congenital stationary night blindness 1C

Summary

congenital stationary night blindness 1C (MONDO:0013183) is a disease caused by TRPM1 (GenCC Definitive), with 6 cohort genes.

At a glance

• Causal gene: TRPM1 (GenCC Definitive)
• Cohort genes: 6
• ClinVar variants: 189

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital stationary night blindness 1C
Mondo ID	MONDO:0013183
MeSH	C567704
OMIM	613216
DOID	DOID:0110867
UMLS	C2750747
MedGen	416373
GARD	0015631
Is cancer (heuristic)	no

Also known as: congenital stationary night blindness 1C · congenital stationary night blindness caused by mutation in TRPM1 · congenital stationary night blindness type 1C · CSNB1C · night blindness, congenital stationary (complete), 1C, autosomal recessive · night blindness, congenital stationary, type 1C · TRPM1 congenital stationary night blindness

Data availability: 189 ClinVar variants · 3 GenCC gene-disease records.

Disease family

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 › congenital stationary night blindness 1C

Related subtypes (13): congenital stationary night blindness autosomal dominant 2, congenital stationary night blindness 1B, cone-rod synaptic disorder, congenital nonprogressive, congenital stationary night blindness autosomal dominant 3, congenital stationary night blindness autosomal dominant 1, congenital stationary night blindness 1D, congenital stationary night blindness 1E, congenital stationary night blindness 1F, congenital stationary night blindness 1G, congenital stationary night blindness 1H, Oguchi disease, night blindness, congenital stationary, type1i, X-linked 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

189 retrieved; paginated sample, class counts are floors:

56 uncertain significance, 46 conflicting classifications of pathogenicity, 29 benign, 17 likely pathogenic, 16 pathogenic, 14 benign/likely benign, 7 pathogenic/likely pathogenic, 4 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
195958	NM_001252024.2(TRPM1):c.3571del (p.Glu1191fs)	LOC126862088	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812125	NC_000015.10:g.(?31001061)(31161273_?)del	MIR211	Pathogenic	criteria provided, single submitter
1072860	NM_001252024.2(TRPM1):c.2543C>T (p.Ala848Val)	TRPM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1323717	NM_001252024.2(TRPM1):c.2013C>A (p.Tyr671Ter)	TRPM1	Pathogenic	criteria provided, single submitter
1325238	NM_001252024.2(TRPM1):c.3104_3105dup (p.Val1036fs)	TRPM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1459633	NM_001252024.2(TRPM1):c.482del (p.Gly161fs)	TRPM1	Pathogenic	criteria provided, single submitter
1517049	NM_001252024.2(TRPM1):c.3127+1G>A	TRPM1	Pathogenic	criteria provided, multiple submitters, no conflicts
1710199	NM_001252024.2(TRPM1):c.1305_1324del (p.Glu436fs)	TRPM1	Pathogenic	no assertion criteria provided
2137643	NM_001252024.2(TRPM1):c.2343del (p.Thr782fs)	TRPM1	Pathogenic	criteria provided, multiple submitters, no conflicts
30363	NM_001252024.2(TRPM1):c.2711C>A (p.Ser904Ter)	TRPM1	Pathogenic	no assertion criteria provided
30364	NM_001252024.2(TRPM1):c.1089+3_1089+6del	TRPM1	Pathogenic	criteria provided, single submitter
3363168	NM_001252024.2(TRPM1):c.2373T>A (p.Tyr791Ter)	TRPM1	Pathogenic	criteria provided, single submitter
593857	NM_001252024.2(TRPM1):c.2695C>T (p.Arg899Ter)	TRPM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
6223	NM_001252024.2(TRPM1):c.2087+2T>C	TRPM1	Pathogenic	no assertion criteria provided
6226	NM_001252024.2(TRPM1):c.97C>T (p.Gln33Ter)	TRPM1	Pathogenic	no assertion criteria provided
6229	NG_016453.2:g.66830_103274del	TRPM1	Pathogenic	no assertion criteria provided
631727	NM_001252024.2(TRPM1):c.3148+1G>A	TRPM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
645561	NM_001252024.2(TRPM1):c.1966C>T (p.Arg656Ter)	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
931853	NM_001252024.2(TRPM1):c.4793_4796dup (p.Ser1600fs)	TRPM1	Pathogenic	criteria provided, single submitter
3363166	NM_001252024.2(TRPM1):c.3496_3496+1del	TRPM1-AS1	Pathogenic	criteria provided, single submitter
3363167	NM_001252024.2(TRPM1):c.3572del (p.Glu1191fs)	TRPM1-AS1	Pathogenic	criteria provided, single submitter
6225	NM_001252024.2(TRPM1):c.3171T>A (p.Tyr1057Ter)	TRPM1-AS1	Pathogenic	criteria provided, single submitter
3366905	NM_144499.3(GNAT1):c.98T>C (p.Leu33Pro)	GNAT1	Likely pathogenic	criteria provided, single submitter
3366971	NM_144499.3(GNAT1):c.124A>G (p.Lys42Glu)	GNAT1	Likely pathogenic	criteria provided, single submitter
3363122	NM_000843.4(GRM6):c.2497G>C (p.Gly833Arg)	GRM6	Likely pathogenic	criteria provided, single submitter
4849361	NM_001252024.2(TRPM1):c.3336del (p.Val1111_Trp1112insTer)	LOC126862088	Likely pathogenic	criteria provided, single submitter
1184564	NM_001252024.2(TRPM1):c.4842del (p.Lys1615fs)	TRPM1	Likely pathogenic	no assertion criteria provided
2115434	NM_001252024.2(TRPM1):c.83+1G>A	TRPM1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
224740	NM_001252024.2(TRPM1):c.773T>C (p.Leu258Pro)	TRPM1	Likely pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 3 · 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
TRPM1	Definitive	Autosomal recessive	congenital stationary night blindness 1C	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRPM1	Orphanet:714079	Complete congenital stationary night blindness, Schubert-Bornschein type
GNAT1	Orphanet:714096	Congenital stationary night blindness, Riggs type
GRM6	Orphanet:714079	Complete congenital stationary night blindness, Schubert-Bornschein type

