Congenital nystagmus

Summary

Congenital nystagmus (MONDO:0005712) is a disease (an umbrella term covering 10 Mondo subtypes) with 5 cohort genes and 11 clinical trials. Top therapeutic interventions include memantine and neramexane mesylate.

At a glance

• Umbrella term: 10 Mondo subtypes
• Cohort genes: 5
• ClinVar variants: 4
• Clinical trials: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital nystagmus
Mondo ID	MONDO:0005712
EFO	EFO:0007217
MeSH	D020417
OMIM	310700
Orphanet	651
DOID	DOID:9649
ICD-10-CM	H55.01
ICD-11	1626567380
SNOMED CT	64635004
UMLS	C0700501
MedGen	195995
Is cancer (heuristic)	no

Also known as: congenital idiopathic nystagmus · congenital pathologic nystagmus · motor congenital nystagmus · nystagmus · nystagmus, congenital

Data availability: 4 ClinVar variants · 1 GenCC gene-disease record · 1 HPO phenotype.

Disease family

An umbrella term covering 10 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › congenital nystagmus

Related subtypes (216): polymicrogyria, congenital myasthenic syndrome with tubular aggregates, prenatal-onset spinal muscular atrophy with congenital bone fractures, anencephaly, cerebral cavernous malformation, meningocele, progressive external ophthalmoplegia, congenital toxoplasmosis, congenital contractural arachnodactyly, congenital trigeminal anesthesia, familial congenital palsy of trochlear nerve, Myhre syndrome, Aase-Smith syndrome, KBG syndrome, autosomal dominant primary microcephaly, Mobius syndrome, MYH7-related skeletal myopathy, congenital stationary night blindness autosomal dominant 2, Prader-Willi syndrome, congenital myopathy 7A, myosin storage, autosomal dominant, Smith-Magenis syndrome, spina bifida, Freeman-Sheldon syndrome, isolated cerebellar hypoplasia/agenesis, Chediak-Higashi syndrome, Cohen syndrome, multiple pterygium-malignant hyperthermia syndrome, corpus callosum, agenesis of, congenital lactic acidosis, Saguenay-Lac-Saint-Jean type, facial dysmorphism-macrocephaly-myopia-Dandy-Walker malformation syndrome, diastematomyelia, EEM syndrome, Mowat-Wilson syndrome, Johanson-Blizzard syndrome, intellectual disability, Buenos-Aires type, myasthenia, congenital, refractory to acetylcholinesterase inhibitors, congenital myasthenic syndrome 6, Bailey-Bloch congenital myopathy, congenital stationary night blindness 1B, radioulnar synostosis-developmental delay-hypotonia syndrome, Schinzel-Giedion syndrome, schizencephaly, intellectual disability, Wolff type, X-linked intellectual disability-plagiocephaly syndrome, X-linked adrenal hypoplasia congenita, syndromic X-linked intellectual disability 7, syndromic X-linked intellectual disability Shashi type, syndromic X-linked intellectual disability Lubs type, syndromic X-linked intellectual disability Abidi type, syndromic X-linked intellectual disability Siderius type, X-linked intellectual disability, Cabezas type, X-linked intellectual disability-cubitus valgus-dysmorphism syndrome, syndromic X-linked intellectual disability Claes-Jensen type, moyamoya angiopathy-short stature-facial dysmorphism-hypergonadotropic hypogonadism syndrome, multiple congenital anomalies-hypotonia-seizures syndrome 2, developmental and epileptic encephalopathy, 36, blepharophimosis - intellectual disability syndrome, MKB type, X-linked intellectual disability-short stature-overweight syndrome, intellectual disability, X-linked, syndromic 33, syndromic X-linked intellectual disability 34, infantile-onset X-linked spinal muscular atrophy, syndromic X-linked intellectual disability 5, holoprosencephaly-hypokinesia-congenital contractures syndrome, X-linked intellectual disability with marfanoid habitus, Wieacker-Wolff syndrome, MERRF syndrome, macrocephaly-spastic paraplegia-dysmorphism syndrome, intellectual disability-sparse hair-brachydactyly syndrome, myofibrillar myopathy 1, isolated hereditary congenital facial paralysis, fibrosis of extraocular muscles, congenital, 2, Pierpont syndrome, congenital cataracts-facial dysmorphism-neuropathy syndrome, Bohring-Opitz syndrome, PHACE syndrome, B4GALT1-congenital disorder of glycosylation, developmental malformations-deafness-dystonia syndrome, sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, AICA-ribosiduria, myofibrillar myopathy 3, fibrosis of extraocular muscles, congenital, 3c, myofibrillar myopathy 4, myofibrillar myopathy 5, cone-rod synaptic disorder, congenital nonprogressive, congenital stationary night blindness autosomal dominant 3, congenital stationary night blindness autosomal dominant 1, intellectual disability, autosomal recessive 12, progressive myoclonic epilepsy type 3, chromosome 15q13.3 microdeletion syndrome, combined pituitary hormone deficiencies, genetic form, congenital stationary night blindness 1D, DYRK1A-related intellectual disability syndrome, Pitt-Hopkins-like syndrome 2, developmental and epileptic encephalopathy, 15, Schuurs-Hoeijmakers syndrome, severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome, severe intellectual disability-progressive spastic diplegia syndrome, hypotonia, infantile, with psychomotor