FBXO38 Gene (Protein Coding)

F-Box Protein 38

GC05P148383
GIFtS:
39
This gene encodes a large protein that contains an F-box domain and may participate in protein ubiquitination. The encoded protein is a transcriptional co-activator of Krueppel-like factor 7 (Klf7). A heterozygous mutation in this gene was found in individuals with autosomal dominant distal hereditary motor neuronopathy type IID. There is a pseudogene for this gene on chromosom... See more...

Aliases for FBXO38 Gene

Aliases for FBXO38 Gene

  • F-Box Protein 38 2 3 5
  • F-Box Only Protein 38 3 4
  • Modulator Of KLF7 Activity Homolog 3
  • Fbx38 3
  • HMN2D 3
  • SP329 3
  • MOKA 3

External Ids for FBXO38 Gene

Previous GeneCards Identifiers for FBXO38 Gene

  • GC05P147795
  • GC05P147743
  • GC05P142910

Summaries for FBXO38 Gene

Entrez Gene Summary for FBXO38 Gene

  • This gene encodes a large protein that contains an F-box domain and may participate in protein ubiquitination. The encoded protein is a transcriptional co-activator of Krueppel-like factor 7 (Klf7). A heterozygous mutation in this gene was found in individuals with autosomal dominant distal hereditary motor neuronopathy type IID. There is a pseudogene for this gene on chromosome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

GeneCards Summary for FBXO38 Gene

FBXO38 (F-Box Protein 38) is a Protein Coding gene. Diseases associated with FBXO38 include Neuronopathy, Distal Hereditary Motor, Type Iid and Distal Hereditary Motor Neuronopathy Type 2.

UniProtKB/Swiss-Prot Summary for FBXO38 Gene

  • 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 PDCD1/PD-1, thereby regulating T-cells-mediated immunity (PubMed:30487606). Required for anti-tumor activity of T-cells by promoting the degradation of PDCD1/PD-1; the PDCD1-mediated inhibitory pathway being exploited by tumors to attenuate anti-tumor immunity and facilitate tumor survival (PubMed:30487606). May indirectly stimulate the activity of transcription factor KLF7, a regulator of neuronal differentiation, without promoting KLF7 ubiquitination (By similarity).

Additional gene information for FBXO38 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for FBXO38 Gene

Genomics for FBXO38 Gene

GeneHancer (GH) Regulatory Elements for FBXO38 Gene

Promoters and enhancers for FBXO38 Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH05J148382 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 780.2 +0.1 130 3.3 FOXK2 ZBTB40 SIX5 LCORL RBPJ POLR2A ATF1 CREB1 HCFC1 ZNF362 FBXO38 ENSG00000247199 LOC102546294 ENSG00000251330 SPINK7 JAKMIP2 RF00994-869
GH05J148394 Promoter 1 EPDnew 750.4 +10.7 10720 0.1 TCF7L2 NR2F6 ATF1 CREB1 MIXL1 RERE ELF3 SP1 PPARG ZNF384 FBXO38 HSALNG0045702 PRELID3BP9
GH05J148385 Promoter/Enhancer 0.5 Ensembl dbSUPER 750.6 +2.0 1966 0.2 ENSG00000247199 FBXO38 RF00994-869
GH05J149343 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 40.9 +962.8 962762 6.4 FOXK2 SIN3A SP1 ZBTB40 SREBF1 SIX5 LCORL RBPJ SMARCE1 POLR2A GRPEL2 ENSG00000285736 ENSG00000251330 FBXO38 HMGXB3 PCYOX1L CARMN RPL7P1 ENSG00000248696 ENSG00000253865
GH05J149356 Promoter/Enhancer 2.2 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 20.1 +974.1 974096 2.6 SP1 POLR2A CTBP1 FOS HCFC1 MYC NFYC L3MBTL2 MAX MNT PCYOX1L GRPEL2-AS1 lnc-PCYOX1L-3 FBXO38 TCOF1 MIR145 MIR143 RNU6-588P CARMN IL17B
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around FBXO38 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the FBXO38 gene promoter:
  • AML1a
  • c-Ets-1
  • En-1
  • GR
  • GR-alpha
  • GR-beta
  • POU2F1a
  • POU3F1
  • Spz1
  • YY1

