Pulmonary fibrosis and/or bone marrow failure, telomere-related

disease

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Summary

Pulmonary fibrosis and/or bone marrow failure, telomere-related (MONDO:0000148) is a disease (an umbrella term covering 9 Mondo subtypes) caused by ZCCHC8 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: ZCCHC8 (GenCC Strong)
Umbrella term: 9 Mondo subtypes
Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pulmonary fibrosis and/or bone marrow failure, telomere-related
Mondo ID	MONDO:0000148
OMIM	614742
GARD	0022715
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

Disease family

An umbrella term covering 9 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › respiratory system disorder › lower respiratory tract disorder › lung disorder › interstitial lung disease › pulmonary fibrosis › pulmonary fibrosis and/or bone marrow failure, telomere-related

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
ZCCHC8	Strong	Autosomal dominant	pulmonary fibrosis and/or bone marrow failure, telomere-related	4

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
ZCCHC8	HGNC:25265	ENSG00000033030	Q6NZY4	Zinc finger CCHC domain-containing protein 8	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZCCHC8	Zinc finger CCHC domain-containing protein 8	Scaffolding subunit of the trimeric nuclear exosome targeting (NEXT) complex that is involved in the surveillance and turnover of aberrant transcripts and non-coding RNAs.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ZCCHC8	Transcription factor	no		Znf_CCHC, PSP_pro-rich, NEXT_complex_subunit_ZCCHC8

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
cervix squamous epithelium	1
endothelial cell	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZCCHC8	282	ubiquitous	marker	cervix squamous epithelium, sperm, endothelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ZCCHC8	1,903

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ZCCHC8	Q6NZY4	8

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
Nuclear RNA decay	1	308.6×	0.006	ZCCHC8
Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex	1	163.1×	0.006	ZCCHC8

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
co-transcriptional lncRNA 3’ end processing, cleavage and polyadenylation pathway	1	16852.0×	3e-04	ZCCHC8
snRNA catabolic process	1	5617.3×	4e-04	ZCCHC8
mRNA 3’-end processing	1	561.7×	0.003	ZCCHC8
RNA processing	1	218.9×	0.006	ZCCHC8
mRNA splicing, via spliceosome	1	91.6×	0.011	ZCCHC8

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
ZCCHC8	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
ZCCHC8	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	ZCCHC8

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)
ZCCHC8	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: ZCCHC8