FBXL3

F-box and leucine rich repeat protein 3, the group of F-box and leucine rich repeat proteins

Basic information

Region (hg38): 13:76992598-77027195

Previous symbols: [ "FBXL3A" ]

Links

ENSG00000005812 ∙ NCBI:26224 ∙ OMIM:605653 ∙ HGNC:13599 ∙ Uniprot:Q9UKT7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, short stature, facial anomalies, and joint dislocations (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with short stature, facial anomalies, and speech defects	AR	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	Craniofacial; Musculoskeletal; Neurologic	11477608; 30481285

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FBXL3 gene.

• Intellectual disability, short stature, facial anomalies, and joint dislocations (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FBXL3 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				2	1	3
missense			10			10
nonsense	1					1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				2	1	3
Total	1	0	10	4	2

Variants in FBXL3

This is a list of pathogenic ClinVar variants found in the FBXL3 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-76994779-C-A			Likely benign (Jul 06, 2018)
13-76995043-G-A		Neuronal ceroid lipofuscinosis	Likely benign (Jun 24, 2022)
13-76995044-G-A		Neuronal ceroid lipofuscinosis	Likely benign (Sep 10, 2023)
13-76995050-TTTTC-T		Neuronal ceroid lipofuscinosis	Likely benign (Nov 28, 2023)
13-76995054-CTTT-C		Neuronal ceroid lipofuscinosis	Likely benign (Jun 19, 2023)
13-76995057-T-C		Neuronal ceroid lipofuscinosis	Likely benign (Nov 22, 2020)
13-76995058-A-G		Neuronal ceroid lipofuscinosis	Likely benign (Jul 10, 2023)
13-76995058-AT-A		Neuronal ceroid lipofuscinosis	Likely benign (Oct 22, 2023)
13-76995061-A-G		Neuronal ceroid lipofuscinosis 5	Likely pathogenic (Mar 12, 2024)
13-76995062-G-A		Abnormality of metabolism/homeostasis	Pathogenic (Jul 10, 2021)
13-76995064-C-A		Neuronal ceroid lipofuscinosis	Uncertain significance (Sep 01, 2021)
13-76995064-C-T		Neuronal ceroid lipofuscinosis • Neuronal ceroid lipofuscinosis 5	Uncertain significance (Sep 07, 2022)
13-76995065-G-A		Neuronal ceroid lipofuscinosis • Neuronal ceroid lipofuscinosis 5 • Inborn genetic diseases	Uncertain significance (Oct 12, 2022)
13-76995065-G-T		Neuronal ceroid lipofuscinosis	Uncertain significance (Feb 04, 2022)
13-76995066-C-T		Neuronal ceroid lipofuscinosis	Likely benign (Oct 02, 2023)
13-76995074-TC-T		Neuronal ceroid lipofuscinosis • Neuronal ceroid lipofuscinosis 5	Pathogenic/Likely pathogenic (Feb 11, 2023)
13-76995076-C-T		Neuronal ceroid lipofuscinosis 5 • Neuronal ceroid lipofuscinosis • Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 17, 2023)
13-76995077-G-A		Neuronal ceroid lipofuscinosis 5 • Neuronal ceroid lipofuscinosis	Pathogenic/Likely pathogenic (Jan 15, 2024)
13-76995077-G-C		Neuronal ceroid lipofuscinosis 5 • Neuronal ceroid lipofuscinosis • not specified	Conflicting classifications of pathogenicity (May 23, 2024)
13-76995077-G-T		Neuronal ceroid lipofuscinosis • not specified	Uncertain significance (Jun 03, 2024)
13-76995078-T-C		Neuronal ceroid lipofuscinosis	Likely benign (May 07, 2019)
13-76995078-TC-T		Neuronal ceroid lipofuscinosis 5	Likely pathogenic (May 23, 2018)
13-76995081-A-G		Neuronal ceroid lipofuscinosis	Likely benign (Sep 08, 2023)
13-76995092-C-T		Neuronal ceroid lipofuscinosis	Uncertain significance (Nov 25, 2021)
13-76995093-T-G		Neuronal ceroid lipofuscinosis	Likely benign (May 01, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FBXL3	protein_coding	protein_coding	ENST00000355619	4	34591

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.981	0.0193	125578	0	3	125581	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.83	111	233	0.477	0.0000122	2808
Missense in Polyphen		35	98.417	0.35563		1251
Synonymous	-0.180	84	81.9	1.03	0.00000395	820
Loss of Function	3.53	1	16.5	0.0607	9.19e-7	215

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000181	0.0000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Substrate-recognition component of the SCF(FBXL3) E3 ubiquitin ligase complex involved in circadian rhythm function. Plays a key role in the maintenance of both the speed and the robustness of the circadian clock oscillation (PubMed:17463251, PubMed:23452855, PubMed:27565346). The SCF(FBXL3) complex mainly acts in the nucleus and mediates ubiquitination and subsequent degradation of CRY1 and CRY2 (PubMed:17463251, PubMed:23452855, PubMed:27565346). Activity of the SCF(FBXL3) complex is counteracted by the SCF(FBXL21) complex (PubMed:23452855). {ECO:0000269|PubMed:17463251, ECO:0000269|PubMed:23452855, ECO:0000269|PubMed:27565346}.
• Pathway: Circadian rhythm - Homo sapiens (human);Circadian Clock;Post-translational protein modification;Metabolism of proteins;Chaperonin-mediated protein folding;Immune System;Association of TriC/CCT with target proteins during biosynthesis;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;Neddylation;Protein folding (Consensus)

Recessive Scores

• pRec: 0.111

Intolerance Scores

• rvis_EVS: -0.32
• rvis_percentile_EVS: 31.46

Haploinsufficiency Scores

• pHI: 0.397
• hipred: Y
• hipred_score: 0.783
• ghis: 0.693

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.871

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fbxl3
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: protein polyubiquitination;protein ubiquitination;SCF-dependent proteasomal ubiquitin-dependent protein catabolic process;protein destabilization;regulation of circadian rhythm;entrainment of circadian clock by photoperiod;post-translational protein modification;rhythmic process
• Cellular component: ubiquitin ligase complex;nucleus;cytosol;nuclear body;SCF ubiquitin ligase complex
• Molecular function: ubiquitin-protein transferase activity;protein binding;ubiquitin protein ligase activity