Cone-rod dystrophy 12

Summary

Cone-rod dystrophy 12 (MONDO:0012983) is a disease caused by PROM1 (GenCC Strong), with 3 cohort genes.

At a glance

• Causal gene: PROM1 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 149

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cone-rod dystrophy 12
Mondo ID	MONDO:0012983
MeSH	C567206
OMIM	612657
DOID	DOID:0111019
UMLS	C2675210
MedGen	393334
GARD	0015577
Is cancer (heuristic)	no

Also known as: cone-rod dystrophy 12 · cone-rod dystrophy caused by mutation in PROM1 · cone-rod dystrophy type 12 · CORD12 · PROM1 cone-rod dystrophy

Data availability: 149 ClinVar variants · 1 GenCC gene-disease record · 1 cell line.

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 12

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 13, cone-rod dystrophy 10, cone-rod dystrophy 11, retinal cone dystrophy 4, 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

149 retrieved; paginated sample, class counts are floors:

59 conflicting classifications of pathogenicity, 46 uncertain significance, 12 pathogenic, 12 benign, 10 pathogenic/likely pathogenic, 6 likely pathogenic, 3 benign/likely benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
3358939	NM_033100.4(CDHR1):c.849C>A (p.Tyr283Ter)	CDHR1	Pathogenic	criteria provided, single submitter
2504415	NM_004750.5(CRLF1):c.397+1G>A	CRLF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
100577	NM_006017.3(PROM1):c.1557C>A (p.Tyr519Ter)	PROM1	Pathogenic	criteria provided, multiple submitters, no conflicts
1070960	NM_006017.3(PROM1):c.2023C>T (p.Gln675Ter)	PROM1	Pathogenic	criteria provided, multiple submitters, no conflicts
1709261	NM_006017.3(PROM1):c.1902C>G (p.Tyr634Ter)	PROM1	Pathogenic	criteria provided, single submitter
253326	NM_006017.3(PROM1):c.1157T>A (p.Leu386Ter)	PROM1	Pathogenic	criteria provided, multiple submitters, no conflicts
253327	NM_006017.3(PROM1):c.2281-20_2281-11del	PROM1	Pathogenic	no assertion criteria provided
3337982	NM_006017.3(PROM1):c.914dup (p.Leu306fs)	PROM1	Pathogenic	criteria provided, single submitter
3544454	NM_006017.3(PROM1):c.45dup (p.Asn16fs)	PROM1	Pathogenic	criteria provided, multiple submitters, no conflicts
372711	NM_006017.3(PROM1):c.1354dup (p.Tyr452fs)	PROM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3780492	NM_006017.3(PROM1):c.154del (p.Ile52fs)	PROM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
402237	NM_006017.3(PROM1):c.622del (p.Thr208fs)	PROM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
438215	NM_006017.3(PROM1):c.730C>T (p.Arg244Ter)	PROM1	Pathogenic	criteria provided, multiple submitters, no conflicts
560486	NM_006017.3(PROM1):c.262dup (p.Ile88fs)	PROM1	Pathogenic	no assertion criteria provided
5610	NM_006017.3(PROM1):c.1117C>T (p.Arg373Cys)	PROM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
623211	NM_006017.3(PROM1):c.1301+2T>C	PROM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
634483	NM_006017.3(PROM1):c.2050C>T (p.Arg684Ter)	PROM1	Pathogenic	criteria provided, multiple submitters, no conflicts
636063	NM_006017.3(PROM1):c.2461C>T (p.Arg821Ter)	PROM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
694038	NM_006017.3(PROM1):c.139del (p.His47fs)	PROM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
802057	NM_006017.3(PROM1):c.652C>T (p.Gln218Ter)	PROM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
809626	NM_006017.3(PROM1):c.1142-1G>A	PROM1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
836421	NM_006017.3(PROM1):c.642T>A (p.Tyr214Ter)	PROM1	Pathogenic	criteria provided, multiple submitters, no conflicts
1048148	NM_006017.3(PROM1):c.2476G>C (p.Asp826His)	PROM1	Likely pathogenic	criteria provided, single submitter
1048165	NM_006017.3(PROM1):c.380G>A (p.Gly127Glu)	PROM1	Likely pathogenic	criteria provided, single submitter
236522	NM_006017.3(PROM1):c.2309del (p.Pro770fs)	PROM1	Likely pathogenic	no assertion criteria provided
2500900	NM_006017.3(PROM1):c.2118del (p.Asn707fs)	PROM1	Likely pathogenic	criteria provided, single submitter
2920639	NM_006017.3(PROM1):c.1853T>G (p.Leu618Arg)	PROM1	Likely pathogenic	no assertion criteria provided
3251979	NM_006017.3(PROM1):c.1984-1G>A	PROM1	Likely pathogenic	criteria provided, single submitter
167535	NM_006017.3(PROM1):c.1497C>T (p.Ile499=)	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191189	NM_006017.3(PROM1):c.604C>G (p.Arg202Gly)	PROM1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 9 · 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
PROM1	Definitive	Autosomal dominant	retinal macular dystrophy type 2	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PROM1	Orphanet:1872	Cone rod dystrophy
PROM1	Orphanet:319640	Retinal macular dystrophy type 2
PROM1	Orphanet:791	Retinitis pigmentosa
PROM1	Orphanet:827	Stargardt disease
CDHR1	Orphanet:1872	Cone rod dystrophy
CDHR1	Orphanet:791	Retinitis pigmentosa
CRLF1	Orphanet:1545	Crisponi syndrome
CRLF1	Orphanet:157820	Cold-induced sweating syndrome
CRLF1	Orphanet:930	Idiopathic achalasia

