FOXL2

Protein identityUniProt · HPA

UniProt accession

P58012

Gene

FOXL2

Ensembl

ENSG00000183770

Chromosome

3

Canonical length

376 aa

Protein class

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

Subcellular location

Nucleoplasm

OverviewNCBI Gene

This gene encodes a forkhead transcription factor. The protein contains a fork-head DNA-binding domain and may play a role in ovarian development and function. Expansion of a polyalanine repeat region and other mutations in this gene are a cause of blepharophimosis syndrome and premature ovarian failure 3. [provided by RefSeq, Jul 2016]

Canonical amino-acid sequenceUniProt

376 residues, UniProt reviewed canonical sequence.

>P58012|FOXL2
     1  MMASYPEPED AAGALLAPET GRTVKEPEGP PPSPGKGGGG GGGTAPEKPD PAQKPPYSYV
    61  ALIAMAIRES AEKRLTLSGI YQYIIAKFPF YEKNKKGWQN SIRHNLSLNE CFIKVPREGG
   121  GERKGNYWTL DPACEDMFEK GNYRRRRRMK RPFRPPPAHF QPGKGLFGAG GAAGGCGVAG
   181  AGADGYGYLA PPKYLQSGFL NNSWPLPQPP SPMPYASCQM AAAAAAAAAA AAAAGPGSPG
   241  AAAVVKGLAG PAASYGPYTR VQSMALPPGV VNSYNGLGGP PAAPPPPPHP HPHPHAHHLH
   301  AAAAPPPAPP HHGAAAPPPG QLSPASPATA APPAPAPTSA PGLQFACARQ PELAMMHCSY
   361  WDHDSKTGAL HSRLDL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FOXL2 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)

0.65

Highest tissue expression

43 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FOXL2.

Disease | AllUniProt

Conditions FOXL2 is implicated in, by any mechanism.

• Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) MIM:110100
• Premature ovarian failure 3 (POF3) MIM:608996

Disease | GeneticClinVar

176 pathogenic / likely-pathogenic of 302 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Blepharophimosis, ptosis, and epicanthus inversus syndrome
• Premature ovarian failure 3
• BLEPHAROPHIMOSIS, PTOSIS, AND EPICANTHUS INVERSUS, TYPE I
• BLEPHAROPHIMOSIS, PTOSIS, AND EPICANTHUS INVERSUS, TYPE II
• Inborn genetic diseases

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)

0.44

gnomAD pLI

0.88

gnomAD missense Z

1.76

DepMap mean gene effect

-0.14

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• anatomical structure morphogenesis
• apoptotic DNA fragmentation
• cell differentiation
• embryonic eye morphogenesis
• extraocular skeletal muscle development
• negative regulation of DNA-templated transcription
• negative regulation of transcription by RNA polymerase II
• oocyte growth
• ovarian follicle development
• positive regulation of apoptotic process
• positive regulation of DNA-templated transcription
• positive regulation of follicle-stimulating hormone secretion
• positive regulation of luteinizing hormone secretion
• regulation of transcription by RNA polymerase II
• single fertilization
• uterus development
• female somatic sex determination
• granulosa cell differentiation

Molecular functions

• cysteine-type endopeptidase regulator activity involved in apoptotic process
• DNA binding
• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity
• DNA-binding transcription factor activity, RNA polymerase II-specific
• nuclear estrogen receptor binding
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• sequence-specific double-stranded DNA binding
• ubiquitin conjugating enzyme binding

Cellular components

• chromatin
• Flemming body
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Fork head domain
• Fork head domain conserved site1
• Fork head domain conserved site 2
• Winged helix-like DNA-binding domain superfamily
• Winged helix DNA-binding domain superfamily
• Forkhead box domain-containing protein
• Forkhead domain
• Forkhead box protein L2, forkhead domain

KeywordsUniProt

• Differentiation
• DNA-binding
• Isopeptide bond
• Nucleus
• Phosphoprotein
• Premature ovarian failure
• Transcription
• Transcription regulation
• Triplet repeat expansion
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of FOXL2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• DDX20
• ESR1
• SMAD3
• UBE2I