Cohort genes → proteins

6 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TRPM1	HGNC:7146	ENSG00000134160	Q7Z4N2	Transient receptor potential cation channel subfamily M member 1	gencc,clinvar
MIR211	HGNC:31588	ENSG00000207702		microRNA 211	clinvar
GNAT1	HGNC:4393	ENSG00000114349	P11488	Guanine nucleotide-binding protein G(t) subunit alpha-1	clinvar
GRM6	HGNC:4598	ENSG00000113262	O15303	Metabotropic glutamate receptor 6	clinvar
TRPM1-AS1	HGNC:58477	ENSG00000259720		TRPM1 antisense RNA 1	clinvar
NYX	HGNC:8082	ENSG00000188937	Q9GZU5	Nyctalopin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
GNAT1	Guanine nucleotide-binding protein G(t) subunit alpha-1	Functions as a signal transducer for the rod photoreceptor RHO.
GRM6	Metabotropic glutamate receptor 6	G-protein coupled receptor for glutamate.
NYX	Nyctalopin	Required for normal vision.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 4 · Druggable fraction: 0.33

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	18.6×	0.158
GPCR	1	4.0×	0.339
Other/Unknown	4	1.2×	0.458

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRPM1	Ion channel	yes		Ion_trans_dom, TRPM_tetra, TRPM_tetra_sf
MIR211	Other/Unknown	no
GNAT1	Other/Unknown	no		Gprotein_alpha_su, Gprotein_alpha_I, GproteinA_insert
GRM6	GPCR	yes		GPCR_3__mGluR6, GPCR_3_mtglu_rcpt, GPCR_3
TRPM1-AS1	Other/Unknown	no
NYX	Other/Unknown	no		Cys-rich_flank_reg_C, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp

Expression context

Cohort genes with no expression data: 0.

3 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
pancreatic ductal cell	2
nipple	1
pigmented layer of retina	1
retina	1
blood	1
gastrocnemius	1
placenta	1
endometrium epithelium	1
frontal pole	1
neuron projection bundle connecting eye with brain	1
male germ line stem cell (sensu Vertebrata) in testis	1
tibialis anterior	1
left testis	1
right testis	1
sperm	1
primordial germ cell in gonad	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRPM1	119	tissue_specific	marker	pigmented layer of retina, retina, nipple
MIR211	39		yes	blood, gastrocnemius, placenta
GNAT1	97	tissue_specific	marker	neuron projection bundle connecting eye with brain, endometrium epithelium, frontal pole
GRM6	140	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, pancreatic ductal cell, tibialis anterior
TRPM1-AS1	92		yes	left testis, right testis, sperm
NYX	20	tissue_specific	yes	tendon of biceps brachii, primordial germ cell in gonad, pancreatic ductal cell