retardation and characteristic facies, developmental and epileptic encephalopathy, 18, CTCF-related neurodevelopmental disorder, autism spectrum disorder due to AUTS2 deficiency, developmental and epileptic encephalopathy, 23, ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder, Bardet-Biedl syndrome 11, cerebellar-facial-dental syndrome, fibrosis of extraocular muscles, congenital, 5, congenital myasthenic syndrome 15, lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome, congenital myasthenic syndrome 18, autosomal recessive spinocerebellar ataxia 20, Houge-Janssens syndrome 1, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome, congenital stationary night blindness 1G, hypomyelinating leukodystrophy 10, developmental and epileptic encephalopathy, 50, congenital insensitivity to pain-hypohidrosis syndrome, macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome, SLC39A8-CDG, spastic paraplegia-severe developmental delay-epilepsy syndrome, cardiac anomalies - developmental delay - facial dysmorphism syndrome, severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome, intellectual disability, autosomal recessive 53, TELO2-related intellectual disability-neurodevelopmental disorder, micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome, autosomal recessive limb-girdle muscular dystrophy type 2Y, myofibrillar myopathy 7, short stature-brachydactyly-obesity-global developmental delay syndrome, autosomal recessive limb-girdle muscular dystrophy type 2R1, severe microbrachycephaly-intellectual disability-athetoid cerebral palsy syndrome, congenital laryngeal palsy, congenital or early infantile CACH syndrome, congenital epulis, severe congenital nemaline myopathy, intermediate nemaline myopathy, typical nemaline myopathy, childhood-onset nemaline myopathy, adult-onset nemaline myopathy, qualitative or quantitative defects of protein involved in O-glycosylation of alpha-dystroglycan, holoprosencephaly, congenital insensitivity to pain with hyperhidrosis, congenital hydrocephalus, familial congenital mirror movements, macrocephaly-short stature-paraplegia syndrome, cephalocele, mitochondrial neurogastrointestinal encephalomyopathy, X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome, 7p22.1 microduplication syndrome, congenital achiasma, congenital retinal arteriovenous communication, 3q27.3 microdeletion syndrome, Prader-Willi-like syndrome, 9q31.1q31.3 microdeletion syndrome, congenital oculomotor nerve palsy, congenital abducens nerve palsy, neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome, congenital insensitivity to pain with severe intellectual disability, X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, lissencephaly spectrum disorders, hyaline body myopathy, 22q11.2 deletion syndrome, craniorachischisis, Leber congenital amaurosis, Ritscher-Schinzel syndrome, Rubinstein-Taybi syndrome, X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome, X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome, X-linked intellectual disability, Pai type, X-linked intellectual disability, Stevenson type, X-linked intellectual disability, Stoll type, congenital muscular dystrophy, congenital vitreoretinal dysplasia, periventricular nodular heterotopia, postsynaptic congenital myasthenic syndrome, subcortical band heterotopia, congenital fibrosis of extraocular muscles type 1, Al Gazali Khidr Prem Chandran syndrome, distal arthrogryposis Moore weaver type, congenital myotonic dystrophy, myasthenic syndrome, congenital, 7B, presynaptic, autosomal recessive, intellectual disability, autosomal dominant 47, intellectual disability, autosomal dominant 48, spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and leber congenital amaurosis, myasthenic syndrome, congenital, 23, presynaptic, myasthenic syndrome, congenital, 24, presynaptic, myasthenic syndrome, congenital, 25, presynaptic, developmental and epileptic encephalopathy, 77, night blindness, congenital stationary, type1i, neuropathy, congenital hypomelinating, congenital axonal neuropathy with encephalopathy, developmental and epileptic encephalopathy, 73, PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome, isolated exencephaly, myasthenic syndrome, congenital, 22, intellectual developmental disorder with gastrointestinal difficulties and high pain threshold, intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies, 9q33.3q34.11 microdeletion syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome, SIN3A-related intellectual disability syndrome, childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder, X-linked congenital stationary night blindness, neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, FOXG1 disorder, alpha-actinopathy, TPM3-related myopathy, X-linked recessive mitochondrial myopathy, RYR1-related myopathy, TTN-related myopathy, TPM2-related myopathy, myopathy caused by variation in POMGNT1, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, segmental spinal dysgenesis, myopathy, myofibrillar, 13, with rimmed vacuoles, congenital neuronal ceroid lipofuscinosis 10