Genomic Locations for FBXO38 Gene

Genomic Locations for FBXO38 Gene
chr5:148,383,935-148,442,836
(GRCh38/hg38)
Size:
58,902 bases
Orientation:
Plus strand
chr5:147,763,498-147,822,399
(GRCh37/hg19)
Size:
58,902 bases
Orientation:
Plus strand

Genomic View for FBXO38 Gene

Genes around FBXO38 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FBXO38 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FBXO38 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for FBXO38 Gene

Proteins for FBXO38 Gene

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  • Protein details for FBXO38 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6PIJ6-FBX38_HUMAN
    Recommended name:
    F-box only protein 38
    Protein Accession:
    Q6PIJ6
    Secondary Accessions:
    • Q6PK72
    • Q7Z2U0
    • Q86VN3
    • Q9BXY6
    • Q9H837
    • Q9HC40

    Protein attributes for FBXO38 Gene

    Size:
    1188 amino acids
    Molecular mass:
    133944 Da
    Quaternary structure:
    • Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXO38) composed of CUL1, SKP1, RBX1 and FBXO38 (Probable). Interacts with KLF7 (By similarity). Interacts with PDCD1/PD-1 (PubMed:30487606).
    SequenceCaution:
    • Sequence=AAG17983.1; Type=Frameshift; Positions=783; Evidence={ECO:0000305}; Sequence=AAH56147.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=AAK34945.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAB14783.1; Type=Frameshift; Positions=349; Evidence={ECO:0000305};

    Alternative splice isoforms for FBXO38 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for FBXO38 Gene

Protein Expression for FBXO38 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for FBXO38 Gene

  • Ubiquitination at Lys250
  • Modification sites at PhosphoSitePlus

Other Protein References for FBXO38 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for FBXO38 Gene

Domains & Families for FBXO38 Gene

Gene Families for FBXO38 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins

Protein Domains for FBXO38 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for FBXO38 Gene

GenScript: Design optimal peptide antigens:
  • FBXO38 protein (A0PJ52_HUMAN)
  • Modulator of KLF7 activity homolog (FBX38_HUMAN)
  • FBXO38 protein (Q6AZE0_HUMAN)
genes like me logo Genes that share domains with FBXO38: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for FBXO38 Gene

Function for FBXO38 Gene

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Molecular function for FBXO38 Gene

UniProtKB/Swiss-Prot 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 PDCD1/PD-1, thereby regulating T-cells-mediated immunity (PubMed:30487606). Required for anti-tumor activity of T-cells by promoting the degradation of PDCD1/PD-1; the PDCD1-mediated inhibitory pathway being exploited by tumors to attenuate anti-tumor immunity and facilitate tumor survival (PubMed:30487606). May indirectly stimulate the activity of transcription factor KLF7, a regulator of neuronal differentiation, without promoting KLF7 ubiquitination (By similarity).
UniProtKB/Swiss-Prot Induction:
Up-regulated by IL2 (PubMed:30487606). Down-regulated in tumor-infiltrating T-cells (PubMed:30487606).

Phenotypes From GWAS Catalog for FBXO38 Gene

Gene Ontology (GO) - Molecular Function for FBXO38 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 30487606
genes like me logo Genes that share ontologies with FBXO38: view
genes like me logo Genes that share phenotypes with FBXO38: view

Human Phenotype Ontology for FBXO38 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

miRNA for FBXO38 Gene

miRTarBase miRNAs that target FBXO38

Inhibitory RNA Products

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Clone Products

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for FBXO38 Gene

Localization for FBXO38 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FBXO38 Gene

