Table 2.

Risk loci identified in cross-ancestry genome-wide association study (GWAS), the associated function and disease mechanism in amyotrophic lateral sclerosis.

S.No.	Gene (ALS)	Function	Disease Mechanism
1	C9orf72	Regulates vesicular transport and autophagy	C9ORF72 haploinsufficiency (loss of function) Sense and antisense RNA (GGGGCC)n the function of RNA binding protein (gain of function)
2	UNC13A	Facilitates Neurotransmission	Impaired synaptic transmission [95]
3	SOD1	Antioxidant role	Oxidative stress, mitochondrial dysfunction, and excitotoxicity
4	SCFD1	Regulates ER to Golgi anterograde vesicular transport	Protein misfolding and aggregation [96]
5	MOBP-RPSA	Neurons myelination	Demyelination of neurons [97]
6	HLA	Antigen presentation and immune response	Inflammation due to suppressed immune response [98]
7	KIF5A	Engaged in anterograde transport of cargos along the microtubule rails in neurons	Impaired axonal transport, synaptic transmission, and motor neuronal toxicity [99]
8	CFAP410	Cytoskeletal organization and ciliary function	Decreased stability and increased degradation of mutant protein causes dysfunction of primary cilium [100]
9	GPX3-TNIP	Antioxidant	Oxidative stress, mitochondrial dysfunction, and excitotoxicity [101]
10	SLC9A8	Na/H exchanger	Excitotoxicity and axonal degeneration [102]
11	TBK1	Requires in cargo recruitment during autophagy	Neuroinflammation and autophagy [103]
12	ERGIC1	Maintains ER-Golgi structure	Disintegration of ER and mitophagy [104]
13	NEK1	A protein kinase that regulates cell cycle, DNA damage repair, apoptosis, and ciliary function	Induces DNA damage [105]
14	COG3	Regulating Golgi processes, protein trafficking, and glycosylation in neurons	Protein trafficking by Golgi fragmentation [106]
15	PTPRN2	Involved in vesicle-mediated secretory process in hippocampus [107]	Not clear. Probably motor neuron dysfunction [108]