Table 1.
The C2H2-ZNFs involved in brain development, NDDs, and/or other neuropsychiatric disorders.
| Name | Additional domains | Biologic activities | Pathologic implications | References |
|---|---|---|---|---|
| Poly-ZNFs | ||||
| ADNP2 | Homeobox | Expressed in oligodendrocytes | Schizophrenia | (34, 35) |
| BCL11A (ZNF858A) | Controls migration of cortical neurons | ID, ASDs, seizures, dyspraxia, childhood apraxia of speech, severe speech disorder, brain malformation, and microcephaly | (17, 36, 37) | |
| BCL11B (ZNF858B) | Controls hippocampal neurogenesis and development of corpus striatum | (38) | ||
| FEZF1 and FEZF2 | Involved in cortical development and promote differentiation of neural stem cells Specifically expressed in subcortical projection neurons and regulates cell fate of residing neurons |
Autism spectrum disorders and intellectual disabilities | (39–41) | |
| GLI3 | Controls progression of cell cycle in RGS cells through regulating the G1 phase length | Greig cephalopolysyndactyly syndrome, acrocallosal syndrome and Pallister-Hall syndrome | (9, 42, 43) | |
| GLIS1 | Promotes generation of the induced pluripotent stem cells | ASDs and Parkinson disease | (44, 45) | |
| GLIS2 | Regulates neuronal differentiation | (46) | ||
| TSHZ3 | Homeobox | Influences synapse development by impairing cortico-striatal connectivity | Autistic traits, intellectual disabilities and speech disturbances | (47) |
| ZIC1 | Controls cerebellar size | Dany-Walker malformation | (18) | |
| ZIC2 | Regulates migration of forebrain neurons, CR cells, and pallial-derived neurons | Holoprosencephaly and schizophrenia | (48–50) | |
| ZIC3 | Participates in neural crest formation, neurulation, and maintenance of NPCs | Hydrocephalus | (51–53) | |
| ZIC4 | Controls cerebellar size | Dany-Walker malformation | (18) | |
| ZIC5 | Mediates neural crest development and formation of the neural tube | (54) | ||
| ZNF148 | Crucial for the development of corpus callosum | Underdevelopment of corpus callosum and aberrant neuron proliferation, microcephaly, and intellectual disabilities | (19) | |
| ZNF292 | Coiled coil | ID and ASDs | (55, 56) | |
| ZNF385B | Mediates neuronal apoptosis | ASDs and ID | (57) | |
| ZNF407 | ID, ASDs and cognitive impairment. | (58) | ||
| ZNF462 | Expressed in the ventricular zone and hippocampus Essential for hippocampal formation |
ASDs | (59) | |
| ZNF507 | Schizophrenia | (60) | ||
| ZNF521 | Promotes early neuronal differentiation | Anxiety and schizophrenic behavior | (61, 62) | |
| ZNF536 | Highly expressed in the developing CNS Promotes neural differentiation |
MDD and BD | (63) | |
| ZNF711 | Zfx/Zfy transcription activation region | Activates the genes essential for brain development | ID | (64, 65) |
| ZNF774 | ASDs | (66) | ||
| ZNF804A* | Implicates in brain connectivity (in the hippocampus and the dorsolateral prefrontal cortex) Implicates in episodic and working memory |
Schizophrenia, ID, and ASDs | (67, 68) | |
| ZNF865 | ID and cerebral ataxia | (69) | ||
| POZ/BTB-ZNFs | ||||
| ZBTB7C | Highly expressed in the granular layers of the dentate gyrus and the pyramidal layer of the hippocampal gyrus | ID | (70) | |
| ZBTB16 | ASDs | (71) | ||
| ZBTB20 | Highly expressed in the forebrain Involved in hippocampal neurogenesis, neuronal differentiation and neuronal connectivity Promotes astrocytogenesis |
