Congenital stationary night blindness

disease

On this page

Also known as congenital essential nyctalopiacongenital night blindnesshereditary night blindnessnight blindness, congenital stationaryOguchi's disease

Summary

Congenital stationary night blindness (MONDO:0016293) is a disease (an umbrella term covering 14 Mondo subtypes) with 21 cohort genes and 2 clinical trials. The dominant Reactome pathway is The canonical retinoid cycle in rods (twilight vision) (5 cohort genes).

At a glance

Prevalence: Unknown (Worldwide)
Umbrella term: 14 Mondo subtypes
Cohort genes: 21
ClinVar variants: 66
Phenotypes (HPO): 15
Clinical trials: 2

Clinical features

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0000545	Myopia	Very frequent (80-99%)
HP:0000662	Nyctalopia	Very frequent (80-99%)
HP:0007663	Reduced visual acuity	Very frequent (80-99%)
HP:0030469	Abnormal dark-adapted electroretinogram	Very frequent (80-99%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0030638	Congenital stationary night blindness with normal fundus	Frequent (30-79%)
HP:0030639	Congenital stationary night blindness with abnormal fundus	Frequent (30-79%)
HP:0000540	Hypermetropia	Occasional (5-29%)
HP:0007984	Electronegative electroretinogram	Occasional (5-29%)
HP:0030483	Reduced amplitude of dark-adapted bright flash electroretinogram a-wave	Occasional (5-29%)
HP:0031705	Compensatory head posture	Occasional (5-29%)
HP:0000551	Color vision defect	Very rare (<1-4%)
HP:0007703	Abnormality of retinal pigmentation	Very rare (<1-4%)
HP:0030329	Retinal thinning	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital stationary night blindness
Mondo ID	MONDO:0016293
MeSH	C536122
OMIM	310500
Orphanet	215
DOID	DOID:0050534, DOID:8498
ICD-11	122338861, 587494652
SNOMED CT	193687000, 232061009
UMLS	C0339535
MedGen	83289
GARD	0025068
Is cancer (heuristic)	no

Also known as: congenital essential nyctalopia · congenital night blindness · hereditary night blindness · night blindness, congenital stationary · Oguchi’s disease

Data availability: 66 ClinVar variants · 12 GenCC gene-disease records.

Disease family

An umbrella term covering 14 Mondo subtypes.

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

Related subtypes (2): acquired night blindness, abnormal threshold of rods

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

66 retrieved; paginated sample, class counts are floors:

