FBXO11

F-box protein 11, the group of F-boxes other|Ubiquitin protein ligase E3 component n-recognins

Basic information

Region (hg38): 2:47789316-47906498

Links

ENSG00000138081 ∙ NCBI:80204 ∙ OMIM:607871 ∙ HGNC:13590 ∙ Uniprot:Q86XK2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder with dysmorphic facies and behavioral abnormalities (Definitive), mode of inheritance: AD
• intellectual developmental disorder with dysmorphic facies and behavioral abnormalities (Strong), mode of inheritance: AD
• intellectual developmental disorder with dysmorphic facies and behavioral abnormalities (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities	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	Craniofacial; Musculoskeletal; Neurologic	27620904; 29796876; 30057029

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FBXO11 gene.

• not_provided (925 variants)
• Intellectual_developmental_disorder_with_dysmorphic_facies_and_behavioral_abnormalities (150 variants)
• Inborn_genetic_diseases (61 variants)
• FBXO11-related_disorder (23 variants)
• Neurodevelopmental_disorder (21 variants)
• not_specified (21 variants)
• Intellectual_disability (8 variants)
• See_cases (6 variants)
• Developmental_disorder (2 variants)
• Obesity (1 variants)
• Lynch_syndrome_5 (1 variants)
• Delayed_speech_and_language_development (1 variants)
• Marfanoid_habitus_and_intellectual_disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FBXO11 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001190274.2. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	6	191	12	210
missense	2	62	306	69	13	452
nonsense	5	7	1			13
start loss						0
frameshift	19	14	2			35
splice donor/acceptor (+/-2bp)	9	14	1			24
Total	35	98	316	260	25

Highest pathogenic variant AF is 0.000030796313

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FBXO11	protein_coding	protein_coding	ENST00000403359	23	116478

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.07e-7	125632	0	5	125637	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.38	208	477	0.436	0.0000235	6136
Missense in Polyphen		33	191.33	0.17247		2342
Synonymous	-2.44	188	150	1.25	0.00000705	1682
Loss of Function	6.35	1	48.9	0.0205	0.00000255	622

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000145	0.000145
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: Substrate recognition component of a SCF (SKP1-CUL1-F- box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as DTL/CDT2, BCL6 and PRDM1/BLIMP1. The SCF(FBXO11) complex mediates ubiquitination and degradation of BCL6, thereby playing a role in the germinal center B-cells terminal differentiation toward memory B-cells and plasma cells. The SCF(FBXO11) complex also mediates ubiquitination and degradation of DTL, an important step for the regulation of TGF- beta signaling, cell migration and the timing of the cell-cycle progression and exit. Binds to and neddylates phosphorylated p53/TP53, inhibiting its transcriptional activity. SCF(FBXO11) does not seem to direct ubiquitination of p53/TP53. {ECO:0000269|PubMed:17098746, ECO:0000269|PubMed:22113614, ECO:0000269|PubMed:23478441, ECO:0000269|PubMed:23478445, ECO:0000269|PubMed:23892434, ECO:0000269|PubMed:24613396}.
• Disease: DISEASE: Note=Defects in FBXO11 may be a cause of diffuse large B- cell lymphoma by allowing the accumulation of BCL6, an oncoprotein that has a critical role in lymphomas. {ECO:0000269|PubMed:22113614}.
• Pathway: Post-translational protein modification;Metabolism of proteins;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation;Neddylation;p53 pathway (Consensus)

Recessive Scores

• pRec: 0.126

Intolerance Scores

• loftool: 0.112
• rvis_EVS: -0.69
• rvis_percentile_EVS: 15.12

Haploinsufficiency Scores

• pHI: 0.567
• hipred: Y
• hipred_score: 0.825
• ghis: 0.680

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.781

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fbxo11
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); craniofacial phenotype; homeostasis/metabolism phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); digestive/alimentary phenotype; hearing/vestibular/ear phenotype; vision/eye phenotype; immune system phenotype

Gene ontology

• Biological process: protein polyubiquitination;cellular protein modification process;ubiquitin-dependent protein catabolic process;sensory perception of sound;protein ubiquitination;peptidyl-arginine N-methylation;post-translational protein modification
• Cellular component: ubiquitin ligase complex;nucleus;chromosome;nucleolus;cytoplasm;cytosol
• Molecular function: ubiquitin-protein transferase activity;protein binding;zinc ion binding;protein-arginine N-methyltransferase activity