Atlas of Genetics and Cytogenetics in Oncology and Haematology

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FANCB (FA complementation group B)

Written2019-02Sylvie van Twest, Andrew Deans
St Vincent's Institute of Medical Research, 9 Princes St, Fitzroy VIC 3065, Australia;;

Abstract FANCB protein is a component of the Fanconi Anemia (FA) core complex needed for DNA repair. Within the core complex, FANCB forms a protein subcomplex with two other proteins, FAAP100, and an E3 RING ligase FANCL (BL100) to monoubiquitinate FANCD2 and FANCI (ID2), a process that is defective in 95% of all FA patients. FA is a rare, genetic cancer pre-disposition syndrome characterized by chromosomal instability and hypersensitivity to DNA crosslinking agents, such as those used in chemotherapy like mitomycin C (MMC) (Kennedy & D'Andrea, 2006). FANCB is the only known X-linked FA gene, and mutations account for 1% of FA cases (Alter & Rosenberg, 2013).

Keywords FANCB, Fanconi Anemia; Ubiquitination, VACTERL-H; Cancer pre-disposition; Chromosome X

(Note : for Links provided by Atlas : click)


HGNC Alias symbFAB
HGNC Previous nameFanconi anemia complementation group B
LocusID (NCBI) 2187
Atlas_Id 49864
Location Xp22.2  [Link to chromosome band Xp22]
Location_base_pair Starts at 14843407 and ends at 14873069 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping FANCB.png]
  Figure 1: Genomic context of FANCB on chromosome (Adapted from NCBI).
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)


  Figure 2: Schematic of FANCB gene. Black represents exons (protein coding regions), white represents introns (non-coding). Adapted from McCauley et al. 2011.
Description FANCB has 10 exons, and the translation start site is in exon 3 (Meetei et al., 2004).
Transcription The FANCB gene undergoes X-inactivation. The mutated FANCB allele is preferentially inactivated in female carriers (so the wild-type allele is expressed), while males with mutations in FANCB get FA (Meetei et al., 2004). FANCB linked FA accounts for 1% of FA cases, and only affects male patients.


Description The FANCB gene encodes FANCB protein comprised of 859 amino acids, with a molecular mass of 97726 Da. It has a putative C-terminal nuclear localization signal (Meetei et al., 2004).
  Figure 3: The 9 protein core complex associates in 3 distinct subcomplexes: AG20 (FANC A, G, FAAP20), BL100 (FANC B, L, FAAP100), and CEF (FANC C,E,F). Dashed lines indicate groupings of sub-complexes, while triple lines indicate putative direct protein interactions.
Expression Low expression in tissues. Results from Illumina bodyMap2 transcriptome (BioProject: PRJEB2445) of high throughput sequencing of individual and mixture of 16 human tissue RNA showed highest expression in white blood cells (mean RPKM 0.32), testes (mean RPKM 0.23), brain (mean RPKM 0.168), adrenal (mean RPKM 0.164), ovary (mean RPKM 0.153), and lymph nodes (mean PRKM 0.149). Another RNA sequencing project of total RNA from 20 human tissues (BioProject: PRJNA280600) found highest FANCB expression in brain cerebellum (mean RPKM 0.789), and thymus (mean RPKM 0.524). BioProject PRJEB4337 performed HPA RNA sequencing of normal tissues found highest FANCB expression in bone marrow and in lymph nodes. BioProject PRJNA270632 looked at tissue specific FANCB RNA induction during human fetal development from 6 tissues between 10-20 weeks gestational time.
Function FANCB is a component of the Fanconi Anemia 9 protein "core complex" that acts as a multiunit ubiquitin ligase to ubiquitinate FANCD2 and FANCI in response to DNA damage incurred during DNA replication in S-phase, or to detection of interstand cross links (ICL) (Ceccaldi, Sarangi, & D'Andrea, 2016). The key event in the FA pathway is the monoubiquitination of ID2 that activates downstream DNA repair proteins.
The core complex is comprised of 3 separate sub-complexes, , FANCG, FAAP20 (AG20), FANCC, FANCE, FANCF (CEF), and FANCB, FANCL, FAAP100 (BL100) (Huang et al., 2014; Medhurst et al., 2006). The BL100 sub-complex is critical to core complex assembly as it forms a bridge between AG20 and CEF (van Twest et al., 2017). The BL100 subcomplex is dimeric, and FANCB homodimer forms the interface between two copies of FANCL (a RING E3 ligase), and FAAP100 to simultaneously ubiquitinate FANCD2 and FANCI (ID2) (Swuec et al., 2016; van Twest et al., 2017). Correspondingly, FANCB and FAAP100 stabilize FANCL (Rajendra et al., 2014), and enhance its activity by 5-fold in invitro assays (Ling et al., 2007). Mutation in any one of the 19 FA genes results in defective DNA repair.
  Figure 4: Schematic of Fanconi Anemia DNA damage response pathway. In response to interstrand cross links (ICL), or DNA damage from DNA replication, FANCM recruits the 9 protein core complex to DNA damage sites to monoubiquitinate FANC D2 and I. The core complex is comprised of 3 sub-complexes AG20 (FANC A, G, FAAP20), BL100 (FANC B, L, FAAP100), and CEF (FANC C,E,F). Dashed lines indicate groupings of sub-complexes, while triple lines indicate putative direct protein interactions. Within the core complex, FANCL has a RING E3 domain with ubiquitin ligase activity, but mutation in any one of the FA genes leads to defective DNA repair. Ubiquitinated ID2 is activated, and localized to chromatin in nuclear foci to interact with downstream DNA repair proteins (FANCD1, PALB2 (FANCN)) to repair DNA via homologous recombination. Once DNA repair is completed, USP1 deubiquitinates ID2 so that DNA damage response can be reinitiated. Figure adapted from
  Figure 5: FANCB dimer coordinates FANCD2:FANCI monoubiquitination by two FANCL RING-ligases.


