Cone-rod dystrophy and hearing loss 1

Summary

Cone-rod dystrophy and hearing loss 1 (MONDO:0020778) is a disease caused by CEP78 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CEP78 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 35

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cone-rod dystrophy and hearing loss 1
Mondo ID	MONDO:0020778
OMIM	617236
UMLS	C5193018
MedGen	1682048
Is cancer (heuristic)	no

Also known as: cone-rod dystrophy and hearing loss · CRDHL1

Data availability: 35 ClinVar variants · 2 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 1

Related subtypes (1): cone-rod dystrophy and hearing loss 2

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

35 retrieved; paginated sample, class counts are floors:

14 pathogenic, 7 uncertain significance, 6 pathogenic/likely pathogenic, 3 conflicting classifications of pathogenicity, 3 likely pathogenic, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1065756	NM_001330691.3(CEP78):c.1447C>T (p.Arg483Ter)	CEP78	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1171013	NM_001330691.3(CEP78):c.1459-1G>T	CEP78	Pathogenic	criteria provided, single submitter
1171014	NM_001330691.3(CEP78):c.449T>C (p.Leu150Ser)	CEP78	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1399492	NM_001330691.3(CEP78):c.1454del (p.Ser485fs)	CEP78	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457961	NM_001330691.3(CEP78):c.1009C>T (p.Gln337Ter)	CEP78	Pathogenic	criteria provided, multiple submitters, no conflicts
2098548	NM_001330691.3(CEP78):c.1205+2T>A	CEP78	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2164471	NM_001330691.3(CEP78):c.1698_1701del (p.Ser567fs)	CEP78	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2498281	NM_001330691.3(CEP78):c.1369G>T (p.Glu457Ter)	CEP78	Pathogenic	criteria provided, single submitter
3370363	CEP78, PRO392LEU	CEP78	Pathogenic	no assertion criteria provided
372266	NM_001330691.3(CEP78):c.499+1G>T	CEP78	Pathogenic	no assertion criteria provided
372267	NM_001330691.3(CEP78):c.633del (p.Trp212fs)	CEP78	Pathogenic	criteria provided, single submitter
372268	NM_001330691.3(CEP78):c.499+5G>A	CEP78	Pathogenic	no assertion criteria provided
372269	NM_001330691.3(CEP78):c.893-1G>A	CEP78	Pathogenic	no assertion criteria provided
372270	NM_001330691.3(CEP78):c.534del (p.Lys179fs)	CEP78	Pathogenic	criteria provided, single submitter
372271	NM_001330691.3(CEP78):c.1251+5G>A	CEP78	Pathogenic	criteria provided, multiple submitters, no conflicts
372272	NM_001330691.3(CEP78):c.1626-2A>G	CEP78	Pathogenic	no assertion criteria provided
4292797	NM_001330691.3(CEP78):c.755_756del (p.Leu252fs)	CEP78	Pathogenic	criteria provided, single submitter
561260	46,XX,der(9)(q21.2,q21.2).seq[GRCh37/hg19]der(9)(9pter->9q21.2(+)(8084369{7-8})::q21.2(-)(808497{60-59}),q21.2(-)(8084946{5-3})::q21.2(+)(808596{79-81}->9qter)	CEP78	Pathogenic	no assertion criteria provided
813161	NM_001330691.3(CEP78):c.1424del (p.Val475fs)	CEP78	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
836906	NM_001330691.3(CEP78):c.1206-2A>C	CEP78	Pathogenic	criteria provided, single submitter
2579255	GRCh38/hg38 9q21.2(chr9:78235965-78243734)x1	CEP78	Likely pathogenic	criteria provided, single submitter
3336680	NM_001330691.3(CEP78):c.604-2A>C	CEP78	Likely pathogenic	criteria provided, single submitter
844272	NM_001330691.3(CEP78):c.440C>T (p.Ser147Leu)	CEP78	Likely pathogenic	criteria provided, single submitter
1058404	NM_001330691.3(CEP78):c.473G>T (p.Cys158Phe)	CEP78	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
667214	NM_001330691.3(CEP78):c.1846-1G>C	CEP78	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
667216	NM_001330691.3(CEP78):c.491G>A (p.Gly164Asp)	CEP78	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1006577	NM_001330691.3(CEP78):c.1571T>C (p.Ile524Thr)	CEP78	Uncertain significance	criteria provided, multiple submitters, no conflicts
1364999	NM_001330691.3(CEP78):c.830T>C (p.Leu277Pro)	CEP78	Uncertain significance	criteria provided, single submitter
1391227	NM_001330691.3(CEP78):c.106G>A (p.Ala36Thr)	CEP78	Uncertain significance	criteria provided, multiple submitters, no conflicts
848911	NM_001330691.3(CEP78):c.1915_1916insGGG (p.Pro639delinsArgAla)	CEP78	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
CEP78	Definitive	Autosomal recessive	cone-rod dystrophy and hearing loss	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CEP78	Orphanet:231183	Usher syndrome type 3

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
CEP78	HGNC:25740	ENSG00000148019	Q5JTW2	Centrosomal protein of 78 kDa	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CEP78	Centrosomal protein of 78 kDa	Centriole wall protein that localizes to mature centrioles and regulates centriole and cilia biogenesis.

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)
CEP78	Other/Unknown	no		Leu-rich_rpt, Cep78, LRR_dom_sf

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
buccal mucosa cell	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CEP78	239	ubiquitous	marker	secondary oocyte, oocyte, buccal mucosa cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CEP78	1,373

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CEP78	Q5JTW2	64.28

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. 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
Centrosome maturation	1	253.8×	0.013	CEP78
Loss of Nlp from mitotic centrosomes	1	158.6×	0.013	CEP78
Loss of proteins required for interphase microtubule organization from the centrosome	1	158.6×	0.013	CEP78
AURKA Activation by TPX2	1	152.3×	0.013	CEP78
Recruitment of mitotic centrosome proteins and complexes	1	135.9×	0.013	CEP78
Regulation of PLK1 Activity at G2/M Transition	1	126.9×	0.013	CEP78
Mitotic G2-G2/M phases	1	126.9×	0.013	CEP78
G2/M Transition	1	126.9×	0.013	CEP78
Recruitment of NuMA to mitotic centrosomes	1	116.5×	0.013	CEP78
Anchoring of the basal body to the plasma membrane	1	113.1×	0.013	CEP78
Cilium Assembly	1	108.8×	0.013	CEP78
Mitotic Prometaphase	1	69.2×	0.017	CEP78
Organelle biogenesis and maintenance	1	66.0×	0.017	CEP78
M Phase	1	66.0×	0.017	CEP78
Cell Cycle, Mitotic	1	48.2×	0.022	CEP78
Cell Cycle	1	36.0×	0.028	CEP78

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 centrosome	1	674.1×	0.004	CEP78
cilium organization	1	601.9×	0.004	CEP78
protein localization to cilium	1	401.2×	0.004	CEP78
negative regulation of protein ubiquitination	1	285.6×	0.004	CEP78
flagellated sperm motility	1	117.0×	0.009	CEP78

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
CEP78	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	CEP78

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)
CEP78	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.