ZFHX3 zinc finger homeobox 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ZFHX3provided by HGNC
Official Full Name: zinc finger homeobox 3provided by HGNC
Primary source: HGNC:HGNC:777
See related: Ensembl:ENSG00000140836 MIM:104155; AllianceGenome:HGNC:777
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ATBT; SCA4; ATBF1; ATFB8; ZFH-3; ZNF927; C16orf47
Summary: This gene encodes a transcription factor with multiple homeodomains and zinc finger motifs, and regulates myogenic and neuronal differentiation. The encoded protein suppresses expression of the alpha-fetoprotein gene by binding to an AT-rich enhancer motif. The protein has also been shown to negatively regulate c-Myb, and transactivate the cell cycle inhibitor cyclin-dependent kinase inhibitor 1A (also known as p21CIP1). This gene is reported to function as a tumor suppressor in several cancers, and sequence variants of this gene are also associated with atrial fibrillation. Multiple transcript variants expressed from alternate promoters and encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]
Expression: Ubiquitous expression in thyroid (RPKM 3.0), prostate (RPKM 2.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16q22.2-q22.3

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (72782885..73891930, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (78600697..79709756, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (72816784..73925829, complement)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Spinocerebellar ataxia type 4 is caused by a GGC expansion in the ZFHX3 gene and is associated with prominent dysautonomia and motor neuron signs.
Title: Spinocerebellar ataxia type 4 is caused by a GGC expansion in the ZFHX3 gene and is associated with prominent dysautonomia and motor neuron signs.
ZFHX3 variants cause childhood partial epilepsy and infantile spasms with favourable outcomes.
Title: ZFHX3 variants cause childhood partial epilepsy and infantile spasms with favourable outcomes.
Adaptive Long-Read Sequencing Reveals GGC Repeat Expansion in ZFHX3 Associated with Spinocerebellar Ataxia Type 4.
Title: Adaptive Long-Read Sequencing Reveals GGC Repeat Expansion in ZFHX3 Associated with Spinocerebellar Ataxia Type 4.
Haploinsufficiency of ZFHX3, encoding a key player in neuronal development, causes syndromic intellectual disability.
Title: Haploinsufficiency of ZFHX3, encoding a key player in neuronal development, causes syndromic intellectual disability.
Myeloid Zfhx3 deficiency protects against hypercapnia-induced suppression of host defense against influenza A virus.
Title: Myeloid Zfhx3 deficiency protects against hypercapnia-induced suppression of host defense against influenza A virus.
Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease.
Title: Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease.
Loss of the Atrial Fibrillation-Related Gene, Zfhx3, Results in Atrial Dilation and Arrhythmias.
Title: Loss of the Atrial Fibrillation-Related Gene, Zfhx3, Results in Atrial Dilation and Arrhythmias.
Influence of ZFHX3 Polymorphisms on the Risk of Ischemic Stroke in Chinese Han Population.
Title: Influence of ZFHX3 Polymorphisms on the Risk of Ischemic Stroke in Chinese Han Population.
Inactivation of PTEN and ZFHX3 in Mammary Epithelial Cells Alters Patterns of Collective Cell Migration.
Title: Inactivation of PTEN and ZFHX3 in Mammary Epithelial Cells Alters Patterns of Collective Cell Migration.
ATBF1 is a potential diagnostic marker of histological grade and functions via WNT5A in breast cancer.
Title: ATBF1 is a potential diagnostic marker of histological grade and functions via WNT5A in breast cancer.

Submit: New GeneRIF Correction See all GeneRIFs (69)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Atrial fibrillation, familial, 8 MedGen: C2751607 OMIM: 613055 GeneReviews: Not available	Compare labs
Malignant tumor of prostate MedGen: C0376358 GeneReviews: Not available	Compare labs
Spinocerebellar ataxia type 4 MedGen: C0752122 OMIM: 600223 GeneReviews: Hereditary Ataxia Overview	Compare labs

EBI GWAS Catalog

Description
A genome-wide association study identifies novel and functionally related susceptibility Loci for Kawasaki disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): a meta-analysis of genome-wide association studies. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analyses identify variants in developmental genes associated with hypospadias. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis identifies six new susceptibility loci for atrial fibrillation. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH65836 (e-PCR)
- UniSTS:17957

RH69880 (e-PCR)
- UniSTS:42299

WI-22495 (e-PCR)
- UniSTS:45920

RH119763 (e-PCR)
- UniSTS:133239

ATBF1_4388 (e-PCR)
- UniSTS:463552

SHGC-154914 (e-PCR)
- UniSTS:182987

RH68561 (e-PCR)
- UniSTS:30675

RH65127 (e-PCR)
- UniSTS:37848

RH120639 (e-PCR)
- UniSTS:132580

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA-binding transcription factor activity	NAS Non-traceable Author Statement more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	TAS Traceable Author Statement more info	PubMed
enables DNA-binding transcription repressor activity, RNA polymerase II-specific	EXP Inferred from Experiment more info	PubMed
enables DNA-binding transcription repressor activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transcription cis-regulatory region binding	IDA Inferred from Direct Assay more info	PubMed
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in circadian regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
involved_in muscle organ development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of myoblast differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell adhesion	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of myoblast differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of DNA-templated transcription	TAS Traceable Author Statement more info	PubMed
involved_in regulation of locomotor rhythm	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of neuron differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to transforming growth factor beta	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in chromatin	ISA Inferred from Sequence Alignment more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear body	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	TAS Traceable Author Statement more info	PubMed
part_of transcription regulator complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: zinc finger homeobox protein 3

