Isolated osteopoikilosis

Summary

Isolated osteopoikilosis (MONDO:0015634) is a disease with 1 cohort gene.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 33

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	2	Worldwide	Validated
Point prevalence	1-9 / 100 000	2	Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

33 HPO clinical features (Orphanet curated; top 33 by frequency):

HPO ID	Term	Frequency
HP:0011001	Increased bone mineral density	Very frequent (80-99%)
HP:0011849	Abnormal bone ossification	Very frequent (80-99%)
HP:0040068	Abnormality of limb bone	Very frequent (80-99%)
HP:0004289	Sclerotic foci in hand bones	Frequent (30-79%)
HP:0009106	Abnormal pelvis bone ossification	Frequent (30-79%)
HP:0011314	Abnormality of long bone morphology	Frequent (30-79%)
HP:0040163	Abnormal pelvis bone morphology	Frequent (30-79%)
HP:0100774	Hyperostosis	Frequent (30-79%)
HP:0100925	Sclerosis of foot bone	Frequent (30-79%)
HP:0000620	Dacryocystitis	Occasional (5-29%)
HP:0001376	Limitation of joint mobility	Occasional (5-29%)
HP:0001387	Joint stiffness	Occasional (5-29%)
HP:0001474	Sclerotic scapulae	Occasional (5-29%)
HP:0002653	Bone pain	Occasional (5-29%)
HP:0002823	Abnormality of femur morphology	Occasional (5-29%)
HP:0002829	Arthralgia	Occasional (5-29%)
HP:0004240	Sclerotic foci within carpal bones	Occasional (5-29%)
HP:0012758	Neurodevelopmental delay	Occasional (5-29%)
HP:0030838	Hip pain	Occasional (5-29%)
HP:0030840	Ankle pain	Occasional (5-29%)
HP:0030955	Alcoholism	Occasional (5-29%)
HP:0031051	Tarsal sclerosis	Occasional (5-29%)
HP:0032148	Episodic pain	Occasional (5-29%)
HP:0100569	Abnormally ossified vertebrae	Occasional (5-29%)
HP:0000077	Abnormality of the kidney	Very rare (<1-4%)
HP:0000175	Cleft palate	Very rare (<1-4%)
HP:0000818	Abnormality of the endocrine system	Very rare (<1-4%)
HP:0001159	Syndactyly	Very rare (<1-4%)
HP:0001627	Abnormal heart morphology	Very rare (<1-4%)
HP:0002960	Autoimmunity	Very rare (<1-4%)
HP:0007417	Discoid lupus rash	Very rare (<1-4%)
HP:0010562	Keloids	Very rare (<1-4%)
HP:0100324	Scleroderma	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	isolated osteopoikilosis
Mondo ID	MONDO:0015634
Orphanet	166119
UMLS	C1833699
MedGen	318940
GARD	0017027
Is cancer (heuristic)	no

Also known as: isolated osteopoikilosis (disease) · nonsyndromic osteopoikilosis (disease)

Data availability: 1 GenCC gene-disease record.

Disease family

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

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: 7 · Orphanet: 3 · 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
LEMD3	Supportive	Autosomal dominant	isolated osteopoikilosis	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LEMD3	Orphanet:166119	Isolated osteopoikilosis
LEMD3	Orphanet:1879	Melorheostosis with osteopoikilosis
LEMD3	Orphanet:94063	12q14 microdeletion syndrome

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
LEMD3	HGNC:28887	ENSG00000174106	Q9Y2U8	Inner nuclear membrane protein Man1	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LEMD3	Inner nuclear membrane protein Man1	Can function as a specific repressor of TGF-beta, activin, and BMP signaling through its interaction with the R-SMAD proteins.

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)
LEMD3	Other/Unknown	no		LEM_dom, LEM/LEM-like_dom_sf, Nucleotide-bd_a/b_plait_sf

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
cerebellar vermis	1
endothelial cell	1
germinal epithelium of ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LEMD3	289	ubiquitous	marker	endothelial cell, cerebellar vermis, germinal epithelium of ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LEMD3	2,735

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LEMD3	Q9Y2U8	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. 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
Depolymerization of the Nuclear Lamina	1	761.3×	0.011	LEMD3
Initiation of Nuclear Envelope (NE) Reformation	1	601.0×	0.011	LEMD3
Nuclear Envelope Breakdown	1	456.8×	0.011	LEMD3
Mitotic Prophase	1	368.4×	0.011	LEMD3
Nuclear Envelope (NE) Reassembly	1	292.8×	0.011	LEMD3
RND1 GTPase cycle	1	265.6×	0.011	LEMD3
RND3 GTPase cycle	1	259.6×	0.011	LEMD3
RND2 GTPase cycle	1	259.6×	0.011	LEMD3
RHOD GTPase cycle	1	203.9×	0.012	LEMD3
RHOG GTPase cycle	1	148.3×	0.015	LEMD3
RAC2 GTPase cycle	1	126.9×	0.015	LEMD3
RAC3 GTPase cycle	1	119.0×	0.015	LEMD3
Mitotic Metaphase and Anaphase	1	96.8×	0.016	LEMD3
Mitotic Anaphase	1	96.8×	0.016	LEMD3
M Phase	1	66.0×	0.022	LEMD3
RAC1 GTPase cycle	1	61.1×	0.022	LEMD3
RHO GTPase cycle	1	60.1×	0.022	LEMD3
Cell Cycle, Mitotic	1	48.2×	0.025	LEMD3
Cell Cycle	1	36.0×	0.031	LEMD3
Signaling by Rho GTPases	1	34.2×	0.031	LEMD3
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.031	LEMD3
Signal Transduction	1	10.2×	0.098	LEMD3

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
negative regulation of activin receptor signaling pathway	1	1404.3×	0.002	LEMD3
negative regulation of BMP signaling pathway	1	290.6×	0.005	LEMD3
negative regulation of transforming growth factor beta receptor signaling pathway	1	173.7×	0.006	LEMD3

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
LEMD3	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	LEMD3

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)
LEMD3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.