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PROM1	HGNC:9454	ENSG00000007062	O43490	Prominin-1	gencc,clinvar
CDHR1	HGNC:14550	ENSG00000148600	Q96JP9	Cadherin-related family member 1	clinvar
CRLF1	HGNC:2364	ENSG00000006016	O75462	Cytokine receptor-like factor 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PROM1	Prominin-1	May play a role in cell differentiation, proliferation and apoptosis.
CDHR1	Cadherin-related family member 1	Potential calcium-dependent cell-adhesion protein.
CRLF1	Cytokine receptor-like factor 1	In complex with CLCF1, forms a heterodimeric neurotropic cytokine that plays a crucial role during neuronal development.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Antibody/Immunoglobulin	1	9.7×	0.199
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PROM1	Other/Unknown	no		Prominin
CDHR1	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS
CRLF1	Antibody/Immunoglobulin	yes	1.1.1.105	FN3_dom, Ig-like_fold, Growth/epo_recpt_lig-bind

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	1
bronchus	1
epithelium of bronchus	1
skin of abdomen	1
skin of leg	1
upper arm skin	1
popliteal artery	1
right coronary artery	1
tibial artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PROM1	252	broad	marker	bronchial epithelial cell, epithelium of bronchus, bronchus
CDHR1	186	broad	marker	upper arm skin, skin of leg, skin of abdomen
CRLF1	227	ubiquitous	marker	right coronary artery, popliteal artery, tibial artery

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PROM1	3,302
CDHR1	1,020
CRLF1	589

Intra-cohort edges

A	B	Sources
CDHR1	PROM1	biogrid_interaction, string_interaction

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CRLF1	O75462	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PROM1	O43490	85.68
CDHR1	Q96JP9	78.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 3 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
Interleukin-27 signaling	1	519.1×	0.005	CRLF1
IL-6-type cytokine receptor ligand interactions	1	317.2×	0.005	CRLF1
Developmental Lineage of Pancreatic Ductal Cells	1	114.2×	0.009	PROM1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
photoreceptor cell maintenance	2	239.0×	4e-04	PROM1, CDHR1
glomerular parietal epithelial cell differentiation	1	2808.7×	0.003	PROM1
positive regulation of nephron tubule epithelial cell differentiation	1	1872.4×	0.003	PROM1
camera-type eye photoreceptor cell differentiation	1	1123.5×	0.004	PROM1
photoreceptor cell morphogenesis	1	936.2×	0.004	CDHR1
retina morphogenesis in camera-type eye	1	624.1×	0.005	PROM1
negative regulation of motor neuron apoptotic process	1	510.7×	0.005	CRLF1
podocyte differentiation	1	468.1×	0.005	PROM1
photoreceptor cell outer segment organization	1	351.1×	0.005	CDHR1
retina layer formation	1	216.1×	0.008	PROM1
cell surface receptor signaling pathway via STAT	1	187.2×	0.008	CRLF1
ureteric bud development	1	151.8×	0.009	CRLF1
homophilic cell-cell adhesion	1	46.8×	0.028	CDHR1
cytokine-mediated signaling pathway	1	43.5×	0.028	CRLF1
negative regulation of neuron apoptotic process	1	37.0×	0.030	CRLF1
cell adhesion	1	12.5×	0.083	CDHR1
positive regulation of cell population proliferation	1	11.2×	0.087	CRLF1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 3 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
PROM1	0	0
CDHR1	0	0
CRLF1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CRLF1	1.1.1.105	all-trans-retinol dehydrogenase (NAD+)

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	1	CRLF1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	PROM1, CDHR1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PROM1	0	—
CDHR1	0	—
CRLF1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.