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

ENSG00000138081NCBI:80204OMIM:607871HGNC:13590Uniprot:Q86XK2AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Intellectual developmental disorder with dysmorphic facies and behavioral abnormalitiesADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Musculoskeletal; Neurologic27620904; 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
6
clinvar
191
clinvar
12
clinvar
210
missense
2
clinvar
62
clinvar
306
clinvar
69
clinvar
13
clinvar
452
nonsense
5
clinvar
7
clinvar
1
clinvar
13
start loss
0
frameshift
19
clinvar
14
clinvar
2
clinvar
35
splice donor/acceptor (+/-2bp)
9
clinvar
14
clinvar
1
clinvar
24
Total 35 98 316 260 25

Highest pathogenic variant AF is 0.000030796313

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
FBXO11protein_codingprotein_codingENST00000403359 23116478
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.001.07e-7125632051256370.0000199
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense4.382084770.4360.00002356136
Missense in Polyphen33191.330.172472342
Synonymous-2.441881501.250.000007051682
Loss of Function6.35148.90.02050.00000255622

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001450.000145
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.000.00
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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