Names: AT motif-binding factor 1; AT-binding transcription factor 1; alpha-fetoprotein enhancer binding protein; zinc finger homeodomain protein 3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_013211.2 RefSeqGene

Range

848804..1114047

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001164766.2 → NP_001158238.1 zinc finger homeobox protein 3 isoform B

Status: REVIEWED

Description

Transcript Variant: This variant (B) represents use of an alternate promoter and 5' UTR, lacks an alternate coding exon, and uses a downstream start codon, compared to variant A. The resulting isoform (B) has a shorter N-terminus, compared to isoform A.

Source sequence(s)

AC004943, AC116667, D10250, L32832

Consensus CDS

CCDS54035.1

UniProtKB/Swiss-Prot

Q15911

Related

ENSP00000438926.3, ENST00000397992.5

Conserved Domains (5) summary

smart00389
Location:1231 → 1287

HOX; Homeodomain

COG5576
Location:1680 → 1824

COG5576; Homeodomain-containing transcription factor [Transcription]

sd00017
Location:633 → 657

ZF_C2H2; C2H2 Zn finger [structural motif]

sd00020
Location:489 → 509

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam00046
Location:1731 → 1783

Homeobox; Homeobox domain
NM_001386735.1 → NP_001373664.1 zinc finger homeobox protein 3 isoform A

Status: REVIEWED

Source sequence(s)

AC004943, AC009033, AC009104, AC092128, AC092344, AC116667, AC132068, AC137520

Consensus CDS

CCDS10908.1

UniProtKB/Swiss-Prot

D3DWS8, O15101, Q13719, Q15911, Q6ZP98

Related

ENSP00000493252.1, ENST00000641206.2

Conserved Domains (6) summary

smart00389
Location:2145 → 2201

HOX; Homeodomain

COG5576
Location:2594 → 2738

COG5576; Homeodomain-containing transcription factor [Transcription]

sd00017
Location:1547 → 1571

ZF_C2H2; C2H2 Zn finger [structural motif]

sd00020
Location:1403 → 1423

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam05109
Location:3104 → 3191

Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)

pfam00046
Location:2245 → 2299

Homeobox; Homeobox domain
NM_006885.4 → NP_008816.3 zinc finger homeobox protein 3 isoform A

See identical proteins and their annotated locations for NP_008816.3

Status: REVIEWED

Description

Transcript Variant: This variant (A) encodes the longer isoform (A). Variants A and D both encode the same isoform (A. Expression of this variant is activated during neuronal differentiation.

Source sequence(s)

AC002044, AC004943, AC132068, BC029653

Consensus CDS

CCDS10908.1

UniProtKB/Swiss-Prot

D3DWS8, O15101, Q13719, Q15911, Q6ZP98

Related

ENSP00000268489.5, ENST00000268489.10

Conserved Domains (6) summary

smart00389
Location:2145 → 2201

HOX; Homeodomain

COG5576
Location:2594 → 2738

COG5576; Homeodomain-containing transcription factor [Transcription]

sd00017
Location:1547 → 1571

ZF_C2H2; C2H2 Zn finger [structural motif]

sd00020
Location:1403 → 1423

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam05109
Location:3104 → 3191

Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)

pfam00046
Location:2245 → 2299

Homeobox; Homeobox domain

RNA

NR_163978.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC116667

Related

ENST00000358463.2

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000016.10 Reference GRCh38.p14 Primary Assembly

Range

72782885..73891930 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047434166.1 → XP_047290122.1 zinc finger homeobox protein 3 isoform X1

UniProtKB/Swiss-Prot

D3DWS8, O15101, Q13719, Q15911, Q6ZP98
XM_024450291.2 → XP_024306059.1 zinc finger homeobox protein 3 isoform X4

Conserved Domains (6) summary

smart00389
Location:1261 → 1317

HOX; Homeodomain

sd00017
Location:663 → 687

ZF_C2H2; C2H2 Zn finger [structural motif]

sd00020
Location:519 → 539

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam00046
Location:1761 → 1813

Homeobox; Homeobox domain

cl25496
Location:2220 → 2307

Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)

cl27820
Location:1710 → 1854

Abdominal-A; Homeobox protein
XM_017023251.3 → XP_016878740.1 zinc finger homeobox protein 3 isoform X3
XM_047434167.1 → XP_047290123.1 zinc finger homeobox protein 3 isoform X1

UniProtKB/Swiss-Prot

D3DWS8, O15101, Q13719, Q15911, Q6ZP98
XM_047434165.1 → XP_047290121.1 zinc finger homeobox protein 3 isoform X1

UniProtKB/Swiss-Prot

D3DWS8, O15101, Q13719, Q15911, Q6ZP98
XM_047434168.1 → XP_047290124.1 zinc finger homeobox protein 3 isoform X2
XM_047434169.1 → XP_047290125.1 zinc finger homeobox protein 3 isoform X5