SIX1 SIX homeobox 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SIX1provided by HGNC
Official Full Name: SIX homeobox 1provided by HGNC
Primary source: HGNC:HGNC:10887
See related: Ensembl:ENSG00000126778 MIM:601205; AllianceGenome:HGNC:10887
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: BOS3; TIP39; DFNA23
Summary: The protein encoded by this gene is a homeobox protein that is similar to the Drosophila 'sine oculis' gene product. This gene is found in a cluster of related genes on chromosome 14 and is thought to be involved in limb development. Defects in this gene are a cause of autosomal dominant deafness type 23 (DFNA23) and branchiootic syndrome type 3 (BOS3). [provided by RefSeq, Jul 2008]
Expression: Biased expression in salivary gland (RPKM 12.9), prostate (RPKM 9.2) and 6 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 14q23.1

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (60643421..60649477, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (54849879..54855949, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (61110139..61116195, complement)

Chromosome 14 - NC_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

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?

SIX1 amplification modulates stemness and tumorigenesis in breast cancer.
Title: SIX1 amplification modulates stemness and tumorigenesis in breast cancer.
Altered binding affinity of SIX1-Q177R correlates with enhanced WNT5A and WNT pathway effector expression in Wilms tumor.
Title: Altered binding affinity of SIX1-Q177R correlates with enhanced WNT5A and WNT pathway effector expression in Wilms tumor.
Phenotypic and molecular basis of SIX1 variants linked to non-syndromic deafness and atypical branchio-otic syndrome in South Korea.
Title: Phenotypic and molecular basis of SIX1 variants linked to non-syndromic deafness and atypical branchio-otic syndrome in South Korea.
[Effect of Inhibiting SIX1 Expression on Drug-resistance of Acute Myeloid Leukemia Cell Line HL-60/ADR Cells].
Title: [Effect of Inhibiting SIX1 Expression on Drug-resistance of Acute Myeloid Leukemia Cell Line HL-60/ADR Cells].
Association of SIX1-SIX6 polymorphisms with peripapillary retinal nerve fibre layer thickness in children.
Title: Association of SIX1-SIX6 polymorphisms with peripapillary retinal nerve fibre layer thickness in children.
FOXC2-induced circCASK aggravates colorectal cancer progression by upregulating SIX1 expression.
Title: FOXC2-induced circCASK aggravates colorectal cancer progression by upregulating SIX1 expression.
LRRC75A-AS1 delivered by M2 macrophage exosomes promotes cervical cancer progression via enhancing SIX1 expression.
Title: LRRC75A-AS1 delivered by M2 macrophage exosomes promotes cervical cancer progression via enhancing SIX1 expression.
The SIX1/LDHA Axis Promotes Lactate Accumulation and Leads to NK Cell Dysfunction in Pancreatic Cancer.
Title: The SIX1/LDHA Axis Promotes Lactate Accumulation and Leads to NK Cell Dysfunction in Pancreatic Cancer.
Lack of association between SIX1/SIX6 locus polymorphisms and pseudoexfoliation syndrome in a population from the Republic of Korea.
Title: Lack of association between SIX1/SIX6 locus polymorphisms and pseudoexfoliation syndrome in a population from the Republic of Korea.
Impairment of a NIK-SIX Feedback Axis Results in Dysregulation of Intestinal Immune Homeostasis and Promotes Early-onset Fatal Spontaneous Colitis.
Title: Impairment of a NIK-SIX Feedback Axis Results in Dysregulation of Intestinal Immune Homeostasis and Promotes Early-onset Fatal Spontaneous Colitis.

Submit: New GeneRIF Correction See all GeneRIFs (134)

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
Autosomal dominant nonsyndromic hearing loss 23 MedGen: C1854594 OMIM: 605192 GeneReviews: Genetic Hearing Loss Overview	Compare labs
Branchiootic syndrome 3 MedGen: C1842124 OMIM: 608389 GeneReviews: Branchiootorenal Spectrum Disorder	Compare labs
Branchiootorenal syndrome 1 MedGen: C4551702 OMIM: 113650 GeneReviews: Branchiootorenal Spectrum Disorder	Compare labs

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2012-03-22) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2012-03-22) ClinGen Genome Curation Page

EBI GWAS Catalog

Description
A genome-wide association study in the Japanese population confirms 9p21 and 14q23 as susceptibility loci for primary open angle glaucoma. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study of optic disc parameters. EBI GWAS Catalog EBI GWAS CatalogPubMed
A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association identifies ATOH7 as a major gene determining human optic disc size. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process. 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

