Paget disease of bone 6

Summary

Paget disease of bone 6 (MONDO:0014792) is a disease caused by ZNF687 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ZNF687 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Paget disease of bone 6
Mondo ID	MONDO:0014792
OMIM	616833
DOID	DOID:0081369
UMLS	C4085250
MedGen	908743
Is cancer (heuristic)	no

Also known as: Paget disease of bone 6 · Paget disease of bone 6; PDB6 · Paget disease of bone type 6 · PDB6

Data availability: 10 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › skeletal system disorder › bone disorder › bone remodeling disease › hyperostosis › bone Paget disease › Paget disease of bone 6

Related subtypes (4): Paget disease of bone 3, juvenile Paget disease, Paget disease of bone 2, early-onset, paget disease of bone 4

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

10 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 3 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
222988	NM_020832.3(ZNF687):c.725G>T (p.Ser242Ile)	ZNF687	Pathogenic	no assertion criteria provided
2174642	NM_020832.3(ZNF687):c.557G>A (p.Arg186Gln)	ZNF687	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2192982	NM_020832.3(ZNF687):c.3455G>A (p.Arg1152Gln)	ZNF687	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
222987	NM_020832.3(ZNF687):c.2810C>G (p.Pro937Arg)	ZNF687	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1518826	NM_020832.3(ZNF687):c.2810C>T (p.Pro937Leu)	ZNF687	Uncertain significance	criteria provided, multiple submitters, no conflicts
1934169	NM_020832.3(ZNF687):c.2927A>T (p.Asp976Val)	ZNF687	Uncertain significance	criteria provided, multiple submitters, no conflicts
2979044	NM_020832.3(ZNF687):c.3461G>A (p.Arg1154His)	ZNF687	Uncertain significance	criteria provided, multiple submitters, no conflicts
4278039	NM_020832.3(ZNF687):c.3709_*17del (p.Asp1236_Asn1237insTer)	ZNF687	Uncertain significance	criteria provided, single submitter
801543	NM_020832.3(ZNF687):c.2810C>A (p.Pro937His)	ZNF687	Uncertain significance	criteria provided, multiple submitters, no conflicts
977102	NM_020832.3(ZNF687):c.1695C>G (p.His565Gln)	ZNF687	Uncertain significance	criteria provided, multiple submitters, no conflicts

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
ZNF687	Strong	Autosomal dominant	Paget disease of bone 6	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
ZNF687	HGNC:29277	ENSG00000143373	Q8N1G0	Zinc finger protein 687	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZNF687	Zinc finger protein 687	May be involved in transcriptional regulation.

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)
ZNF687	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Znf-C2H2_11

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
cardiac muscle of right atrium	1
kidney epithelium	1
left ventricle myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZNF687	197	ubiquitous	yes	kidney epithelium, cardiac muscle of right atrium, left ventricle myocardium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ZNF687	1,405

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ZNF687	Q8N1G0	53.34

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
Interaction of NuRD complexes with transcription factors	1	126.9×	0.008	ZNF687

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
ZNF687	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	ZNF687

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)
ZNF687	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.