Dyskeratosis congenita, autosomal dominant 4

Summary

Dyskeratosis congenita, autosomal dominant 4 (MONDO:0800366) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dyskeratosis congenita, autosomal dominant 4
Mondo ID	MONDO:0800366
DOID	DOID:0070020
UMLS	C3808802
MedGen	815132
GARD	0026525
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › dyskeratosis congenita › dyskeratosis congenita, autosomal dominant 4

Related subtypes (15): dyskeratosis congenita, autosomal dominant 1, dyskeratosis congenita, autosomal recessive 1, Revesz syndrome, dyskeratosis congenita, autosomal recessive 2, dyskeratosis congenita, autosomal recessive 3, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, dyskeratosis congenita, autosomal recessive 6, dyskeratosis congenita, autosomal dominant 6, autosomal recessive dyskeratosis congenita 4, dyskeratosis congenita, digenic, DKC1-related disorder, dyskeratosis congenita, autosomal recessive 7, dyskeratosis congenita and related telomere biology disorder, dyskeratosis congenita, autosomal recessive 8

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

2 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
65417	NM_001283009.2(RTEL1):c.2956C>T (p.Arg986Ter)	RTEL1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
65418	NM_001283009.2(RTEL1):c.1861G>A (p.Ala621Thr)	RTEL1	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RTEL1	Orphanet:1775	Dyskeratosis congenita
RTEL1	Orphanet:2032	Idiopathic pulmonary fibrosis
RTEL1	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
RTEL1	HGNC:15888	ENSG00000258366	Q9NZ71	Regulator of telomere elongation helicase 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RTEL1	Regulator of telomere elongation helicase 1	A probable ATP-dependent DNA helicase implicated in telomere-length regulation, DNA repair and the maintenance of genomic stability.

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)
RTEL1	Other/Unknown	no		Helicase-like_DEXD_c2, ATP-dep_Helicase_C, RAD3-like_helicase_DEAD

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
cerebellar hemisphere	1
right hemisphere of cerebellum	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RTEL1	134	ubiquitous	yes	sural nerve, right hemisphere of cerebellum, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RTEL1	2,324

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RTEL1	Q9NZ71	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. 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
Cytosolic iron-sulfur cluster assembly	1	761.3×	0.006	RTEL1
Resolution of D-Loop Structures	1	634.4×	0.006	RTEL1
Extension of Telomeres	1	601.0×	0.006	RTEL1
Telomere Extension By Telomerase	1	456.8×	0.006	RTEL1
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	393.8×	0.006	RTEL1
Telomere Maintenance	1	368.4×	0.006	RTEL1
Homology Directed Repair	1	308.6×	0.006	RTEL1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1	308.6×	0.006	RTEL1
DNA Double-Strand Break Repair	1	248.3×	0.006	RTEL1
Chromosome Maintenance	1	211.5×	0.007	RTEL1
HDR through Homologous Recombination (HRR)	1	190.3×	0.007	RTEL1
DNA Repair	1	98.5×	0.012	RTEL1
Cell Cycle	1	36.0×	0.030	RTEL1
Metabolism	1	11.6×	0.086	RTEL1

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
DNA strand displacement	1	16852.0×	3e-04	RTEL1
negative regulation of telomere maintenance in response to DNA damage	1	16852.0×	3e-04	RTEL1
positive regulation of telomeric loop disassembly	1	16852.0×	3e-04	RTEL1
telomeric loop disassembly	1	8426.0×	4e-04	RTEL1
mitotic telomere maintenance via semi-conservative replication	1	5617.3×	4e-04	RTEL1
negative regulation of t-circle formation	1	5617.3×	4e-04	RTEL1
positive regulation of telomere capping	1	3370.4×	6e-04	RTEL1
positive regulation of telomere maintenance via telomere lengthening	1	2808.7×	7e-04	RTEL1
telomere maintenance in response to DNA damage	1	1872.4×	9e-04	RTEL1
negative regulation of DNA recombination	1	1123.5×	0.001	RTEL1
regulation of double-strand break repair via homologous recombination	1	991.3×	0.001	RTEL1
positive regulation of telomere maintenance	1	510.7×	0.002	RTEL1
replication fork processing	1	421.3×	0.003	RTEL1
telomere maintenance	1	267.5×	0.004	RTEL1
DNA repair	1	63.8×	0.016	RTEL1

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
RTEL1	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	RTEL1

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)
RTEL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.