. Author manuscript; available in PMC: 2024 Mar 1.

Published in final edited form as: Mass Spectrom Rev. 2021 Oct 31;42(2):796–821. doi: 10.1002/mas.21741

TABLE 1.

Discovery and validation of protein mutations using targeted proteomics

Bottom-up targeted proteomics
Mutation type	Disease type	Protein	Mutation site	Specimen	Assay type	Clinical application	Ref.
SAAVs	Pancreatic cancer	Serotransferrin	I448V	Serum samples	LC-SRM	Diagnosis biomarker	Nie et al., 2017
	Pancreatic and colorectal cancer	KRAS	G12V	Cell lines, tissue and cyst fluids	Immuno-SRM	Diagnosis biomarker	Wang et al., 2011
	Pancreatic and colorectal cancer	KRAS	G12D	Cell lines, tissue and cyst fluids	Immuno-SRM	Diagnosis biomarker	Wang et al., 2011
	Pancreatic and colorectal cancer	KRAS	G12D	Tissues	Immuno-SRM	Diagnosis biomarker	Ruppen-Cañás et al., 2012
	Pancreatic cancer	KRAS	G12D	Cell Lines	PRISM-SRM	Therapeutic target	Tan et al., 2020
		p53	R273H
		SLC37A4	G88D
	Pancreatic disease	KRAS	G12D	Cell lines and tissues	SDS-PAGE-based MRM (GeLC-MRM)	Diagnosis biomarker	Halvey et al., 2012
			G13D
			G12V
			G12S
	Pancreatitis	SPINK1	N34S	Serum samples	Immuno-pseudo-MRM	Prediction of chronic pancreatitis	Ravela et al., 2018
	Pancreatitis	SPINK1	P55S	Serum samples	Immuno-pseudo-MRM	Prediction of chronic pancreatitis	Ravela et al., 2018
	Prostate cancer	PSA	L132I	Plasma and seminal samples	Immuno-SRM (plasma depletion)	Diagnosis biomarker	Vegvari et al., 2013
	Prostate Cancer	CAPN2	D22E	Cell lines and tissues	PRM	Prognosis and prediction of advanced prostate cancer	Kwon et al., 2019
	Prostate cancer	SPOP	Y87N	Cell lines	PRISM-SRM	Diagnosis biomarker	Wang et al., 2017
			F102C
			F133V
	Neurodegenerative disease	Heat shock 70 kDa protein 12A (HSPA12A)	E365G	Brain tissues	PRM	Diagnosis biomarker	Wingo et al., 2017
		AHNAK nucleoprotein 2 (AHNAK2)	P1072S
		lysosomal alpha-glucosidase (GAA)	V220L
	Obesity and diabetes	Complement component C7	P587T	Plasma samples	LC-SRM	Diagnosis biomarker	Su et al., 2011
		Complement factor H	V62I
		Complement component C5	D966Y
	Age-related macular degeneration	Complement factor H (CFH)	Y402H	Plasma samples	LC-SRM	Diagnosis biomarker	Zhang et al., 2017
	Age-related macular degeneration	Complement factor H (CFH)	I62V	Plasma samples	LC-SRM	Diagnosis biomarker	Zhang et al., 2017
	Brain disease	ALDH5A1	H180Y	Brain tissues	LC-SRM	Diagnosis biomarker	Su et al., 2014
		HADH	P215T
		RBP1	M50V
		GRIA1	N768S
		CDC42	K163R
	Glioblastoma	Cytoplasmic C-1-tetrahydrofolate synthase (MTHFD1)	R653Q	Stem cells	LC-PRM	Therapeutic target	Mostovenko et al., 2018
	Neurological and developmental disorder	HSP10	L73F	Primary cells	LC-SRM	Diagnosis biomarker	Bie et al., 2016
	Breast cancer	p53	R273C	Cell lines and tissues	LC-SRM and PRM	Diagnosis biomarker	Dimitrakopoulos et al., 2017
	Dileucineopathies	GLUT1	P485L	Cell lines and primary cells	LC-PRM	Diagnosis biomarker	Meyer et al., 2018
		ITPR1	P1059L
		CACNA1H	P648L
	Infertility	TEX101	G99V	Spermatozoa	Immuno-PRM (anti-TEX101)	Diagnosis biomarker	Schiza et al., 2019
