Cone-rod dystrophy 13

Summary

Cone-rod dystrophy 13 (MONDO:0011987) is a disease caused by RPGRIP1 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: RPGRIP1 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 952

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cone-rod dystrophy 13
Mondo ID	MONDO:0011987
MeSH	C567698
OMIM	608194
DOID	DOID:0111016
UMLS	C2750720
MedGen	413025
GARD	0015426
Is cancer (heuristic)	no

Also known as: cone-rod dystrophy 13 · cone-rod dystrophy caused by mutation in RPGRIP1 · cone-rod dystrophy type 13 · CORD13 · RPGRIP1 cone-rod dystrophy

Data availability: 952 ClinVar variants · 2 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 › cone-rod dystrophy › cone-rod dystrophy 13

Related subtypes (27): cone-rod dystrophy 2, macular degeneration, X-linked atrophic, cone-rod dystrophy 1, cone-rod dystrophy 5, cone-rod dystrophy 6, cone dystrophy 3, cone-rod dystrophy 7, cone-rod dystrophy 3, Leber congenital amaurosis 4, cone-rod dystrophy 8, Newfoundland cone-rod dystrophy, cone-rod dystrophy 10, cone-rod dystrophy 11, retinal cone dystrophy 4, cone-rod dystrophy 12, cone-rod dystrophy 9, cone-rod dystrophy 15, cone-rod dystrophy 16, cone-rod dystrophy 17, cone-rod dystrophy 18, cone-rod dystrophy 19, cone-rod dystrophy 20, cone-rod dystrophy 21, X-linked cone-rod dystrophy, cone-rod dystrophy 22, cone-rod dystrophy 14, cone-rod dystrophy 24

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

600 retrieved; paginated sample, class counts are floors:

303 uncertain significance, 212 likely benign, 46 pathogenic, 14 conflicting classifications of pathogenicity, 10 likely pathogenic, 6 benign, 6 benign/likely benign, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1075073	NC_000014.8:g.(?21756136)(22005055_?)del	CHD8	Pathogenic	criteria provided, single submitter
1069706	NM_020366.4(RPGRIP1):c.711del (p.Lys239fs)	RPGRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1069749	NM_020366.4(RPGRIP1):c.14_29dup (p.Asp11fs)	RPGRIP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073081	NC_000014.8:g.(?21795782)(21795966_?)del	RPGRIP1	Pathogenic	criteria provided, single submitter
1073082	NC_000014.8:g.(?21798388)(21798566_?)del	RPGRIP1	Pathogenic	criteria provided, single submitter
1074385	NM_020366.4(RPGRIP1):c.1363del (p.Glu455fs)	RPGRIP1	Pathogenic	criteria provided, single submitter
1074924	NM_020366.4(RPGRIP1):c.313C>T (p.Gln105Ter)	RPGRIP1	Pathogenic	criteria provided, single submitter
1357904	NM_020366.4(RPGRIP1):c.663dup (p.Asn222Ter)	RPGRIP1	Pathogenic	criteria provided, single submitter
1369938	NM_020366.4(RPGRIP1):c.2024del (p.Leu675fs)	RPGRIP1	Pathogenic	criteria provided, single submitter
1375717	NM_020366.4(RPGRIP1):c.1111C>T (p.Arg371Ter)	RPGRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1382627	NM_020366.4(RPGRIP1):c.1145T>A (p.Leu382Ter)	RPGRIP1	Pathogenic	criteria provided, single submitter
1387428	NM_020366.4(RPGRIP1):c.1867C>T (p.Gln623Ter)	RPGRIP1	Pathogenic	criteria provided, single submitter
1395639	NM_020366.4(RPGRIP1):c.2308_2311del (p.Lys770fs)	RPGRIP1	Pathogenic	criteria provided, single submitter
1415268	NM_020366.4(RPGRIP1):c.931-2_935delinsT	RPGRIP1	Pathogenic	criteria provided, single submitter
1436742	NM_020366.4(RPGRIP1):c.3617+1G>T	RPGRIP1	Pathogenic	criteria provided, single submitter
1437865	NM_020366.4(RPGRIP1):c.3275_3276dup (p.Ala1093fs)	RPGRIP1	Pathogenic	criteria provided, single submitter
1451134	NM_020366.4(RPGRIP1):c.898del (p.Val300fs)	RPGRIP1	Pathogenic	criteria provided, single submitter
1451517	NM_020366.4(RPGRIP1):c.808_826del (p.Ser269_Ile270insTer)	RPGRIP1	Pathogenic	criteria provided, single submitter
1452635	NM_020366.4(RPGRIP1):c.1995T>A (p.Cys665Ter)	RPGRIP1	Pathogenic	criteria provided, single submitter
1452857	NM_020366.4(RPGRIP1):c.3610C>T (p.Gln1204Ter)	RPGRIP1	Pathogenic	criteria provided, single submitter
1455333	NM_020366.4(RPGRIP1):c.767C>G (p.Ser256Ter)	RPGRIP1	Pathogenic	criteria provided, single submitter
1455614	NM_020366.4(RPGRIP1):c.1930C>T (p.Gln644Ter)	RPGRIP1	Pathogenic	criteria provided, single submitter
1456668	NC_000014.8:g.(?21785835)(21788356_?)del	RPGRIP1	Pathogenic	criteria provided, single submitter
1458554	NM_020366.4(RPGRIP1):c.1089_1090dup (p.Val364fs)	RPGRIP1	Pathogenic	criteria provided, single submitter
1459285	NM_020366.4(RPGRIP1):c.282_283dup (p.Ala95fs)	RPGRIP1	Pathogenic	criteria provided, single submitter
1459438	NC_000014.8:g.(?21756136)(21756240_?)del	RPGRIP1	Pathogenic	criteria provided, single submitter
156387	NM_020366.4(RPGRIP1):c.832C>T (p.Arg278Ter)	RPGRIP1	Pathogenic	criteria provided, multiple submitters, no conflicts
1929443	NM_020366.4(RPGRIP1):c.442A>T (p.Arg148Ter)	RPGRIP1	Pathogenic	criteria provided, single submitter
195355	NM_020366.4(RPGRIP1):c.154C>T (p.Arg52Ter)	RPGRIP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2034155	NM_020366.4(RPGRIP1):c.3463G>T (p.Glu1155Ter)	RPGRIP1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 5 · 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
RPGRIP1	Definitive	Autosomal recessive	cone-rod dystrophy 13	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPGRIP1	Orphanet:1872	Cone rod dystrophy
RPGRIP1	Orphanet:564	Meckel syndrome
RPGRIP1	Orphanet:65	Leber congenital amaurosis
CHD8	Orphanet:261229	14q11.2 microduplication syndrome
CHD8	Orphanet:642675	CHD8 overgrowth syndrome

