Amyotrophic lateral sclerosis type 11

disease

On this page

Also known as ALS11amyotrophic lateral sclerosis 11amyotrophic lateral sclerosis caused by mutation in FIG4FIG4 amyotrophic lateral sclerosis

Summary

Amyotrophic lateral sclerosis type 11 (MONDO:0012945) is a disease caused by FIG4 (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

Causal gene: FIG4 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 88
Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	amyotrophic lateral sclerosis type 11
Mondo ID	MONDO:0012945
MeSH	C567244
OMIM	612577
DOID	DOID:0060202
UMLS	C2675491
MedGen	393399
GARD	0010496
Is cancer (heuristic)	no

Also known as: ALS11 · amyotrophic lateral sclerosis 11 · amyotrophic lateral sclerosis caused by mutation in FIG4 · amyotrophic lateral sclerosis type 11 · FIG4 amyotrophic lateral sclerosis

Data availability: 88 ClinVar variants · 3 GenCC gene-disease records · 2 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 › amyotrophic lateral sclerosis type 11

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

88 retrieved; paginated sample, class counts are floors:

34 uncertain significance, 19 conflicting classifications of pathogenicity, 12 benign, 10 benign/likely benign, 5 pathogenic, 4 likely pathogenic, 3 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1721	NM_014845.6(FIG4):c.122T>C (p.Ile41Thr)	FIG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1723	NM_014845.6(FIG4):c.547C>T (p.Arg183Ter)	FIG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2431047	NM_014845.6(FIG4):c.1049C>T (p.Ala350Val)	FIG4	Pathogenic	no assertion criteria provided
254668	NM_014845.6(FIG4):c.759del (p.Phe254fs)	FIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
355036	NM_014845.6(FIG4):c.262C>T (p.Arg88Ter)	FIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
420149	NM_014845.6(FIG4):c.737G>A (p.Trp246Ter)	FIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
802256	NM_014845.6(FIG4):c.1150del (p.Arg384fs)	FIG4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
916868	NM_014845.6(FIG4):c.2247dup (p.Ser750fs)	FIG4	Pathogenic	criteria provided, multiple submitters, no conflicts
1333978	NM_014845.6(FIG4):c.2376+2T>G	FIG4	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1709974	NM_014845.6(FIG4):c.647-2_647-1insG	FIG4	Likely pathogenic	criteria provided, single submitter
3382272	NM_014845.6(FIG4):c.1389-2A>G	FIG4	Likely pathogenic	criteria provided, single submitter
3892147	NM_014845.6(FIG4):c.1150A>T (p.Arg384Ter)	FIG4	Likely pathogenic	criteria provided, single submitter
1728	NM_014845.6(FIG4):c.157G>T (p.Asp53Tyr)	FIG4	Conflicting classifications of pathogenicity	no assertion criteria provided
260446	NM_014845.6(FIG4):c.1584-8T>A	FIG4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
260448	NM_014845.6(FIG4):c.2097-10C>G	FIG4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
355035	NM_014845.6(FIG4):c.243A>G (p.Lys81=)	FIG4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
355037	NM_014845.6(FIG4):c.350C>T (p.Ala117Val)	FIG4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
355039	NM_014845.6(FIG4):c.1272-10C>G	FIG4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
355042	NM_014845.6(FIG4):c.1863C>A (p.Thr621=)	FIG4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
355044	NM_014845.6(FIG4):c.2223G>T (p.Thr741=)	FIG4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
355046	NM_014845.6(FIG4):c.2547-11A>G	FIG4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
355047	NM_014845.6(FIG4):c.2547-5T>G	FIG4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
355048	NM_014845.6(FIG4):c.2547-4A>G	FIG4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
355049	NM_014845.6(FIG4):c.2568G>T (p.Ser856=)	FIG4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
381005	NM_014845.6(FIG4):c.446+9G>A	FIG4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
389842	NM_014845.6(FIG4):c.33G>C (p.Ser11=)	FIG4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
407082	NM_014845.6(FIG4):c.834A>T (p.Lys278Asn)	FIG4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
543496	NM_014845.6(FIG4):c.640G>A (p.Gly214Arg)	FIG4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
663445	NM_014845.6(FIG4):c.1271+5A>G	FIG4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
695179	NM_014845.6(FIG4):c.658A>G (p.Ile220Val)	FIG4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · Orphanet: 4 · 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
FIG4	Strong	Autosomal dominant	amyotrophic lateral sclerosis type 11	15

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FIG4	Orphanet:139515	Charcot-Marie-Tooth disease type 4J
FIG4	Orphanet:208441	Bilateral parasagittal parieto-occipital polymicrogyria
FIG4	Orphanet:3472	Yunis-Varon syndrome
FIG4	Orphanet:803	Amyotrophic lateral sclerosis

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
FIG4	HGNC:16873	ENSG00000112367	Q92562	Polyphosphoinositide phosphatase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FIG4	Polyphosphoinositide phosphatase	Dual specificity phosphatase component of the PI(3,5)P2 regulatory complex which regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2).

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)
FIG4	Other/Unknown	no		SAC_dom, Fig4-like

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
endothelial cell	1
lateral nuclear group of thalamus	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FIG4	295	ubiquitous	marker	middle temporal gyrus, endothelial cell, lateral nuclear group of thalamus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FIG4	1,257

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FIG4	Q92562	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Synthesis of PIPs at the late endosome membrane	1	951.7×	0.002	FIG4
Synthesis of PIPs at the early endosome membrane	1	713.8×	0.002	FIG4
Synthesis of PIPs at the Golgi membrane	1	634.4×	0.002	FIG4

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of myelination	1	1872.4×	0.002	FIG4
myelin assembly	1	1872.4×	0.002	FIG4
vacuole organization	1	1532.0×	0.002	FIG4
pigmentation	1	702.2×	0.003	FIG4
phosphatidylinositol dephosphorylation	1	648.1×	0.003	FIG4
phosphatidylinositol biosynthetic process	1	366.4×	0.004	FIG4
neuron development	1	255.3×	0.005	FIG4
locomotory behavior	1	179.3×	0.006	FIG4
positive regulation of neuron projection development	1	137.0×	0.007	FIG4

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
FIG4	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	FIG4

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)
FIG4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01772888	Not specified	COMPLETED	Chewing Efficiency Measured by a Two Colour Chewing Gum Test in Amyotrophic Lateral Sclerosis (ALS) Patients?

Cohort genes: FIG4