Table 2.

Genes and genetic alterations related to systemic mast cell activation disease

Gene	Function	Genetic alteration	Cells investigated	Summary of findings	Reference
KIT	Tyrosine kinase Kit	Multiple alterations	Mast cells and multiple other haematopoetic lineages	Clearly associated with pathological mast cell activation	Present paper
JAK2	Janus kinase 2	V617F	BMMC	Associated with pathological mast cell activation	79,80
PDGFRα	Tyrosine kinase platelet-derived growth factor receptor α	Fusion of FIP1L1 gene to PDGFRα gene in exon 12	PBMC; BMMC; multiple other haematopoetic lineages including mast cells	Associated with pathological mast cell activation	81–84
NRAS	Protein with intrinsic GTPase activity	G12D	BMMC	Aggressive systemic mastocytosis	85
		G13D
RASGRP4	Ras guanyl nucleotide-releasing protein	Failure to remove intron 5	Bone marrow mast cells	Systemic mastocytosis	35
CBL	E3-ligase	Multiple alterations	Retroviral expression of Cbl mutants in transplanted bone marrow in mice	Cytokine-independent mast cell activation	86
HRH4	Histamine H4 receptor	Truncated splice variants	Cord blood-derived mast cells; eosinophils; basophils; dendritic cells	Inhibition of full-length histamine-H4-receptor function	87
IL13	Interleukin 13	−1112C/T	PBMC	Association with KitD816V-positive systemic mastocytosis	52
IL4	Interleukin 4	Q576R	PBMC	Association with KitD816V-positive systemic mastocytosis	54
TET2	Candidate tumour suppressor gene	Multiple	BMMC; cord blood-derived mast cells and eosinophils	Association with KitD816V-positive systemic mastocytosis	88,89
TNF	Tumour necrosis factor α	238G/A	No information provided	Association with KitD816V-positive systemic mastocytosis	90
VEGFA	Vascular endothelial growth factor	−1154A/G	No information provided	Association with KitD816V-positive systemic mastocytosis	91

BMMC, bone marrow mononuclear cells; PBMC, peripheral blood mononuclear cells/leucocytes.