FOSL2

FOS like 2, AP-1 transcription factor subunit, the group of Fos transcription factor family|Basic leucine zipper proteins

Basic information

Region (hg38): 2:28392448-28417317

Links

ENSG00000075426 ∙ NCBI:2355 ∙ OMIM:601575 ∙ HGNC:3798 ∙ Uniprot:P15408 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aplasia cutis-enamel dysplasia syndrome	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	Dental; Dermatologic; Musculoskeletal; Neurologic	36197437

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FOSL2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FOSL2 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			15			15
nonsense						0
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	1	15	0	0

Variants in FOSL2

This is a list of pathogenic ClinVar variants found in the FOSL2 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-28393736-C-T		not specified	Uncertain significance (Feb 15, 2023)
2-28404161-G-A		not specified	Uncertain significance (Dec 04, 2023)
2-28404209-A-G		not specified	Uncertain significance (Oct 06, 2021)
2-28404220-G-A		not specified	Uncertain significance (May 18, 2022)
2-28404227-C-G		not specified	Uncertain significance (Sep 17, 2021)
2-28404236-C-T		not specified	Uncertain significance (Sep 01, 2023)
2-28404252-G-T		not specified	Uncertain significance (Dec 11, 2023)
2-28408802-G-A		not specified	Uncertain significance (Oct 30, 2024)
2-28412045-TTAGCCCCGAGG-T		Aplasia cutis-enamel dysplasia syndrome	Pathogenic (Apr 18, 2024)
2-28412059-C-T		not specified	Uncertain significance (Oct 07, 2024)
2-28412062-C-T		Aplasia cutis-enamel dysplasia syndrome	Pathogenic (Apr 18, 2024)
2-28412067-GC-G		Aplasia cutis-enamel dysplasia syndrome	Pathogenic (Apr 18, 2024)
2-28412074-G-A		not specified	Uncertain significance (Dec 21, 2022)
2-28412075-C-T		not specified	Uncertain significance (Jul 02, 2024)
2-28412086-C-T		Aplasia cutis-enamel dysplasia syndrome	Pathogenic (Apr 18, 2024)
2-28412095-C-T		not specified	Uncertain significance (Oct 29, 2024)
2-28412096-G-A		not specified	Uncertain significance (Aug 02, 2021)
2-28412105-G-C		not specified	Uncertain significance (Aug 06, 2024)
2-28412111-C-T		not specified	Uncertain significance (Dec 12, 2023)
2-28412127-GGT-G		Aplasia cutis-enamel dysplasia syndrome	Pathogenic (Apr 18, 2024)
2-28412162-C-T		not specified	Uncertain significance (Mar 01, 2023)
2-28412173-G-A		not specified	Uncertain significance (Aug 19, 2023)
2-28412212-A-C		not specified	Uncertain significance (Jun 22, 2021)
2-28412273-CCA-C		Neurodevelopmental disorder	Likely pathogenic (Nov 15, 2021)
2-28412275-A-G		not specified	Uncertain significance (Aug 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FOSL2	protein_coding	protein_coding	ENST00000264716	4	24865

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.983	0.0171	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.60	143	208	0.688	0.0000131	2065
Missense in Polyphen		30	71.242	0.4211		673
Synonymous	0.495	86	92.0	0.934	0.00000598	708
Loss of Function	3.26	0	12.4	0.00	6.90e-7	137

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: Controls osteoclast survival and size. As a dimer with JUN, activates LIF transcription. Activates CEBPB transcription in PGE2-activated osteoblasts. {ECO:0000250}.
• Pathway: Osteoclast differentiation - Homo sapiens (human);Tacrolimus/Cyclosporine Pathway, Pharmacodynamics;Corticotropin-releasing hormone signaling pathway;bone remodeling;Validated transcriptional targets of deltaNp63 isoforms;AP-1 transcription factor network;Validated transcriptional targets of AP1 family members Fra1 and Fra2;CD4 T cell receptor signaling-JNK cascade;CD4 T cell receptor signaling (Consensus)

Recessive Scores

• pRec: 0.290

Intolerance Scores

• rvis_EVS: -0.69
• rvis_percentile_EVS: 14.97

Haploinsufficiency Scores

• pHI: 0.894
• hipred: Y
• hipred_score: 0.825
• ghis: 0.538

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fosl2
• Phenotype: growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism 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); hematopoietic system phenotype; immune system phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: fosl2
• Affected structure: bulbus arteriosus
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: keratinocyte development;regulation of transcription by RNA polymerase II;cell death;positive regulation of transcription by RNA polymerase II;positive regulation of fibroblast proliferation
• Cellular component: nucleus;nucleoplasm
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;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;chromatin binding;DNA-binding transcription factor activity;protein binding