Table 1 Expression, function, and linked diseases and disorders for transcription factors AP-2

AP-2α/ TFAP2A

Neural crest cells & tube of CNS PNS including facial and limb mesenchyme, extraembryonic trophectoderm, human villous cytotrophoblast cells, breast, skin, kidney, retina, adipose tissue, and bone. cartilage and others [42, 61, 242,243,244,245,246]

Regulation of monoamine turnover [62]

Specification of GABAergic and glycinergic interneurons [63]

Regulate melanocyte [247] and nephron differentiation [248]

Play a key role in trophectoderm development [249]

A suppressor of chondrocyte differentiation during cartilage development [243, 245, 246]

Mutation causes Branchio-oculo-facial syndrome (BOFS) and ectopic thymus; anophthalmia-microphthalmia syndrome [115, 250]

As an activator of gallbladder carcinoma [251]

As a suppressor of hepatocellular carcinoma, breast cancer, glioblastoma, melanoma, gastric, prostate, and colorectal cancers[115, 252,253,254,255,256,257]

As an oncogene in acute myeloid leukaemia, squamous cell, nasopharyngeal and pancreatic cancers and neuroblastoma [115, 258,259,260,261,262]

AP-2β/ TFAP2B

Fatal neural crest cells, sympathetic neuroblasts of CNS and PNS including facial and limb mesenchyme

Heart, smooth and skeletal muscles, collecting duct and distal tubules, kidney, parts of the reproductive system such as prostate and endometrium, retina, adipose tissue, respiratory and endocrine systems including thyroid, adrenal medulla, mammary, sweat, salivary glands and skin [34, 42, 46, 58, 61, 80, 82, 214, 216, 242]

Enhance monoaminergic neurotransmitter activity including serotonergic, dopaminergic and adrenergic transmission through controlling the key genes in monoaminergic neurotransmitter systems [24, 30, 46, 62, 82, 149]

Crucial for intrauterine growth, differentiation of distal nephrons and the sympathetic ganglia and neurons, maturation of chromaffin cells of the adrenal medulla and specification of GABAergic and glycinergic interneurons[46, 46, 63, 80]

Regulation of adipocytokines, insulin signalling and fat metabolism[29, 34, 134, 135, 263]

Proliferation and differentiation of extraembryonic trophectodermal cells [244, 264]

Mutation causes Char syndrome and Patent ductus arteriosus 2, dental anomalies, and terminal renal failure [64,65,66,67, 265]

Unfavourable prognostic factor in neuroblastoma[33], lung adenocarcinoma[216], breast [221,222,223] & thyroid cancers [215]

Favourable prognostic factor in endometrial carcinoma [217], cervical cancer [224, 225], & renal cell cancer [218,219,220]

Its dysregulation is associated with obesity and adiposity-related disorders including, binge‐eating disorders, anorexia and bulimia nervosa and diabetic Mellitus [26, 29, 30, 35, 36, 79, 81, 125]

AP-2γ/ TFAP2C

Kidney, neural crest cells, and human villous cytotrophoblast cells [42, 244]

As a negative regulator of the other AP-2 family members [42]

Play a key role in trophectoderm development [244, 264]

Regulates key genes responsible for eyes, face, and limb formation or neural tube development[115]

Control the expression of other genes such as FOXA1, WWOX, GREB1, CDH2, HPSE, IGSF11 and others [263]

Mutation causes Exencephaly, melanoma and pre-eclampsia [115]

Act as an oncogenic factor in many cancers such as melanoma. neuroblastoma, breast, testicular and lung cancers [115, 266,267,268,269]

AP-2δ /TFAP2D

Brain, placenta, skeletal muscle, thymus, small intestine, retina, heart, and prostata [270, 271]

Important during embryogenesis and in retina development [271, 272]

Regulation of the HMOX1 gene[273]

Associated with aggressive prostate cancer[274]

AP-2ε /TFAP2E

Neural tissue of the midbrain and hindbrain [275], cells and vomeronasal sensory neurons of the olfactory bulb [276, 277], and cartilage [278]

Important for development of GABAergic interneurons in olfactory bulb [276, 277, 279]

Regulation of integrin α10 transcription and the core promoter of type II collagen (COL2A1) Crucial for chondrogenesis and the development of cartilage during embryogenesis [278, 280, 281]

Associated with colorectal cancer [282] and neuroblastoma [263, 283]

Implicated in hypertrophic cartilage and the development of osteoarthritis [278]