FOSL2

protein-coding

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

Gene summary

The Fos gene family consists of 4 members: FOS, FOSB, FOSL1, and FOSL2. These genes encode leucine zipper proteins that can dimerize with proteins of the JUN family, thereby forming the transcription factor complex AP-1. As such, the FOS proteins have been implicated as regulators of cell proliferation, differentiation, and transformation. [provided by RefSeq, Jul 2014]

MANE transcript

NM_005253.4

Inheritance

ClinVar variants

P:5U:38B:4

Top phenotype

Aplasia cutis-enamel dysplasia syndrome

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr2:28,392,448-28,417,317

External References & Databases

Ensembl (ENSG00000075426)

Transcript & Mutation Effects

hg38 • Region Span ~24.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

aplasia cutis-enamel dysplasia syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0968978

Submitter: PanelApp Australia

aplasia cutis-enamel dysplasia syndromeMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0968978

Submitter: G2P

Clinical Genomic Database (CGD)

Aplasia cutis-enamel dysplasia syndromeAD

Manifestation: Dental; Dermatologic; Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 36197437

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FOSL2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 39

Aplasia cutis-enamel dysplasia syndromeTotal: 5

not providedTotal: 2

Neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005253.4. 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 clinvar			1
missense			35 clinvar	4 clinvar		39
nonsense		1 clinvar	2 clinvar			3
start loss						0
frameshift	3 clinvar	1 clinvar				4
splice donor/acceptor (+/-2bp)						0
Total	3	2	38	4	0	47

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005253.4	RefSeq	NP_005244.1	4	MANE Select
ENST00000264716.9	Ensembl	ENSP00000264716.4	4	MANE Select
ENST00000379619.5	Ensembl	ENSP00000368939.1	4	Standard
ENST00000436647.1	Ensembl	ENSP00000396497.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
fosl2	Danio rerio	Structure: bulbus arteriosus Quality: increased amount abnormal

Gene / Model

Organism

Observed Phenotype

fosl2

Danio rerio

Structure: bulbus arteriosus

Quality: increased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Osteoclast differentiation - Homo sapiens (human)
Tacrolimus/Cyclosporine Pathway, Pharmacodynamics
Corticotropin-releasing hormone signaling pathway
bone remodeling
Validated transcriptional targets of deltaNp63 isoforms

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

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

Cellular Component

nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000264716
Coding exons: 4
Length: 24865
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.60	143	208	0.688	0.0000131	2065
Missense (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

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	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.290

Intolerance Scores

RVIS EVS: -0.69
RVIS percentile EVS: 14.97

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

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