Autosomal recessive osteopetrosis 8

Summary

Autosomal recessive osteopetrosis 8 (MONDO:0014040) is a disease caused by SNX10 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SNX10 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive osteopetrosis 8
Mondo ID	MONDO:0014040
OMIM	615085
DOID	DOID:0110940
NCIT	C150556
UMLS	C3554478
MedGen	767392
GARD	0015905
Is cancer (heuristic)	no

Also known as: autosomal recessive malignant osteopetrosis caused by mutation in SNX10 · autosomal recessive osteopetrosis caused by mutation in SNX10 · autosomal recessive osteopetrosis type 8 · OPTB8 · osteopetrosis, autosomal recessive 8 · osteopetrosis, autosomal recessive type 8 · SNX10 autosomal recessive malignant osteopetrosis · SNX10 autosomal recessive osteopetrosis

Data availability: 12 ClinVar variants · 3 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive osteopetrosis › autosomal recessive osteopetrosis 8

Related subtypes (9): autosomal recessive osteopetrosis 1, autosomal recessive osteopetrosis 2, autosomal recessive osteopetrosis 5, autosomal recessive osteopetrosis 3, autosomal recessive osteopetrosis 4, autosomal recessive osteopetrosis 6, autosomal recessive osteopetrosis 7, leukocyte adhesion deficiency 3, osteopetrosis, autosomal recessive 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

12 retrieved; paginated sample, class counts are floors:

4 likely pathogenic, 3 uncertain significance, 2 pathogenic, 1 benign, 1 likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
139565	NM_013322.3(SNX10):c.46C>T (p.Arg16Ter)	SNX10	Pathogenic	criteria provided, single submitter
40050	NM_013322.3(SNX10):c.152G>A (p.Arg51Gln)	SNX10	Pathogenic	criteria provided, multiple submitters, no conflicts
804401	NM_013322.3(SNX10):c.151C>T (p.Arg51Ter)	SNX10	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3066034	NC_000007.14:g.26544156_26548212del		Likely pathogenic	no assertion criteria provided
2663932	NM_013322.3(SNX10):c.302del (p.Phe101fs)	SNX10	Likely pathogenic	criteria provided, single submitter
3376537	NM_013322.3(SNX10):c.295G>T (p.Glu99Ter)	SNX10	Likely pathogenic	criteria provided, single submitter
3594492	NM_013322.3(SNX10):c.86dup (p.Tyr29Ter)	SNX10	Likely pathogenic	criteria provided, single submitter
1679112	NC_000007.14:g.26263639_26335651delinsCA	LOC129998147	Uncertain significance	criteria provided, single submitter
3594493	NM_013322.3(SNX10):c.398G>A (p.Cys133Tyr)	SNX10	Uncertain significance	criteria provided, single submitter
635163	NM_013322.3(SNX10):c.284G>A (p.Arg95His)	SNX10	Uncertain significance	criteria provided, multiple submitters, no conflicts
1243137	NM_013322.3(SNX10):c.24+36T>A	SNX10	Benign	criteria provided, multiple submitters, no conflicts
734655	NM_013322.3(SNX10):c.212+4A>T	SNX10	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
SNX10	Strong	Autosomal recessive	autosomal recessive osteopetrosis 8	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SNX10	Orphanet:667	Autosomal recessive malignant osteopetrosis

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
SNX10	HGNC:14974	ENSG00000086300	Q9Y5X0	Sorting nexin-10	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SNX10	Sorting nexin-10	Probable phosphoinositide-binding protein involved in protein sorting and membrane trafficking in endosomes.

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)
SNX10	Other/Unknown	no		PX_dom, PX_dom_sf, SNX10/11

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
lateral nuclear group of thalamus	1
substantia nigra pars compacta	1
substantia nigra pars reticulata	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SNX10	252	ubiquitous	marker	lateral nuclear group of thalamus, substantia nigra pars compacta, substantia nigra pars reticulata

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SNX10	820

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SNX10	Q9Y5X0	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
tooth eruption	1	3370.4×	0.003	SNX10
bone mineralization involved in bone maturation	1	2808.7×	0.003	SNX10
gastric acid secretion	1	2106.5×	0.003	SNX10
ruffle assembly	1	1296.3×	0.003	SNX10
vesicle organization	1	1123.5×	0.003	SNX10
cellular homeostasis	1	802.5×	0.003	SNX10
protein localization to centrosome	1	674.1×	0.003	SNX10
bone resorption	1	581.1×	0.003	SNX10
calcium ion homeostasis	1	443.5×	0.004	SNX10
protein localization to cilium	1	401.2×	0.004	SNX10
endosome organization	1	374.5×	0.004	SNX10
osteoclast differentiation	1	343.9×	0.004	SNX10
cellular response to leukemia inhibitory factor	1	159.0×	0.008	SNX10
endocytosis	1	95.2×	0.012	SNX10
cilium assembly	1	73.6×	0.014	SNX10
intracellular protein transport	1	64.8×	0.015	SNX10

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
SNX10	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	SNX10

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)
SNX10	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.