T>C	MT-ND6	Uncertain significance	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 20 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RHO	Orphanet:215	Congenital stationary night blindness
RHO	Orphanet:52427	Retinitis punctata albescens
RHO	Orphanet:791	Retinitis pigmentosa
USH2A	Orphanet:231178	Usher syndrome type 2
USH2A	Orphanet:791	Retinitis pigmentosa
PMPCA	Orphanet:1170	Autosomal recessive cerebelloparenchymal disorder type 3
CEP290	Orphanet:110	Bardet-Biedl syndrome
CEP290	Orphanet:2318	Joubert syndrome with oculorenal defect
CEP290	Orphanet:3156	Senior-Loken syndrome
CEP290	Orphanet:564	Meckel syndrome
CEP290	Orphanet:65	Leber congenital amaurosis
EFEMP1	Orphanet:75376	Familial drusen
EFEMP1	Orphanet:98977	Juvenile glaucoma
ABCA4	Orphanet:1872	Cone rod dystrophy
ABCA4	Orphanet:791	Retinitis pigmentosa
ABCA4	Orphanet:827	Stargardt disease
MT-ND6	Orphanet:104	Leber hereditary optic neuropathy
MT-ND6	Orphanet:255210	Mitochondrial DNA-associated Leigh syndrome
MT-ND6	Orphanet:550	MELAS
MT-ND6	Orphanet:99718	Leber plus disease

Cohort genes → proteins

8 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RHO	HGNC:10012	ENSG00000163914	P08100	Rhodopsin	clinvar
USH2A	HGNC:12601	ENSG00000042781	O75445	Usherin	clinvar
PMPCA	HGNC:18667	ENSG00000165688	Q10713	Mitochondrial-processing peptidase subunit alpha	clinvar
CEP290	HGNC:29021	ENSG00000198707	O15078	Centrosomal protein of 290 kDa	clinvar
ARV1	HGNC:29561	ENSG00000173409	Q9H2C2	Protein ARV1	clinvar
EFEMP1	HGNC:3218	ENSG00000115380	Q12805	EGF-containing fibulin-like extracellular matrix protein 1	clinvar
ABCA4	HGNC:34	ENSG00000198691	P78363	Retinal-specific phospholipid-transporting ATPase ABCA4	clinvar
MT-ND6	HGNC:7462	ENSG00000198695	P03923	NADH-ubiquinone oxidoreductase chain 6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RHO	Rhodopsin	Photoreceptor required for image-forming vision at low light intensity.
USH2A	Usherin	Involved in hearing and vision as member of the USH2 complex.
PMPCA	Mitochondrial-processing peptidase subunit alpha	Substrate recognition and binding subunit of the essential mitochondrial processing protease (MPP), which cleaves the mitochondrial sequence off newly imported precursors proteins.
CEP290	Centrosomal protein of 290 kDa	Involved in early and late steps in cilia formation.
ARV1	Protein ARV1	Plays a role as a mediator in the endoplasmic reticulum (ER) cholesterol and bile acid homeostasis.
EFEMP1	EGF-containing fibulin-like extracellular matrix protein 1	Binds EGFR, the EGF receptor, inducing EGFR autophosphorylation and the activation of downstream signaling pathways.
ABCA4	Retinal-specific phospholipid-transporting ATPase ABCA4	Flippase that catalyzes in an ATP-dependent manner the transport of retinal-phosphatidylethanolamine conjugates like 11-cis and all-trans isomers of N-retinylidene-phosphatidylethanolamine (N-Ret-PE) from the lumen to the cytoplasmic leafl…
MT-ND6	NADH-ubiquinone oxidoreductase chain 6	Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor.