Cytoplasm, cytosol. Nucleus. Note=Accumulates predominantly in the cytosol. Exported from the nucleus in a XPO1/CRM1-dependent manner. {ECO:0000250 UniProtKB:Q8BMI0}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for FBXO38 gene
Compartment Confidence
nucleus 5
cytosol 4
plasma membrane 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (3)
  • Plasma membrane (3)
  • Cytokinetic bridge (2)
  • Cytosol (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for FBXO38 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus ISS --
GO:0005737 cytoplasm ISS --
GO:0005829 cytosol IEA --
GO:0019005 SCF ubiquitin ligase complex TAS 30487606
genes like me logo Genes that share ontologies with FBXO38: view

Pathways & Interactions for FBXO38 Gene

PathCards logo

SuperPathways for FBXO38 Gene

No Data Available

UniProtKB/Swiss-Prot Q6PIJ6-FBX38_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

SIGNOR curated interactions for FBXO38 Gene

Activates:

Gene Ontology (GO) - Biological Process for FBXO38 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002250 adaptive immune response IEA --
GO:0002376 immune system process IEA --
GO:0002842 positive regulation of T cell mediated immune response to tumor cell IDA 30487606
GO:0010976 positive regulation of neuron projection development IEA --
GO:0016567 protein ubiquitination IEA --
genes like me logo Genes that share ontologies with FBXO38: view

No data available for Pathways by source for FBXO38 Gene

Drugs & Compounds for FBXO38 Gene

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No Compound Related Data Available

Transcripts for FBXO38 Gene

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  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for FBXO38 Gene

(3) REFSEQ mRNAs :
(16) Additional mRNA sequences :
(168) Selected AceView cDNA sequences:
(20) Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for FBXO38

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for FBXO38 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6a · 6b · 6c ^ 7a · 7b ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b ^ 13a · 13b ^ 14 ^ 15 ^ 16a · 16b ^ 17a · 17b ^
SP1: - - - - - - -
SP2: - - - - - -
SP3: - -
SP4: -
SP5: - -
SP6: -
SP7: -
SP8: - - - - - - - - - - - - - - - - -
SP9: - -
SP10:
SP11:
SP12:
SP13:
SP14:

ExUns: 18a · 18b ^ 19a · 19b · 19c ^ 20 ^ 21a · 21b ^ 22 ^ 23 ^ 24a · 24b ^ 25a · 25b ^ 26
SP1: - - - -
SP2: - - - - - -
SP3: - - -
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:
SP12:
SP13:
SP14:

Relevant External Links for FBXO38 Gene

GeneLoc Exon Structure for
FBXO38
ECgene alternative splicing isoforms for
FBXO38

Expression for FBXO38 Gene

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  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for FBXO38 Gene

mRNA expression in normal human tissues for FBXO38 Gene
mRNA expression by BioGPS for FBXO38 GenemRNA expression by GTEx for FBXO38 Gene

Protein differential expression in normal tissues from HIPED for FBXO38 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (33.8), Blymphocyte (19.2), and Placenta (6.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for FBXO38 Gene



Protein tissue co-expression partners for FBXO38 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of FBXO38 Gene:

FBXO38

SOURCE GeneReport for Unigene cluster for FBXO38 Gene:

Hs.483772

Evidence on tissue expression from TISSUES for FBXO38 Gene

  • Nervous system(4.7)
  • Liver(4.2)
  • Muscle(4.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for FBXO38 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • nervous
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cerebellum
  • head
Limb:
  • digit
  • foot
  • hand
  • lower limb
  • toe
  • upper limb
General:
  • peripheral nerve
  • peripheral nervous system
  • spinal cord
genes like me logo Genes that share expression patterns with FBXO38: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for FBXO38 Gene

Orthologs for FBXO38 Gene

This gene was present in the common ancestor of chordates.