21 pathogenic, 20 likely pathogenic, 11 uncertain significance, 9 pathogenic/likely pathogenic, 5 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
438093	NM_000350.3(ABCA4):c.3259G>T (p.Glu1087Ter)	ABCA4	Pathogenic	criteria provided, single submitter
8003	NM_002905.5(RDH5):c.712G>T (p.Gly238Trp)	BLOC1S1-RDH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11615	NM_001256789.3(CACNA1F):c.2872C>T (p.Arg958Ter)	CACNA1F	Pathogenic	criteria provided, multiple submitters, no conflicts
11617	NM_001256789.3(CACNA1F):c.2650C>T (p.Arg884Ter)	CACNA1F	Pathogenic	criteria provided, single submitter
438118	NM_001256789.3(CACNA1F):c.1218del (p.Trp407fs)	CACNA1F	Pathogenic	no assertion criteria provided
438128	NM_001256789.3(CACNA1F):c.784C>T (p.Arg262Ter)	CACNA1F	Pathogenic	criteria provided, single submitter
438129	NM_001256789.3(CACNA1F):c.946TTC[2] (p.Phe318del)	CACNA1F	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
624415	NM_001256789.3(CACNA1F):c.2086-2A>G	CACNA1F	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812245	NM_001256789.3(CACNA1F):c.4051C>T (p.Arg1351Ter)	CACNA1F	Pathogenic	criteria provided, multiple submitters, no conflicts
812246	NM_001256789.3(CACNA1F):c.3921G>A (p.Trp1307Ter)	CACNA1F	Pathogenic	no assertion criteria provided
812247	NM_001256789.3(CACNA1F):c.2772del (p.Cys925fs)	CACNA1F	Pathogenic	no assertion criteria provided
812248	NM_001256789.3(CACNA1F):c.2470G>T (p.Glu824Ter)	CACNA1F	Pathogenic	no assertion criteria provided
812249	NM_001256789.3(CACNA1F):c.2225T>G (p.Phe742Cys)	CACNA1F	Pathogenic	criteria provided, single submitter
812252	NM_001256789.3(CACNA1F):c.187_193dup (p.Ala65fs)	CACNA1F	Pathogenic	no assertion criteria provided
813026	NM_001256789.3(CACNA1F):c.1118+1G>C	CACNA1F	Pathogenic	criteria provided, multiple submitters, no conflicts
286815	NC_000017.11:g.38339517_38339521delinsGTAGATCA	GPR179	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31204	NM_001004334.4(GPR179):c.984del (p.Ser329fs)	GPR179	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
437970	NM_000843.4(GRM6):c.577del (p.Val193fs)	GRM6	Pathogenic	criteria provided, single submitter
852296	NM_000843.4(GRM6):c.2041C>T (p.Gln681Ter)	GRM6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812359	NM_001378477.3(NYX):c.782T>C (p.Leu261Pro)	NYX	Pathogenic	no assertion criteria provided
812361	NM_001378477.3(NYX):c.1054_1055del (p.Val352fs)	NYX	Pathogenic	criteria provided, single submitter
812362	NM_001378477.3(NYX):c.1246_1247dup (p.Ala417fs)	NYX	Pathogenic	no assertion criteria provided
8005	NM_002905.5(RDH5):c.839G>A (p.Arg280His)	RDH5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
438219	NM_001252024.2(TRPM1):c.3214dup (p.Trp1072fs)	TRPM1	Pathogenic	criteria provided, single submitter
438221	NM_001252024.2(TRPM1):c.618+3_618+6del	TRPM1	Pathogenic	criteria provided, multiple submitters, no conflicts
593857	NM_001252024.2(TRPM1):c.2695C>T (p.Arg899Ter)	TRPM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812434	NM_001252024.2(TRPM1):c.2633G>A (p.Trp878Ter)	TRPM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812435	NM_001252024.2(TRPM1):c.946A>T (p.Lys316Ter)	TRPM1	Pathogenic	no assertion criteria provided
2351	NM_206933.4(USH2A):c.2299del (p.Glu767fs)	USH2A	Pathogenic	criteria provided, multiple submitters, no conflicts
636219	NM_000843.4(GRM6):c.2003T>C (p.Leu668Pro)	ZNF454	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 72 · Orphanet: 33 · 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
CABP4	Definitive	Autosomal recessive	cone-rod synaptic disorder, congenital nonprogressive	4
GNAT1	Definitive	Autosomal dominant	congenital stationary night blindness autosomal dominant 3	7
GPR179	Definitive	Autosomal recessive	congenital stationary night blindness 1E	4
GRM6	Definitive	Autosomal recessive	congenital stationary night blindness 1B	6
NYX	Definitive	X-linked	congenital stationary night blindness 1A	4
RHO	Definitive	Autosomal dominant	congenital stationary night blindness autosomal dominant 1	13
TRPM1	Definitive	Autosomal recessive	congenital stationary night blindness 1C	4
CACNA1F	Strong	X-linked	congenital stationary night blindness 2A	7
GNB3	Strong	Autosomal recessive	congenital stationary night blindness 1H	5
LRIT3	Strong	Autosomal recessive	congenital stationary night blindness 1F	5
PDE6B	Strong	Autosomal dominant	congenital stationary night blindness autosomal dominant 2	10
SLC24A1	Strong	Autosomal recessive	congenital stationary night blindness 1D	3

