SIX6

Protein identityUniProt · HPA

UniProt accession

O95475

Gene

SIX6

Ensembl

ENSG00000184302

Chromosome

14

Canonical length

246 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors

Subcellular location

Nucleoplasm

OverviewNCBI Gene

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 eye development. Defects in this gene are a cause of isolated microphthalmia with cataract type 2 (MCOPCT2). [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

246 residues, UniProt reviewed canonical sequence.

>O95475|SIX6
     1  MFQLPILNFS PQQVAGVCET LEESGDVERL GRFLWSLPVA PAACEALNKN ESVLRARAIV
    61  AFHGGNYREL YHILENHKFT KESHAKLQAL WLEAHYQEAE KLRGRPLGPV DKYRVRKKFP
   121  LPRTIWDGEQ KTHCFKERTR HLLREWYLQD PYPNPSKKRE LAQATGLTPT QVGNWFKNRR
   181  QRDRAAAAKN RLQQQVLSQG SGRALRAEGD GTPEVLGVAT SPAASLSSKA ATSAISITSS
   241  DSECDI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SIX6 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.43

Highest tissue expression

29 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SIX6.

Disease | AllUniProt

Conditions SIX6 is implicated in, by any mechanism.

• Optic disk anomalies with retinal and/or macular dystrophy (ODRMD) MIM:212550

Disease | GeneticClinVar

8 pathogenic / likely-pathogenic of 154 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Colobomatous optic disc-macular atrophy-chorioretinopathy syndrome
• Developmental cataract
• Sclerocornea
• Nystagmus
• Microcornea

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.6

gnomAD pLI

0.52

gnomAD missense Z

0.71

DepMap mean gene effect

-0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• animal organ morphogenesis
• eye development
• regulation of transcription by RNA polymerase II
• visual perception

Molecular functions

• DNA-binding transcription factor activity, RNA polymerase II-specific
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• sequence-specific double-stranded DNA binding

Cellular components

• chromatin
• nucleus
• transcription regulator complex

Protein domainsUniProt · Pfam · InterPro

• Homeodomain
• Homedomain-like superfamily
• Homeobox protein SIX1, N-terminal SD domain
• Homeodomain
• Transcriptional regulator, SIX1, N-terminal SD domain

KeywordsUniProt

• Cataract
• Developmental protein
• DNA-binding
• Homeobox
• Microphthalmia
• Nucleus
• Phosphoprotein

InteractionsUniProt · HPA

Protein binding partners of SIX6 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• TLE4
• TLE5
• DACH1
• DACH2