Subtypes (10): nystagmus 2, congenital, autosomal dominant, nystagmus, hereditary vertical, spinocerebellar ataxia 27A, nystagmus, congenital, autosomal recessive, nystagmus 5, congenital, X-linked, nystagmus 6, congenital, X-linked, nystagmus 1, congenital, X-linked, nystagmus, myoclonic, nystagmus 3, congenital, autosomal dominant, nystagmus 7, congenital, autosomal dominant

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

4 retrieved; paginated sample, class counts are floors:

3 conflicting classifications of pathogenicity, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
194918	NM_000275.3(OCA2):c.2020C>G (p.Leu674Val)	OCA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1342665	NM_002941.4(ROBO1):c.4565C>T (p.Ser1522Leu)	ROBO1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
99528	NM_000372.5(TYR):c.1063G>C (p.Ala355Pro)	TYR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4279941	GRCh37/hg19 Xp22.2(chrX:9733608-9736005)x1	GPR143	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 13 · 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
MANBA	Moderate	Autosomal dominant	congenital nystagmus	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MANBA	Orphanet:118	Beta-mannosidosis
ROBO1	Orphanet:95496	Pituitary stalk interruption syndrome
TYR	Orphanet:352734	Minimal pigment oculocutaneous albinism type 1
TYR	Orphanet:352737	Temperature-sensitive oculocutaneous albinism type 1
TYR	Orphanet:79431	Oculocutaneous albinism type 1A
TYR	Orphanet:79434	Oculocutaneous albinism type 1B
TYR	Orphanet:895	Waardenburg syndrome type 2
GPR143	Orphanet:54	X-linked recessive ocular albinism
OCA2	Orphanet:177901	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 1
OCA2	Orphanet:177904	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 2
OCA2	Orphanet:79432	Oculocutaneous albinism type 2
OCA2	Orphanet:98754	Prader-Willi syndrome due to maternal uniparental disomy of chromosome 15
OCA2	Orphanet:98794	Angelman syndrome due to maternal 15q11q13 deletion

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
MANBA	HGNC:6831	ENSG00000109323	O00462	Beta-mannosidase	gencc
ROBO1	HGNC:10249	ENSG00000169855	Q9Y6N7	Roundabout homolog 1	clinvar
TYR	HGNC:12442	ENSG00000077498	P14679	Tyrosinase	clinvar
GPR143	HGNC:20145	ENSG00000101850	P51810	G-protein coupled receptor 143	clinvar
OCA2	HGNC:8101	ENSG00000104044	Q04671	P protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MANBA	Beta-mannosidase	Exoglycosidase that cleaves the single beta-linked mannose residue from the non-reducing end of all N-linked glycoprotein oligosaccharides.
ROBO1	Roundabout homolog 1	Receptor for SLIT1 and SLIT2 that mediates cellular responses to molecular guidance cues in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuro…
TYR	Tyrosinase	This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds.
GPR143	G-protein coupled receptor 143	Receptor for tyrosine, L-DOPA and dopamine.
OCA2	P protein	Contributes to a melanosome-specific anion (chloride) current that modulates melanosomal pH for optimal tyrosinase activity required for melanogenesis and the melanosome maturation.