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
CABP4	Orphanet:714070	Incomplete congenital stationary night blindness, Schubert-Bornschein type
CABP4	Orphanet:98784	Sleep-related hypermotor epilepsy
CACNA1F	Orphanet:178333	Åland Islands eye disease
CACNA1F	Orphanet:1872	Cone rod dystrophy
CACNA1F	Orphanet:714070	Incomplete congenital stationary night blindness, Schubert-Bornschein type
GPR179	Orphanet:714079	Complete congenital stationary night blindness, Schubert-Bornschein type
GRM6	Orphanet:714079	Complete congenital stationary night blindness, Schubert-Bornschein type
TRPM1	Orphanet:714079	Complete congenital stationary night blindness, Schubert-Bornschein type
PDE6B	Orphanet:714096	Congenital stationary night blindness, Riggs type
PDE6B	Orphanet:791	Retinitis pigmentosa
LRIT3	Orphanet:714079	Complete congenital stationary night blindness, Schubert-Bornschein type
GNAT1	Orphanet:714096	Congenital stationary night blindness, Riggs type
GRK1	Orphanet:75382	Oguchi disease
RLBP1	Orphanet:227796	Fundus albipunctatus
RLBP1	Orphanet:52427	Retinitis punctata albescens
RLBP1	Orphanet:791	Retinitis pigmentosa
RLBP1	Orphanet:85128	Bothnia retinal dystrophy
RPGR	Orphanet:1872	Cone rod dystrophy
RPGR	Orphanet:244	Primary ciliary dyskinesia
RPGR	Orphanet:247522	Primary ciliary dyskinesia-retinitis pigmentosa syndrome
RPGR	Orphanet:49382	Achromatopsia
RPGR	Orphanet:791	Retinitis pigmentosa
USH2A	Orphanet:231178	Usher syndrome type 2
USH2A	Orphanet:791	Retinitis pigmentosa
ABCA4	Orphanet:1872	Cone rod dystrophy
ABCA4	Orphanet:791	Retinitis pigmentosa
ABCA4	Orphanet:827	Stargardt disease
RBP3	Orphanet:791	Retinitis pigmentosa
RDH5	Orphanet:227796	Fundus albipunctatus
RDH5	Orphanet:52427	Retinitis punctata albescens

Cohort genes → proteins

21 cohort genes, 21 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	21

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RHO	HGNC:10012	ENSG00000163914	P08100	Rhodopsin	gencc,clinvar
CABP4	HGNC:1386	ENSG00000175544	P57796	Calcium-binding protein 4	gencc,clinvar
CACNA1F	HGNC:1393	ENSG00000102001	O60840	Voltage-dependent L-type calcium channel subunit alpha-1F	gencc,clinvar
GPR179	HGNC:31371	ENSG00000277399	Q6PRD1	Probable G-protein coupled receptor 179	gencc,clinvar
GRM6	HGNC:4598	ENSG00000113262	O15303	Metabotropic glutamate receptor 6	gencc,clinvar
TRPM1	HGNC:7146	ENSG00000134160	Q7Z4N2	Transient receptor potential cation channel subfamily M member 1	gencc,clinvar
NYX	HGNC:8082	ENSG00000188937	Q9GZU5	Nyctalopin	gencc,clinvar
PDE6B	HGNC:8786	ENSG00000133256	P35913	Rod cGMP-specific 3’,5’-cyclic phosphodiesterase subunit beta	gencc,clinvar
SLC24A1	HGNC:10975	ENSG00000074621	O60721	Sodium/potassium/calcium exchanger 1	gencc
LRIT3	HGNC:24783	ENSG00000183423	Q3SXY7	Leucine-rich repeat, immunoglobulin-like domain and transmembrane domain-containing protein 3	gencc
GNAT1	HGNC:4393	ENSG00000114349	P11488	Guanine nucleotide-binding protein G(t) subunit alpha-1	gencc
GNB3	HGNC:4400	ENSG00000111664	P16520	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3	gencc
GRK1	HGNC:10013	ENSG00000185974	Q15835	Rhodopsin kinase GRK1	clinvar
RLBP1	HGNC:10024	ENSG00000140522	P12271	Retinaldehyde-binding protein 1	clinvar
RPGR	HGNC:10295	ENSG00000156313	Q92834	X-linked retinitis pigmentosa GTPase regulator	clinvar
USH2A	HGNC:12601	ENSG00000042781	O75445	Usherin	clinvar
ZNF454	HGNC:21200	ENSG00000178187	Q8N9F8	Zinc finger protein 454	clinvar
NLRP9	HGNC:22941	ENSG00000185792	Q7RTR0	NACHT, LRR and PYD domains-containing protein 9	clinvar
ABCA4	HGNC:34	ENSG00000198691	P78363	Retinal-specific phospholipid-transporting ATPase ABCA4	clinvar
RBP3	HGNC:9921	ENSG00000265203	P10745	Retinol-binding protein 3	clinvar
RDH5	HGNC:9940	ENSG00000135437	Q92781	Retinol dehydrogenase 5	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.
CABP4	Calcium-binding protein 4	Involved in normal synaptic function through regulation of Ca(2+) influx and neurotransmitter release in photoreceptor synaptic terminals and in auditory transmission.
CACNA1F	Voltage-dependent L-type calcium channel subunit alpha-1F	Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene exp…
GPR179	Probable G-protein coupled receptor 179	Orphan receptor involved in vision.
GRM6	Metabotropic glutamate receptor 6	G-protein coupled receptor for glutamate.
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.
NYX	Nyctalopin	Required for normal vision.
PDE6B	Rod cGMP-specific 3’,5’-cyclic phosphodiesterase subunit beta	Rod-specific cGMP phosphodiesterase that catalyzes the hydrolysis of 3’,5’-cyclic GMP.
SLC24A1	Sodium/potassium/calcium exchanger 1	Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+).
LRIT3	Leucine-rich repeat, immunoglobulin-like domain and transmembrane domain-containing protein 3	Plays a role in the synapse formation and synaptic transmission between cone photoreceptor cells and retinal bipolar cells.
GNAT1	Guanine nucleotide-binding protein G(t) subunit alpha-1	Functions as a signal transducer for the rod photoreceptor RHO.
GNB3	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3	Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems.
GRK1	Rhodopsin kinase GRK1	Retina-specific kinase involved in the signal turnoff via phosphorylation of rhodopsin (RHO), the G protein- coupled receptor that initiates the phototransduction cascade.
RLBP1	Retinaldehyde-binding protein 1	Soluble retinoid carrier essential the proper function of both rod and cone photoreceptors.
RPGR	X-linked retinitis pigmentosa GTPase regulator	Acts as a guanine-nucleotide releasing factor (GEF) for RAB8A and RAB37 by promoting the conversion of inactive RAB-GDP to the active form RAB-GTP.
USH2A	Usherin	Involved in hearing and vision as member of the USH2 complex.
ZNF454	Zinc finger protein 454	May be involved in transcriptional regulation.
NLRP9	NACHT, LRR and PYD domains-containing protein 9	As the sensor component of the NLRP9 inflammasome, plays a crucial role in innate immunity and inflammation.
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…
RBP3	Retinol-binding protein 3	IRBP shuttles 11-cis and all trans retinoids between the retinol isomerase in the pigment epithelium and the visual pigments in the photoreceptor cells of the retina.
RDH5	Retinol dehydrogenase 5	Catalyzes the oxidation of cis-isomers of retinol, including 11-cis-, 9-cis-, and 13-cis-retinol in an NAD-dependent manner.

