ZFHX3 (AT-binding transcription factor 1)

2003-10-01 Nadine Van Roy , Frank Speleman Affiliation

Center for Medical Genetics, Ghent University Hospital, 1K5, De Pintelaan 185, B-9000 Gent, Belgium

Identity

HGNC

ZFHX3

LOCATION

16q22.2

IMAGE

LEGEND

Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics

LOCUSID

463

ALIAS

ATBF1,ATBT,C16orf47,ZFH-3,ZNF927

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

10 exons, DNA size: 261.32 kb.

Transcription

two isoforms ATBF1-A and ATBF1-B, due to alternative promotor usage combined with alternative splicing, mRNA-size: 11893 bp.

Proteins

Description

3703 amino acids; 404 kDa; four homeodomains and 23 zinc fingers including 1 pseudo zinc finger motif, one DEAD and one DEAH box, a RNA and an ATP binding site, two large RS domains and multiple phosphorylation sites.

Expression

Embryonic and neonatal brain.

Localisation

nuclear

Function

Transcription factor that binds to the AT-rich core sequence of the enhancer element of the AFP gene and downregulates AFP gene expression, possibly involved in neuronal differentiation (ATBF1-A).

Homology

mouse atbf1, drosophila zfh2 and C. Elegans ZC 123.3

Mutations

Somatic

Amplification, in one early neural crest derived cell line SJNB-12 under the form of extrachromosomally double minutes, non-syntenic co-amplification with MYC.
Absence of ATBF1 expression in alpha-fetoprotein expressing gastric cancer cell lines, lack of ATBF1 expression not due to mutation, deletion or translocation but to strong repression at the transcriptional level.

Implicated in

Disease

Early neural crest derived cell line (SJNB-12).

Prognosis

unknown

Cytogenetics

Several structural and numerical chromosomal aberrations and presence of extrachromosomally double minutes and homogenously staining regions, presence of a reciprocal unbalanced t(8;16)(q24.3;q22.3).

Oncogenesis

Amplification in one neural crest derived cell line (SJNB-12), non-syntenic co-amplification with MYC.

Disease

Alpha-fetoprotein producing gastric cancer cell lines (GCIY and Ist-I).

Prognosis

poor (very malignant and highly metastatic cancer)

Oncogenesis

Alpha-fetoprotein producing cancer cell lines show absence of ATBF1 expression, lack of ATBF1 expression not due to deletion mutation or translocation but to strong repression at the transcriptional level.

Article Bibliography

Pubmed ID	Last Year	Title	Authors
11312261	2001	Positive and negative regulation of myogenic differentiation of C2C12 cells by isoforms of the multiple homeodomain zinc finger transcription factor ATBF1.	Berry FB et al
9034713	1997	Regulation and activities of alpha-fetoprotein.	Chen H et al
12926016	2003	ATBF1-A protein, but not ATBF1-B, is preferentially expressed in developing rat brain.	Ishii Y et al
10318867	1999	Myb-interacting protein, ATBF1, represses transcriptional activity of Myb oncoprotein.	Kaspar P et al
10623580	2000	AT motif binding factor 1-A (ATBF1-A) negatively regulates transcription of the aminopeptidase N gene in the crypt-villus axis of small intestine.	Kataoka H et al
11314020	2001	Alpha-fetoprotein producing gastric cancer lacks transcription factor ATBF1.	Kataoka H et al
10855793	2000	Characterization of trinucleotide- and tandem repeat-containing transcripts obtained from human spinal cord cDNA library by high-density filter hybridization.	Kaushik N et al
11755205	2001	DNA/RNA-dependent ATPase activity is associated with ATBF1, a multiple homeodomain-zinc finger protein.	Kawaguchi M et al
11812077	2002	Expression of homeobox genes in cervical cancer.	Li H et al
7592926	1995	Cloning and characterization of an ATBF1 isoform that expresses in a neuronal differentiation-dependent manner.	Miura Y et al
1719379	1991	A human alpha-fetoprotein enhancer-binding protein, ATBF1, contains four homeodomains and seventeen zinc fingers.	Morinaga T et al
11786962	2002	Regulation of the alpha-fetoprotein gene by the isoforms of ATBF1 transcription factor in human hepatoma.	Ninomiya T et al
11004489	2000	Cloning and characterization of a novel RNA-binding protein SRL300 with RS domains.	Sawada Y et al
8588896	1995	Automated fluorescent dye-terminator sequencing of G+C-rich tracts with the aid of dimethyl sulfoxide.	Scheidl TM et al
8827889	1996	[ZFH/ATBF1 gene family: transcription factors containing both homeo- and zinc finger-domains].	Tamaoki T et al
11550280	2001	Combined M-FISH and CGH analysis allows comprehensive description of genetic alterations in neuroblastoma cell lines.	Van Roy N et al
9013792	1996	Developmental changes in expression of the ATBF1 transcription factor gene.	Watanabe M et al
8666409	1995	Assignment of the human ATBF1 transcription factor gene to chromosome 16q22.3-q23.1.	Yamada K et al
7507206	1994	ATBF1, a multiple-homeodomain zinc finger protein, selectively down-regulates AT-rich elements of the human alpha-fetoprotein gene.	Yasuda H et al

