congenital stationary night blindness 1B

Summary

congenital stationary night blindness 1B (MONDO:0009758) is a disease caused by GRM6 (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: GRM6 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 41

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital stationary night blindness 1B
Mondo ID	MONDO:0009758
OMIM	257270
DOID	DOID:0110865
UMLS	C1850362
MedGen	342484
GARD	0015212
Is cancer (heuristic)	no

Also known as: congenital stationary night blindness 1B · congenital stationary night blindness caused by mutation in GRM6 · congenital stationary night blindness type 1B · CSNB1B · GRM6 congenital stationary night blindness · night blindness, congenital stationary (complete), 1B, autosomal recessive · night blindness, congenital stationary, type 1B

Data availability: 41 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › congenital stationary night blindness 1B

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 nystagmus, 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, 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

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

41 retrieved; paginated sample, class counts are floors:

11 uncertain significance, 9 benign, 6 likely pathogenic, 5 pathogenic, 5 conflicting classifications of pathogenicity, 4 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1072852	NM_000843.4(GRM6):c.1336C>T (p.Arg446Ter)	GRM6	Pathogenic	criteria provided, multiple submitters, no conflicts
1323038	NM_000843.4(GRM6):c.722-1G>T	GRM6	Pathogenic	criteria provided, single submitter
1323039	NM_000843.4(GRM6):c.2066del (p.Pro689fs)	GRM6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5840	NM_000843.4(GRM6):c.1861C>T (p.Arg621Ter)	GRM6	Pathogenic	criteria provided, multiple submitters, no conflicts
99658	NM_000843.4(GRM6):c.727dup	GRM6	Pathogenic	criteria provided, single submitter
5842	NM_000843.4(GRM6):c.2122C>T (p.Gln708Ter)	ZNF454	Pathogenic	criteria provided, multiple submitters, no conflicts
3234913	NM_001004334.4(GPR179):c.1144del (p.Ala382fs)	GPR179	Likely pathogenic	criteria provided, single submitter
2664907	NM_000843.4(GRM6):c.340C>T (p.Gln114Ter)	GRM6	Likely pathogenic	criteria provided, single submitter
5843	NM_000843.4(GRM6):c.448G>A (p.Gly150Ser)	GRM6	Likely pathogenic	criteria provided, single submitter
5844	NM_000843.4(GRM6):c.137C>T (p.Pro46Leu)	GRM6	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3065763	NM_000843.4(GRM6):c.2236_2237del (p.Met746fs)	ZNF454	Likely pathogenic	criteria provided, single submitter
3377670	NM_000843.4(GRM6):c.2560C>T (p.Arg854Ter)	ZNF454	Likely pathogenic	criteria provided, single submitter
1443702	NM_000843.4(GRM6):c.575G>A (p.Arg192Gln)	GRM6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
225382	NM_000843.4(GRM6):c.1537G>A (p.Val513Met)	GRM6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
5847	NM_000843.4(GRM6):c.1214T>C (p.Ile405Thr)	GRM6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
441099	NM_000843.4(GRM6):c.2213_2219del (p.Ala738fs)	ZNF454	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
834737	NM_000843.4(GRM6):c.2029C>T (p.Arg677Cys)	ZNF454	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2432309	NM_000843.4(GRM6):c.824G>A (p.Gly275Asp)	GRM6	Uncertain significance	criteria provided, single submitter
3775452	NM_000843.4(GRM6):c.143A>G (p.His48Arg)	GRM6	Uncertain significance	criteria provided, single submitter
3893159	NM_000843.4(GRM6):c.524C>G (p.Ala175Gly)	GRM6	Uncertain significance	criteria provided, single submitter
4278211	NM_000843.4(GRM6):c.2030G>A (p.Arg677His)	GRM6	Uncertain significance	criteria provided, single submitter
5841	NM_000843.4(GRM6):c.2341G>A (p.Glu781Lys)	GRM6	Uncertain significance	criteria provided, single submitter
636174	NM_000843.4(GRM6):c.527C>T (p.Ser176Phe)	GRM6	Uncertain significance	criteria provided, single submitter
3615898	NM_000843.4(GRM6):c.1402G>A (p.Gly468Arg)	ZNF454	Uncertain significance	criteria provided, multiple submitters, no conflicts
4292543	NM_000843.4(GRM6):c.1175A>T (p.Asp392Val)	ZNF454	Uncertain significance	criteria provided, single submitter
4294087	NM_000843.4(GRM6):c.1160A>C (p.Glu387Ala)	ZNF454	Uncertain significance	criteria provided, single submitter
5846	NM_000843.4(GRM6):c.1565G>A (p.Cys522Tyr)	ZNF454	Uncertain significance	criteria provided, single submitter
957582	NM_000843.4(GRM6):c.2240C>T (p.Ser747Leu)	ZNF454	Uncertain significance	criteria provided, multiple submitters, no conflicts
198107	NM_000843.4(GRM6):c.1307C>T (p.Thr436Ile)	GRM6	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
522285	NM_000843.4(GRM6):c.1533C>T (p.His511=)	GRM6	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
GRM6	Definitive	Autosomal recessive	congenital stationary night blindness 1B	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GRM6	Orphanet:714079	Complete congenital stationary night blindness, Schubert-Bornschein type
GPR179	Orphanet:714079	Complete congenital stationary night blindness, Schubert-Bornschein type