Protein-family classification

Druggable: 11 · Difficult: 3 · Unknown: 7 · Druggable fraction: 0.52

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	2	10.6×	0.150
GPCR	3	3.4×	0.276
Antibody/Immunoglobulin	2	2.8×	0.536
Transporter	1	3.7×	0.595
Protease	1	1.7×	0.882
Kinase	1	1.3×	0.896
Scaffold/PPI	1	0.8×	0.927
Transcription factor	2	0.8×	0.927
Enzyme (other)	1	0.6×	0.933
Other/Unknown	7	0.6×	0.989

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RHO	GPCR	yes		GPCR_Rhodpsn, Rhodopsin, Opsin
CABP4	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS
CACNA1F	Ion channel	yes		VDCCAlpha1, VDCC_L_a1su, Ion_trans_dom
GPR179	GPCR	yes		GPCR_3_C, GPR158/179, GPR158_179_extracellular
GRM6	GPCR	yes		GPCR_3__mGluR6, GPCR_3_mtglu_rcpt, GPCR_3
TRPM1	Ion channel	yes		Ion_trans_dom, TRPM_tetra, TRPM_tetra_sf
NYX	Other/Unknown	no		Cys-rich_flank_reg_C, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
PDE6B	Transcription factor	no		PDEase_catalytic_dom, GAF, HD/PDEase_dom
SLC24A1	Other/Unknown	no		K/Na/Ca-exchanger, SLC24A1, NaCa_Exmemb
LRIT3	Antibody/Immunoglobulin	yes		Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, Ig_sub2
GNAT1	Other/Unknown	no		Gprotein_alpha_su, Gprotein_alpha_I, GproteinA_insert
GNB3	Scaffold/PPI	no		WD40_G-protein_beta-like, WD40_rpt, WD40/YVTN_repeat-like_dom_sf
GRK1	Kinase	yes	2.7.11.14	GPCR_kinase, Prot_kinase_dom, AGC-kinase_C
RLBP1	Other/Unknown	no		CRAL-TRIO_dom, CRAL/TRIO_N_dom, CRAL/TRIO_N_dom_sf
RPGR	Other/Unknown	no		Reg_chr_condens, RCC1/BLIP-II, Signaling_Regulatory_Domain
USH2A	Antibody/Immunoglobulin	yes		Laminin_G, LE_dom, FN3_dom
ZNF454	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
NLRP9	Other/Unknown	no		Leu-rich_rpt, DAPIN, NACHT_NTPase
ABCA4	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABCA4/ABCR
RBP3	Protease	yes		Tail-specific_protease, ClpP/crotonase-like_dom_sf
RDH5	Enzyme (other)	yes	1.1.1.300	SDR_fam, NAD(P)-bd_dom_sf

