Frontotemporal dementia and/or amyotrophic lateral sclerosis 7
diseaseOn this page
Also known as amyotrophic lateral sclerosis caused by mutation in CHMP2Bamyotrophic lateral sclerosis, Chmp2B-relatedCHMP2B amyotrophic lateral sclerosisCHMP2B-related amyotrophic lateral sclerosisfrontotemporal dementia, chromosome 3-linkedFTD3
Summary
Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 (MONDO:0010936) is a disease caused by CHMP2B (GenCC Definitive), with 2 cohort genes.
At a glance
- Causal gene: CHMP2B (GenCC Definitive)
- Cohort genes: 2
- ClinVar variants: 146
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | frontotemporal dementia and/or amyotrophic lateral sclerosis 7 |
| Mondo ID | MONDO:0010936 |
| MeSH | C563708, C579991 |
| OMIM | 600795, 614696 |
| DOID | DOID:0060208, DOID:0111227 |
| SNOMED CT | 702393003 |
| UMLS | C1833296 |
| MedGen | 318833 |
| GARD | 0015322 |
| Is cancer (heuristic) | no |
Also known as: amyotrophic lateral sclerosis caused by mutation in CHMP2B · amyotrophic lateral sclerosis, Chmp2B-related · CHMP2B amyotrophic lateral sclerosis · CHMP2B-related amyotrophic lateral sclerosis · frontotemporal dementia, chromosome 3-linked · FTD3
Data availability: 146 ClinVar variants · 5 GenCC gene-disease records · 9 cell lines.
Disease family
Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › spinal cord disorder › anterior horn disorder › amyotrophic lateral sclerosis › familial amyotrophic lateral sclerosis › frontotemporal dementia and/or amyotrophic lateral sclerosis 7
Related subtypes (29): amyotrophic lateral sclerosis type 1, frontotemporal dementia and/or amyotrophic lateral sclerosis 1, spinocerebellar ataxia type 2, amyotrophic lateral sclerosis type 15, amyotrophic lateral sclerosis type 4, amyotrophic lateral sclerosis type 21, amyotrophic lateral sclerosis type 3, amyotrophic lateral sclerosis type 6, amyotrophic lateral sclerosis type 7, amyotrophic lateral sclerosis type 8, amyotrophic lateral sclerosis type 9, amyotrophic lateral sclerosis type 10, amyotrophic lateral sclerosis type 11, amyotrophic lateral sclerosis type 12, frontotemporal dementia and/or amyotrophic lateral sclerosis 6, amyotrophic lateral sclerosis type 18, amyotrophic lateral sclerosis type 20, amyotrophic lateral sclerosis type 19, frontotemporal dementia and/or amyotrophic lateral sclerosis 2, amyotrophic lateral sclerosis type 22, frontotemporal dementia and/or amyotrophic lateral sclerosis 3, frontotemporal dementia and/or amyotrophic lateral sclerosis 4, juvenile amyotrophic lateral sclerosis, amyotrophic lateral sclerosis type 23, frontotemporal dementia and/or amyotrophic lateral sclerosis 8, frontotemporal dementia and/or amyotrophic lateral sclerosis 5, amyotrophic lateral sclerosis 26 with or without frontotemporal dementia, amyotrophic lateral sclerosis 27, juvenile, amyotrophic lateral sclerosis 28
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
146 retrieved; paginated sample, class counts are floors:
78 uncertain significance, 33 likely benign, 15 benign, 9 benign/likely benign, 5 conflicting classifications of pathogenicity, 4 pathogenic, 1 not provided, 1 likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1654 | NM_014043.4(CHMP2B):c.618A>C (p.Gln206His) | CHMP2B | Pathogenic | no assertion criteria provided |
| 1655 | NM_014043.4(CHMP2B):c.493C>T (p.Gln165Ter) | CHMP2B | Pathogenic | no assertion criteria provided |
| 35472 | NM_014043.4(CHMP2B):c.311C>A (p.Thr104Asn) | CHMP2B | Pathogenic | no assertion criteria provided |
| 98003 | NM_014043.4(CHMP2B):c.532-1G>C | CHMP2B | Pathogenic | no assertion criteria provided |
| 3896799 | NM_014043.4(CHMP2B):c.617A>C (p.Gln206Pro) | CHMP2B | Likely pathogenic | criteria provided, single submitter |
| 346806 | NM_014043.4(CHMP2B):c.218C>T (p.Thr73Met) | CHMP2B | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 704339 | NM_014043.4(CHMP2B):c.64C>T (p.Arg22Ter) | CHMP2B | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 872081 | NM_014043.4(CHMP2B):c.206G>A (p.Arg69Gln) | CHMP2B | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 902088 | NM_014043.4(CHMP2B):c.56G>A (p.Arg19Gln) | CHMP2B | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 902967 | NM_014043.4(CHMP2B):c.531+8C>T | CHMP2B | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1037550 | NM_014043.4(CHMP2B):c.613C>T (p.Arg205Trp) | CHMP2B | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1210544 | NM_014043.4(CHMP2B):c.94C>T (p.Arg32Ter) | CHMP2B | Uncertain significance | criteria provided, single submitter |
