Amyotrophic lateral sclerosis type 18

disease

On this page

Also known as ALS18amyotrophic lateral sclerosis 18amyotrophic lateral sclerosis caused by mutation in PFN1PFN1 amyotrophic lateral sclerosis

Summary

Amyotrophic lateral sclerosis type 18 (MONDO:0013891) is a disease caused by PFN1 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: PFN1 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	amyotrophic lateral sclerosis type 18
Mondo ID	MONDO:0013891
OMIM	614808
DOID	DOID:0060209
UMLS	C3553719
MedGen	766633
GARD	0015841
Is cancer (heuristic)	no

Also known as: ALS18 · amyotrophic lateral sclerosis 18 · amyotrophic lateral sclerosis caused by mutation in PFN1 · amyotrophic lateral sclerosis type 18 · PFN1 amyotrophic lateral sclerosis

Data availability: 9 ClinVar variants · 4 GenCC gene-disease records · 6 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 18

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

9 retrieved; paginated sample, class counts are floors:

3 pathogenic, 2 uncertain significance, 1 likely pathogenic, 1 benign/likely benign, 1 benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
37034	NM_005022.4(PFN1):c.211T>G (p.Cys71Gly)	PFN1	Pathogenic	criteria provided, single submitter
37035	NM_005022.4(PFN1):c.341T>C (p.Met114Thr)	PFN1	Pathogenic	criteria provided, single submitter
37036	NM_005022.4(PFN1):c.353G>T (p.Gly118Val)	PFN1	Pathogenic	criteria provided, single submitter
1676224	NM_005022.4(PFN1):c.318_319dup (p.Asp107fs)	PFN1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
37037	NM_005022.4(PFN1):c.350A>G (p.Glu117Gly)	PFN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1803758	NM_005022.4(PFN1):c.280G>T (p.Gly94Cys)	PFN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2721147	NM_005022.4(PFN1):c.409C>T (p.Arg137Cys)	PFN1	Uncertain significance	criteria provided, single submitter
1806047	NM_005022.4(PFN1):c.351A>T (p.Glu117Asp)	PFN1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
259607	NM_005022.4(PFN1):c.334C>T (p.Leu112=)	PFN1	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
PFN1	Strong	Autosomal dominant	amyotrophic lateral sclerosis type 18	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PFN1	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
PFN1	HGNC:8881	ENSG00000108518	P07737	Profilin-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PFN1	Profilin-1	Binds to actin and affects the structure of the cytoskeleton.

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)
PFN1	Other/Unknown	no		Profilin1/2/3_vertebrate, PFN_euk, Profilin_CS

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
granulocyte	1
ileal mucosa	1
mucosa of transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PFN1	289	ubiquitous	marker	granulocyte, mucosa of transverse colon, ileal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PFN1	3,926

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PFN1	P07737	22

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
PCP/CE pathway	1	300.5×	0.013	PFN1
Signaling by ROBO receptors	1	124.1×	0.013	PFN1
Platelet degranulation	1	87.8×	0.013	PFN1
RHO GTPases Activate Formins	1	77.7×	0.013	PFN1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of actin filament bundle assembly	1	2808.7×	0.003	PFN1
modification of postsynaptic actin cytoskeleton	1	1404.3×	0.003	PFN1
positive regulation of actin filament bundle assembly	1	1203.7×	0.003	PFN1
positive regulation of ruffle assembly	1	991.3×	0.003	PFN1
synapse maturation	1	936.2×	0.003	PFN1
regulation of actin filament polymerization	1	581.1×	0.003	PFN1
negative regulation of stress fiber assembly	1	581.1×	0.003	PFN1
positive regulation of epithelial cell migration	1	411.0×	0.004	PFN1
positive regulation of actin filament polymerization	1	330.4×	0.005	PFN1
neural tube closure	1	187.2×	0.007	PFN1
modulation of chemical synaptic transmission	1	183.2×	0.007	PFN1
actin cytoskeleton organization	1	79.1×	0.015	PFN1
protein stabilization	1	66.9×	0.016	PFN1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	PFN1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PFN1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PFN1	1	Binding:1

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	PFN1

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)
PFN1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: PFN1