Adult onset neurodegenerative disorder
Gene: SPTLC2EnsemblGeneIds (GRCh38): ENSG00000100596
EnsemblGeneIds (GRCh37): ENSG00000100596
OMIM: 605713, Gene2Phenotype
SPTLC2 is in 13 panels
2 reviews
Achchuthan Shanmugasundram (Genomics England Curator)
The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.Created: 11 Mar 2026, 10:56 a.m. | Last Modified: 11 Mar 2026, 10:56 a.m.
Panel Version: 8.15
Ida Ertmanska (Genomics England Curator)
Comment on list classification: There are at least 10 unrelated patients reported with juvenile onset ALS with monoallelic variants in SPTLC2 (9 de novo, 1 familial case with demonstrated autosomal dominant inheritance). Based on the available evidence, this gene should be rated Green for Adult onset neurodegenerative disorder.Created: 13 Oct 2025, 2:25 p.m. | Last Modified: 13 Oct 2025, 2:25 p.m.
Panel Version: 8.3
Monoallelic variants in SPTLC2 have been associated with juvenile-onset amyotrophic lateral sclerosis:
PMID: 38041679 Syeda 2024 - 6 unrelated patients with a recurrent de novo variant p.Glu260Lys - trio WES/WGS. Phenotype: early-childhood-onset spasticity, followed by rapidly progressive weakness involving upper and lower extremities, bulbar muscles, tongue fasciculations and eventual respiratory insufficiency. Onset: congenital - 4 years of age.
PMID: 38316966 Naruse 2024 - 2 unrelated Japanese families with early-onset ALS - p.Ala71Val, p.Met68Arg. Method: WES. Onset of symptoms: 22-31 years.
PMID: 38041684 Dohrn 2024 - 2 unrelated patients (one African American and one Turkish-Bulgarian) with the same de novo variant p.Met68Arg. Childhood onset. Method: WGS/WES +Sanger confirmation.
SPTLC2 is associated with Neuropathy, hereditary sensory and autonomic, type IC in OMIM (613640) - accessed 13th Oct 2025).
Created: 13 Oct 2025, 2:08 p.m. | Last Modified: 13 Oct 2025, 2:21 p.m.
Panel Version: 8.3
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Neuropathy, hereditary sensory and autonomic, type IC, OMIM:613640; amyotrophic lateral sclerosis 27, juvenile, MONDO:0859529
Publications
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
- Sources
-
- Expert Review Green
- NHS GMS
- Literature
- Phenotypes
-
- Neuropathy, hereditary sensory and autonomic, type IC, OMIM:613640
- amyotrophic lateral sclerosis 27, juvenile, MONDO:0859529
- OMIM
- 605713
- Clinvar variants
- Variants in SPTLC2
- Penetrance
- None
- Publications
- Mode of Pathogenicity
- Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
- Panels with this gene
-
- Familial dysautonomia
- Likely inborn error of metabolism
- Childhood onset dystonia, chorea or related movement disorder
- Pain syndromes
- Undiagnosed metabolic disorders
- Adult onset neurodegenerative disorder
- Intellectual disability
- Hereditary neuropathy or pain disorder
- DDG2P
- Retinal disorders
- Hereditary neuropathy
- Paroxysmal central nervous system disorders
- Fetal anomalies
History Filter Activity
Set mode of pathogenicity
Achchuthan Shanmugasundram (Genomics England Curator)Mode of pathogenicity for gene: SPTLC2 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Removed Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q3_25_promote_green was removed from gene: SPTLC2.
Added New Source, Added New Source, Status Update
Achchuthan Shanmugasundram (Genomics England Curator)Source NHS GMS was added to SPTLC2. Source Expert Review Green was added to SPTLC2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Entity classified by Genomics England curator
Achchuthan Shanmugasundram (Genomics England Curator)Gene: sptlc2 has been classified as Amber List (Moderate Evidence).
Added Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q3_25_promote_green tag was added to gene: SPTLC2.
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes
Ida Ertmanska (Genomics England Curator)gene: SPTLC2 was added gene: SPTLC2 was added to Adult onset neurodegenerative disorder. Sources: Literature Mode of inheritance for gene: SPTLC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SPTLC2 were set to 38041684; 38041679; 38316966 Phenotypes for gene: SPTLC2 were set to Neuropathy, hereditary sensory and autonomic, type IC, OMIM:613640; amyotrophic lateral sclerosis 27, juvenile, MONDO:0859529 Review for gene: SPTLC2 was set to GREEN