Adult onset neurodegenerative disorder

Gene: UBA1

Green List (high evidence)

Germline UBA1 variants cause SMAX2, an anterior horn cell disorder that presents with progressive lower motor neuron degeneration. It is a direct clinical and biological mimic of PMA/LMN-variant ALS and should be included on the MND panel to prevent diagnostic misses. Needs inclusion in R460.1
Sources: Expert Review, Literature

Created: 22 May 2026, 1:42 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Spinal muscular atrophy, X-linked 2, OMIM:301830

Publications

• 18179898
• 31932168
• 26456228
• 27797960
• 35919735
• 33108101

Mode of pathogenicity
Other

Variants in this GENE are reported as part of current diagnostic practice