ALS1_NIPA1
- Gene
- NIPA
- Disease
- ALS1
- Inheritance
- AD
- Classification
- Disputed
- Total Score
- 3
- Publications Reviewed
- 3
- Publication Span
- 2.33 years
- Last Updated
- 06/06/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt, Harriet Dashnow
Description
The NIPA1 exon 1 GCG/polyalanine repeat has been reported as an ALS risk or modifier locus, with some European cohorts showing enrichment or survival effects for long alleles (≥9 or >8 GCG repeats), whereas African-ancestry and broader Project MinE STR studies did not confirm an ALS susceptibility or age-at-onset association. The evidence is conflicting and largely association-based, with limited direct locus-specific evidence, supporting the disputed classification. The evidence does not currently support a Mendelian association between the NIPA1 repeat and ALS.
Genetic evidence
Total: 2
| Singular Evidence | Probands | PMID:31286297 | 0 | 6 patients with the NIPA1 expansion, co-occuring with a C9orf72 expansion. The source reports cohort-level NIPA1 repeat genotyping but does not describe individual NIPA1-expanded ALS probands with phenotype, family, or functional details suitable for singular proband scoring. Therefore, a score of 0 is assigned for this evidence. |
| Collective Evidence | Computational | PMID:34179866 | 0 | ExpansionHunter WGS analysis of Southern African ALS cases and African controls found similar NIPA1 GCG-repeat distributions (p = 0.67); long alleles (≥9 GCG repeats) were rare in Africans and not associated with ALS, while 9–10-repeat alleles were more common in European than African controls (6% vs 0.4%, p = 0.016). Score of 0 assigned as this evidence does not support an association between the NIPA1 repeat and ALS. |
| Statistics | Case-control data | PMID:31286297 | 2 | Project MinE STR analysis found NIPA1 ≥9-repeat alleles in 232 ALS cases (4.6%) and 78 controls (4.6%), with no significant ALS susceptibility association; NIPA1 showed only a nominal survival association. They used two methods of variant detection. |
Experimental evidence
Total: 1
| Function | Protein interaction | PMID:30342764 | 1 | Authors found altered protein to protein interactions and sequesteration of RNA-binding protein. |
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.