Macrocephaly (autistic features) Intellectual disabilities and autism |
(72) | |
| ZBTB21 | Down syndrome | (73) | ||
| ZBTB32 | MDD | (74) | ||
| ZBTB45 | Highly expressed in the developing brain Regulates differentiation of glial progenitor cells, glial cells and oligodendrocyte precursors |
(75) | ||
| ZmC2H2-1 | Stress intolerance | (76) | ||
| KRAB-ZNFs | ||||
| PRDM15 (ZNF298) | SET | Acts in neural cell fate decision | Down syndrome and BD | (77, 78) |
| ZBTB11 | Integrase H2C2 | ID | (79) | |
| ZBTB18 | Coordinates corticogenesis and promotes radial cell migration | ID, microcephaly and corpus callosum anomalies. | (80) | |
| ZEB1 | Homeobox | Controls neuron differentiation Maintains integrity of the blood brain barrier |
Schizophrenia | (81, 82) |
| ZEB2 | Homeobox | Regulates the transition of radial glia to Bergmann glia | Mowar-Wilson syndrome | (83) |
| ZKSCAN4 | SCAN | Schizophrenia | (67) | |
| ZNF8 | Transcriptional regulation | ASDs | (84) | |
| ZNF18 | SCAN | Regulates neuronal activity and/or development | Congenital form of ASDs | (85) |
| ZNF30 | Microcephaly, intellectual disabilities, and poor speech development | (86) | ||
| ZNF34 | MDD | (87) | ||
| ZNF41 | XLMR and cognitive defects | (88) | ||
| ZNF74 | Regulates of synaptic transmission | Schizophrenia and intellectual disabilities | (89, 90) | |
| ZNF81 | XLMR and autistic symptoms | (91) | ||
| ZNF181 | Microcephaly, intellectual disabilities, and poor speech development | (86) | ||
| ZNF182 | XLMR and autistic symptoms | (91) | ||
| ZNF302 | Developmental delay, microcephaly, and intellectual disabilities | (86) | ||
| ZNF354C | Regulates gene expression during early embryonic brain development | Schizophrenia and depression | (92, 93) | |
| ZNF439 | Amyotrophic lateral sclerosis | |||
| ZNF496 | SCAN | Upregulated during the differentiation of P19 neural precursor cells | Epilepsy and hyperactivity Microcephaly and abnormal corpus callosum |
(94, 95) |
| ZNF517 | ASDs | (96) | ||
| ZNF519 | Microcephaly, lissencephaly, and ID | (97) | ||
| ZNF528 | ID | (98) | ||
| ZNF534 | Epilepsy and ID | (99) | ||
| ZNF541 | ID | (100) | ||
| ZNF546 | ID | (101) | ||
| ZNF559 | ASDs | (102, 103) | ||
| ZNF568 | Maintains neuron stem cells and regulate neurogenesis | Microcephaly | (104) | |
| ZNF589 | ID | (105, 106) | ||
| ZNF599 | Microcephaly, ID, and poor speech development | (86, 107) | ||
| ZNF673 | ID and learning disabilities | (108) | ||
| ZNF674 | ID and the X-linked cognitive disabilities | (108, 109) | ||
| ZNF713 | ASDs and frontotemporal dementia | (110) | ||
| ZNF717 | ID and polymicrogyria | (101, 111) | ||
| ZNF746 | Coiled coil | Regulates neuronal death | Parkinson disease | |
| ZNF778 | ASDs and cognitive impairment | (112) | ||
| ZNF780B | ID | (101) | ||
| ZNF860 | Schizophrenia | (113) | ||
| ZNF862 | HATC-C, RNase H-like | ID, language development, and information processing | (114) | |
| SCAN-ZNFs | ||||
| ZNF24/ZNF191 | Controls the transition stage from proliferation to differentiation in NPCs | (115) | ||
| ZSCAN10 | Controls pluripotency of embryonic stem cells | Schizophrenia | (92) | |
| ZSCAN31 (ZNF323) | Involves in early stages of brain development | Schizophrenia | (116) | |
*
ZNF804A has only one ZF.