Table 1.

Peculiarities of tissue expression, cellular localization, function, relation to the various diseases, pathological mutations, and pathological mechanisms of disordered proteins discussed in the present study

Protein (UniProt ID)	Tissue expression: cellular localization	Function	Disease and associated mutation	Pathological mechanism
α-Synuclein (P37840)	Tissue-enhanced expression in bone marrow and brain (substantia nigra, cerebellum, and prefrontal cortex): cytoplasm, nucleus, synapse, axon, can be membrane-bound, can be secreted	Involved in synaptic activity, acts as molecular chaperone, regulates dopamine neurotransmission	Sporadic Parkinson’s disease (PD): wild type;	Aggregation and amyloid fibril formation; Lewy bodies, Lewy neurites (Kao et al. 2009)
			Familial early-onset PD: A30P, E46K, H50Q, A53T, gene duplication and triplication;
			Dementia with Lewy bodies (DLB): E46K
			Multiple other synucleinopathies: wild type
Aβ peptides (derived from APP, P05067)	Expressed with low tissue specificity	APP: Cell surface receptor, regulates neurite outgrowth, acts as protease inhibitor	Sporadic Alzheimer disease (AD): wild type;	Aggregation and amyloid fibril formation; extracellular amyloid plaques; vascular amyloid deposits; promotes tau phosphorylation and fibrillation (Sadigh-Eteghad et al. 2015)
			Familial early-onset AD: D678N, A692G, E693G, A713T, T714A/I, V516M, I716V, V717F/G/I/L, L73P
	APP: Cell surface single-pass type I transmembrane protein, cytoplasmic vesicles, Golgi apparatus, early endosome, can be secreted	Aβ peptides: Lipophilic metal chelators with metal-reducing activity, bind to lipoproteins and apolipoproteins E and J, activate mononuclear phagocytes
			Cerebral amyloid angiopathy, APP-related (CAA-APP): E693K/Q, D694N, L705V
	Aβ peptides: cell surface
Microtubule-associated protein tau (P10636)	Tissue-enhanced expression in brain, skeletal muscle: cell membrane, cell projection, cytoplasm, cytoskeleton, membrane (cytoplasmic site of peripheral membrane), microtubule, secreted	Regulates microtubule assembly and stability, as well as neuronal polarity, acts as linker between axonal microtubules and plasma membrane components	Sporadic AD: wild type;	Disruption of the neuronal cytoskeleton;
			Frontotemporal dementia (FTD): R5H, L583V, G589V, G590R, N596K, ΔK597, N613H, P618L/S, S622N, K634M, V654M, E659V
				tau aggregation and formation of paired helical filaments (PHF) and straight filaments (Liu and Gong 2008)
			Pick disease of the brain (PIDB): K574T, S637F, K686I, G706R
			Progressive supranuclear palsy 1 (PSNP1): R5L, G620V
			Parkinson-dementia syndrome (PARDE): wild type
			Multiple other taupathies: wild type
Coiled-coil-helix-coiled-coil-helix domain containing protein-10 CHCHD10 (Q8WYQ3)	Tissue-enhanced expression in heart muscle and skeletal muscle: mitochondrion intermembrane space	Maintenance of mitochondrial organization and mitochondrial cristae structure	Amyotrophic lateral sclerosis (ALS): R11G, P12S, R15L, G66V, P80L, Y92C, Q102H, Q108P	Loss of function, mitochondrial/synaptic damage and cytoplasmic TDP-43 accumulation (Woo et al. 2017)
			FTD: H22Y, P23T, P23S, P23L, A32D, A35D, V57E, Q82X
			PD: S30L Mitochondrial myopathy: R15S, G58R, S59L
			Charcot–Marie–Tooth disease: G66V
			Jokela type spinal muscular atrophy (SMAJ): G66V
Coiled-coil-helix-coiled-coil-helix domain containing protein-2 CHCHD2 (Q8WYQ3)	Expressed with low tissue specificity: mitochondrion intermembrane space, nucleus	Transcription factor; bi-organellar mediator of oxidative phosphorylation; regulates cell migration and differentiation, mitochondrial cristae structure, and apoptosis (Kee et al. 2021)	PD, AD, DLB, FTD, multiple system atrophy (MSA): P2L, G4R, S5R, R8H, P14S, R18Q, A32T, P34L, A37V, A49V, T61I, V66M, A71P, A79S, I80V, S85R, A93V, Q126X, R145Q	Mitochondrial dysfunction (Kee et al. 2021)
G-Protein coupled receptors (GPCRs; more than 800)	Multi-pass membrane protein	Membrane receptors that utilize trimeric G proteins to transduce information from the extracellular environment to intracellular signals; can recognize a wide spectrum of extracellular ligands and trigger a large variety of intracellular signaling cascades; can interact with (and be activated by) more than a 1000 natural and artificial extracellular ligands; play a role in multiple physiological functions, such as sight, taste, smell, neurotransmission, pain perception, and immune responses	Over 600 inactivating and almost 100 activating mutations in GPCRs have been identified, which are responsible for more than 30 different human diseases (Schöneberg et al. 2004). For example, GPCR mutations can cause acquired and inherited diseases, such as retinitis pigmentosa (RP), hypo- and hyperthyroidism, nephrogenic diabetes insipidus, fertility disorders, carcinomas (Schöneberg et al. 2004), and neurodegeneration	Loss of function, pathological gain of function (Schöneberg et al. 2004)

Most of information is retrieved from UniProt