Retinitis pigmentosa 49

disease

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Also known as CNGA1 retinitis pigmentosaretinitis pigmentosa caused by mutation in CNGA1retinitis pigmentosa type 49RP49

Summary

Retinitis pigmentosa 49 (MONDO:0013405) is a disease caused by CNGA1 (GenCC Definitive), with 2 cohort genes.

At a glance

Causal gene: CNGA1 (GenCC Definitive)
Cohort genes: 2
ClinVar variants: 60

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 49
Mondo ID	MONDO:0013405
OMIM	613756
DOID	DOID:0110377
UMLS	C3151059
MedGen	462409
GARD	0015701
Is cancer (heuristic)	no

Also known as: CNGA1 retinitis pigmentosa · retinitis pigmentosa 49 · retinitis pigmentosa caused by mutation in CNGA1 · retinitis pigmentosa type 49 · RP49

Data availability: 60 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › retinitis pigmentosa › retinitis pigmentosa 49

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

60 retrieved; paginated sample, class counts are floors:

16 pathogenic/likely pathogenic, 12 pathogenic, 10 uncertain significance, 10 likely pathogenic, 7 conflicting classifications of pathogenicity, 3 benign, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
424770	NM_000087.3(CNGA1):c.[652C>T];[959C>T]		Pathogenic	criteria provided, single submitter
1068762	NM_001379270.1(CNGA1):c.1525G>A (p.Gly509Arg)	CNGA1	Pathogenic	criteria provided, multiple submitters, no conflicts
1451495	NM_001379270.1(CNGA1):c.1722del (p.Asp575fs)	CNGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454108	NM_001379270.1(CNGA1):c.528del (p.Asn175_Trp176insTer)	CNGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16930	NM_001379270.1(CNGA1):c.226G>T (p.Glu76Ter)	CNGA1	Pathogenic	no assertion criteria provided
16931	NM_001379270.1(CNGA1):c.415A>T (p.Lys139Ter)	CNGA1	Pathogenic	no assertion criteria provided
16932	NM_001379270.1(CNGA1):c.947C>T (p.Ser316Phe)	CNGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
16933	NM_001379270.1(CNGA1):c.1960del (p.Arg654fs)	CNGA1	Pathogenic	no assertion criteria provided
2203541	NM_001379270.1(CNGA1):c.1417del (p.Val473fs)	CNGA1	Pathogenic	criteria provided, single submitter
242520	NM_001379270.1(CNGA1):c.640C>T (p.Arg214Ter)	CNGA1	Pathogenic	criteria provided, multiple submitters, no conflicts
2443933	NM_001379270.1(CNGA1):c.614_615del (p.Ile205fs)	CNGA1	Pathogenic	no assertion criteria provided
2443938	NM_001379270.1(CNGA1):c.610G>A (p.Asp204Asn)	CNGA1	Pathogenic	no assertion criteria provided
2501675	NM_001379270.1(CNGA1):c.219del (p.Gln74fs)	CNGA1	Pathogenic	criteria provided, single submitter
3590579	NM_001379270.1(CNGA1):c.1327del (p.Thr443fs)	CNGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
548707	NM_001379270.1(CNGA1):c.82C>T (p.Arg28Ter)	CNGA1	Pathogenic	criteria provided, multiple submitters, no conflicts
802071	NM_001379270.1(CNGA1):c.546-1G>C	CNGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812274	NM_001379270.1(CNGA1):c.1044C>A (p.Ser348Arg)	CNGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
850020	NM_001379270.1(CNGA1):c.1327dup (p.Thr443fs)	CNGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
850709	NM_001379270.1(CNGA1):c.530del (p.Thr177fs)	CNGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
866760	NM_001379270.1(CNGA1):c.1258C>T (p.Arg420Ter)	CNGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
866975	NM_001379270.1(CNGA1):c.105C>A (p.Cys35Ter)	CNGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
972420	NM_001379270.1(CNGA1):c.1873C>T (p.Arg625Ter)	CNGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1297149	NM_001379270.1(CNGA1):c.234C>A (p.Tyr78Ter)	LOC101927157	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
143099	NM_001379270.1(CNGA1):c.179del (p.Gly60fs)	LOC101927157	Pathogenic	criteria provided, multiple submitters, no conflicts
2015100	NM_001379270.1(CNGA1):c.527G>A (p.Trp176Ter)	LOC101927157	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
225315	NM_001379270.1(CNGA1):c.253del (p.Leu85fs)	LOC101927157	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
236443	NM_001379270.1(CNGA1):c.1528C>T (p.Arg510Ter)	LOC101927157	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
866019	NM_001379270.1(CNGA1):c.1743_1746del (p.Thr582fs)	LOC101927157	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065777	NM_001379270.1(CNGA1):c.1704_1705insT (p.Leu569fs)	CNGA1	Likely pathogenic	criteria provided, single submitter
1690446	NM_001379270.1(CNGA1):c.349G>T (p.Glu117Ter)	CNGA1	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
CNGA1	Definitive	Autosomal recessive	retinitis pigmentosa 49	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CNGA1	Orphanet:791	Retinitis pigmentosa
CNGB1	Orphanet:791	Retinitis pigmentosa