Expression context

Cohort genes with no expression data: 0.

17 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)	1
broad (>20)	20
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	9
primordial germ cell in gonad	4
pancreatic ductal cell	3
pigmented layer of retina	3
neuron projection bundle connecting eye with brain	2
optic choroid	2
right hemisphere of cerebellum	2
superior frontal gyrus	2
retina	2
right uterine tube	2
cerebellar hemisphere	2
right lobe of liver	2
diaphragm	1
cardia of stomach	1
vena cava	1
ventral tegmental area	1
granulocyte	1
parotid gland	1
prefrontal cortex	1
tibialis anterior	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
CABP4	226	broad	marker	vena cava, cardia of stomach, ventral tegmental area
CACNA1F	143	tissue_specific	marker	parotid gland, granulocyte, right hemisphere of cerebellum
GPR179	73	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, prefrontal cortex, superior frontal gyrus
GRM6	140	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, pancreatic ductal cell, tibialis anterior
TRPM1	119	tissue_specific	marker	pigmented layer of retina, retina, nipple
NYX	20	tissue_specific	yes	tendon of biceps brachii, primordial germ cell in gonad, pancreatic ductal cell
PDE6B	183	broad	marker	C1 segment of cervical spinal cord, right uterine tube, spinal cord
SLC24A1	220	ubiquitous	marker	endothelial cell, sural nerve, male germ line stem cell (sensu Vertebrata) in testis
LRIT3	114	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, superior frontal gyrus, cerebellar hemisphere
GNAT1	97	tissue_specific	marker	neuron projection bundle connecting eye with brain, endometrium epithelium, frontal pole
GNB3	185	tissue_specific	marker	adenohypophysis, right hemisphere of cerebellum, cerebellar hemisphere
GRK1	52	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, right lobe of thyroid gland, left lobe of thyroid gland
RLBP1	126	tissue_specific	marker	pigmented layer of retina, retina, optic choroid
RPGR	281	ubiquitous	marker	sperm, bronchial epithelial cell, right uterine tube
USH2A	30	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, right lobe of liver, buccal mucosa cell
ZNF454	130	broad	yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, cortical plate
NLRP9	52		marker	secondary oocyte, oocyte, primordial germ cell in gonad
ABCA4	164	tissue_specific	marker	pigmented layer of retina, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis
RBP3	38	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, pancreatic ductal cell, skeletal muscle tissue of biceps brachii
RDH5	141	broad	marker	subcutaneous adipose tissue, right lobe of liver, adipose tissue

Protein interactions among cohort

Intra-cohort edges: 55.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RHO	3,578
GNB3	3,205
USH2A	2,332
RPGR	2,231
LRIT3	1,992
CABP4	1,897
GNAT1	1,865
CACNA1F	1,616
GRM6	1,614
ABCA4	1,532