RH106538 (e-PCR)
- UniSTS:100611

RH78873 (e-PCR)
- UniSTS:2398

RH70939 (e-PCR)
- UniSTS:49314

D14S290 (e-PCR)
- UniSTS:61893

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IMP Inferred from Mutant Phenotype more info	PubMed
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity	ISS Inferred from Sequence or Structural Similarity more info
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 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	IMP Inferred from Mutant Phenotype more info	PubMed
enables chromatin binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables sequence-specific double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables transcription cis-regulatory region binding	IDA Inferred from Direct Assay more info	PubMed
enables transcription coactivator binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in Notch signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in aorta morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in branching involved in ureteric bud morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to 3,3',5-triiodo-L-thyronine	IEA Inferred from Electronic Annotation more info
involved_in cochlea morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in embryonic cranial skeleton morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in embryonic skeletal system morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in endothelin receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in epithelial cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in facial nerve morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in fungiform papilla morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in gene expression	IEA Inferred from Electronic Annotation more info
involved_in generation of neurons	ISS Inferred from Sequence or Structural Similarity more info
involved_in inner ear development	ISS Inferred from Sequence or Structural Similarity more info
involved_in inner ear morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in kidney development	ISS Inferred from Sequence or Structural Similarity more info
involved_in mesenchymal cell proliferation involved in ureter development	IEA Inferred from Electronic Annotation more info
involved_in mesonephric tubule formation	ISS Inferred from Sequence or Structural Similarity more info
involved_in metanephric mesenchyme development	ISS Inferred from Sequence or Structural Similarity more info
involved_in middle ear morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in myoblast migration	ISS Inferred from Sequence or Structural Similarity more info
involved_in myoblast proliferation	IEA Inferred from Electronic Annotation more info
involved_in myotome development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of neuron apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in neural crest cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in neuron fate specification	IEA Inferred from Electronic Annotation more info
involved_in olfactory placode formation	IEA Inferred from Electronic Annotation more info
involved_in organ induction	ISS Inferred from Sequence or Structural Similarity more info
involved_in otic vesicle development	IEA Inferred from Electronic Annotation more info
involved_in outflow tract morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in pattern specification process	ISS Inferred from Sequence or Structural Similarity more info
involved_in pharyngeal system development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of branching involved in ureteric bud morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of brown fat cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of mesenchymal cell proliferation involved in ureter development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of myoblast proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of secondary heart field cardioblast proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of ureteric bud formation	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein localization to nucleus	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of branch elongation involved in ureteric bud branching	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in regulation of neuron differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of protein localization	IEA Inferred from Electronic Annotation more info
involved_in regulation of skeletal muscle cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in regulation of skeletal muscle cell proliferation	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of skeletal muscle satellite cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in regulation of synaptic assembly at neuromuscular junction	IEA Inferred from Electronic Annotation more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in sensory perception of sound	IEA Inferred from Electronic Annotation more info
involved_in skeletal muscle fiber development	IBA Inferred from Biological aspect of Ancestor more info
involved_in skeletal muscle tissue development	ISS Inferred from Sequence or Structural Similarity more info
involved_in thymus development	ISS Inferred from Sequence or Structural Similarity more info
involved_in thyroid gland development	ISS Inferred from Sequence or Structural Similarity more info
involved_in trigeminal ganglion development	IEA Inferred from Electronic Annotation more info
involved_in ureter smooth muscle cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in ureteric bud development	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
part_of chromatin	ISA Inferred from Sequence Alignment more info
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleolus	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay 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
part_of transcription regulator complex	IBA Inferred from Biological aspect of Ancestor more info
part_of transcription regulator complex	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: homeobox protein SIX1

Names: sine oculis homeobox homolog 1

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_008231.1 RefSeqGene

Range

4961..11017

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001425142.1 → NP_001412071.1 homeobox protein SIX1 isoform 2

Status: REVIEWED

Source sequence(s)

AL049874
NM_005982.4 → NP_005973.1 homeobox protein SIX1 isoform 1

See identical proteins and their annotated locations for NP_005973.1

Status: REVIEWED

Source sequence(s)

AL049874, BC008874, X91868

Consensus CDS

CCDS9748.1

UniProtKB/Swiss-Prot

Q15475, Q53Y16, Q96H64

Related

ENSP00000494686.1, ENST00000645694.3

Conserved Domains (2) summary

cd00086
Location:129 → 180

homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.

pfam16878
Location:9 → 118

SIX1_SD; Transcriptional regulator, SIX1, N-terminal SD domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000014.9 Reference GRCh38.p14 Primary Assembly

Range

60643421..60649477 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017021602.3 → XP_016877091.1 homeobox protein SIX1 isoform X1

Conserved Domains (2) summary

pfam16878
Location:9 → 118

SIX1_SD; Transcriptional regulator, SIX1, N-terminal SD domain

cl00084
Location:142 → 167

homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.