SIX2 SIX homeobox 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SIX2provided by HGNC
Official Full Name: SIX homeobox 2provided by HGNC
Primary source: HGNC:HGNC:10888
See related: Ensembl:ENSG00000170577 MIM:604994; AllianceGenome:HGNC:10888
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
Summary: This gene is a member of the vertebrate gene family which encode proteins homologous to the Drosophila 'sine oculis' homeobox protein. The encoded protein is a transcription factor which, like other members of this gene family, may be involved in limb or eye development. [provided by RefSeq, Dec 2008]
Expression: Biased expression in salivary gland (RPKM 4.1), prostate (RPKM 2.7) and 4 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2p21

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (45005182..45009452, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (45010408..45014884, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (45232321..45236591, complement)

Chromosome 2 - NC_000002.12 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

De novo SIX2 activation in human kidneys treated with neonatal kidney stem/progenitor cells.
Title: De novo SIX2 activation in human kidneys treated with neonatal kidney stem/progenitor cells.
Analysis of the mutational status of SIX1/2 and microRNA processing genes in paired primary and relapsed Wilms tumors and association with relapse.
Title: Analysis of the mutational status of SIX1/2 and microRNA processing genes in paired primary and relapsed Wilms tumors and association with relapse.
Overexpression of Sine Oculis Homeobox Homolog 2 Predicts Poor Survival and Clinical Parameters of Patients with Colon Adenocarcinoma.
Title: Overexpression of Sine Oculis Homeobox Homolog 2 Predicts Poor Survival and Clinical Parameters of Patients with Colon Adenocarcinoma.
SIX2 Regulates Human beta Cell Differentiation from Stem Cells and Functional Maturation In Vitro.
Title: SIX2 Regulates Human β Cell Differentiation from Stem Cells and Functional Maturation In Vitro.
Maternal SLE and brachytelephalangic chondrodysplasia punctata in a patient with unrelated de novo RAF1 and SIX2 variants.
Title: Maternal SLE and brachytelephalangic chondrodysplasia punctata in a patient with unrelated de novo RAF1 and SIX2 variants.
The six2 knockdown attenuated the stemness of Renal cell carcinoma (RCC) cells, which was evident by decreased spheroid formation ability and stemness marker (sox2 and nanog) expression.
Title: Transcription factor Six2 induces a stem cell-like phenotype in renal cell carcinoma cells.
Elevated Six2 expression in hepatocellular carcinoma patients was associated with negative prognosis. Upregulated Six2 promoted tumor growth and facilitated HCC metastasis via TGF-beta/Smad signal pathway.
Title: Six2 is negatively correlated with prognosis and facilitates epithelial-mesenchymal transition via TGF-β/Smad signal pathway in hepatocellular carcinoma.
Glomerular Six-2 deposits in renal biopsy should be validated in prospective series as a predictor of renal outcome in renal amyloidosis
Title: Six-2 glomerular expression for the prediction of renal outcome in systemic amyloidosis.
High Six2 expression is associated with Late-Stage Metastasis in triple-negative breast cancer.
Title: SIX2 Mediates Late-Stage Metastasis via Direct Regulation of SOX2 and Induction of a Cancer Stem Cell Program.
findings identify a NIK-SIX signalling axis that fine-tunes inflammatory gene expression programs under both physiological and pathological conditions
Title: A NIK-SIX signalling axis controls inflammation by targeted silencing of non-canonical NF-κB.

Submit: New GeneRIF Correction See all GeneRIFs (25)

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

EBI GWAS Catalog

Description
Genome-wide association meta-analysis identifies novel variants associated with fasting plasma glucose in East Asians. EBI GWAS Catalog EBI GWAS CatalogPubMed
Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits. 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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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	IEA Inferred from Electronic Annotation more info
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IEA Inferred from Electronic Annotation more info
enables DNA-binding transcription factor activity	IEA Inferred from Electronic Annotation more info
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	IEA Inferred from Electronic Annotation 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	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IEA Inferred from Electronic Annotation more info
enables sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
enables sequence-specific double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in anatomical structure morphogenesis	TAS Traceable Author Statement more info	PubMed
involved_in anterior/posterior axis specification	IEA Inferred from Electronic Annotation more info
involved_in anterior/posterior axis specification	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within cell population proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within chondrocyte differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within condensed mesenchymal cell proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within embryonic cranial skeleton morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in embryonic digestive tract morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in embryonic digestive tract morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within embryonic skeletal system morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of epithelial cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in kidney development	IBA Inferred from Biological aspect of Ancestor more info
involved_in kidney development	IEA Inferred from Electronic Annotation more info
involved_in kidney development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in kidney development	ISS Inferred from Sequence or Structural Similarity more info
involved_in mesenchymal cell differentiation involved in kidney development	IEA Inferred from Electronic Annotation more info
involved_in mesenchymal cell differentiation involved in kidney development	ISS Inferred from Sequence or Structural Similarity more info
involved_in mesenchymal stem cell maintenance involved in nephron morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in mesenchymal stem cell maintenance involved in nephron morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in mesenchymal stem cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in mesenchymal stem cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in mesenchymal to epithelial transition involved in metanephros morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in mesenchymal to epithelial transition involved in metanephros morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in mesodermal cell fate specification	IEA Inferred from Electronic Annotation more info
involved_in mesodermal cell fate specification	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within metanephros development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within middle ear morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of epithelial cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in nephron development	IEA Inferred from Electronic Annotation more info
involved_in nephron development	ISS Inferred from Sequence or Structural Similarity more info
involved_in nephron morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in nephron morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of chondrocyte proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of chondrocyte proliferation	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within protein import into nucleus	IEA Inferred from Electronic Annotation more info
involved_in regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in regulation of branching involved in ureteric bud morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in regulation of branching involved in ureteric bud morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of chondrocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in regulation of ossification	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

Component	Evidence Code	Pubs
located_in chromatin	ISA Inferred from Sequence Alignment more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
part_of transcription regulator complex	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: homeobox protein SIX2

Names: sine oculis homeobox homolog 2

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_009360.1 RefSeqGene

Range

4952..9222

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_016932.5 → NP_058628.3 homeobox protein SIX2

See identical proteins and their annotated locations for NP_058628.3

Status: REVIEWED

Source sequence(s)

AC012354, AF332197, AI299144, AI697804, BC024033

Consensus CDS

CCDS1822.1

UniProtKB/Swiss-Prot

Q9BXH7, Q9NPC8

UniProtKB/TrEMBL

Q8TBA2

Related

ENSP00000304502.6, ENST00000303077.7

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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

45005182..45009452 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005264100.4 → XP_005264157.1 homeobox protein SIX2 isoform X1

See identical proteins and their annotated locations for XP_005264157.1

UniProtKB/TrEMBL

Q8TBA2

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