Protein-family classification

Druggable: 4 · Difficult: 0 · Unknown: 4 · 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
Transporter	1	9.7×	0.362
Protease	1	4.6×	0.362
Antibody/Immunoglobulin	1	3.6×	0.362
GPCR	1	3.0×	0.362
Other/Unknown	4	0.9×	0.755

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RHO	GPCR	yes		GPCR_Rhodpsn, Rhodopsin, Opsin
USH2A	Antibody/Immunoglobulin	yes		Laminin_G, LE_dom, FN3_dom
PMPCA	Protease	yes	3.4.24.64	Pept_M16_Zn_BS, Peptidase_M16_C, Metalloenz_LuxS/M16
CEP290	Other/Unknown	no		Cep290, Cep209_CC5
ARV1	Other/Unknown	no		Arv1
EFEMP1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
ABCA4	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABCA4/ABCR
MT-ND6	Other/Unknown	no		NADH_UbQ/plastoQ_OxRdtase_su6, ComplexI_Subunit6

Expression context

Cohort genes with no expression data: 0.

8 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)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	3
right lobe of liver	2
right uterine tube	2
diaphragm	1
neuron projection bundle connecting eye with brain	1
optic choroid	1
buccal mucosa cell	1
adrenal tissue	1
apex of heart	1
ventricular zone	1
cardiac muscle of right atrium	1
left ventricle myocardium	1
myocardium	1
descending thoracic aorta	1
right coronary artery	1
thoracic aorta	1
pigmented layer of retina	1
primordial germ cell in gonad	1
left uterine tube	1
mucosa of stomach	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RHO	38	tissue_specific	marker	optic choroid, neuron projection bundle connecting eye with brain, diaphragm
USH2A	30	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, right lobe of liver, buccal mucosa cell
PMPCA	276	ubiquitous	marker	right lobe of liver, adrenal tissue, apex of heart
CEP290	278	ubiquitous	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, ventricular zone
ARV1	258	ubiquitous	marker	cardiac muscle of right atrium, myocardium, left ventricle myocardium
EFEMP1	286	ubiquitous	marker	right coronary artery, thoracic aorta, descending thoracic aorta
ABCA4	164	tissue_specific	marker	pigmented layer of retina, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
MT-ND6	134	ubiquitous	marker	mucosa of stomach, left uterine tube, right uterine tube

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PMPCA	3,679
RHO	3,578
EFEMP1	2,988
CEP290	2,778
USH2A	2,332
ABCA4	1,532
MT-ND6	1,208
ARV1	476

Intra-cohort edges

A	B	Sources
ABCA4	RHO	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 5 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCA4	P78363	8
MT-ND6	P03923	5
RHO	P08100	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PMPCA	Q10713	88.46
ARV1	Q9H2C2	82.17
EFEMP1	Q12805	77.67
CEP290	O15078	60.90
USH2A	O75445

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 48. Enrichment computed across 8 evidence-associated genes (7 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 7 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)	2	148.3×	0.004	RHO, ABCA4
Defective visual phototransduction due to ABCA4 loss of function	1	1631.4×	0.015	ABCA4
Retinoid cycle disease events	1	407.9×	0.020	ABCA4
Diseases associated with visual transduction	1	407.9×	0.020	ABCA4
Diseases of the neuronal system	1	407.9×	0.020	ABCA4
Mitochondrial protein degradation	2	32.6×	0.020	PMPCA, MT-ND6
Opsins	1	181.3×	0.037	RHO
Cholesterol biosynthesis	1	163.1×	0.037	ARV1
Activation of the phototransduction cascade	1	135.9×	0.039	RHO
Processing of SMDT1	1	90.6×	0.053	PMPCA
Mitochondrial calcium ion transport	1	77.7×	0.054	PMPCA
VxPx cargo-targeting to cilium	1	74.2×	0.054	RHO
Inactivation, recovery and regulation of the phototransduction cascade	1	45.3×	0.077	RHO
Molecules associated with elastic fibres	1	44.1×	0.077	EFEMP1
Visual phototransduction	1	37.1×	0.082	ABCA4
Centrosome maturation	1	36.2×	0.082	CEP290
Transport of small molecules	2	7.2×	0.082	PMPCA, ABCA4
Protein localization	1	27.2×	0.091	PMPCA
Mitochondrial protein import	1	24.0×	0.091	PMPCA
Complex I biogenesis	1	23.6×	0.091	MT-ND6
Loss of Nlp from mitotic centrosomes	1	22.7×	0.091	CEP290
Loss of proteins required for interphase microtubule organization from the centrosome	1	22.7×	0.091	CEP290
AURKA Activation by TPX2	1	21.8×	0.091	CEP290
Metabolism of steroids	1	19.7×	0.091	ARV1
Recruitment of mitotic centrosome proteins and complexes	1	19.4×	0.091	CEP290
Regulation of PLK1 Activity at G2/M Transition	1	18.1×	0.091	CEP290
Mitotic G2-G2/M phases	1	18.1×	0.091	CEP290
G2/M Transition	1	18.1×	0.091	CEP290
ABC-family protein mediated transport	1	17.4×	0.091	ABCA4
Recruitment of NuMA to mitotic centrosomes	1	16.6×	0.091	CEP290

