Autosomal recessive osteopetrosis 5
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Also known as autosomal recessive osteopetrosis type 5OPTB5osteopetrosis (disease) caused by mutation in OSTM1osteopetrosis autosomal recessive 5osteopetrosis infantile malignant 3osteopetrosis, autosomal recessive 5osteopetrosis, autosomal recessive type 5OSTM1 osteopetrosis (disease)
Summary
Autosomal recessive osteopetrosis 5 (MONDO:0009817) is a disease caused by OSTM1 (GenCC Definitive), with 1 cohort gene.
At a glance
- Causal gene: OSTM1 (GenCC Definitive)
- Cohort genes: 1
- ClinVar variants: 101
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | autosomal recessive osteopetrosis 5 |
| Mondo ID | MONDO:0009817 |
| MeSH | C566883 |
| OMIM | 259720 |
| DOID | DOID:0110939 |
| UMLS | C1968603 |
| MedGen | 409627 |
| GARD | 0004153 |
| Is cancer (heuristic) | no |
Also known as: autosomal recessive osteopetrosis 5 · autosomal recessive osteopetrosis type 5 · OPTB5 · osteopetrosis (disease) caused by mutation in OSTM1 · osteopetrosis autosomal recessive 5 · osteopetrosis infantile malignant 3 · osteopetrosis, autosomal recessive 5 · osteopetrosis, autosomal recessive type 5 · OSTM1 osteopetrosis (disease)
Data availability: 101 ClinVar variants · 4 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › skeletal dysplasia › osteopetrosis › infantile osteopetrosis with neuroaxonal dysplasia › autosomal recessive osteopetrosis 5
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
101 retrieved; paginated sample, class counts are floors:
50 uncertain significance, 27 benign, 8 conflicting classifications of pathogenicity, 7 pathogenic, 4 likely benign, 4 benign/likely benign, 1 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 2903667 | NM_014028.4(OSTM1):c.25C>T (p.Gln9Ter) | LOC129996933 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2944 | NM_014028.4(OSTM1):c.36T>A (p.Cys12Ter) | LOC129996933 | Pathogenic | no assertion criteria provided |
| 1453192 | NM_014028.4(OSTM1):c.692dup (p.Ser232fs) | OSTM1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 195291 | NM_014028.4(OSTM1):c.415_416del (p.Gln140fs) | OSTM1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 2942 | NM_014028.4(OSTM1):c.949+5G>A | OSTM1 | Pathogenic | no assertion criteria provided |
| 3255027 | NM_014028.4(OSTM1):c.811C>T (p.Arg271Ter) | OSTM1 | Pathogenic | criteria provided, single submitter |
| 488566 | NM_014028.4(OSTM1):c.783+5G>T | OSTM1 | Pathogenic | criteria provided, single submitter |
| 802255 | NM_014028.4(OSTM1):c.486del (p.Phe162fs) | OSTM1 | Pathogenic | criteria provided, single submitter |
| 193369 | NM_014028.4(OSTM1):c.134A>G (p.Asp45Gly) | LOC129996933 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354991 | NM_014028.4(OSTM1):c.67C>T (p.Leu23=) | LOC129996933 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 906826 | NM_014028.4(OSTM1):c.49T>G (p.Trp17Gly) | LOC129996933 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354982 | NM_014028.4(OSTM1):c.950-12T>C | OSTM1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354983 | NM_014028.4(OSTM1):c.933A>G (p.Lys311=) | OSTM1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 354984 | NM_014028.4(OSTM1):c.784-10C>G | OSTM1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 905235 | NM_014028.4(OSTM1):c.279C>T (p.Asn93=) | OSTM1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 907771 | NM_014028.4(OSTM1):c.558A>G (p.Thr186=) | OSTM1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1002233 | NM_014028.4(OSTM1):c.25C>G (p.Gln9Glu) | LOC129996933 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 354993 | NM_014028.4(OSTM1):c.-67G>T | LOC129996933 | Uncertain significance | criteria provided, single submitter |
| 354929 | NM_014028.4(OSTM1):c.*2990T>C | OSTM1 | Uncertain significance | criteria provided, single submitter |
| 354931 | NM_014028.4(OSTM1):c.*2858A>G | OSTM1 | Uncertain significance | criteria provided, single submitter |
| 354932 | NM_014028.4(OSTM1):c.*2773G>A | OSTM1 | Uncertain significance | criteria provided, single submitter |
| 354940 | NM_014028.4(OSTM1):c.*2371G>A | OSTM1 | Uncertain significance | criteria provided, single submitter |
| 354941 | NM_014028.4(OSTM1):c.*2364A>G | OSTM1 | Uncertain significance | criteria provided, single submitter |
| 354945 | NM_014028.4(OSTM1):c.*2317A>C | OSTM1 | Uncertain significance | criteria provided, single submitter |
| 354948 | NM_014028.4(OSTM1):c.*2277G>A | OSTM1 | Uncertain significance | criteria provided, single submitter |
| 354949 | NM_014028.4(OSTM1):c.*2145A>T | OSTM1 | Uncertain significance | criteria provided, single submitter |
| 354952 | NM_014028.4(OSTM1):c.*2035A>G | OSTM1 | Uncertain significance | criteria provided, single submitter |
| 354955 | NM_014028.4(OSTM1):c.*1634A>G | OSTM1 | Uncertain significance | criteria provided, single submitter |
| 354957 | NM_014028.4(OSTM1):c.*1469G>A | OSTM1 | Uncertain significance | criteria provided, single submitter |
| 354958 | NM_014028.4(OSTM1):c.*1455C>T | OSTM1 | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 5 · Orphanet: 1 · 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 |
|---|---|---|---|---|
| OSTM1 | Definitive | Autosomal recessive | autosomal recessive osteopetrosis 5 | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| OSTM1 | Orphanet:85179 | Infantile osteopetrosis with neuroaxonal dysplasia |
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 |
|---|---|---|---|---|---|
| OSTM1 | HGNC:21652 | ENSG00000081087 | Q86WC4 | Osteopetrosis-associated transmembrane protein 1 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| OSTM1 | Osteopetrosis-associated transmembrane protein 1 | Required for osteoclast and melanocyte maturation and function. |
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) |
|---|---|---|---|---|
| OSTM1 | Other/Unknown | no | Osteopetrosis-assoc_TM_1 |
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 |
|---|---|
| adrenal tissue | 1 |
| choroid plexus epithelium | 1 |
| popliteal artery | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| OSTM1 | 287 | ubiquitous | marker | choroid plexus epithelium, adrenal tissue, popliteal artery |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| OSTM1 | 1,108 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| OSTM1 | Q86WC4 | 9 |
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 |
|---|---|---|---|---|
| Stimuli-sensing channels | 1 | 135.9× | 0.007 | OSTM1 |
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 |
|---|---|---|---|---|
| transepithelial chloride transport | 1 | 1872.4× | 0.001 | OSTM1 |
| osteoclast differentiation | 1 | 343.9× | 0.003 | OSTM1 |
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 |
|---|---|---|
| OSTM1 | 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 | OSTM1 |
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) |
|---|---|---|
| OSTM1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: OSTM1