Hyperostosis

Summary

Hyperostosis (MONDO:0002185) is a disease (an umbrella term covering 9 Mondo subtypes) with 1 cohort gene.

At a glance

• Umbrella term: 9 Mondo subtypes
• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hyperostosis
Mondo ID	MONDO:0002185
MeSH	D015576
DOID	DOID:205
ICD-10-CM	M89.3
NCIT	C34712
SNOMED CT	203514008
UMLS	C0020492
MedGen	9366
Is cancer (heuristic)	no

Also known as: bone hypertrophy · hypertrophy of bone · hypertrophy of bone (morphologic abnormality)

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 9 Mondo subtypes.

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

Related subtypes (5): bone resorption disease, fibrous dysplasia, osteomalacia, osteosclerosis, rickets

Subtypes (9): exostosis, bone Paget disease, diffuse idiopathic skeletal hyperostosis, Caffey disease, autosomal dominant osteosclerosis, Worth type, craniodiaphyseal dysplasia, hyperostosis corticalis generalisata, X-linked calvarial hyperostosis, sclerosteosis

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
617636	NM_032305.3(POLR3GL):c.326-1G>A	LOC129931343	Pathogenic/Likely pathogenic	no assertion criteria provided
617676	NM_032305.3(POLR3GL):c.-41-1G>A	POLR3GL	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
POLR3GL	HGNC:28466	ENSG00000121851	Q9BT43	DNA-directed RNA polymerase III subunit RPC7-like	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
POLR3GL	DNA-directed RNA polymerase III subunit RPC7-like	DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.

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)
POLR3GL	Other/Unknown	no		RNA_pol_III_Rpc31

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
gastrocnemius	1
muscle of leg	1
skeletal muscle tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
POLR3GL	134	ubiquitous	marker	gastrocnemius, muscle of leg, skeletal muscle tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
POLR3GL	1,010

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
POLR3GL	Q9BT43	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. 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
RNA Polymerase III Chain Elongation	1	634.4×	0.005	POLR3GL
RNA Polymerase III Transcription Termination	1	496.5×	0.005	POLR3GL
RNA Polymerase III Transcription Initiation From Type 2 Promoter	1	423.0×	0.005	POLR3GL
RNA Polymerase III Transcription Initiation From Type 1 Promoter	1	407.9×	0.005	POLR3GL
RNA Polymerase III Transcription Initiation From Type 3 Promoter	1	407.9×	0.005	POLR3GL
RNA Polymerase III Transcription Initiation	1	335.9×	0.005	POLR3GL
RNA Polymerase III Transcription	1	326.3×	0.005	POLR3GL
Cytosolic sensors of pathogen-associated DNA	1	285.5×	0.005	POLR3GL
RNA Polymerase III Abortive And Retractive Initiation	1	278.5×	0.005	POLR3GL
Innate Immune System	1	25.5×	0.047	POLR3GL
Gene expression (Transcription)	1	17.8×	0.061	POLR3GL
Immune System	1	13.0×	0.077	POLR3GL

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
transcription by RNA polymerase III	1	766.0×	0.001	POLR3GL

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
POLR3GL	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	POLR3GL

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)
POLR3GL	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.