Amyotrophic lateral sclerosis 27, juvenile

disease

On this page

Summary

Amyotrophic lateral sclerosis 27, juvenile (MONDO:0859529) is a disease caused by SPTLC1 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: SPTLC1 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	amyotrophic lateral sclerosis 27, juvenile
Mondo ID	MONDO:0859529
OMIM	620285
DOID	DOID:0081381
UMLS	C5830359
MedGen	1840995
GARD	0026740
Is cancer (heuristic)	no

Data availability: 14 ClinVar variants · 3 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 27, juvenile

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

14 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
2444011	NM_006415.4(SPTLC1):c.113T>G (p.Leu38Arg)	SPTLC1	Pathogenic	no assertion criteria provided
246520	NM_006415.4(SPTLC1):c.58G>T (p.Ala20Ser)	SPTLC1	Pathogenic	criteria provided, multiple submitters, no conflicts
372788	NM_006415.4(SPTLC1):c.992C>A (p.Ser331Tyr)	SPTLC1	Pathogenic	criteria provided, multiple submitters, no conflicts
4801	NM_006415.4(SPTLC1):c.431T>A (p.Val144Asp)	SPTLC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
802489	NM_006415.4(SPTLC1):c.112CTT[1] (p.Leu39del)	SPTLC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
450572	NM_006415.4(SPTLC1):c.68A>T (p.Tyr23Phe)	SPTLC1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
997832	NM_006415.4(SPTLC1):c.118_123del (p.Phe40_Ser41del)	SPTLC1	Likely pathogenic	criteria provided, single submitter
1042690	NM_006415.4(SPTLC1):c.1393A>G (p.Lys465Glu)	SPTLC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
732005	NM_006415.4(SPTLC1):c.1111G>A (p.Gly371Arg)	SPTLC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3597799	NM_006415.4(SPTLC1):c.571G>A (p.Ala191Thr)	SPTLC1	Uncertain significance	criteria provided, single submitter
3600479	NM_006415.4(SPTLC1):c.*12G>A	SPTLC1	Uncertain significance	criteria provided, single submitter
3892554	NM_006415.4(SPTLC1):c.973A>G (p.Ile325Val)	SPTLC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3897029	NM_006415.4(SPTLC1):c.93_123dup (p.Lys42delinsAspProLeuAspAsnGlnThrSerPheLeuTer)	SPTLC1	Uncertain significance	criteria provided, single submitter
3897552	NM_006415.4(SPTLC1):c.1082-2A>G	SPTLC1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
SPTLC1	Strong	Autosomal dominant	amyotrophic lateral sclerosis 27, juvenile	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SPTLC1	Orphanet:300605	Juvenile amyotrophic lateral sclerosis
SPTLC1	Orphanet:36386	Hereditary sensory and autonomic neuropathy type 1

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
SPTLC1	HGNC:11277	ENSG00000090054	O15269	Serine palmitoyltransferase 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SPTLC1	Serine palmitoyltransferase 1	Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SPTLC1	Enzyme (other)	yes	2.3.1.50	Aminotransferase_I/II_large, PyrdxlP-dep_Trfase_major, PyrdxlP-dep_Trfase_small

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
epithelium of esophagus	1
esophagus squamous epithelium	1
oral cavity	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SPTLC1	300	ubiquitous	marker	esophagus squamous epithelium, oral cavity, epithelium of esophagus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SPTLC1	3,288

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SPTLC1	O15269	17

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
Sphingolipid de novo biosynthesis	1	285.5×	0.012	SPTLC1
Sphingolipid metabolism	1	167.9×	0.012	SPTLC1
Metabolism of lipids	1	31.6×	0.042	SPTLC1
Metabolism	1	11.6×	0.086	SPTLC1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of fat cell apoptotic process	1	16852.0×	5e-04	SPTLC1
sphinganine biosynthetic process	1	8426.0×	5e-04	SPTLC1
positive regulation of lipophagy	1	3370.4×	8e-04	SPTLC1
sphingomyelin biosynthetic process	1	1404.3×	0.001	SPTLC1
sphingosine biosynthetic process	1	1053.2×	0.001	SPTLC1
sphingolipid metabolic process	1	991.3×	0.001	SPTLC1
ceramide biosynthetic process	1	421.3×	0.003	SPTLC1
sphingolipid biosynthetic process	1	358.6×	0.003	SPTLC1

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
SPTLC1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
SPTLC1	4	Binding:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SPTLC1	2.3.1.50	serine C-palmitoyltransferase

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	1	SPTLC1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
SPTLC1	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: SPTLC1