FOXH1

Protein identityUniProt · HPA

UniProt accession

O75593

Gene

FOXH1

Ensembl

ENSG00000160973

Chromosome

8

Canonical length

365 aa

Protein class

Predicted intracellular proteins, Transcription factors

OverviewNCBI Gene

FOXH1 encodes a human homolog of Xenopus forkhead activin signal transducer-1. FOXH1 protein binds SMAD2 and activates an activin response element via binding the DNA motif TGT(G/T)(T/G)ATT. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

365 residues, UniProt reviewed canonical sequence.

>O75593|FOXH1
     1  MGPCSGSRLG PPEAESPSQP PKRRKKRYLR HDKPPYTYLA MIALVIQAAP SRRLKLAQII
    61  RQVQAVFPFF REDYEGWKDS IRHNLSSNRC FRKVPKDPAK PQAKGNFWAV DVSLIPAEAL
   121  RLQNTALCRR WQNGGARGAF AKDLGPYVLH GRPYRPPSPP PPPSEGFSIK SLLGGSGEGA
   181  PWPGLAPQSS PVPAGTGNSG EEAVPTPPLP SSERPLWPLC PLPGPTRVEG ETVQGGAIGP
   241  STLSPEPRAW PLHLLQGTAV PGGRSSGGHR ASLWGQLPTS YLPIYTPNVV MPLAPPPTSC
   301  PQCPSTSPAY WGVAPETRGP PGLLCDLDAL FQGVPPNKSI YDVWVSHPRD LAAPGPGWLL
   361  SWCSL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FOXH1 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)

0.57

Highest tissue expression

14 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FOXH1.

Disease | GeneticClinVar

6 pathogenic / likely-pathogenic of 273 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Conotruncal defect

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)

0.84

gnomAD pLI

0.04

gnomAD missense Z

-2.55

DepMap mean gene effect

-0.03

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• aorta morphogenesis
• axial mesoderm development
• cardiac right ventricle morphogenesis
• cellular response to cytokine stimulus
• determination of left/right asymmetry in lateral mesoderm
• embryonic heart tube anterior/posterior pattern specification
• heart looping
• hepatocyte differentiation
• negative regulation of androgen receptor signaling pathway
• negative regulation of transcription by RNA polymerase II
• nodal signaling pathway
• outflow tract morphogenesis
• positive regulation of DNA-templated transcription
• positive regulation of transcription by RNA polymerase II
• secondary heart field specification
• transforming growth factor beta receptor signaling pathway
• ventricular trabecula myocardium morphogenesis

Molecular functions

• bHLH transcription factor binding
• cis-regulatory region sequence-specific DNA binding
• co-SMAD binding
• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity, RNA polymerase II-specific
• DNA-binding transcription factor binding
• nuclear androgen receptor binding
• protein domain specific binding
• R-SMAD binding
• sequence-specific DNA binding
• SMAD binding
• transcription cis-regulatory region binding
• transcription corepressor activity

Cellular components

• activin responsive factor complex
• chromatin
• nucleus
• transcription regulator complex

Protein domainsUniProt · Pfam · InterPro

• Fork head domain
• Fork head domain conserved site 2
• Winged helix-like DNA-binding domain superfamily
• Winged helix DNA-binding domain superfamily
• Forkhead domain
• Forkhead box protein H1, forkhead domain
• Activin-responsive transcriptional regulator

KeywordsUniProt

• Activator
• DNA-binding
• Nucleus
• Transcription
• Transcription regulation

InteractionsUniProt · HPA

Protein binding partners of FOXH1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SMAD3
• SMAD2