Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia

disease

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Also known as ALS26

Summary

Amyotrophic lateral sclerosis 26 with or without frontotemporal dementia (MONDO:0030885) is a disease with 1 cohort gene.

At a glance

Cohort genes: 1
ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	amyotrophic lateral sclerosis 26 with or without frontotemporal dementia
Mondo ID	MONDO:0030885
OMIM	619133
DOID	DOID:0081380
UMLS	C5436882
MedGen	1771903
GARD	0016425
Is cancer (heuristic)	no

Also known as: ALS26

Data availability: 5 ClinVar variants · 2 GenCC gene-disease records.

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 26 with or without frontotemporal dementia

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

5 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1592491	NM_022173.4(TIA1):c.474+15_474+17dup	TIA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
261567	NM_022173.4(TIA1):c.1070A>G (p.Asn357Ser)	TIA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3067925	NM_022173.4(TIA1):c.889-1G>A	TIA1	Uncertain significance	criteria provided, single submitter
3897042	NM_022173.4(TIA1):c.799G>A (p.Val267Ile)	TIA1	Uncertain significance	criteria provided, single submitter
992596	NM_022173.4(TIA1):c.1141G>A (p.Ala381Thr)	TIA1	Uncertain significance	criteria provided, single submitter

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
TIA1	Moderate	Semidominant	amyotrophic lateral sclerosis 26 with or without frontotemporal dementia	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TIA1	Orphanet:603	Distal myopathy, Welander type

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
TIA1	HGNC:11802	ENSG00000116001	P31483	Cytotoxic granule associated RNA binding protein TIA1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TIA1	Cytotoxic granule associated RNA binding protein TIA1	RNA-binding protein involved in the regulation of alternative pre-RNA splicing and mRNA translation by binding to uridine-rich (U-rich) RNA sequences.

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)
TIA1	Other/Unknown	no		RRM_dom, RRM_euk-type, Nucleotide-bd_a/b_plait_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
ganglionic eminence	1
right ovary	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TIA1	297	ubiquitous	marker	right uterine tube, right ovary, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TIA1	3,482

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TIA1	P31483	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
FGFR2 alternative splicing	1	423.0×	0.005	TIA1
Signaling by FGFR2	1	407.9×	0.005	TIA1
Signaling by FGFR	1	346.1×	0.005	TIA1
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.024	TIA1
Signal Transduction	1	10.2×	0.098	TIA1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein localization to cytoplasmic stress granule	1	2106.5×	0.004	TIA1
positive regulation of epithelial cell apoptotic process	1	1296.3×	0.004	TIA1
regulation of mRNA splicing, via spliceosome	1	887.0×	0.004	TIA1
stress granule assembly	1	601.9×	0.004	TIA1
negative regulation of cytokine production	1	510.7×	0.004	TIA1
regulation of alternative mRNA splicing, via spliceosome	1	244.2×	0.007	TIA1
negative regulation of translation	1	195.9×	0.007	TIA1
RNA splicing	1	88.2×	0.014	TIA1
mRNA processing	1	78.8×	0.014	TIA1
apoptotic process	1	28.7×	0.035	TIA1

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
TIA1	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
TIA1	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	TIA1

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)
TIA1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: TIA1