Cataracts, hearing impairment, nephrotic syndrome, and enterocolitis 1

Summary

Cataracts, hearing impairment, nephrotic syndrome, and enterocolitis 1 (MONDO:0958178) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cataracts, hearing impairment, nephrotic syndrome, and enterocolitis 1
Mondo ID	MONDO:0958178
OMIM	301108
UMLS	C5829571
MedGen	1840207
Is cancer (heuristic)	no

Data availability: 9 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › cataracts, hearing impairment, nephrotic syndrome, and enterocolitis › cataracts, hearing impairment, nephrotic syndrome, and enterocolitis 1

Related subtypes (1): cataracts, hearing impairment, nephrotic syndrome, and enterocolitis 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

9 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 2 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2506511	NM_001363.5(DKC1):c.616G>A (p.Glu206Lys)	DKC1	Pathogenic	no assertion criteria provided
1434341	NM_001363.5(DKC1):c.253G>A (p.Asp85Asn)	DKC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
800194	NM_001363.5(DKC1):c.1350G>C (p.Glu450Asp)	DKC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1163206	NM_001363.5(DKC1):c.1353T>A (p.Ser451Arg)	DKC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2444898	NM_001363.5(DKC1):c.1240C>G (p.Gln414Glu)	DKC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3598197	NM_001363.5(DKC1):c.352A>C (p.Thr118Pro)	DKC1	Uncertain significance	criteria provided, single submitter
3598198	NM_001363.5(DKC1):c.901A>G (p.Met301Val)	DKC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3598200	NM_001363.5(DKC1):c.1396A>G (p.Ile466Val)	DKC1	Uncertain significance	criteria provided, single submitter
459583	NM_001363.5(DKC1):c.1515A>C (p.Lys505Asn)	DKC1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DKC1	Orphanet:1775	Dyskeratosis congenita
DKC1	Orphanet:3322	Hoyeraal-Hreidarsson syndrome

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
DKC1	HGNC:2890	ENSG00000130826	O60832	H/ACA ribonucleoprotein complex subunit DKC1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DKC1	H/ACA ribonucleoprotein complex subunit DKC1	Catalytic subunit of H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA.

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)
DKC1	Other/Unknown	no		PUA, PsdUridine_synth_N, Uncharacterised_CHP00451

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
gingival epithelium	1
secondary oocyte	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DKC1	287	ubiquitous	marker	secondary oocyte, sural nerve, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DKC1	4,882

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DKC1	O60832	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Telomere Extension By Telomerase	1	456.8×	0.004	DKC1
rRNA modification in the nucleus and cytosol	1	187.2×	0.005	DKC1

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
box H/ACA sno(s)RNA 3’-end processing	1	8426.0×	5e-04	DKC1
protein localization to Cajal body	1	8426.0×	5e-04	DKC1
snRNA pseudouridine synthesis	1	5617.3×	5e-04	DKC1
enzyme-directed rRNA pseudouridine synthesis	1	4213.0×	5e-04	DKC1
rRNA pseudouridine synthesis	1	4213.0×	5e-04	DKC1
telomerase RNA stabilization	1	4213.0×	5e-04	DKC1
regulation of telomerase RNA localization to Cajal body	1	4213.0×	5e-04	DKC1
scaRNA localization to Cajal body	1	3370.4×	6e-04	DKC1
telomerase holoenzyme complex assembly	1	2808.7×	6e-04	DKC1
positive regulation of telomerase RNA localization to Cajal body	1	1872.4×	8e-04	DKC1
mRNA pseudouridine synthesis	1	1685.2×	8e-04	DKC1
telomere maintenance via telomerase	1	732.7×	0.002	DKC1
positive regulation of telomere maintenance via telomerase	1	732.7×	0.002	DKC1
RNA processing	1	218.9×	0.005	DKC1
rRNA processing	1	141.6×	0.007	DKC1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DKC1	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	DKC1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
DKC1	8	Binding:8

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

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	DKC1

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	DKC1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.