Orthologs for FBXO38 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia FBXO38 33
  • 93 (a)
 OneToOne
cow
(Bos Taurus)
 Mammalia FBXO38 33
  • 92 (a)
 OneToOne
dog
(Canis familiaris)
 Mammalia FBXO38 33
  • 92 (a)
 OneToOne
mouse
(Mus musculus)
 Mammalia Fbxo38 33
  • 88 (a)
 OneToOne
oppossum
(Monodelphis domestica)
 Mammalia FBXO38 33
  • 80 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia FBXO38 33
  • 75 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves FBXO38 33
  • 78 (a)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia FBXO38 33
  • 74 (a)
 OneToOne
zebrafish
(Danio rerio)
 Actinopterygii FBXO38 33
  • 71 (a)
 OneToOne
Species where no ortholog for FBXO38 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rat (Rattus norvegicus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for FBXO38 Gene

ENSEMBL:
Gene Tree for FBXO38 (if available)
TreeFam:
Gene Tree for FBXO38 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for FBXO38: view image

Paralogs for FBXO38 Gene

Pseudogenes.org Pseudogenes for FBXO38 Gene

genes like me logo Genes that share paralogs with FBXO38: view

No data available for Paralogs for FBXO38 Gene

Variants for FBXO38 Gene

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Sequence variations from dbSNP and Humsavar for FBXO38 Gene

SNP ID Clin Chr 05 pos Variation AA Info Type
rs112383068 likely-benign, Distal hereditary motor neuronopathy 2D 148,438,493(+) C/A coding_sequence_variant, missense_variant, non_coding_transcript_variant
rs116266000 likely-benign, Distal hereditary motor neuronopathy 2D 148,427,635(+) C/A/T coding_sequence_variant, intron_variant, missense_variant, non_coding_transcript_variant
rs1188977922 uncertain-significance, Distal hereditary motor neuronopathy 2D 148,427,551(+) T/C/G coding_sequence_variant, intron_variant, missense_variant, non_coding_transcript_variant
rs11949133 benign, Distal hereditary motor neuronopathy 2D, - 148,433,450(+) G/A coding_sequence_variant, missense_variant, non_coding_transcript_variant
rs1306910725 uncertain-significance, Distal hereditary motor neuronopathy 2D 148,402,056(+) C/T 5_prime_UTR_variant, coding_sequence_variant, non_coding_transcript_variant, stop_gained

Structural Variations from Database of Genomic Variants (DGV) for FBXO38 Gene

Variant ID Type Subtype PubMed ID
esv3398458 CNV insertion 20981092
nsv477478 CNV novel sequence insertion 20440878
nsv830516 CNV loss 17160897

Variation tolerance for FBXO38 Gene

Residual Variation Intolerance Score: 11.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 10.39; 90.87% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for FBXO38 Gene

Human Gene Mutation Database (HGMD)
FBXO38
SNPedia medical, phenotypic, and genealogical associations of SNPs for
FBXO38

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for FBXO38 Gene

Disorders for FBXO38 Gene

MalaCards: The human disease database

(4) MalaCards diseases for FBXO38 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

FBX38_HUMAN
  • Neuronopathy, distal hereditary motor, 2D (HMN2D) [MIM:615575]: A disorder characterized by onset of slowly progressive distal lower limb weakness and atrophy between the second and fourth decades of life. Weakness usually begins in the calf muscles and later involves more proximal muscles. The severity is variable, and some patients have difficulty walking or running. Most also have upper limb involvement, particularly of the triceps and intrinsic hand muscles. Some patients may lose independent ambulation later in the disease course. Sensory impairment is typically not present, and cognition and bulbar function are normal. {ECO:0000269 PubMed:24207122}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for FBXO38

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with FBXO38: view

No data available for Genatlas for FBXO38 Gene

Publications for FBXO38 Gene

  1. A dominant mutation in FBXO38 causes distal spinal muscular atrophy with calf predominance. (PMID: 24207122) Sumner CJ … Houlden H (American journal of human genetics 2013) 2 3 4 56
  2. FBXO38 mediates PD-1 ubiquitination and regulates anti-tumour immunity of T cells. (PMID: 30487606) Meng X … Xu C (Nature 2018) 3 4 56
  3. Genome-wide searching of rare genetic variants in WTCCC data. (PMID: 20549515) Feng T … Zhu X (Human genetics 2010) 3 43 56
  4. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4 56
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 56

ExternalLinks

View latest publications for FBXO38 gene in Mastermind

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