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GRM6	HGNC:4598	ENSG00000113262	O15303	Metabotropic glutamate receptor 6	gencc,clinvar
ZNF454	HGNC:21200	ENSG00000178187	Q8N9F8	Zinc finger protein 454	clinvar
GPR179	HGNC:31371	ENSG00000277399	Q6PRD1	Probable G-protein coupled receptor 179	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GRM6	Metabotropic glutamate receptor 6	G-protein coupled receptor for glutamate.
ZNF454	Zinc finger protein 454	May be involved in transcriptional regulation.
GPR179	Probable G-protein coupled receptor 179	Orphan receptor involved in vision.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.67

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
GPCR	2	16.0×	0.010
Transcription factor	1	2.8×	0.321

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GRM6	GPCR	yes		GPCR_3__mGluR6, GPCR_3_mtglu_rcpt, GPCR_3
ZNF454	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
GPR179	GPCR	yes		GPCR_3_C, GPR158/179, GPR158_179_extracellular

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	3
pancreatic ductal cell	1
tibialis anterior	1
cortical plate	1
primordial germ cell in gonad	1
prefrontal cortex	1
superior frontal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GRM6	140	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, pancreatic ductal cell, tibialis anterior
ZNF454	130	broad	yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, cortical plate
GPR179	73	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, prefrontal cortex, superior frontal gyrus

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GRM6	1,614
GPR179	959
ZNF454	324

Intra-cohort edges

A	B	Sources
GPR179	GRM6	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GRM6	O15303	5
GPR179	Q6PRD1	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ZNF454	Q8N9F8	73.66

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Class C/3 (Metabotropic glutamate/pheromone receptors)	1	146.4×	0.027	GRM6
Regulation of endogenous retroelements by KRAB-ZFP proteins	1	53.4×	0.037	ZNF454
G alpha (i) signalling events	1	19.5×	0.068	GRM6
Generic Transcription Pathway	1	7.5×	0.128	ZNF454

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
detection of visible light	1	5617.3×	0.002	GRM6
positive regulation of calcium ion import across plasma membrane	1	561.7×	0.012	GRM6
G protein-coupled glutamate receptor signaling pathway	1	351.1×	0.012	GRM6
detection of light stimulus involved in visual perception	1	216.1×	0.015	GRM6
regulation of synaptic transmission, glutamatergic	1	170.2×	0.015	GRM6
retina development in camera-type eye	1	85.1×	0.024	GRM6
synapse assembly	1	77.0×	0.024	GRM6
locomotory behavior	1	59.8×	0.027	GRM6
protein localization to plasma membrane	1	36.2×	0.039	GPR179
gene expression	1	26.6×	0.042	GRM6
visual perception	1	26.5×	0.042	GPR179
chemical synaptic transmission	1	25.8×	0.042	GRM6
regulation of transcription by RNA polymerase II	1	3.9×	0.236	ZNF454

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 1 of 3 evidence-associated genes (33%) 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
ZNF454	0	0
GPR179	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: 3; 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	1	GPR179
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ZNF454

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GPR179	0	GRM6
ZNF454	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.