| 1307577 | NM_014043.4(CHMP2B):c.187A>G (p.Lys63Glu) | CHMP2B | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1333969 | NM_014043.4(CHMP2B):c.421A>G (p.Met141Val) | CHMP2B | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1333970 | NM_014043.4(CHMP2B):c.423G>A (p.Met141Ile) | CHMP2B | Uncertain significance | criteria provided, single submitter |
| 1361744 | NM_014043.4(CHMP2B):c.321+3A>G | CHMP2B | Uncertain significance | criteria provided, single submitter |
| 1366006 | NM_014043.4(CHMP2B):c.614G>A (p.Arg205Gln) | CHMP2B | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1376594 | NM_014043.4(CHMP2B):c.545C>T (p.Pro182Leu) | CHMP2B | Uncertain significance | criteria provided, single submitter |
| 1385104 | NM_014043.4(CHMP2B):c.205C>T (p.Arg69Trp) | CHMP2B | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1392585 | NM_014043.4(CHMP2B):c.339C>G (p.Asn113Lys) | CHMP2B | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1403282 | NM_014043.4(CHMP2B):c.126+4A>G | CHMP2B | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1411771 | NC_000003.11:g.(?87276673)(87325612_?)del | CHMP2B | Uncertain significance | criteria provided, single submitter |
| 1430692 | NM_014043.4(CHMP2B):c.248C>T (p.Thr83Ile) | CHMP2B | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1434414 | NM_014043.4(CHMP2B):c.90A>C (p.Arg30Ser) | CHMP2B | Uncertain significance | criteria provided, single submitter |
| 1462278 | NM_014043.4(CHMP2B):c.532-3T>C | CHMP2B | Uncertain significance | criteria provided, single submitter |
| 1477866 | NM_014043.4(CHMP2B):c.287T>C (p.Met96Thr) | CHMP2B | Uncertain significance | criteria provided, single submitter |
| 1491936 | NM_014043.4(CHMP2B):c.427A>G (p.Asn143Asp) | CHMP2B | Uncertain significance | criteria provided, single submitter |
| 1508277 | NM_014043.4(CHMP2B):c.28G>A (p.Val10Met) | CHMP2B | Uncertain significance | criteria provided, single submitter |
| 1512209 | NM_014043.4(CHMP2B):c.554C>A (p.Ala185Asp) | CHMP2B | Uncertain significance | criteria provided, single submitter |
| 1653 | NM_014043.4(CHMP2B):c.442G>T (p.Asp148Tyr) | CHMP2B | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 7 · Orphanet: 5 · 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 |
|---|---|---|---|---|
| CHMP2B | Definitive | Autosomal dominant | frontotemporal dementia and/or amyotrophic lateral sclerosis 7 | 7 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| CHMP2B | Orphanet:100069 | Semantic dementia |
| CHMP2B | Orphanet:100070 | Progressive non-fluent aphasia |
| CHMP2B | Orphanet:275864 | Behavioral variant of frontotemporal dementia |
| CHMP2B | Orphanet:803 | Amyotrophic lateral sclerosis |
| JAGN1 | Orphanet:423384 | Severe congenital neutropenia due to JAGN1 deficiency |
Cohort genes → proteins
2 cohort genes, 2 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 2 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| CHMP2B | HGNC:24537 | ENSG00000083937 | Q9UQN3 | Charged multivesicular body protein 2b | gencc,clinvar |
| JAGN1 | HGNC:26926 | ENSG00000171135 | Q8N5M9 | Protein jagunal homolog 1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| CHMP2B | Charged multivesicular body protein 2b | Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. |
| JAGN1 | Protein jagunal homolog 1 | Endoplasmic reticulum transmembrane protein involved in vesicle-mediated transport, which is required for neutrophil function. |
Protein-family classification
Druggable: 0 · Difficult: 0 · Unknown: 2 · 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 | 2 | 1.8× | 0.312 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| CHMP2B | Other/Unknown | no | Snf7_fam | |
| JAGN1 | Other/Unknown | no | Jagunal |
Expression context
Cohort genes with no expression data: 0.
