Table 3.

Genetic and epigenetic modifiers of 22q11.2 deletion syndrome with disease connections.

Gene name	Chromosome Location a	Function	Human syndromes	Mechanism
Genes on chromosome 22q11.2
TBX1	22q11.2	T-box transcription factor regulates expression of 2000 genes	22q11.2del	Interacts with histone3 methyltransferases, BAF60a, and SMAD1
DGCR8	22q11.2	MicroRNA binding protein	22q11.2del	Epigenetically regulates gene expression through miRNAs
DGCR6	22q11.2	Regulates neural crest migration	CHDb (with PRODH deletion)	Negatively regulates TBX1 expression
Morphogens
Retinoic acid	–	Morphogen involved in embryonic patterning	22q11.2del-like	Complexes retinoic acid receptor to regulate gene expression
Gestational Diabetes	–	Teratogen during pregnancy	22q11.2del-like	Affects multiple developmental processes in the embryo, with the pharyngeal apparatus particularly sensitive
Genes at other chromosomal locations
KMT2	7q36.1	Histone methyltransferase	Kleefstra syndrome 2 (neurodevelopmental disorder)	Interacts with TBX1 and mono-methylates lysine 27 on histone 3
BAF60a (SMARCD1)	12q13.2	Component of the SWI-SNF chromatin remodeling complex	–	Component of a chromosome remodeling complex that interacts with TBX1
MOZ	8p11.21	Histone acetyl transferase	CHD b , intellectual disability, and dysmorphic facial features	positively regulated by RA and, in turn affects TBX1 expression
SMAD1	4q31.21	Signaling protein downstream of Bmp4		Interacts with TBX1, which antagonizes its association with SMAD4
JMJD1C	10q21.3	Histone demethylase	Rett syndrome and intellectual disability	Demethylates lysine residues on histones
MINA	3q11.2	Lysine-Specific Demethylase and Histidyl-Hydroxylase	Preeclampsia	Demethylates lysine residues on histones
KDM7A	7q34	Lysine demethylase	–	Demethylates lysine residues on histones
RREB1	6p24.3	Zn finger transcription factor	–	Regulates RAS-responsive elements
SEC24C	10q22.2	Coat Protein II complex	–	Involved in protein export from ER to Golgi
GLUT3	12p13.31	Glucose transporter	-	High affinity interaction with glucose to translocate across the membrane
KANSL1	17q21.31	Histone modification	Koolen-De Vries syndrome	Nuclear protein forming part of a complex that has histone acetyltransferase activity
PAX1	20p11.22	Transcription factor	Octofaciocervical syndrome	Regulates embryonic tissue patterning
VEGF	6p21.1	Vascular endothelial growth factor	Tetralogy of Fallot	Vascular endothelial growth factor supports cell growth
FGF8	10q24.32	Fibroblast growth factor	Hypogonadotropic hypogonadism 6	Fibroblast growth factor supports cell growth
PDGFRα	4q12	Platelet derived growth factor receptor	–	Regulates neural crest cell development
SHH	7q36.3	Sonic hedgehog protein	Holoprosencephaly 3, Microphthalmia with coloboma 5	Regulates Tbx1 expression and vertebrate organogenesis

^aHuman chromosomal location.

^bCongenital heart disease.