Dyskeratosis congenita, autosomal recessive 8

Summary

Dyskeratosis congenita, autosomal recessive 8 (MONDO:0859319) is a disease caused by DCLRE1B (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: DCLRE1B (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	dyskeratosis congenita, autosomal recessive 8
Mondo ID	MONDO:0859319
OMIM	620133
UMLS	C5774257
MedGen	1824030
GARD	0026695
Is cancer (heuristic)	no

Data availability: 4 ClinVar variants · 3 GenCC gene-disease records.

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 recessive 8

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 dominant 4, dyskeratosis congenita, autosomal recessive 7, dyskeratosis congenita and related telomere biology disorder

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

4 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1801220	NM_022836.4(DCLRE1B):c.426A>T (p.Leu142Phe)	DCLRE1B	Pathogenic	no assertion criteria provided
1801221	NM_022836.4(DCLRE1B):c.364C>T (p.Arg122Ter)	DCLRE1B	Pathogenic	no assertion criteria provided
1801222	NM_022836.4(DCLRE1B):c.425T>C (p.Leu142Ser)	DCLRE1B	Pathogenic	no assertion criteria provided
1053302	NM_022836.4(DCLRE1B):c.472C>T (p.Arg158Ter)	DCLRE1B	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
DCLRE1B	Strong	Autosomal recessive	dyskeratosis congenita, autosomal recessive 8	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
DCLRE1B	HGNC:17641	ENSG00000118655	Q9H816	5’ exonuclease Apollo	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DCLRE1B	5’ exonuclease Apollo	5’-3’ exonuclease that plays a central role in telomere maintenance and protection during S-phase.

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)
DCLRE1B	Other/Unknown	no		DRMBL, RibonucZ/Hydroxyglut_hydro

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
oocyte	1
primordial germ cell in gonad	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DCLRE1B	224	ubiquitous	yes	secondary oocyte, primordial germ cell in gonad, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DCLRE1B	1,528

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DCLRE1B	Q9H816	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Fanconi Anemia Pathway	1	278.5×	0.004	DCLRE1B

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
telomeric loop formation	1	8426.0×	9e-04	DCLRE1B
telomeric 3’ overhang formation	1	4213.0×	9e-04	DCLRE1B
protection from non-homologous end joining at telomere	1	2407.4×	0.001	DCLRE1B
telomere maintenance via telomere lengthening	1	1872.4×	0.001	DCLRE1B
telomere capping	1	1296.3×	0.001	DCLRE1B
interstrand cross-link repair	1	432.1×	0.003	DCLRE1B
double-strand break repair via nonhomologous end joining	1	421.3×	0.003	DCLRE1B
telomere maintenance	1	267.5×	0.004	DCLRE1B

Therapeutics

Drug target analysis

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

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
DCLRE1B	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
DCLRE1B	1	Binding:1

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	DCLRE1B

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)
DCLRE1B	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.