FOXL2
forkhead box L2, the group of Forkhead boxes
Basic information
Region (hg38): 3:138944223-138947137
Previous symbols: [ "BPES" ]
Links
Phenotypes
GenCC
Source:
- blepharophimosis, ptosis, and epicanthus inversus syndrome (Strong), mode of inheritance: AD
- blepharophimosis, ptosis, and epicanthus inversus syndrome (Definitive), mode of inheritance: AD
- blepharophimosis, ptosis, and epicanthus inversus syndrome (Strong), mode of inheritance: AD
- premature ovarian failure 3 (Limited), mode of inheritance: Unknown
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Blepharophimosis, epicanthus inversus, and ptosis; Premature ovarian failure 3 | AD | Obstetric | Awareness may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency (which is also reported in women with BPES) | Craniofacial; Endocrine; Genitourinary; Obstetric; Ophthalmologic | 11175783; 12149404; 15962237; 16283882; 17089161; 19429596; 21325395 |
ClinVar
This is a list of variants' phenotypes submitted to
- Blepharophimosis, ptosis, and epicanthus inversus syndrome (77 variants)
- not provided (64 variants)
- Inborn genetic diseases (20 variants)
- not specified (7 variants)
- BLEPHAROPHIMOSIS, PTOSIS, AND EPICANTHUS INVERSUS, TYPE I (6 variants)
- Premature ovarian failure 3 (5 variants)
- BLEPHAROPHIMOSIS, PTOSIS, AND EPICANTHUS INVERSUS, TYPE II (4 variants)
- FOXL2-related condition (3 variants)
- Premature ovarian failure 3;Blepharophimosis, ptosis, and epicanthus inversus syndrome (2 variants)
- Blepharophimosis, ptosis, and epicanthus inversus, type II with Duane retraction syndrome (1 variants)
- Blepharophimosis, ptosis, and epicanthus inversus syndrome;Premature ovarian failure 3 (1 variants)
- Premature ovarian insufficiency (1 variants)
- Granulosa cell tumor (1 variants)
- See cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the FOXL2 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 11 | |||||
| missense | 12 | 42 | 60 | |||
| nonsense | 16 | 18 | ||||
| start loss | 1 | |||||
| frameshift | 37 | 42 | ||||
| inframe indel | 11 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 4 | |||||
| Total | 62 | 21 | 47 | 7 | 10 |
Highest pathogenic variant AF is 0.0000264
Variants in FOXL2
This is a list of pathogenic ClinVar variants found in the FOXL2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| FOXL2 | protein_coding | protein_coding | ENST00000330315 | 1 | 2917 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.878 | 0.121 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.76 | 109 | 175 | 0.624 | 0.00000801 | 2370 |
| Missense in Polyphen | 13 | 40.537 | 0.32069 | 468 | ||
| Synonymous | -0.521 | 84 | 78.1 | 1.07 | 0.00000390 | 822 |
| Loss of Function | 2.42 | 0 | 6.85 | 0.00 | 2.93e-7 | 90 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Transcriptional regulator. Critical factor essential for ovary differentiation and maintenance, and repression of the genetic program for somatic testis determination. Prevents trans- differentiation of ovary to testis through transcriptional repression of the Sertoli cell-promoting gene SOX9 (By similarity). Has apoptotic activity in ovarian cells. Suppresses ESR1-mediated transcription of PTGS2/COX2 stimulated by tamoxifen (By similarity). Is a regulator of CYP19 expression (By similarity). Participates in SMAD3-dependent transcription of FST via the intronic SMAD-binding element (By similarity). Is a transcriptional repressor of STAR. Activates SIRT1 transcription under cellular stress conditions. Activates transcription of OSR2. {ECO:0000250, ECO:0000269|PubMed:16153597, ECO:0000269|PubMed:19010791, ECO:0000269|PubMed:19429596, ECO:0000269|PubMed:19744555}.;
- Disease
- DISEASE: Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) [MIM:110100]: A disorder characterized by eyelid dysplasia, small palpebral fissures, drooping eyelids and a skin fold curving in the mediolateral direction, inferior to the inner canthus. In type I BPSE (BPES1) eyelid abnormalities are associated with female infertility. Affected females show an ovarian deficit due to primary amenorrhea or to premature ovarian failure (POF). In type II BPSE (BPES2) affected individuals show only the eyelid defects. {ECO:0000269|PubMed:11175783, ECO:0000269|PubMed:11468277, ECO:0000269|PubMed:12400065, ECO:0000269|PubMed:12529855, ECO:0000269|PubMed:12630957, ECO:0000269|PubMed:12938087, ECO:0000269|PubMed:15257268, ECO:0000269|PubMed:16454982, ECO:0000269|PubMed:17089161, ECO:0000269|PubMed:18372316, ECO:0000269|PubMed:18484667, ECO:0000269|PubMed:18642388, ECO:0000269|Ref.2}. Note=The disease is caused by mutations affecting the gene represented in this entry. There is a mutational hotspot in the region coding for the poly-Ala domain, since 30% of all mutations in the ORF lead to poly-Ala expansions, resulting mainly in BPES type II.; DISEASE: Premature ovarian failure 3 (POF3) [MIM:608996]: An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol. {ECO:0000269|PubMed:12149404, ECO:0000269|PubMed:19429596}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- SUMOylation of transcription factors;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;SUMOylation
(Consensus)
Recessive Scores
- pRec
- 0.416
Haploinsufficiency Scores
- pHI
- 0.165
- hipred
- hipred_score
- ghis
- 0.458
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.953
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Foxl2
- Phenotype
- reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; vision/eye phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype;
Zebrafish Information Network
- Gene name
- foxl2b
- Affected structure
- oocyte
- Phenotype tag
- abnormal
- Phenotype quality
- increased occurrence
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;ovarian follicle development;oocyte growth;extraocular skeletal muscle development;apoptotic DNA fragmentation;regulation of transcription by RNA polymerase II;single fertilization;anatomical structure morphogenesis;female somatic sex determination;cell differentiation;positive regulation of luteinizing hormone secretion;positive regulation of apoptotic process;positive regulation of cysteine-type endopeptidase activity involved in apoptotic process;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;positive regulation of follicle-stimulating hormone secretion;embryonic eye morphogenesis;granulosa cell differentiation;uterus development
- Cellular component
- nucleus;nucleoplasm;intercellular bridge
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding;estrogen receptor binding;ubiquitin conjugating enzyme binding;cysteine-type endopeptidase regulator activity involved in apoptotic process