Protein interactions among cohort

Intra-cohort edges: 5.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GNAT1	1,865
GRM6	1,614
NYX	1,227
TRPM1	1,190
MIR211	0
TRPM1-AS1	0

Intra-cohort edges

A	B	Sources
GNAT1	GRM6	string_interaction
GNAT1	NYX	string_interaction
GRM6	NYX	string_interaction
GRM6	TRPM1	string_interaction
NYX	TRPM1	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GRM6	O15303	5
GNAT1	P11488	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NYX	Q9GZU5	82.68
TRPM1	Q7Z4N2	66.74

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 6 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Regulation of MITF-M-dependent genes involved in apoptosis	2	317.2×	8e-05	TRPM1, MIR211
Activation of the phototransduction cascade	1	237.9×	0.008	GNAT1
G alpha (i) signalling events	2	19.5×	0.008	GNAT1, GRM6
TRP channels	1	102.0×	0.014	TRPM1
Inactivation, recovery and regulation of the phototransduction cascade	1	79.3×	0.014	GNAT1
Class C/3 (Metabotropic glutamate/pheromone receptors)	1	73.2×	0.014	GRM6

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
G protein-coupled glutamate receptor signaling pathway	2	526.6×	1e-04	TRPM1, GRM6
visual perception	3	59.6×	1e-04	TRPM1, GNAT1, NYX
detection of light stimulus involved in visual perception	2	324.1×	2e-04	GNAT1, GRM6
detection of visible light	1	4213.0×	0.002	GRM6
negative regulation of cyclic-nucleotide phosphodiesterase activity	1	4213.0×	0.002	GNAT1
background adaptation	1	2106.5×	0.003	GNAT1
dopamine secretion	1	1404.3×	0.003	GNAT1
retinal cone cell differentiation	1	1404.3×	0.003	GNAT1
neural tissue regeneration	1	1053.2×	0.004	GNAT1
G protein-coupled opsin signaling pathway	1	842.6×	0.004	GNAT1
visual behavior	1	702.2×	0.005	GNAT1
sensory perception of umami taste	1	601.9×	0.005	GNAT1
retinal rod cell differentiation	1	468.1×	0.006	GNAT1
regulation of opsin-mediated signaling pathway	1	421.3×	0.006	GNAT1
positive regulation of calcium ion import across plasma membrane	1	421.3×	0.006	GRM6
phototransduction, visible light	1	324.1×	0.006	GNAT1
cellular response to electrical stimulus	1	324.1×	0.006	GNAT1
cellular response to light stimulus	1	263.3×	0.007	TRPM1
response to light stimulus	1	221.7×	0.008	GNAT1
eye photoreceptor cell development	1	210.7×	0.008	GNAT1
protein tetramerization	1	156.0×	0.010	TRPM1
monoatomic cation transmembrane transport	1	156.0×	0.010	TRPM1
calcium ion import across plasma membrane	1	135.9×	0.011	TRPM1
regulation of synaptic transmission, glutamatergic	1	127.7×	0.011	GRM6
detection of chemical stimulus involved in sensory perception of bitter taste	1	120.4×	0.012	GNAT1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1	84.3×	0.016	GNAT1
retina development in camera-type eye	1	63.8×	0.020	GRM6
synapse assembly	1	57.7×	0.022	GRM6
calcium ion transmembrane transport	1	52.7×	0.023	TRPM1
calcium ion transport	1	45.3×	0.025	TRPM1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 6 evidence-associated genes (17%) 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
GRM6	MICONAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GRM6	3	4
TRPM1	0	0
MIR211	0	0
GNAT1	0	0
TRPM1-AS1	0	0
NYX	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MICONAZOLE	4	GRM6
GLUTAMIC ACID	3	GRM6
EGLUMETAD	2	GRM6

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GRM6	103	Functional:55, Binding:48

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
GRM6	103

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

3 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)
MICONAZOLE	4	GRM6
GLUTAMIC ACID	3	GRM6
EGLUMETAD	2	GRM6

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GRM6
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	TRPM1
E	Difficult family or no structure, no drug	4	MIR211, GNAT1, TRPM1-AS1, NYX

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)
TRPM1	0	GRM6
NYX	0	GRM6
MIR211	0	—
GNAT1	0	—
TRPM1-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.