Genome- and Exome-Wide Association Studies Revealed Candidate Genes Associated with DaTscan Imaging Features

Table 4

Some of the suggestive genes with their possible roles in Parkinson’s disease.

Gene	Original role	Possible role in Parkinson’s disease	Expression level in basal ganglia based on The Human Protein Atlas	References
IGFN1	Synaptic assembly in the muscular tissue	Autophagy and protein synthesis	Low	[24–27]
TMEM169	Integral component of the membrane	Intracellular trafficking	High	[22, 23, 28]
TMEM9	Lysosomal acidification	Autophagic degradation of damaged organelles and protein aggregates	High	[22, 29–31]
SLC13A4	Transmembrane transporter	Specific variants may be involved in early-onset Parkinson’s disease	High	[32, 33]
SLC39A4	Transmembrane transporter	Specific variants may be involved in early-onset Parkinson’s disease	Low	[32, 33]
CACNA1A	Calcium channel	Trinucleotide expansion in CACNA1A causes slowly progressive, late-onset cerebellar ataxia, and parkinsonism	High	[34, 35]
OGDH	Krebs cycle	Its loss impairs autophagy and leads to neurodegeneration	High	[36, 37]
TBC1D15	Mitochondria-lysosome contact and autophagy	Impaired autophagy and mitochondria-lysosome contact	High	[38, 39]
F13A1	Coagulation	F13A1 was significantly associated with Alzheimer’s disease, MCI, and Parkinson’s disease, without a clear mechanism	Low	[40, 41]
CD80	A costimulatory molecule in T cell activation	Promoting T cell infiltration, inflammation, and neurodegeneration	Low	[42, 43]
CBLB	Proto-oncogene	It prevents JNK-mediated neuronal death	High	[44, 45]
FECH	Heme synthesis by adding ferrous to protoporphyrin IX	Heme can form complexes with α-synuclein, and excessive heme can cause neurodegeneration	High	[46–48]
GAK	Regulating clathrin-coated vesicle trafficking and α-synuclein overexpression	Maybe, by regulating vesicle trafficking and α-synuclein expression	High	[49–51]
KIF25	A microtubule-dependent motor protein	Impaired microtubule trafficking can lead to mitochondrial dysfunction and neurodegeneration	High	[52–54]
SAMD12	Involved in transmembrane receptor protein tyrosine kinase signaling pathway	N/A	High	[55, 56]
ZNF586	Involved in protein-protein and protein-nucleic acid interaction	Maybe, involved in neurodegenerative diseases	High	[57, 58],
CYP2A6	Metabolizing nicotine	Accelerating neurodegeneration by removing nicotine	Low	[59–61]
DACT3	Inhibition of autophagy and WNT/catenin signaling pathway	Inhibiting α-synuclein removal and contributing to neurodegeneration	High	[62–65]
GALNT8	O-linked glycosylation	Maybe, in neurogenesis and neurodegeneration	High	[66–68]
DLG2	Involved in synaptic function	Maybe, accelerates motor symptoms	Moderate-to-high	[69, 70]
GPC5	Cell membrane proteoglycan involved in growth and cell division	Maybe, differentiation of dopaminergic neurons	High	[71]
TRPV1	A cell surface receptor and ion channel	α-Synuclein removal and prevention of neurodegeneration	High	[72, 73]
GRM7	Involved in glutamatergic neurotransmission	Improving motor dysfunction in PD	High	[74, 75]