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
photoreceptor cell maintenance	3	134.5×	5e-05	RHO, USH2A, ABCA4
visual perception	4	39.8×	5e-05	RHO, USH2A, EFEMP1, ABCA4
phototransduction, visible light	2	324.1×	3e-04	RHO, ABCA4
camera-type eye development	2	89.6×	0.003	CEP290, EFEMP1
regulation of plasma membrane sterol distribution	1	2106.5×	0.006	ARV1
thermotaxis	1	1053.2×	0.008	RHO
obsolete ciliary basal body-plasma membrane docking	1	1053.2×	0.008	CEP290
rod bipolar cell differentiation	1	1053.2×	0.008	RHO
phospholipid transfer to membrane	1	702.2×	0.008	ABCA4
post-embryonic eye morphogenesis	1	702.2×	0.008	EFEMP1
detection of temperature stimulus involved in thermoception	1	702.2×	0.008	RHO
ciliary transition zone assembly	1	702.2×	0.008	CEP290
regulation of intracellular cholesterol transport	1	526.6×	0.009	ARV1
G protein-coupled opsin signaling pathway	1	421.3×	0.009	RHO
intracellular sterol transport	1	421.3×	0.009	ARV1
maintenance of animal organ identity	1	421.3×	0.009	USH2A
inner ear receptor cell differentiation	1	421.3×	0.009	USH2A
absorption of visible light	1	351.1×	0.010	RHO
pronephros development	1	300.9×	0.010	CEP290
regulation of establishment of protein localization	1	300.9×	0.010	CEP290
obsolete protein processing involved in protein targeting to mitochondrion	1	263.3×	0.010	PMPCA
response to light intensity	1	263.3×	0.010	RHO
otic vesicle formation	1	263.3×	0.010	CEP290
hair cell differentiation	1	263.3×	0.010	USH2A
podosome assembly	1	263.3×	0.010	RHO
sensory perception of light stimulus	1	234.1×	0.010	USH2A
embryonic eye morphogenesis	1	191.5×	0.012	EFEMP1
inner ear auditory receptor cell differentiation	1	150.5×	0.015	USH2A
hindbrain development	1	140.4×	0.015	CEP290
regulation of cholesterol metabolic process	1	140.4×	0.015	ARV1

Therapeutics

Drugs indicated for this disease

0 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Aspirin	Phase 3 (in late-stage trials)
Ranibizumab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Metformin.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 8

Druggability breadth: 3 of 8 evidence-associated genes (38%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RHO	0	0
USH2A	0	0
PMPCA	0	0
CEP290	0	0
ARV1	0	0
EFEMP1	0	0
ABCA4	0	0
MT-ND6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
MT-ND6	4	Binding:4
RHO	1	Binding:1
PMPCA	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PMPCA	3.4.24.64	mitochondrial processing peptidase

Pharmacogenomics

Cohort genes with a PharmGKB record: 8; 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	RHO, ABCA4
D	Druggable family + AlphaFold only, no drug	2	USH2A, PMPCA
E	Difficult family or no structure, no drug	4	CEP290, ARV1, EFEMP1, MT-ND6

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RHO	1	—
USH2A	0	—
PMPCA	1	—
CEP290	0	—
ARV1	0	—
EFEMP1	0	—
ABCA4	0	—
MT-ND6	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.