2 cohort genes 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) | 2 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| amniotic fluid | 1 |
| medial globus pallidus | 1 |
| mucosa of sigmoid colon | 1 |
| ileal mucosa | 1 |
| right adrenal gland | 1 |
| tibialis anterior | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| CHMP2B | 300 | ubiquitous | marker | medial globus pallidus, amniotic fluid, mucosa of sigmoid colon |
| JAGN1 | 253 | ubiquitous | marker | ileal mucosa, tibialis anterior, right adrenal gland |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| CHMP2B | 1,527 |
| JAGN1 | 1,200 |
Structural data
PDB: 2 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| CHMP2B | Q9UQN3 | 1 |
| JAGN1 | Q8N5M9 | 1 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 2 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 |
|---|---|---|---|---|
| Translation of Replicase and Assembly of the Replication Transcription Complex | 1 | 878.5× | 0.004 | CHMP2B |
| Translation of Replicase and Assembly of the Replication Transcription Complex | 1 | 815.7× | 0.004 | CHMP2B |
| Pyroptosis | 1 | 423.0× | 0.004 | CHMP2B |
| Budding and maturation of HIV virion | 1 | 407.9× | 0.004 | CHMP2B |
| Endosomal Sorting Complex Required For Transport (ESCRT) | 1 | 368.4× | 0.004 | CHMP2B |
| Sealing of the nuclear envelope (NE) by ESCRT-III | 1 | 346.1× | 0.004 | CHMP2B |
| Late endosomal microautophagy | 1 | 326.3× | 0.004 | CHMP2B |
| Macroautophagy | 1 | 115.3× | 0.010 | CHMP2B |
| HCMV Late Events | 1 | 98.5× | 0.010 | CHMP2B |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| granulocyte colony-stimulating factor signaling pathway | 1 | 1685.2× | 0.005 | JAGN1 |
| insulin metabolic process | 1 | 1203.7× | 0.005 | JAGN1 |
| neutrophil differentiation | 1 | 936.2× | 0.005 | JAGN1 |
| endosome transport via multivesicular body sorting pathway | 1 | 936.2× | 0.005 | CHMP2B |
| late endosome to vacuole transport | 1 | 936.2× | 0.005 | CHMP2B |
| regulation of modification of postsynaptic structure | 1 | 936.2× | 0.005 | CHMP2B |
| negative regulation of insulin secretion involved in cellular response to glucose stimulus | 1 | 842.6× | 0.005 | JAGN1 |
| ESCRT III complex disassembly | 1 | 842.6× | 0.005 | CHMP2B |
| vesicle fusion with vacuole | 1 | 766.0× | 0.005 | CHMP2B |
| neutrophil mediated immunity | 1 | 702.2× | 0.005 | JAGN1 |
| multivesicular body-lysosome fusion | 1 | 702.2× | 0.005 | CHMP2B |
| neutrophil migration | 1 | 702.2× | 0.005 | JAGN1 |
| viral budding from plasma membrane | 1 | 648.1× | 0.005 | CHMP2B |
| nuclear membrane reassembly | 1 | 495.6× | 0.006 | CHMP2B |
| late endosome to lysosome transport | 1 | 495.6× | 0.006 | CHMP2B |
| viral release from host cell | 1 | 468.1× | 0.006 | CHMP2B |
| viral budding via host ESCRT complex | 1 | 401.2× | 0.006 | CHMP2B |
| multivesicular body sorting pathway | 1 | 401.2× | 0.006 | CHMP2B |
| regulation of centrosome duplication | 1 | 366.4× | 0.006 | CHMP2B |
| midbody abscission | 1 | 366.4× | 0.006 | CHMP2B |
| regulation of mitotic spindle assembly | 1 | 366.4× | 0.006 | CHMP2B |
| plasma membrane repair | 1 | 290.6× | 0.006 | CHMP2B |
| nucleus organization | 1 | 280.9× | 0.006 | CHMP2B |
| ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway | 1 | 271.8× | 0.006 | CHMP2B |
| multivesicular body assembly | 1 | 263.3× | 0.006 | CHMP2B |
| regulation of postsynapse organization | 1 | 263.3× | 0.006 | CHMP2B |
| neuron cellular homeostasis | 1 | 227.7× | 0.007 | CHMP2B |
| defense response to fungus | 1 | 221.7× | 0.007 | JAGN1 |
| insulin secretion | 1 | 216.1× | 0.007 | JAGN1 |
| endoplasmic reticulum organization | 1 | 210.7× | 0.007 | JAGN1 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2
Druggability breadth: 0 of 2 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 |
|---|---|---|
| CHMP2B | 0 | 0 |
| JAGN1 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Pharmacogenomics
Cohort genes with a PharmGKB record: 2; 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 | 2 | CHMP2B, JAGN1 |
Undrugged target profiles
2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| CHMP2B | 0 | — |
| JAGN1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.