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
CNGA1	HGNC:2148	ENSG00000198515	P29973	Cyclic nucleotide-gated channel alpha-1	gencc,clinvar
CNGB1	HGNC:2151	ENSG00000070729	Q14028	Cyclic nucleotide-gated channel beta-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CNGA1	Cyclic nucleotide-gated channel alpha-1	Pore-forming subunit of the rod cyclic nucleotide-gated channel.
CNGB1	Cyclic nucleotide-gated channel beta-1	Pore-forming subunit of the rod cyclic nucleotide-gated channel.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Ion channel	2	111.5×	8e-05

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CNGA1	Ion channel	yes		cNMP-bd_dom, Ion_trans_dom, RmlC-like_jellyroll
CNGB1	Ion channel	yes		cNMP-bd_dom, Ion_trans_dom, RmlC-like_jellyroll

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
amniotic fluid	1
lower esophagus mucosa	1
right lobe of liver	1
buccal mucosa cell	1
cervix squamous epithelium	1
olfactory bulb	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CNGA1	182	broad	marker	lower esophagus mucosa, amniotic fluid, right lobe of liver
CNGB1	152	tissue_specific	marker	buccal mucosa cell, cervix squamous epithelium, olfactory bulb

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CNGA1	1,181
CNGB1	1,133

Intra-cohort edges

A	B	Sources
CNGA1	CNGB1	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CNGA1	P29973	19
CNGB1	Q14028	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 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
Activation of the phototransduction cascade	2	951.7×	4e-06	CNGA1, CNGB1
Inactivation, recovery and regulation of the phototransduction cascade	2	317.2×	2e-05	CNGA1, CNGB1
VxPx cargo-targeting to cilium	1	259.6×	0.005	CNGB1
Olfactory Signaling Pathway	1	72.3×	0.014	CNGB1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
monoatomic cation transmembrane transport	2	624.1×	5e-05	CNGA1, CNGB1
sodium ion transport	2	271.8×	1e-04	CNGA1, CNGB1
calcium ion transport	2	181.2×	2e-04	CNGA1, CNGB1
visual perception	2	79.5×	8e-04	CNGA1, CNGB1
olfactory nerve maturation	1	2808.7×	0.001	CNGB1
response to odorant	1	1404.3×	0.002	CNGB1
retina homeostasis	1	561.7×	0.004	CNGB1
sensory perception of chemical stimulus	1	561.7×	0.004	CNGA1
photoreceptor cell outer segment organization	1	526.6×	0.004	CNGB1
monoatomic cation transport	1	383.0×	0.005	CNGB1
detection of light stimulus involved in visual perception	1	324.1×	0.006	CNGB1
membrane depolarization	1	255.3×	0.006	CNGB1
phototransduction	1	247.8×	0.006	CNGB1
regulation of cytosolic calcium ion concentration	1	191.5×	0.007	CNGB1
photoreceptor cell maintenance	1	179.3×	0.007	CNGB1
potassium ion transport	1	95.8×	0.013	CNGB1
sensory perception of smell	1	78.0×	0.015	CNGB1
detection of chemical stimulus involved in sensory perception of smell	1	62.0×	0.018	CNGB1
positive regulation of gene expression	1	19.4×	0.054	CNGB1
G protein-coupled receptor signaling pathway	1	18.1×	0.054	CNGB1

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
CNGA1	0	0
CNGB1	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	2	CNGA1, CNGB1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
CNGA1	0	—
CNGB1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: CNGA1, CNGB1