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
RPGRIP1	HGNC:13436	ENSG00000092200	Q96KN7	X-linked retinitis pigmentosa GTPase regulator-interacting protein 1	gencc,clinvar
CHD8	HGNC:20153	ENSG00000100888	Q9HCK8	ATP-dependent chromatin remodeler CHD8	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPGRIP1	X-linked retinitis pigmentosa GTPase regulator-interacting protein 1	May function as scaffolding protein.
CHD8	ATP-dependent chromatin remodeler CHD8	ATP-dependent chromatin-remodeling factor, it slides nucleosomes along DNA; nucleosome sliding requires ATP.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPGRIP1	Other/Unknown	no		C2_dom, C2-C2_1, RPGRIP1_fam
CHD8	Other/Unknown	no		SNF2_N, Chromo/chromo_shadow_dom, Helicase_C-like

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
left testis	1
right testis	1
sperm	1
cortical plate	1
sural nerve	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPGRIP1	168	tissue_specific	marker	left testis, sperm, right testis
CHD8	283	ubiquitous	marker	sural nerve, ventricular zone, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CHD8	4,791
RPGRIP1	1,422

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CHD8	Q9HCK8	2
RPGRIP1	Q96KN7	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Deactivation of the beta-catenin transactivating complex	1	233.1×	0.007	CHD8
CHD6, CHD7, CHD8, CHD9 subfamily	1	148.3×	0.007	CHD8

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
negative regulation of fibroblast apoptotic process	1	1203.7×	0.010	CHD8
retinal rod cell development	1	842.6×	0.010	RPGRIP1
prepulse inhibition	1	561.7×	0.010	CHD8
positive regulation of transcription by RNA polymerase III	1	468.1×	0.010	CHD8
neural precursor cell proliferation	1	337.0×	0.011	RPGRIP1
digestive tract development	1	263.3×	0.012	CHD8
non-motile cilium assembly	1	145.3×	0.017	RPGRIP1
social behavior	1	135.9×	0.017	CHD8
negative regulation of canonical Wnt signaling pathway	1	58.9×	0.035	CHD8
Wnt signaling pathway	1	49.9×	0.035	CHD8
brain development	1	39.8×	0.035	CHD8
visual perception	1	39.8×	0.035	RPGRIP1
mRNA processing	1	39.4×	0.035	CHD8
chromatin remodeling	1	36.5×	0.035	CHD8
in utero embryonic development	1	36.0×	0.035	CHD8
negative regulation of DNA-templated transcription	1	15.8×	0.074	CHD8
positive regulation of DNA-templated transcription	1	14.0×	0.079	CHD8
negative regulation of transcription by RNA polymerase II	1	8.9×	0.116	CHD8
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	CHD8

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHD8	1	2
RPGRIP1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	CHD8

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CHD8	7	Binding:7

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

1 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)
MOLIBRESIB	2	CHD8

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	1	CHD8
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	RPGRIP1

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)
RPGRIP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.