FIGLA
protein-codingfolliculogenesis specific bHLH transcription factor, the group of Basic helix-loop-helix proteins
Gene summary
This gene encodes a protein that functions in postnatal oocyte-specific gene expression. The protein is a basic helix-loop-helix transcription factor that regulates multiple oocyte-specific genes, including genes involved in folliculogenesis and those that encode the zona pellucida. Mutations in this gene cause premature ovarian failure type 6. [provided by RefSeq, Sep 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0012861
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0012861
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0012861
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0012861
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Endocrine; Obstetric
Intervention: Obstetric
Rationale: Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to FIGLA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001004311.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 3 | 1 | 5 | ||
| missense | 1 | 39 | 4 | 2 | 46 | |
| nonsense | 1 | 1 | 2 | |||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 3 | 2 | 41 | 7 | 3 | 56 |
Highest pathogenic variant AF is 0.000012145577
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001004311.2 | 5 | MANE Select | |
| Ensembl | ENSP00000333097.6 | 5 | MANE Select |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ovarian Infertility Genes
Biological Process
- multicellular organism development
- positive regulation of transcription by RNA polymerase II
- oocyte development
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
- transcription factor binding
- sequence-specific DNA binding
Cellular Component
- nucleus
- transcription factor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000332372
- Coding exons
- 5
- Length
- 13334
- Individuals with no LoFs
- 123934
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 123937
- p
- 0.0000121
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0846 | 103 | 105 | 0.977 | 0.00000489 | 1394 |
| Missense (PolyPhen) | 24 | 24.911 | 0.96343 | 315 | ||
| Synonymous | 0.136 | 42 | 43.1 | 0.974 | 0.00000201 | 451 |
| Loss of Function | 0.970 | 5 | 7.95 | 0.629 | 3.36e-7 | 111 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000019 | 0.000018 | rare |
| South Asian | 0.000034 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Germline specific transcription factor implicated in postnatal oocyte-specific gene expression. Plays a key regulatory role in the expression of multiple oocyte-specific genes, including those that initiate folliculogenesis and those that encode the zona pellucida (ZP1, ZP2 and ZP3) required for fertilization and early embryonic survival. Essential for oocytes to survive and form primordial follicles. The persistence of FIGLA in adult females suggests that it may regulate additional pathways that are essential for normal ovarian development. Binds to the E- box (5'-CANNTG-3') of the ZPs (ZP1, ZP2, ZP3) promoters. {ECO:0000269|PubMed:15044608}.;
- Disease
- DISEASE: Premature ovarian failure 6 (POF6) [MIM:612310]: 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:18499083}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.0964
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0370
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |