X-linked cone-rod dystrophy

Summary

X-linked cone-rod dystrophy (MONDO:0021155) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	X-linked cone-rod dystrophy
Mondo ID	MONDO:0021155
GARD	0025295
Is cancer (heuristic)	no

Also known as: cone-rod dystrophy, X-linked

Data availability: 13 ClinVar variants.

Disease family

An umbrella term covering 4 Mondo subtypes.

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

Related subtypes (49): X-linked Opitz G/BBB syndrome, X-linked immunoneurologic disorder, X-linked adrenal hypoplasia congenita, X-linked lissencephaly with abnormal genitalia, X-linked severe congenital neutropenia, X-linked distal spinal muscular atrophy type 3, epilepsy, X-linked 1, with variable learning disabilities and behavior disorders, Aland island eye disease, X-linked erythropoietic protoporphyria, X-linked central congenital hypothyroidism with late-onset testicular enlargement, X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome, X-linked acrogigantism due to Xq26 microduplication, Wiskott-Aldrich syndrome, X-linked Alport syndrome, X-linked mandibulofacial dysostosis, X-linked chondrodysplasia punctata, choroideremia, cone dystrophy, X-linked, with tapetal-like sheen, diabetes insipidus, nephrogenic, X-linked, Dyggve-Melchior-Clausen syndrome, X-linked, dyskeratosis congenita, X-linked, X-linked hypohidrotic ectodermal dysplasia, X-linked Ehlers-Danlos syndrome, epidermodysplasia verruciformis, X-linked, exudative vitreoretinopathy 2, X-linked, Aarskog-Scott syndrome, X-linked, hemophilia A, X-linked hydrocephalus with stenosis of the aqueduct of Sylvius, hyper-IgM syndrome type 1, X-linked lymphoproliferative syndrome, macular dystrophy, X-linked, X-linked Emery-Dreifuss muscular dystrophy, X-linked myotubular myopathy, X-linked lethal multiple pterygium syndrome, X-linked retinoschisis, spondyloepiphyseal dysplasia tarda, X-linked, X-linked cerebellar ataxia, adrenoleukodystrophy, Charcot-Marie-Tooth disease type X, X-linked dominant disease, X-linked recessive disease, X-linked hypophosphatemic rickets, X-linked sideroblastic anemia 1, X-linked deafness, X-linked congenital stationary night blindness, X-linked congenital hemolytic anemia, X-linked complex neurodevelopmental disorder, X-linked intellectual disability, leukemia, acute, X-linked

Subtypes (4): X-linked cone-rod dystrophy 2, X-linked cone-rod dystrophy 3, blue cone monochromacy, X-linked cone-rod dystrophy 1

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

13 retrieved; paginated sample, class counts are floors:

6 pathogenic, 4 likely pathogenic, 2 uncertain significance, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1333218	NM_001034853.2(RPGR):c.1379del (p.Leu460fs)	RPGR	Pathogenic	criteria provided, single submitter
2099210	NM_001034853.2(RPGR):c.550C>T (p.Gln184Ter)	RPGR	Pathogenic	criteria provided, single submitter
2430145	NM_001034853.2(RPGR):c.2360del (p.Gly787fs)	RPGR	Pathogenic	criteria provided, single submitter
2430146	NM_001034853.2(RPGR):c.2536dup (p.Glu846fs)	RPGR	Pathogenic	criteria provided, single submitter
2430150	NM_001034853.2(RPGR):c.248-10A>G	RPGR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2430151	NM_001034853.2(RPGR):c.283G>A (p.Gly95Arg)	RPGR	Pathogenic	reviewed by expert panel
2430152	NM_001034853.2(RPGR):c.597T>G (p.Tyr199Ter)	RPGR	Pathogenic	no assertion criteria provided
2430147	NM_006195.6(PBX3):c.945dup (p.Ala316fs)	PBX3	Likely pathogenic	no assertion criteria provided
2430148	NM_006195.6(PBX3):c.946_947insTA (p.Ala316fs)	PBX3	Likely pathogenic	no assertion criteria provided
2430149	NM_006195.6(PBX3):c.273del (p.Gly92fs)	PBX3	Likely pathogenic	no assertion criteria provided
2430144	NM_001034853.2(RPGR):c.1587del (p.Ile529fs)	RPGR	Likely pathogenic	no assertion criteria provided
2430143	NM_006195.6(PBX3):c.797A>C (p.Glu266Ala)	PBX3	Uncertain significance	no assertion criteria provided
2430153	NM_001034853.2(RPGR):c.934G>A (p.Asp312Asn)	RPGR	Uncertain significance	reviewed by expert panel

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

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPGR	HGNC:10295	ENSG00000156313	Q92834	X-linked retinitis pigmentosa GTPase regulator	clinvar
PBX3	HGNC:8634	ENSG00000167081	P40426	Pre-B-cell leukemia transcription factor 3	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.
PBX3	Pre-B-cell leukemia transcription factor 3	Transcriptional activator that binds the sequence 5’-ATCAATCAA-3'.

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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPGR	Other/Unknown	no		Reg_chr_condens, RCC1/BLIP-II, Signaling_Regulatory_Domain
PBX3	Transcription factor	no		HD, PBX_PBC_dom, KN_HD

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
bronchial epithelial cell	1
right uterine tube	1
sperm	1
left ovary	1
right adrenal gland	1
right adrenal gland cortex	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
PBX3	265	ubiquitous	marker	left ovary, right adrenal gland cortex, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPGR	2,231
PBX3	1,304

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPGR	Q92834	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PBX3	P40426	71.37

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
anterior compartment pattern formation	1	8426.0×	0.001	PBX3
posterior compartment specification	1	8426.0×	0.001	PBX3
protein localization to non-motile cilium	1	2106.5×	0.003	RPGR
dorsal spinal cord development	1	842.6×	0.006	PBX3
regulation of respiratory gaseous exchange by nervous system process	1	648.1×	0.006	PBX3
eye photoreceptor cell development	1	421.3×	0.008	RPGR
respiratory gaseous exchange by respiratory system	1	312.1×	0.009	PBX3
intraciliary transport	1	280.9×	0.009	RPGR
embryonic organ development	1	240.7×	0.009	PBX3
eye development	1	175.5×	0.011	PBX3
adult locomotory behavior	1	150.5×	0.012	PBX3
neuron development	1	127.7×	0.013	PBX3
positive regulation of autophagy	1	104.0×	0.015	RPGR
animal organ morphogenesis	1	95.8×	0.015	PBX3
brain development	1	39.8×	0.030	PBX3
visual perception	1	39.8×	0.030	RPGR
ubiquitin-dependent protein catabolic process	1	37.1×	0.030	RPGR
cilium assembly	1	36.8×	0.030	RPGR
intracellular protein transport	1	32.4×	0.032	RPGR
protein ubiquitination	1	20.7×	0.048	RPGR

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
RPGR	0	0
PBX3	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	RPGR, PBX3

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)
RPGR	0	—
PBX3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.