Night blindness

Summary

Night blindness (MONDO:0004588) is a disease with 5 cohort genes and 2 clinical trials.

At a glance

• Cohort genes: 5
• ClinVar variants: 5
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	night blindness
Mondo ID	MONDO:0004588
MeSH	D009755
DOID	DOID:8499
ICD-10-CM	H53.6
ICD-11	205882698
NCIT	C34850
SNOMED CT	65194006
UMLS	C0028077
MedGen	10349
Is cancer (heuristic)	no

Also known as: nyctalopia

Data availability: 5 ClinVar variants.

Disease family

An umbrella term covering 3 Mondo subtypes.

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

Related subtypes (3): cortical blindness, microcephaly microphthalmos blindness, amaurosis fugax

Subtypes (3): acquired night blindness, abnormal threshold of rods, congenital stationary night blindness

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

5 retrieved; paginated sample, class counts are floors:

2 likely pathogenic, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
654881	NM_025114.4(CEP290):c.322C>T (p.Arg108Ter)	CEP290	Pathogenic	criteria provided, multiple submitters, no conflicts
13014	NM_000539.3(RHO):c.1040C>T (p.Pro347Leu)	RHO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
523365	NM_000390.4(CHM):c.75_77del (p.Ala26del)	CHM	Likely pathogenic	criteria provided, single submitter
523395	NM_001039348.3(EFEMP1):c.1189T>C (p.Tyr397His)	EFEMP1	Likely pathogenic	criteria provided, single submitter
225502	NM_001252024.2(TRPM1):c.1263G>A (p.Pro421=)	TRPM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 12 · 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
CHM	Orphanet:180	Choroideremia
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
TRPM1	Orphanet:714079	Complete congenital stationary night blindness, Schubert-Bornschein type

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RHO	HGNC:10012	ENSG00000163914	P08100	Rhodopsin	clinvar
CHM	HGNC:1940	ENSG00000188419	P24386	Rab proteins geranylgeranyltransferase component A 1	clinvar
CEP290	HGNC:29021	ENSG00000198707	O15078	Centrosomal protein of 290 kDa	clinvar
EFEMP1	HGNC:3218	ENSG00000115380	Q12805	EGF-containing fibulin-like extracellular matrix protein 1	clinvar
TRPM1	HGNC:7146	ENSG00000134160	Q7Z4N2	Transient receptor potential cation channel subfamily M member 1	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.
CHM	Rab proteins geranylgeranyltransferase component A 1	Substrate-binding subunit of the Rab geranylgeranyltransferase (GGTase) complex.
CEP290	Centrosomal protein of 290 kDa	Involved in early and late steps in cilia formation.
EFEMP1	EGF-containing fibulin-like extracellular matrix protein 1	Binds EGFR, the EGF receptor, inducing EGFR autophosphorylation and the activation of downstream signaling pathways.
TRPM1	Transient receptor potential cation channel subfamily M member 1	Constitutively open nonselective divalent cation-conducting channels which mediate the influx of Ca(2+), Mg(2+), Mn(2+), Ba(2+), and Ni(2+) into the cytoplasm, leading to membrane depolarization.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.6

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
Ion channel	1	22.3×	0.176
GPCR	1	4.8×	0.384
Enzyme (other)	1	2.4×	0.471
Other/Unknown	2	0.7×	0.877

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RHO	GPCR	yes		GPCR_Rhodpsn, Rhodopsin, Opsin
CHM	Enzyme (other)	yes	2.5.1.60	Rab_escort, GDP_dissociation_inhibitor, FAD/NAD-bd_sf
CEP290	Other/Unknown	no		Cep290, Cep209_CC5
EFEMP1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
TRPM1	Ion channel	yes		Ion_trans_dom, TRPM_tetra, TRPM_tetra_sf

Expression context

Cohort genes with no expression data: 0.

5 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
diaphragm	1
neuron projection bundle connecting eye with brain	1
optic choroid	1
Brodmann (1909) area 23	1
endothelial cell	1
middle temporal gyrus	1
male germ line stem cell (sensu Vertebrata) in testis	1
right uterine tube	1
ventricular zone	1
descending thoracic aorta	1
right coronary artery	1
thoracic aorta	1
nipple	1
pigmented layer of retina	1
retina	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
CHM	264	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, middle temporal gyrus
CEP290	278	ubiquitous	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, ventricular zone
EFEMP1	286	ubiquitous	marker	right coronary artery, thoracic aorta, descending thoracic aorta
TRPM1	119	tissue_specific	marker	pigmented layer of retina, retina, nipple

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RHO	3,578
EFEMP1	2,988
CEP290	2,778
CHM	1,445
TRPM1	1,190