Intra-cohort edges

A	B	Sources
ABCA4	RDH5	string_interaction
ABCA4	RHO	string_interaction
ABCA4	RPGR	string_interaction
CABP4	CACNA1F	biogrid_interaction, string_interaction
CABP4	GNAT1	string_interaction
CABP4	GPR179	string_interaction
CABP4	GRM6	string_interaction
CABP4	LRIT3	string_interaction
CABP4	NYX	string_interaction
CABP4	PDE6B	string_interaction
CABP4	RDH5	string_interaction
CABP4	SLC24A1	string_interaction
CABP4	TRPM1	string_interaction
CACNA1F	GPR179	string_interaction
CACNA1F	GRM6	string_interaction
CACNA1F	LRIT3	string_interaction
CACNA1F	NYX	string_interaction
CACNA1F	RPGR	string_interaction
CACNA1F	TRPM1	string_interaction
GNAT1	GPR179	string_interaction
GNAT1	GRK1	string_interaction
GNAT1	GRM6	string_interaction
GNAT1	LRIT3	string_interaction
GNAT1	NYX	string_interaction
GNAT1	PDE6B	string_interaction
GNAT1	RHO	string_interaction
GNAT1	SLC24A1	string_interaction
GPR179	GRM6	string_interaction
GPR179	LRIT3	string_interaction
GPR179	NYX	string_interaction
GPR179	PDE6B	string_interaction
GPR179	SLC24A1	string_interaction
GPR179	TRPM1	string_interaction
GRK1	RHO	biogrid_interaction, string_interaction
GRM6	LRIT3	string_interaction
GRM6	NYX	string_interaction
GRM6	RHO	string_interaction
GRM6	TRPM1	string_interaction
LRIT3	NYX	string_interaction
LRIT3	PDE6B	string_interaction
LRIT3	SLC24A1	string_interaction
LRIT3	TRPM1	string_interaction
NYX	PDE6B	string_interaction
NYX	RPGR	string_interaction
NYX	TRPM1	string_interaction
PDE6B	RHO	string_interaction
PDE6B	RPGR	string_interaction
PDE6B	SLC24A1	string_interaction
RBP3	RDH5	string_interaction
RBP3	RHO	string_interaction

Structural data

PDB: 10 · AlphaFold-only: 11 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCA4	P78363	8
GRM6	O15303	5
RHO	P08100	4
RLBP1	P12271	4
RPGR	Q92834	3
GPR179	Q6PRD1	2
GNB3	P16520	2
NLRP9	Q7RTR0	2
GNAT1	P11488	1
GRK1	Q15835	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RDH5	Q92781	96.02
PDE6B	P35913	89.72
RBP3	P10745	85.10
NYX	Q9GZU5	82.68
ZNF454	Q8N9F8	73.66
LRIT3	Q3SXY7	70.06
CACNA1F	O60840	67.46
TRPM1	Q7Z4N2	66.74
CABP4	P57796	65.01
SLC24A1	O60721	55.56
USH2A	O75445

