FIGLA

folliculogenesis specific bHLH transcription factor, the group of Basic helix-loop-helix proteins

Basic information

Region (hg38): 2:70777310-70790643

Links

ENSG00000183733 ∙ NCBI:344018 ∙ OMIM:608697 ∙ HGNC:24669 ∙ Uniprot:Q6QHK4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• premature ovarian failure 6 (Moderate), mode of inheritance: AD
• premature ovarian failure 6 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Premature ovarian failure 6	AD	Obstetric	Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency	Endocrine; Obstetric	18499083

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FIGLA gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FIGLA 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			1	1	1	3
missense			16	2	3	21
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding			2	5	14	21
Total	0	0	19	8	18

Variants in FIGLA

This is a list of pathogenic ClinVar variants found in the FIGLA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-70777314-T-G		Premature ovarian failure 6	Benign (Jan 12, 2018)
2-70777360-T-C		not specified • Premature ovarian failure 6 • FIGLA-related condition	Benign (Aug 10, 2021)
2-70777360-TCA-CCT		Premature ovarian failure	Uncertain significance (Jun 14, 2016)
2-70777362-A-T		not specified • Premature ovarian failure 6 • FIGLA-related condition	Benign (Aug 10, 2021)
2-70777381-G-A		Inborn genetic diseases	Uncertain significance (Apr 12, 2024)
2-70777524-ATTCC-A			Likely benign (Apr 25, 2020)
2-70777656-C-T		Premature ovarian failure 6 • FIGLA-related condition	Benign (Jan 12, 2018)
2-70777778-C-A			Likely benign (Jul 09, 2020)
2-70777846-C-T			Likely benign (Apr 25, 2020)
2-70777956-A-G			Benign (Feb 14, 2019)
2-70777969-C-G			Benign (Jun 26, 2018)
2-70785088-G-A			Benign (Jun 26, 2018)
2-70785213-T-G			Benign (Nov 08, 2018)
2-70785267-A-C			Benign (Jun 26, 2018)
2-70785439-T-C		Premature ovarian failure 6	Likely benign (Jan 13, 2018)
2-70785458-C-T		Premature ovarian failure 6	Uncertain significance (Jan 12, 2018)
2-70785472-G-A		Premature ovarian failure 6	Benign (Aug 10, 2021)
2-70785531-C-G		Inborn genetic diseases	Uncertain significance (Jun 28, 2022)
2-70785533-A-C		Inborn genetic diseases	Uncertain significance (Aug 20, 2023)
2-70785581-G-A		Premature ovarian failure 6 • Inborn genetic diseases	Likely benign (Aug 02, 2022)
2-70785597-C-T		Inborn genetic diseases	Uncertain significance (Dec 28, 2023)
2-70785602-C-G		Premature ovarian failure 6	Benign (Aug 10, 2021)
2-70785602-CTGT-C		Premature ovarian failure 6	Pathogenic (Jun 01, 2008)
2-70785814-C-A			Benign (Jun 26, 2018)
2-70785907-C-T			Benign (Jun 26, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FIGLA	protein_coding	protein_coding	ENST00000332372	5	13334

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00223	0.774	123934	0	3	123937	0.0000121

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0846	103	105	0.977	0.00000489	1394
Missense in 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

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)	0.0000190	0.0000178
Middle Eastern	0.00	0.00
South Asian	0.0000339	0.0000330
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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.
• Pathway: Ovarian Infertility Genes (Consensus)

Recessive Scores

• pRec: 0.0964

Haploinsufficiency Scores

• pHI: 0.167
• hipred: N
• hipred_score: 0.212

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0370

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Figla
• Phenotype: reproductive system phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: multicellular organism development;positive regulation of transcription by RNA polymerase II;oocyte development
• Cellular component: nucleus;transcription factor complex
• 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;protein dimerization activity