congenital stationary night blindness 1H

Summary

congenital stationary night blindness 1H (MONDO:0014872) is a disease caused by GNB3 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: GNB3 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital stationary night blindness 1H
Mondo ID	MONDO:0014872
OMIM	617024
DOID	DOID:0110866
UMLS	C4310758
MedGen	934725
GARD	0016177
Is cancer (heuristic)	no

Also known as: congenital stationary night blindness caused by mutation in GNB3 · congenital stationary night blindness type 1H · CSNB1H · GNB3 congenital stationary night blindness · night blindness, congenital stationary, type 1H

Data availability: 5 ClinVar variants · 4 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 1H

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 1C, congenital stationary night blindness 1D, congenital stationary night blindness 1E, congenital stationary night blindness 1F, congenital stationary night blindness 1G, 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

5 retrieved; paginated sample, class counts are floors:

2 pathogenic, 2 uncertain significance, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
242984	NM_002075.4(GNB3):c.1017G>A (p.Trp339Ter)	CDCA3	Pathogenic	no assertion criteria provided
242985	NM_002075.4(GNB3):c.170_172del (p.Lys57del)	GNB3	Pathogenic	no assertion criteria provided
970744	NM_002075.4(GNB3):c.799G>A (p.Glu267Lys)	CDCA3	Uncertain significance	criteria provided, multiple submitters, no conflicts
242986	NM_002075.4(GNB3):c.200C>T (p.Ser67Phe)	GNB3	Uncertain significance	criteria provided, multiple submitters, no conflicts
226004	NM_002075.4(GNB3):c.825C>T (p.Ser275=)	CDCA3	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 0 · 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
GNB3	Strong	Autosomal recessive	congenital stationary night blindness 1H	5

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GNB3	HGNC:4400	ENSG00000111664	P16520	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3	gencc,clinvar
CDCA3	HGNC:14624	ENSG00000111665	Q99618	Cell division cycle-associated protein 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
CDCA3	Cell division cycle-associated protein 3	F-box-like protein which is required for entry into mitosis.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.0

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
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GNB3	Scaffold/PPI	no		WD40_G-protein_beta-like, WD40_rpt, WD40/YVTN_repeat-like_dom_sf
CDCA3	Other/Unknown	no		CDCA3

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adenohypophysis	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
oocyte	1
secondary oocyte	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GNB3	185	tissue_specific	marker	adenohypophysis, right hemisphere of cerebellum, cerebellar hemisphere
CDCA3	199	ubiquitous	marker	ventricular zone, oocyte, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GNB3	3,205
CDCA3	1,836

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNB3	P16520	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CDCA3	Q99618	59.01

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 31. Enrichment computed across 2 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
G beta:gamma signalling through BTK	1	634.4×	0.005	GNB3
Prostacyclin signalling through prostacyclin receptor	1	601.0×	0.005	GNB3
G beta:gamma signalling through PLC beta	1	571.0×	0.005	GNB3
G beta:gamma signalling through CDC42	1	571.0×	0.005	GNB3
Presynaptic function of Kainate receptors	1	543.8×	0.005	GNB3
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)	1	519.1×	0.005	GNB3
ADP signalling through P2Y purinoceptor 12	1	496.5×	0.005	GNB3
G-protein activation	1	475.8×	0.005	GNB3
Thromboxane signalling through TP receptor	1	475.8×	0.005	GNB3
ADP signalling through P2Y purinoceptor 1	1	456.8×	0.005	GNB3
G beta:gamma signalling through PI3Kgamma	1	439.2×	0.005	GNB3
Activation of G protein gated Potassium channels	1	393.8×	0.005	GNB3
Adrenaline,noradrenaline inhibits insulin secretion	1	393.8×	0.005	GNB3
Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits	1	393.8×	0.005	GNB3
Thrombin signalling through proteinase activated receptors (PARs)	1	356.9×	0.005	GNB3
Glucagon signaling in metabolic regulation	1	346.1×	0.005	GNB3
Glucagon-type ligand receptors	1	346.1×	0.005	GNB3
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	1	300.5×	0.005	GNB3
Sensory perception of sweet, bitter, and umami (glutamate) taste	1	278.5×	0.005	GNB3
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	1	265.6×	0.005	GNB3
Vasopressin regulates renal water homeostasis via Aquaporins	1	265.6×	0.005	GNB3
ADORA2B mediated anti-inflammatory cytokines production	1	253.8×	0.005	GNB3
GPER1 signaling	1	248.3×	0.005	GNB3
G alpha (z) signalling events	1	233.1×	0.006	GNB3
Ca2+ pathway	1	178.4×	0.007	GNB3
Extra-nuclear estrogen signaling	1	170.4×	0.007	GNB3
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	1	160.8×	0.007	GNB3
G alpha (12/13) signalling events	1	137.6×	0.008	GNB3
G alpha (s) signalling events	1	73.2×	0.015	GNB3
G alpha (q) signalling events	1	57.4×	0.018	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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of phospholipid metabolic process	1	8426.0×	0.001	GNB3
regulation of hormone metabolic process	1	1685.2×	0.004	GNB3
regulation of triglyceride metabolic process	1	1053.2×	0.004	GNB3
regulation of fat cell differentiation	1	648.1×	0.004	GNB3
regulation of cholesterol metabolic process	1	561.7×	0.004	GNB3
cell volume homeostasis	1	300.9×	0.006	GNB3
regulation of glucose metabolic process	1	280.9×	0.006	GNB3
regulation of blood pressure	1	110.9×	0.013	GNB3
regulation of gene expression	1	41.7×	0.032	GNB3
cell division	1	23.1×	0.051	CDCA3
protein ubiquitination	1	20.7×	0.052	CDCA3
G protein-coupled receptor signaling pathway	1	18.1×	0.054	GNB3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GNB3	0	0
CDCA3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	GNB3, CDCA3

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)
GNB3	0	—
CDCA3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.