Protein-family classification

Druggable: 4 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.8

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
Antibody/Immunoglobulin	2	11.7×	0.044
Ion channel	1	22.3×	0.088
Enzyme (other)	1	2.4×	0.471
Other/Unknown	1	0.4×	0.983

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MANBA	Antibody/Immunoglobulin	yes		Glyco_hydro_2_cat, Galactose-bd-like_sf, Ig-like_fold
ROBO1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
TYR	Enzyme (other)	yes	1.14.18.1	Tyrosinase_Cu-bd, Di-copper_centre_dom_sf, Tyrosinase/Hemocyanin
GPR143	Other/Unknown	no		GPR143
OCA2	Ion channel	yes		Cit_transptr-like_dom, Diverse_Ion_Transporter

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
pigmented layer of retina	3
secondary oocyte	2
leukocyte	1
monocyte	1
mononuclear cell	1
ganglionic eminence	1
tibia	1
ventricular zone	1
male germ line stem cell (sensu Vertebrata) in testis	1
upper leg skin	1
oocyte	1
choroid plexus epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MANBA	246	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
ROBO1	287	ubiquitous	marker	ventricular zone, ganglionic eminence, tibia
TYR	59	tissue_specific	marker	pigmented layer of retina, male germ line stem cell (sensu Vertebrata) in testis, upper leg skin
GPR143	170	broad	marker	oocyte, secondary oocyte, pigmented layer of retina
OCA2	192	tissue_specific	marker	pigmented layer of retina, choroid plexus epithelium, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TYR	3,663
ROBO1	2,359
OCA2	2,132
MANBA	2,014
GPR143	1,871

Intra-cohort edges

A	B	Sources
GPR143	OCA2	string_interaction
GPR143	TYR	intact, string_interaction
OCA2	TYR	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ROBO1	Q9Y6N7	12
TYR	P14679	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MANBA	O00462	96.05
GPR143	P51810	74.37
OCA2	Q04671	73.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. 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
Melanin biosynthesis	2	913.6×	3e-05	TYR, OCA2
Regulation of MITF-M-dependent genes involved in pigmentation	2	106.2×	0.002	TYR, GPR143
Lysosomal oligosaccharide catabolism	1	571.0×	0.010	MANBA
SLIT2:ROBO1 increases RHOA activity	1	571.0×	0.010	ROBO1
Regulation of cortical dendrite branching	1	456.8×	0.010	ROBO1
Inactivation of CDC42 and RAC1	1	285.5×	0.012	ROBO1
Role of ABL in ROBO-SLIT signaling	1	253.8×	0.012	ROBO1
Regulation of commissural axon pathfinding by SLIT and ROBO	1	190.3×	0.014	ROBO1
Activation of RAC1	1	163.1×	0.015	ROBO1
Netrin-1 signaling	1	87.8×	0.025	ROBO1
Amine ligand-binding receptors	1	69.2×	0.029	GPR143
Signaling by ROBO receptors	1	24.8×	0.069	ROBO1
Metabolism of carbohydrates and carbohydrate derivatives	1	24.0×	0.069	MANBA
Regulation of expression of SLITs and ROBOs	1	13.8×	0.110	ROBO1
G alpha (q) signalling events	1	11.5×	0.123	GPR143
Axon guidance	1	9.0×	0.144	ROBO1
Nervous system development	1	8.6×	0.144	ROBO1
Innate Immune System	1	5.1×	0.222	MANBA
Neutrophil degranulation	1	4.6×	0.230	MANBA
Developmental Biology	1	2.9×	0.331	ROBO1
Immune System	1	2.6×	0.346	MANBA
Metabolism	1	2.3×	0.362	MANBA