Intra-cohort edges

A	B	Sources
CEP290	CHM	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RHO	P08100	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CHM	P24386	81.05
EFEMP1	Q12805	77.67
TRPM1	Q7Z4N2	66.74
CEP290	O15078	60.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 31. Enrichment computed across 5 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Opsins	1	253.8×	0.050	RHO
Activation of the phototransduction cascade	1	190.3×	0.050	RHO
TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain	1	152.3×	0.050	CHM
Regulation of MITF-M-dependent genes involved in apoptosis	1	126.9×	0.050	TRPM1
The canonical retinoid cycle in rods (twilight vision)	1	103.8×	0.050	RHO
VxPx cargo-targeting to cilium	1	103.8×	0.050	RHO
TRP channels	1	81.6×	0.054	TRPM1
Inactivation, recovery and regulation of the phototransduction cascade	1	63.4×	0.055	RHO
Molecules associated with elastic fibres	1	61.7×	0.055	EFEMP1
Centrosome maturation	1	50.8×	0.061	CEP290
RAB geranylgeranylation	1	34.6×	0.064	CHM
Loss of Nlp from mitotic centrosomes	1	31.7×	0.064	CEP290
Loss of proteins required for interphase microtubule organization from the centrosome	1	31.7×	0.064	CEP290
AURKA Activation by TPX2	1	30.4×	0.064	CEP290
Recruitment of mitotic centrosome proteins and complexes	1	27.2×	0.064	CEP290
Regulation of PLK1 Activity at G2/M Transition	1	25.4×	0.064	CEP290
Mitotic G2-G2/M phases	1	25.4×	0.064	CEP290
G2/M Transition	1	25.4×	0.064	CEP290
RAB GEFs exchange GTP for GDP on RABs	1	24.8×	0.064	CHM
Recruitment of NuMA to mitotic centrosomes	1	23.3×	0.064	CEP290
Anchoring of the basal body to the plasma membrane	1	22.6×	0.064	CEP290
Cilium Assembly	1	21.8×	0.064	CEP290
Mitotic Prometaphase	1	13.8×	0.091	CEP290
Organelle biogenesis and maintenance	1	13.2×	0.091	CEP290
M Phase	1	13.2×	0.091	CEP290
Cell Cycle, Mitotic	1	9.6×	0.119	CEP290
G alpha (i) signalling events	1	7.8×	0.140	RHO
Cell Cycle	1	7.2×	0.145	CEP290
Innate Immune System	1	5.1×	0.194	CEP290
Neutrophil degranulation	1	4.6×	0.205	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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
visual perception	4	63.6×	6e-06	RHO, CHM, EFEMP1, TRPM1
cellular response to light stimulus	2	421.3×	2e-04	RHO, TRPM1
camera-type eye development	2	143.4×	0.001	CEP290, EFEMP1
thermotaxis	1	1685.2×	0.005	RHO
obsolete ciliary basal body-plasma membrane docking	1	1685.2×	0.005	CEP290
rod bipolar cell differentiation	1	1685.2×	0.005	RHO
post-embryonic eye morphogenesis	1	1123.5×	0.005	EFEMP1
detection of temperature stimulus involved in thermoception	1	1123.5×	0.005	RHO
ciliary transition zone assembly	1	1123.5×	0.005	CEP290
G protein-coupled opsin signaling pathway	1	674.1×	0.006	RHO
absorption of visible light	1	561.7×	0.006	RHO
protein geranylgeranylation	1	561.7×	0.006	CHM
pronephros development	1	481.5×	0.006	CEP290
regulation of establishment of protein localization	1	481.5×	0.006	CEP290
response to light intensity	1	421.3×	0.006	RHO
otic vesicle formation	1	421.3×	0.006	CEP290
podosome assembly	1	421.3×	0.006	RHO
embryonic eye morphogenesis	1	306.4×	0.008	EFEMP1
phototransduction, visible light	1	259.3×	0.009	RHO
hindbrain development	1	224.7×	0.010	CEP290
G protein-coupled glutamate receptor signaling pathway	1	210.7×	0.010	TRPM1
eye photoreceptor cell development	1	168.5×	0.012	CEP290
negative regulation of chondrocyte differentiation	1	134.8×	0.014	EFEMP1
positive regulation of intracellular protein transport	1	134.8×	0.014	CEP290
protein tetramerization	1	124.8×	0.014	TRPM1
monoatomic cation transmembrane transport	1	124.8×	0.014	TRPM1
calcium ion import across plasma membrane	1	108.7×	0.016	TRPM1
phototransduction	1	99.1×	0.017	RHO
peptidyl-tyrosine phosphorylation	1	84.3×	0.019	EFEMP1
photoreceptor cell maintenance	1	71.7×	0.021	RHO

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 5

Druggability breadth: 2 of 5 evidence-associated genes (40%) 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
CHM	0	0
CEP290	0	0
EFEMP1	0	0
TRPM1	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
RHO	1	Binding:1
CHM	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CHM	2.5.1.60	protein geranylgeranyltransferase type II

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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	1	RHO
D	Druggable family + AlphaFold only, no drug	2	CHM, TRPM1
E	Difficult family or no structure, no drug	2	CEP290, EFEMP1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RHO	1	—
CHM	1	—
CEP290	0	—
EFEMP1	0	—
TRPM1	0	—

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
NCT00569023	Not specified	COMPLETED	Treatment of Congenital Stationary Night Blindness With an Alga Containing High Dose of Beta Carotene
NCT06989879	Not specified	COMPLETED	Knowledge of Students About Vitamin A and Assessment of Eye Manifestations in Quranic Schools (Khalwai) Khartoum State, Sudan 2022