FOXL1

forkhead box L1, the group of Forkhead boxes

Basic information

Region (hg38): 16:86576367-86583478

Previous symbols: [ "FKHL11" ]

Links

ENSG00000176678 ∙ NCBI:2300 ∙ OMIM:603252 ∙ HGNC:3817 ∙ Uniprot:Q12952 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital heart disease (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Otosclerosis 11	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic	34633540
Stapedectomy has been reported as helpful, but cochlear implant may be necessary

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FOXL1 gene.

• Inborn genetic diseases (22 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FOXL1 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						0
missense			22	1		23
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	22	1	0

Variants in FOXL1

This is a list of pathogenic ClinVar variants found in the FOXL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-86578763-G-T		not specified	Uncertain significance (Nov 07, 2022)
16-86578772-A-T		not specified	Uncertain significance (Sep 19, 2022)
16-86578782-T-C		not specified	Uncertain significance (Jul 14, 2021)
16-86578799-C-G		not specified	Uncertain significance (May 09, 2023)
16-86578833-C-T		not specified	Uncertain significance (Feb 07, 2023)
16-86578899-C-T		not specified	Uncertain significance (Sep 17, 2021)
16-86578967-C-T		not specified	Uncertain significance (Apr 25, 2022)
16-86578986-A-T		not specified	Uncertain significance (Sep 27, 2022)
16-86579102-C-T		not specified	Uncertain significance (Nov 15, 2021)
16-86579174-G-A		not specified	Uncertain significance (May 26, 2022)
16-86579181-A-C		not specified	Uncertain significance (May 14, 2015)
16-86579198-G-T		not specified	Uncertain significance (Jun 29, 2023)
16-86579216-A-G		not specified	Likely benign (Jun 18, 2021)
16-86579222-G-A		not specified	Uncertain significance (Jan 17, 2024)
16-86579231-C-T		not specified	Uncertain significance (Apr 25, 2023)
16-86579232-C-A		not specified	Uncertain significance (Nov 08, 2022)
16-86579232-C-T		not specified	Uncertain significance (Oct 10, 2023)
16-86579234-G-A		not specified	Uncertain significance (May 04, 2023)
16-86579309-C-T		not specified	Uncertain significance (Oct 03, 2022)
16-86579348-C-T		not specified	Uncertain significance (Jun 29, 2022)
16-86579364-C-G		not specified	Uncertain significance (Oct 26, 2021)
16-86579388-C-T		not specified	Likely benign (Jan 03, 2024)
16-86579393-G-A		not specified	Uncertain significance (Dec 27, 2023)
16-86579450-C-T		not specified	Uncertain significance (Aug 11, 2022)
16-86579528-G-A		not specified	Uncertain significance (Mar 07, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FOXL1	protein_coding	protein_coding	ENST00000320241	1	5330

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0359	0.841	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.281	199	188	1.06	0.00000887	2177
Missense in Polyphen		60	75.307	0.79674		895
Synonymous	-2.63	119	87.7	1.36	0.00000433	775
Loss of Function	1.23	3	6.34	0.473	2.75e-7	73

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: dbNSFP

• Function: FUNCTION: Transcription factor required for proper proliferation and differentiation in the gastrointestinal epithelium. Target gene of the hedgehog (Hh) signaling pathway via GLI2 AND GLI3 transcription factors (By similarity). {ECO:0000250}.
• Pathway: Ectoderm Differentiation (Consensus)

Haploinsufficiency Scores

• pHI: 0.731
• hipred: N
• hipred_score: 0.369
• ghis: 0.560

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.333

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Foxl1
• Phenotype: cellular phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; digestive/alimentary 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); neoplasm

Zebrafish Information Network

• Gene name: foxl1
• Affected structure: hyosymplectic cartilage
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;multicellular organism development;visceral mesoderm-endoderm interaction involved in midgut development;heart development;anatomical structure morphogenesis;regulation of Wnt signaling pathway;cell differentiation;proteoglycan biosynthetic process;Peyer's patch morphogenesis
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;DNA binding, bending;sequence-specific DNA binding