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
eye pigment biosynthetic process	2	3370.4×	4e-06	TYR, GPR143
melanin biosynthetic process from tyrosine	2	1685.2×	1e-05	TYR, OCA2
melanin biosynthetic process	2	518.5×	9e-05	TYR, OCA2
regulation of melanosome transport	1	3370.4×	0.004	GPR143
chemorepulsion involved in postnatal olfactory bulb interneuron migration	1	1685.2×	0.005	ROBO1
regulation of melanosome organization	1	1685.2×	0.005	GPR143
negative regulation of negative chemotaxis	1	1123.5×	0.006	ROBO1
response to blue light	1	674.1×	0.006	TYR
axon midline choice point recognition	1	674.1×	0.006	ROBO1
melanosome localization	1	674.1×	0.006	GPR143
negative regulation of mammary gland epithelial cell proliferation	1	674.1×	0.006	ROBO1
lysosomal lumen pH elevation	1	674.1×	0.006	OCA2
cell population proliferation	2	41.1×	0.006	TYR, OCA2
visual perception	2	31.8×	0.006	TYR, GPR143
Roundabout signaling pathway	1	561.7×	0.006	ROBO1
negative regulation of chemokine-mediated signaling pathway	1	481.5×	0.007	ROBO1
heart induction	1	421.3×	0.007	ROBO1
oligosaccharide catabolic process	1	306.4×	0.009	MANBA
endocardial cushion formation	1	280.9×	0.010	ROBO1
positive regulation of vascular endothelial growth factor signaling pathway	1	224.7×	0.011	ROBO1
glycoprotein catabolic process	1	210.7×	0.011	MANBA
positive regulation of vascular endothelial growth factor receptor signaling pathway	1	210.7×	0.011	ROBO1
pulmonary valve morphogenesis	1	187.2×	0.012	ROBO1
melanocyte differentiation	1	160.5×	0.013	OCA2
response to vitamin D	1	160.5×	0.013	TYR
melanosome transport	1	153.2×	0.013	GPR143
pigmentation	1	140.4×	0.013	TYR
cell migration involved in sprouting angiogenesis	1	129.6×	0.013	ROBO1
outflow tract septum morphogenesis	1	129.6×	0.013	ROBO1
melanosome organization	1	129.6×	0.013	GPR143

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 5 evidence-associated genes (60%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
TYR	ASCORBIC ACID

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TYR	10	4
MANBA	0	0
ROBO1	0	0
GPR143	0	0
OCA2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ASCORBIC ACID	4	TYR
HEXYLRESORCINOL	4	TYR
HYDROQUINONE	4	TYR
CURCUMIN	3	TYR
RESVERATROL	3	TYR
QUERCETIN	3	TYR
BUTYLATED HYDROXYTOLUENE	2	TYR
LUTEOLIN	2	TYR
ARBUTIN	2	TYR
KAEMPFEROL	1	TYR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TYR	211	Binding:209, ADMET:2
MANBA	13	Binding:11, Functional:2
GPR143	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TYR	1.14.18.1	tyrosinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
TYR	211

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

10 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)
ASCORBIC ACID	4	TYR
HEXYLRESORCINOL	4	TYR
HYDROQUINONE	4	TYR
CURCUMIN	3	TYR
RESVERATROL	3	TYR
QUERCETIN	3	TYR
BUTYLATED HYDROXYTOLUENE	2	TYR
LUTEOLIN	2	TYR
ARBUTIN	2	TYR
KAEMPFEROL	1	TYR

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TYR
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	ROBO1
D	Druggable family + AlphaFold only, no drug	2	MANBA, OCA2
E	Difficult family or no structure, no drug	1	GPR143

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GPR143	3	TYR
OCA2	0	TYR
MANBA	13	—
ROBO1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 11.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	9
PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00001866	PHASE2	COMPLETED	Eye Muscle Surgery to Treat Congenital Nystagmus
NCT00799942	PHASE2	TERMINATED	Open-lable Extension Study on Safety and Efficacy of Neramexane to Treat Congenital and Acquired Nystagmus
NCT04770519	Not specified	RECRUITING	Genetic Studies of Strabismus, Nystagmus, and Associated Disorders
NCT07238387	Not specified	NOT_YET_RECRUITING	Evaluation of Nystagmus Examination Using Wearable AR Glasses in Vertigo Patients
NCT00001861	Not specified	COMPLETED	Screening for Studies on Nystagmus and Strabismus
NCT00702832	Not specified	COMPLETED	Effect of Vestibular Rehabilitation - a Randomized Controlled Trial
NCT00928954	Not specified	COMPLETED	Cross-over Comparison of Gabapentin and Memantine as Treatment for Acquired Nystagmus
NCT03603301	Not specified	UNKNOWN	Vision in Children Born to Opioid-dependent Methadone-maintained Mothers
NCT07126938	Not specified	COMPLETED	Alcohol Impairment Detection in Healthy Adult Users With the Gaize Device
NCT07583901	Not specified	COMPLETED	Effects of Gaze Stabalization Exercises and Optokinetic Training in Peripheral Vestibular Disorders
NCT07587528	Not specified	COMPLETED	Effects of Cervical and Oculomotor Exercises in Young Adults With Benign Paroxysmal Positional Vertigo

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MEMANTINE	4	1
NERAMEXANE MESYLATE	3	1