neuronopathy, distal hereditary motor, type 2D
diseaseOn this page
Also known as FBXO38 neuronopathy, distal hereditary motorHMN2Dneuronopathy, distal hereditary motor caused by mutation in FBXO38neuronopathy, distal hereditary motor, type IID
Summary
neuronopathy, distal hereditary motor, type 2D (MONDO:0014259) is a disease caused by FBXO38 (GenCC Strong), with 1 cohort gene.
At a glance
- Causal gene: FBXO38 (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 34
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | neuronopathy, distal hereditary motor, type 2D |
| Mondo ID | MONDO:0014259 |
| OMIM | 615575 |
| DOID | DOID:0111210 |
| UMLS | C3888271 |
| MedGen | 854832 |
| GARD | 0018265 |
| Is cancer (heuristic) | no |
Also known as: FBXO38 neuronopathy, distal hereditary motor · HMN2D · neuronopathy, distal hereditary motor caused by mutation in FBXO38 · neuronopathy, distal hereditary motor, type IID
Data availability: 34 ClinVar variants · 3 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › neuronopathy, distal hereditary motor, autosomal dominant › distal hereditary motor neuropathy type 2 › neuronopathy, distal hereditary motor, type 2D
Related subtypes (3): neuronopathy, distal hereditary motor, type 2A, neuronopathy, distal hereditary motor, type 2B, neuronopathy, distal hereditary motor, type 2C
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
34 retrieved; paginated sample, class counts are floors:
19 uncertain significance, 6 benign, 5 conflicting classifications of pathogenicity, 2 pathogenic, 2 likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 2431046 | NM_205836.3(FBXO38):c.2215C>A (p.Pro739Thr) | FBXO38 | Pathogenic | no assertion criteria provided |
| 91854 | NM_205836.3(FBXO38):c.616T>C (p.Cys206Arg) | FBXO38 | Pathogenic | criteria provided, single submitter |
| 1045555 | NM_205836.3(FBXO38):c.91A>C (p.Asn31His) | FBXO38 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 541015 | NM_205836.3(FBXO38):c.11G>A (p.Arg4Gln) | FBXO38 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 656377 | NM_205836.3(FBXO38):c.1577G>A (p.Arg526Gln) | FBXO38 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 665522 | NM_205836.3(FBXO38):c.1117G>A (p.Val373Met) | FBXO38 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 836217 | NM_205836.3(FBXO38):c.2683A>G (p.Met895Val) | FBXO38 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1008505 | NM_205836.3(FBXO38):c.2072T>C (p.Ile691Thr) | FBXO38 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1028903 | NM_205836.3(FBXO38):c.155G>A (p.Cys52Tyr) | FBXO38 | Uncertain significance | criteria provided, single submitter |
| 1285478 | NM_205836.3(FBXO38):c.1313A>G (p.His438Arg) | FBXO38 | Uncertain significance | criteria provided, single submitter |
| 1333471 | NM_205836.3(FBXO38):c.1570G>A (p.Asp524Asn) | FBXO38 | Uncertain significance | criteria provided, single submitter |
| 1709150 | NM_205836.3(FBXO38):c.801A>T (p.Leu267Phe) | FBXO38 | Uncertain significance | criteria provided, single submitter |
| 2441399 | NM_205836.3(FBXO38):c.1208A>G (p.Lys403Arg) | FBXO38 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2689060 | NM_205836.3(FBXO38):c.1717G>T (p.Asp573Tyr) | FBXO38 | Uncertain significance | criteria provided, single submitter |
| 4078637 | NM_205836.3(FBXO38):c.1991C>A (p.Pro664His) | FBXO38 | Uncertain significance | criteria provided, single submitter |
| 4277987 | NM_205836.3(FBXO38):c.962+1G>A | FBXO38 | Uncertain significance | criteria provided, single submitter |
| 541008 | NM_205836.3(FBXO38):c.1154G>T (p.Gly385Val) | FBXO38 | Uncertain significance | criteria provided, single submitter |