Other Information

Locus ID:

NCBI: 463
MIM: 104155
HGNC: 777
Ensembl: ENSG00000140836

Variants:

dbSNP: 463
ClinVar: 463
TCGA: ENSG00000140836
COSMIC: ZFHX3

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000140836	ENST00000268489	Q15911
ENSG00000140836	ENST00000397992	Q15911
ENSG00000140836	ENST00000641206	Q15911

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Signaling pathways regulating pluripotency of stem cells	KEGG	hsa04550
Signaling pathways regulating pluripotency of stem cells	KEGG	ko04550

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
38035881	2024	Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease.	2
38197134	2024	Adaptive Long-Read Sequencing Reveals GGC Repeat Expansion in ZFHX3 Associated with Spinocerebellar Ataxia Type 4.	0
38227369	2024	Myeloid Zfhx3 deficiency protects against hypercapnia-induced suppression of host defense against influenza A virus.	0
38412861	2024	Haploinsufficiency of ZFHX3, encoding a key player in neuronal development, causes syndromic intellectual disability.	0
38508705	2024	ZFHX3 variants cause childhood partial epilepsy and infantile spasms with favourable outcomes.	0
38035881	2024	Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease.	2
38197134	2024	Adaptive Long-Read Sequencing Reveals GGC Repeat Expansion in ZFHX3 Associated with Spinocerebellar Ataxia Type 4.	0
38227369	2024	Myeloid Zfhx3 deficiency protects against hypercapnia-induced suppression of host defense against influenza A virus.	0
38412861	2024	Haploinsufficiency of ZFHX3, encoding a key player in neuronal development, causes syndromic intellectual disability.	0
38508705	2024	ZFHX3 variants cause childhood partial epilepsy and infantile spasms with favourable outcomes.	0
36800142	2023	Influence of ZFHX3 Polymorphisms on the Risk of Ischemic Stroke in Chinese Han Population.	1
37449401	2023	Loss of the Atrial Fibrillation-Related Gene, Zfhx3, Results in Atrial Dilation and Arrhythmias.	4
36800142	2023	Influence of ZFHX3 Polymorphisms on the Risk of Ischemic Stroke in Chinese Han Population.	1
37449401	2023	Loss of the Atrial Fibrillation-Related Gene, Zfhx3, Results in Atrial Dilation and Arrhythmias.	4
34953044	2022	AR imposes different effects on ZFHX3 transcription depending on androgen status in prostate cancer cells.	3

Citation

Nadine Van Roy ; Frank Speleman

ZFHX3 (AT-binding transcription factor 1)

Atlas Genet Cytogenet Oncol Haematol. 2003-10-01

Online version: http://atlasgeneticsoncology.org/gene/357/zfhx3-(at-binding-transcription-factor-1)