X-linked cone-rod dystrophy 1

Summary

X-linked cone-rod dystrophy 1 (MONDO:0010566) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 54

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	X-linked cone-rod dystrophy 1
Mondo ID	MONDO:0010566
MeSH	C564438
OMIM	304020
DOID	DOID:0111008
UMLS	C1844776
MedGen	336777
GARD	0010652
Is cancer (heuristic)	no

Also known as: cone dystrophy X-linked 1 · cone-rod dystrophy X-linked 1 · cone-rod dystrophy, X-linked, 1 · cone-rod dystrophy, X-linked, 1, X-linked recessive · cone-rod dystrophy, X-linked, type 1 · CORDX1 · X-linked cone-rod dystrophy type 1

Data availability: 54 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › X-linked disease › X-linked cone-rod dystrophy › X-linked cone-rod dystrophy 1

Related subtypes (3): X-linked cone-rod dystrophy 2, X-linked cone-rod dystrophy 3, blue cone monochromacy

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

54 retrieved; paginated sample, class counts are floors:

19 pathogenic, 10 likely pathogenic, 8 benign, 7 conflicting classifications of pathogenicity, 4 pathogenic/likely pathogenic, 4 uncertain significance, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1701807	NM_001034853.2(RPGR):c.2512del (p.Glu838fs)	RPGR	Pathogenic	criteria provided, single submitter
1707409	NM_001034853.2(RPGR):c.1302dup (p.Leu435fs)	RPGR	Pathogenic	reviewed by expert panel
1708067	NM_001034853.2(RPGR):c.2149C>T (p.Gln717Ter)	RPGR	Pathogenic	criteria provided, multiple submitters, no conflicts
1708318	NM_001034853.2(RPGR):c.1225del (p.Arg409fs)	RPGR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
216990	NM_001034853.2(RPGR):c.3178_3179del (p.Glu1060fs)	RPGR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2678451	NM_001034853.2(RPGR):c.3032del (p.Gly1011fs)	RPGR	Pathogenic	criteria provided, single submitter
2678452	NM_001034853.2(RPGR):c.2624_2643del (p.Glu875fs)	RPGR	Pathogenic	criteria provided, multiple submitters, no conflicts
3249845	NM_001034853.2(RPGR):c.3364del (p.Met1122fs)	RPGR	Pathogenic	criteria provided, multiple submitters, no conflicts
3382894	NM_001034853.2(RPGR):c.2872del (p.Glu958fs)	RPGR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3598278	NM_001034853.2(RPGR):c.1506+1G>T	RPGR	Pathogenic	reviewed by expert panel
438142	NM_001034853.2(RPGR):c.2236_2237del (p.Glu746fs)	RPGR	Pathogenic	reviewed by expert panel
560503	NM_001034853.2(RPGR):c.2993_2996del (p.Glu998fs)	RPGR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812421	NM_001034853.2(RPGR):c.494G>A (p.Gly165Asp)	RPGR	Pathogenic	reviewed by expert panel
866381	NM_001034853.2(RPGR):c.3092del (p.Glu1031fs)	RPGR	Pathogenic	reviewed by expert panel
866844	NM_001034853.2(RPGR):c.2260G>T (p.Glu754Ter)	RPGR	Pathogenic	reviewed by expert panel
91389	NM_001034853.2(RPGR):c.2405_2406del (p.Glu802fs)	RPGR	Pathogenic	reviewed by expert panel
98739	NM_001034853.2(RPGR):c.1377_1378del (p.Leu460fs)	RPGR	Pathogenic	reviewed by expert panel
98749	NM_001034853.2(RPGR):c.1573-2A>G	RPGR	Pathogenic	criteria provided, multiple submitters, no conflicts
98787	NM_001034853.2(RPGR):c.485_486del (p.Phe162fs)	RPGR	Pathogenic	reviewed by expert panel
9910	NM_001034853.2(RPGR):c.3096_3097del (p.Glu1033fs)	RPGR	Pathogenic	criteria provided, multiple submitters, no conflicts
9911	NM_001034853.2(RPGR):c.3092_3093del (p.Glu1031fs)	RPGR	Pathogenic	reviewed by expert panel
9917	NM_001034853.2(RPGR):c.2847_2848inv (p.Glu949_Glu950delinsAspTer)	RPGR	Pathogenic	reviewed by expert panel
9918	NM_001034853.2(RPGR):c.2929G>T (p.Gly977Ter)	RPGR	Pathogenic	no assertion criteria provided
1710110	NM_001034853.2(RPGR):c.3208C>T (p.Gln1070Ter)	RPGR	Likely pathogenic	no assertion criteria provided
1802237	NM_001034853.2(RPGR):c.1753+2T>G	RPGR	Likely pathogenic	criteria provided, single submitter
2110430	NM_001034853.2(RPGR):c.620-2A>G	RPGR	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2664727	NM_001034853.2(RPGR):c.3238C>T (p.Gln1080Ter)	RPGR	Likely pathogenic	criteria provided, single submitter
2678450	NM_001034853.2(RPGR):c.3198_3214dup (p.Thr1072fs)	RPGR	Likely pathogenic	criteria provided, single submitter
3598276	NM_001034853.2(RPGR):c.3255C>G (p.Tyr1085Ter)	RPGR	Likely pathogenic	criteria provided, single submitter
3598277	NM_001034853.2(RPGR):c.3151G>T (p.Glu1051Ter)	RPGR	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPGR	HGNC:10295	ENSG00000156313	Q92834	X-linked retinitis pigmentosa GTPase regulator	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPGR	Other/Unknown	no		Reg_chr_condens, RCC1/BLIP-II, Signaling_Regulatory_Domain

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	1
right uterine tube	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPGR	281	ubiquitous	marker	sperm, bronchial epithelial cell, right uterine tube

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPGR	2,231

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPGR	Q92834	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein localization to non-motile cilium	1	4213.0×	0.002	RPGR
eye photoreceptor cell development	1	842.6×	0.005	RPGR
intraciliary transport	1	561.7×	0.005	RPGR
positive regulation of autophagy	1	208.1×	0.011	RPGR
visual perception	1	79.5×	0.017	RPGR
ubiquitin-dependent protein catabolic process	1	74.2×	0.017	RPGR
cilium assembly	1	73.6×	0.017	RPGR
intracellular protein transport	1	64.8×	0.017	RPGR
protein ubiquitination	1	41.4×	0.024	RPGR

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
RPGR	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	RPGR

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RPGR	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.