Cone-rod dystrophy and hearing loss 2

Summary

Cone-rod dystrophy and hearing loss 2 (MONDO:0020780) is a disease caused by CEP250 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CEP250 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 34

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cone-rod dystrophy and hearing loss 2
Mondo ID	MONDO:0020780
OMIM	618358
UMLS	C5193051
MedGen	1675017
Is cancer (heuristic)	no

Also known as: CRDHL2

Data availability: 34 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › cone-rod dystrophy and hearing loss › cone-rod dystrophy and hearing loss 2

Related subtypes (1): cone-rod dystrophy and hearing loss 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

34 retrieved; paginated sample, class counts are floors:

17 pathogenic, 9 uncertain significance, 3 conflicting classifications of pathogenicity, 3 pathogenic/likely pathogenic, 1 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1071914	NM_007186.6(CEP250):c.5959C>T (p.Gln1987Ter)	CEP250	Pathogenic	criteria provided, single submitter
1441102	NM_007186.6(CEP250):c.4027C>T (p.Arg1343Ter)	CEP250	Pathogenic	criteria provided, multiple submitters, no conflicts
1459241	NM_007186.6(CEP250):c.2155C>T (p.Arg719Ter)	CEP250	Pathogenic	criteria provided, multiple submitters, no conflicts
1901883	NM_007186.6(CEP250):c.2512del (p.Gln838fs)	CEP250	Pathogenic	criteria provided, single submitter
1916440	NM_007186.6(CEP250):c.2654_2675del (p.Met885fs)	CEP250	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1925483	NM_007186.6(CEP250):c.2206C>T (p.Arg736Ter)	CEP250	Pathogenic	criteria provided, multiple submitters, no conflicts
3236827	NM_007186.6(CEP250):c.2908del (p.Gln970fs)	CEP250	Pathogenic	criteria provided, single submitter
3236828	NM_007186.6(CEP250):c.547del (p.Glu183fs)	CEP250	Pathogenic	criteria provided, single submitter
3236829	NM_007186.6(CEP250):c.1494_1503delinsCCT (p.Gln499fs)	CEP250	Pathogenic	criteria provided, single submitter
3236830	NM_007186.6(CEP250):c.4020+1G>A	CEP250	Pathogenic	criteria provided, single submitter
3236831	NM_007186.6(CEP250):c.5171del (p.Leu1724fs)	CEP250	Pathogenic	criteria provided, single submitter
3236832	NM_007186.6(CEP250):c.1510C>T (p.Gln504Ter)	CEP250	Pathogenic	criteria provided, single submitter
3338692	NM_007186.6(CEP250):c.5579_5580dup (p.Leu1861fs)	CEP250	Pathogenic	no assertion criteria provided
620658	NM_007186.6(CEP250):c.3463C>T (p.Arg1155Ter)	CEP250	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
620659	NM_007186.6(CEP250):c.361C>T (p.Arg121Ter)	CEP250	Pathogenic	criteria provided, single submitter
620660	NM_007186.6(CEP250):c.562C>T (p.Arg188Ter)	CEP250	Pathogenic	criteria provided, multiple submitters, no conflicts
620662	NM_007186.6(CEP250):c.4006C>T (p.Arg1336Ter)	CEP250	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
835882	NM_007186.6(CEP250):c.5383dup (p.Glu1795fs)	CEP250	Pathogenic	criteria provided, multiple submitters, no conflicts
848176	NM_007186.6(CEP250):c.5050del (p.Asp1684fs)	CEP250	Pathogenic	criteria provided, multiple submitters, no conflicts
969355	NM_007186.6(CEP250):c.4272_4273delinsT (p.Leu1425fs)	CEP250	Pathogenic	criteria provided, multiple submitters, no conflicts
620661	NM_007186.6(CEP250):c.3337A>T (p.Lys1113Ter)	CEP250	Likely pathogenic	criteria provided, single submitter
1064054	NM_007186.6(CEP250):c.3899-6T>G	CEP250	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
843731	NM_007186.6(CEP250):c.493-1G>A	CEP250	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
859101	NM_007186.6(CEP250):c.1826C>T (p.Ala609Val)	CEP250	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1008052	NM_007186.6(CEP250):c.2254C>T (p.Arg752Trp)	CEP250	Uncertain significance	criteria provided, multiple submitters, no conflicts
1023670	NM_007186.6(CEP250):c.7084C>T (p.Gln2362Ter)	CEP250	Uncertain significance	criteria provided, multiple submitters, no conflicts
1924247	NM_007186.6(CEP250):c.1427G>A (p.Arg476Gln)	CEP250	Uncertain significance	criteria provided, multiple submitters, no conflicts
3377721	NM_007186.6(CEP250):c.3392C>G (p.Ser1131Cys)	CEP250	Uncertain significance	criteria provided, single submitter
4078245	NM_007186.6(CEP250):c.4347G>T (p.Lys1449Asn)	CEP250	Uncertain significance	criteria provided, single submitter
4078246	NM_007186.6(CEP250):c.1951G>A (p.Glu651Lys)	CEP250	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 0 · 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
CEP250	Definitive	Autosomal recessive	cone-rod dystrophy and hearing loss 2	7

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
CEP250	HGNC:1859	ENSG00000126001	Q9BV73	Centrosome-associated protein CEP250	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CEP250	Centrosome-associated protein CEP250	Plays an important role in centrosome cohesion during interphase.

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)
CEP250	Other/Unknown	no		Rootletin-like_CC, CEP250_CC

Expression context

Cohort genes with no expression data: 0.

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
cortical plate	1
sural nerve	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CEP250	186	ubiquitous	yes	sural nerve, ventricular zone, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CEP250	2,707

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CEP250	Q9BV73	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 1 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
Loss of Nlp from mitotic centrosomes	1	158.6×	0.009	CEP250
Loss of proteins required for interphase microtubule organization from the centrosome	1	158.6×	0.009	CEP250
AURKA Activation by TPX2	1	152.3×	0.009	CEP250
Recruitment of mitotic centrosome proteins and complexes	1	135.9×	0.009	CEP250
Regulation of PLK1 Activity at G2/M Transition	1	126.9×	0.009	CEP250
Recruitment of NuMA to mitotic centrosomes	1	116.5×	0.009	CEP250
Anchoring of the basal body to the plasma membrane	1	113.1×	0.009	CEP250

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
regulation of centriole-centriole cohesion	1	8426.0×	0.001	CEP250
positive regulation of protein localization to centrosome	1	2407.4×	0.002	CEP250
centriole-centriole cohesion	1	1296.3×	0.002	CEP250
protein localization to centrosome	1	674.1×	0.003	CEP250
detection of light stimulus involved in visual perception	1	648.1×	0.003	CEP250
non-motile cilium assembly	1	290.6×	0.005	CEP250
mitotic cell cycle	1	133.8×	0.010	CEP250
intracellular protein localization	1	104.7×	0.011	CEP250
cilium assembly	1	73.6×	0.014	CEP250

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
CEP250	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	CEP250

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)
CEP250	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.