| 574620 | NM_205836.3(FBXO38):c.1858C>T (p.Arg620Trp) | FBXO38 | Uncertain significance | criteria provided, single submitter |
| 638363 | NM_205836.3(FBXO38):c.2075C>T (p.Pro692Leu) | FBXO38 | Uncertain significance | criteria provided, single submitter |
| 640185 | NM_205836.3(FBXO38):c.286A>G (p.Thr96Ala) | FBXO38 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 665063 | NM_205836.3(FBXO38):c.679A>C (p.Lys227Gln) | FBXO38 | Uncertain significance | criteria provided, single submitter |
| 828150 | NM_205836.3(FBXO38):c.1618+1G>T | FBXO38 | Uncertain significance | no assertion criteria provided |
| 831074 | NC_000005.10:g.(?148394767)(148406404_?)dup | FBXO38 | Uncertain significance | criteria provided, single submitter |
| 931134 | NM_205836.3(FBXO38):c.3244C>G (p.Pro1082Ala) | FBXO38 | Uncertain significance | criteria provided, single submitter |
| 950489 | NM_205836.3(FBXO38):c.3277G>A (p.Val1093Ile) | FBXO38 | Uncertain significance | criteria provided, single submitter |
| 964250 | NM_205836.3(FBXO38):c.1796A>C (p.Glu599Ala) | FBXO38 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1169149 | NM_205836.3(FBXO38):c.1619-4G>T | FBXO38 | Benign | criteria provided, multiple submitters, no conflicts |
| 1169150 | NM_205836.3(FBXO38):c.1774T>C (p.Ser592Pro) | FBXO38 | Benign | criteria provided, multiple submitters, no conflicts |
| 1235574 | NM_205836.3(FBXO38):c.962+18A>G | FBXO38 | Benign | criteria provided, multiple submitters, no conflicts |
| 1249294 | NM_205836.3(FBXO38):c.3170+11T>C | FBXO38 | Benign | criteria provided, multiple submitters, no conflicts |
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 |
|---|---|---|---|---|
| FBXO38 | Strong | Autosomal dominant | neuronopathy, distal hereditary motor, type 2D | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| FBXO38 | Orphanet:139525 | Distal hereditary motor neuropathy type 2 |
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 |
|---|---|---|---|---|---|
| FBXO38 | HGNC:28844 | ENSG00000145868 | Q6PIJ6 | F-box only protein 38 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| FBXO38 | F-box only protein 38 | Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of PDCD1/PD-1, thereby regulating T-cells-mediated immunity. |
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) |
|---|---|---|---|---|
| FBXO38 | Other/Unknown | no | F-box_dom, LRR_dom_sf, F-box-like_dom_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 |
|---|---|
| adrenal tissue | 1 |
| calcaneal tendon | 1 |
| endothelial cell | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| FBXO38 | 287 | ubiquitous | marker | calcaneal tendon, adrenal tissue, endothelial cell |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| FBXO38 | 1,732 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| FBXO38 | Q6PIJ6 | 67.97 |
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 |
|---|---|---|---|---|
| positive regulation of T cell mediated immune response to tumor cell | 1 | 2407.4× | 0.002 | FBXO38 |
| positive regulation of T cell activation | 1 | 443.5× | 0.005 | FBXO38 |
| SCF-dependent proteasomal ubiquitin-dependent protein catabolic process | 1 | 374.5× | 0.005 | FBXO38 |
| protein K48-linked ubiquitination | 1 | 168.5× | 0.009 | FBXO38 |
| positive regulation of neuron projection development | 1 | 137.0× | 0.009 | FBXO38 |
| adaptive immune response | 1 | 84.3× | 0.012 | FBXO38 |
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 |
|---|---|---|
| FBXO38 | 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 | FBXO38 |
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) |
|---|---|---|
| FBXO38 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: FBXO38