	Colon Cancer	KRAS	G13D	Cell lines	LC-SRM	Monitor of disease progress	Demory Beckler et al., 2013
	Colorectal carcinoma	BRAF	V600E	Tissues	Immuno-SRM	Therapeutic target	Chen et al., 2016
	Colorectal adenocarcinoma	BRAF	V600E	Cell lines	Immuno-SRM	Diagnosis biomarker	Lin et al., 2019
	Lung disease	Pulmonary surfactant protein A (SP-A)	Q223K	Bronchoalveolar lavage	SDS-PAGE-based MRM (GeLC-MRM)	Genotyping validation	Foster et al., 2014
	Congenital adrenal hyperplasia	CYP21A2	L388R	Plasma samples	SDS-PAGE-based MRM (GeLC-MRM)	Diagnosis biomarker	Brønstad et al., 2014
			E140K
			P45L
			V211M
			V281L
	Alexander disease	GFAP	R79C	Tissues	SDS-PAGE-based MRM (GeLC-MRM)	Diagnosis biomarker	Heaven rt al., 2019
			R239H
			R416W
ASVs		PKM1/2		iPSC lines and tissues	LC-PRM	Splicing isoform function	Lau et al., 2019
		MYOM1
		NDUA5
		TENV
		SVIL
		RTR2
		MYBPC3
	Neuronal disease	NRX1	Alternative splicing 3, 4 and 6	Brain tissues	LC-SRM	Cell recognition processes	Schreiner et al., 2014
		NRX2	Alternative splicing 3 and 6
		NRX3	Alternative splicing 3, 4 and 6
	Alzheimer’s disease	Tau	0N3R	Cerebrospinal fluids	Combination of IP and GeLC-MRM	Diagnosis biomarkers and therapeutic targets	Xu et al., 2021
			1N3R
			2N3R
			0N4R
			1N4R
			2N4R
	Premature aging disorders	Lamin A/C	78–89	Cell lines	LC-SRM	Diagnosis biomarker	Al-Qahtani et al., 2019
			547–572
			529–553
			529–615
	Heart disease	TPM1	189–212	Tissues	LC-PRM	Discovering functionally relevant isoforms in the heart.	Han et al., 2021
	Histone-deregulated disease	H2A	22 H2A variants	Mouse testes	LC-MRM/PRM	Histone variant and isoform identification	El Kennani et al., 2018
	Histone-deregulated disease	H2B	3 H2B variants	Mouse testes	LC-MRM/PRM	Histone variant and isoform identification	El Kennani et al., 2018
	Non-small cell lung cancer (NSCLC)	Osteopontin (OPN)	16–81	Plasma samples	Immuno-SRM	Diagnosis biomarker	Wu et al., 2012
			16–58_72–81
			16–30_58–81
Gene fusion product	Prostate cancer	TMPRSS2-ERG		Cell line and tissues	PRISM-SRM	Diagnosis biomarker	He et al., 2014
Gene fusion product	Prostate cancer	TMPRSS2-ERG		Cell lines	Immuno-SRM	Diagnosis biomarker	Fu et al., 2021
Top-down targeted proteomics
Mutation type	Disease type	Protein	Mutation site	Specimen	Assay type	Clinical application	Ref.
SAAVs	Hemoglobinopathies	Hemoglobin A	E6V	whole blood samples	ETD and pseudo-SRM	Diagnosis biomarker	Coelho Graça et al., 2012
	Hemoglobinopathies	Hemoglobin A	E6K	whole blood samples	ETD and pseudo-SRM	Diagnosis biomarker	Coelho Graça et al., 2012
	Muscle-related diseases	Tropomyosin (Tpm)	R38Q	Skeletal muscles	Offline multi-step purification	Diagnosis biomarker	Jin et al., 2016
	Muscle-related diseases	Tropomyosin (Tpm)	P64L	Skeletal muscles	Offline multi-step purification	Diagnosis biomarker	Jin et al., 2016
	Colorectal cancer	KRAS4b	WT	Cell line and tissues	Immunoaffinity enrichment	Therapeutic targets	Ntai et al., 2018
	Colorectal cancer	KRAS4b	G13D	Cell line and tissues	Immunoaffinity enrichment	Therapeutic targets	Ntai et al., 2018