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 60. Enrichment computed across 21 evidence-associated genes (13 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 13 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)	5	199.7×	1e-09	RHO, RLBP1, ABCA4, RBP3, RDH5
Activation of the phototransduction cascade	4	292.8×	1e-08	RHO, PDE6B, SLC24A1, GNAT1
Inactivation, recovery and regulation of the phototransduction cascade	4	97.6×	1e-06	RHO, PDE6B, GRK1, GNAT1
Defective visual phototransduction due to RDH5 loss of function	2	878.5×	2e-05	RLBP1, RDH5
The retinoid cycle in cones (daylight vision)	2	251.0×	3e-04	RLBP1, RBP3
G alpha (i) signalling events	4	12.0×	0.003	RHO, GRM6, GNAT1, GNB3
Defective SLC24A1 causes congenital stationary night blindness 1D (CSNB1D)	1	878.5×	0.008	SLC24A1
Defective visual phototransduction due to ABCA4 loss of function	1	878.5×	0.008	ABCA4
Visual phototransduction	2	39.9×	0.008	SLC24A1, ABCA4
Ca2+ pathway	2	27.4×	0.014	PDE6B, GNB3
Retinoid cycle disease events	1	219.6×	0.021	ABCA4
Diseases associated with visual transduction	1	219.6×	0.021	ABCA4
Diseases of the neuronal system	1	219.6×	0.021	ABCA4
Sensory Perception	2	14.6×	0.034	SLC24A1, ABCA4
The phototransduction cascade	1	97.6×	0.038	SLC24A1
Opsins	1	97.6×	0.038	RHO
Sodium/Calcium exchangers	1	79.9×	0.044	SLC24A1
G beta:gamma signalling through BTK	1	48.8×	0.056	GNB3
Regulation of MITF-M-dependent genes involved in apoptosis	1	48.8×	0.056	TRPM1
Prostacyclin signalling through prostacyclin receptor	1	46.2×	0.056	GNB3
G beta:gamma signalling through PLC beta	1	43.9×	0.056	GNB3
G beta:gamma signalling through CDC42	1	43.9×	0.056	GNB3
Presynaptic function of Kainate receptors	1	41.8×	0.056	GNB3
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)	1	39.9×	0.056	GNB3
VxPx cargo-targeting to cilium	1	39.9×	0.056	RHO
ADP signalling through P2Y purinoceptor 12	1	38.2×	0.056	GNB3
G-protein activation	1	36.6×	0.056	GNB3
Thromboxane signalling through TP receptor	1	36.6×	0.056	GNB3
RA biosynthesis pathway	1	36.6×	0.056	RDH5
ADP signalling through P2Y purinoceptor 1	1	35.1×	0.056	GNB3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 21 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	17	64.3×	2e-27	RHO, CABP4, CACNA1F, GPR179, TRPM1, NYX, PDE6B, GRK1 (+9 more)
phototransduction, visible light	4	246.9×	7e-08	RHO, PDE6B, ABCA4, GNAT1
G protein-coupled opsin signaling pathway	3	481.5×	6e-07	RHO, GRK1, GNAT1
detection of light stimulus involved in visual perception	3	92.6×	1e-04	CACNA1F, GRM6, GNAT1
calcium ion import across plasma membrane	3	77.7×	2e-04	CACNA1F, TRPM1, SLC24A1
retinoid metabolic process	3	70.8×	2e-04	ABCA4, RBP3, RDH5
photoreceptor cell maintenance	3	51.2×	4e-04	RHO, USH2A, ABCA4
response to light intensity	2	200.6×	6e-04	RHO, SLC24A1
regulation of opsin-mediated signaling pathway	2	160.5×	8e-04	GRK1, GNAT1
G protein-coupled glutamate receptor signaling pathway	2	100.3×	0.002	GRM6, TRPM1
cellular response to light stimulus	2	100.3×	0.002	RHO, TRPM1
response to light stimulus	2	84.5×	0.002	LRIT3, GNAT1
eye photoreceptor cell development	2	80.2×	0.002	RPGR, GNAT1
phototransduction	2	47.2×	0.006	RHO, CABP4
detection of visible light	1	802.5×	0.008	GRM6
negative regulation of cyclic-nucleotide phosphodiesterase activity	1	802.5×	0.008	GNAT1
regulation of phospholipid metabolic process	1	802.5×	0.008	GNB3
thermotaxis	1	401.2×	0.012	RHO
synapse assembly involved in innervation	1	401.2×	0.012	LRIT3
background adaptation	1	401.2×	0.012	GNAT1
rod bipolar cell differentiation	1	401.2×	0.012	RHO
retinal cell apoptotic process	1	401.2×	0.012	PDE6B
gene expression	3	11.4×	0.012	RHO, GRM6, LRIT3
retina development in camera-type eye	2	24.3×	0.013	GRM6, PDE6B
phospholipid transfer to membrane	1	267.5×	0.014	ABCA4
dopamine secretion	1	267.5×	0.014	GNAT1
retinal cone cell differentiation	1	267.5×	0.014	GNAT1
detection of temperature stimulus involved in thermoception	1	267.5×	0.014	RHO
calcium ion transmembrane transport	2	20.1×	0.016	TRPM1, SLC24A1
protein localization to non-motile cilium	1	200.6×	0.017	RPGR

Therapeutics

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 4 · Phased (≥1): 4 · Undrugged: 17

