Pulmonary fibrosis and/or bone marrow failure, telomere-related, 5
diseaseOn this page
Also known as PFBMFT5ZCCHC8-related telomere biology disorder
Summary
Pulmonary fibrosis and/or bone marrow failure, telomere-related, 5 (MONDO:0032865) 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 | pulmonary fibrosis and/or bone marrow failure, telomere-related, 5 |
| Mondo ID | MONDO:0032865 |
| OMIM | 618674 |
| UMLS | C5231457 |
| MedGen | 1684878 |
| GARD | 0025762 |
| Is cancer (heuristic) | no |
Also known as: PFBMFT5 · ZCCHC8-related telomere biology disorder
Data availability: 9 ClinVar variants · 1 GenCC gene-disease record.
Disease family
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 › pulmonary fibrosis and/or bone marrow failure, telomere-related, 5
Related subtypes (8): pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 2, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4, pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3, pulmonary fibrosis and/or bone marrow failure, telomere-related, 6, pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7, pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 8, pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 9
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:
4 uncertain significance, 2 benign, 1 conflicting classifications of pathogenicity, 1 pathogenic, 1 benign/likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 694674 | NM_017612.5(ZCCHC8):c.557C>T (p.Pro186Leu) | ZCCHC8 | Pathogenic | criteria provided, single submitter |
| 1029475 | NM_017612.5(ZCCHC8):c.508G>A (p.Gly170Arg) | ZCCHC8 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1462451 | NM_017612.5(ZCCHC8):c.1370A>T (p.Gln457Leu) | ZCCHC8 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1675154 | NM_017612.5(ZCCHC8):c.550G>A (p.Gly184Arg) | ZCCHC8 | Uncertain significance | criteria provided, single submitter |
| 3067833 | NM_017612.5(ZCCHC8):c.574C>G (p.Pro192Ala) | ZCCHC8 | Uncertain significance | criteria provided, single submitter |
| 932915 | NM_017612.5(ZCCHC8):c.1487C>T (p.Thr496Ile) | ZCCHC8 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1684250 | NM_017612.5(ZCCHC8):c.1140+29A>G | ZCCHC8 | Benign | criteria provided, multiple submitters, no conflicts |
| 1684251 | NM_017612.5(ZCCHC8):c.200-44T>C | ZCCHC8 | Benign | criteria provided, multiple submitters, no conflicts |
| 786612 | NM_017612.5(ZCCHC8):c.1345+5G>A | ZCCHC8 | Benign/Likely benign | criteria provided, multiple submitters, no conflicts |
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,clinvar |
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
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 |
|---|---|---|---|---|
| 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.
Related Atlas pages
- Cohort genes: ZCCHC8