Druggability breadth: 5 of 21 evidence-associated genes (24%) 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
CACNA1F	BEPRIDIL
GRM6	MICONAZOLE
PDE6B	VARDENAFIL
GRK1	RUXOLITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CACNA1F	48	4
GRK1	12	4
PDE6B	6	4
GRM6	3	4
RHO	0	0
CABP4	0	0
GPR179	0	0
TRPM1	0	0
NYX	0	0
SLC24A1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEPRIDIL	4	CACNA1F
IMIPRAMINE	4	CACNA1F
HALOFANTRINE	4	CACNA1F
DROPERIDOL	4	CACNA1F
SAQUINAVIR	4	CACNA1F
DULOXETINE	4	CACNA1F
DIAZEPAM	4	CACNA1F
SERTINDOLE	4	CACNA1F
QUINIDINE	4	CACNA1F
LAMIVUDINE	4	CACNA1F
PIMOZIDE	4	CACNA1F
PHENYTOIN	4	CACNA1F
TERFENADINE	4	CACNA1F
CISAPRIDE	4	CACNA1F
SOLIFENACIN	4	CACNA1F
NIFEDIPINE	4	CACNA1F
DILTIAZEM	4	CACNA1F
NILOTINIB	4	CACNA1F
ASTEMIZOLE	4	CACNA1F
TERODILINE	4	CACNA1F
CLOZAPINE	4	CACNA1F
MIBEFRADIL	4	CACNA1F
DOFETILIDE	4	CACNA1F
THIORIDAZINE	4	CACNA1F
PAROXETINE	4	CACNA1F
DONEPEZIL	4	CACNA1F
IBUTILIDE	4	CACNA1F
SUNITINIB	4	CACNA1F, GRK1
HALOPERIDOL	4	CACNA1F
DASATINIB	4	CACNA1F

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
CACNA1F	221	Binding:135, Functional:79, Toxicity:5, ADMET:2
GRK1	123	Binding:123
GRM6	103	Functional:55, Binding:48
PDE6B	57	Binding:54, ADMET:3
RHO	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GRK1	2.7.11.14	rhodopsin kinase
RDH5	1.1.1.300, 1.1.1.315	NADP-retinol dehydrogenase, 11-cis-retinol dehydrogenase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CACNA1F	221
GRM6	103
GRK1	123

Pharmacogenomics

Cohort genes with a PharmGKB record: 21; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 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)
BEPRIDIL	4	CACNA1F
IMIPRAMINE	4	CACNA1F
HALOFANTRINE	4	CACNA1F
DROPERIDOL	4	CACNA1F
SAQUINAVIR	4	CACNA1F
DULOXETINE	4	CACNA1F
DIAZEPAM	4	CACNA1F
SERTINDOLE	4	CACNA1F
QUINIDINE	4	CACNA1F
LAMIVUDINE	4	CACNA1F
PIMOZIDE	4	CACNA1F
PHENYTOIN	4	CACNA1F
TERFENADINE	4	CACNA1F
CISAPRIDE	4	CACNA1F
SOLIFENACIN	4	CACNA1F
NIFEDIPINE	4	CACNA1F
DILTIAZEM	4	CACNA1F
NILOTINIB	4	CACNA1F
ASTEMIZOLE	4	CACNA1F
TERODILINE	4	CACNA1F
CLOZAPINE	4	CACNA1F
MIBEFRADIL	4	CACNA1F
DOFETILIDE	4	CACNA1F
THIORIDAZINE	4	CACNA1F
PAROXETINE	4	CACNA1F
DONEPEZIL	4	CACNA1F
IBUTILIDE	4	CACNA1F
SUNITINIB	4	CACNA1F, GRK1
HALOPERIDOL	4	CACNA1F
DASATINIB	4	CACNA1F

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	CACNA1F, GRM6, PDE6B, GRK1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	3	RHO, GPR179, ABCA4
D	Druggable family + AlphaFold only, no drug	5	TRPM1, LRIT3, USH2A, RBP3, RDH5
E	Difficult family or no structure, no drug	9	CABP4, NYX, SLC24A1, GNAT1, GNB3, RLBP1, RPGR, ZNF454, NLRP9

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RHO	1	GRK1
CABP4	0	CACNA1F
GPR179	0	GRM6
TRPM1	0	GRM6
NYX	0	CACNA1F, GRM6
SLC24A1	0	PDE6B
LRIT3	0	CACNA1F, GRM6
GNAT1	0	—
GNB3	0	—
RLBP1	0	—
RPGR	0	—
USH2A	0	—
ZNF454	0	—
NLRP9	0	—
ABCA4	0	—
RBP3	0	—
RDH5	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
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT02909985	Not specified	COMPLETED	Visual Activity Evoked by Infrared in Humans After Dark Adaptation

Cohort genes: RHO, CABP4, CACNA1F, GPR179, GRM6, TRPM1, NYX, PDE6B, SLC24A1, LRIT3, GNAT1, GNB3, GRK1, RLBP1, RPGR, USH2A, ZNF454, NLRP9, ABCA4, RBP3, RDH5