Somatic Somatic FANCB mutations are very rare, and may occur at normal mutagenesis rate. Small insertions, point mutations, and large deletions have been reported in the FANCB gene (McCauley et al., 2011; Meetei et al., 2004). Most FANCB mutations result in truncation of the encoded protein.

Implicated in

Entity Fanconi Anemia
Disease Mutated FANCB is implicated in Fanconi Anemia (FA), a rare genetic condition that results in progressive bone marrow failure (pancytopenia), congenital malformations in 75% of patients (short stature, urogenital defects, café au lait spots, skeletal malformations), and cancer pre-disposition (primarily acute myeloid leukaemia, and certain solid tumours) (Alter, 2014). As the only X-linked FA gene, FANCB accounts for 1% of FA cases, in all other instances FA is autosomal recessive. Mutations in FANCB (and all other core complex FA proteins) is associated with hypersensitivity to DNA-damaging agents, chromosomal instability with increased chromosome breakage and defective DNA repair. In addition to FA, some patients with FANCB mutations also exhibit hydrocephalus-VACTERL (vertebral, anal, cardiac, tracheo-esophageal fistula, renal, and limb anomalies) syndrome. A frameshift FANCB mutation that results in a truncated protein (stop codon at position 446) was associated with VACTERL-H (Holden et al., 2006; McCauley et al., 2011).
The prognosis for FA is poor as there is no cure, and the average lifespan is 20-30 years. If no congenital abnormalities are apparent at birth, patients are often diagnosed with FA when they present with aplastic anemia ages 8-10 (>700 fold risk) (Alter, 2014). Bone marrow transplants are often conducted to correct the haematological issues associated with FA, however due to faulty DNA repair FA patients retain high cancer risk particularly leukaemia, and head and neck squamous cell carcinomas (approximately 500 fold risk) (Shimamura & Alter, 2010).
Diagnostics for FA is done with a chromosomal breakage test; when treated with interstand crosslinking agents such as mitomycin C (MMC) or diepoxybutane (DEB) FA cells exhibit high number chromosomal breakages, and abnormalities as compared to normal cells.


Diagnosis, genetics, and management of inherited bone marrow failure syndromes
Alter BP
Hematology Am Soc Hematol Educ Program 2007:29-39
PMID 18024606
VACTERL-H Association and Fanconi Anemia
Alter BP, Rosenberg PS
Mol Syndromol 2013 Feb;4(1-2):87-93
PMID 23653579
The Fanconi anaemia pathway: new players and new functions
Ceccaldi R, Sarangi P, D'Andrea AD
Nat Rev Mol Cell Biol 2016 Jun;17(6):337-49
PMID 27145721
[Early determination of handicaps in the newborn and infants]
Frischknecht W
Schweiz Rundsch Med Prax 1971 Jul 27;60(30):1021-2
PMID 4254647
Fanconi anaemia complementation group B presenting as X linked VACTERL with hydrocephalus syndrome
Holden ST, Cox JJ, Kesterton I, Thomas NS, Carr C, Woods CG
J Med Genet 2006 Sep;43(9):750-4
PMID 16679491
Modularized functions of the Fanconi anemia core complex
Huang Y, Leung JW, Lowery M, Matsushita N, Wang Y, Shen X, Huong D, Takata M, Chen J, Li L
Cell Rep 2014 Jun 26;7(6):1849-57
PMID 24910428
DNA repair pathways in clinical practice: lessons from pediatric cancer susceptibility syndromes
Kennedy RD, D'Andrea AD
J Clin Oncol 2006 Aug 10;24(23):3799-808
PMID 16896009
FAAP100 is essential for activation of the Fanconi anemia-associated DNA damage response pathway
Ling C, Ishiai M, Ali AM, Medhurst AL, Neveling K, Kalb R, Yan Z, Xue Y, Oostra AB, Auerbach AD, Hoatlin ME, Schindler D, Joenje H, de Winter JP, Takata M, Meetei AR, Wang W
EMBO J 2007 Apr 18;26(8):2104-14
PMID 17396147
X-linked VACTERL with hydrocephalus syndrome: further delineation of the phenotype caused by FANCB mutations
McCauley J, Masand N, McGowan R, Rajagopalan S, Hunter A, Michaud JL, Gibson K, Robertson J, Vaz F, Abbs S, Holden ST
Am J Med Genet A 2011 Oct;155A(10):2370-80
PMID 21910217
Evidence for subcomplexes in the Fanconi anemia pathway
Medhurst AL, Laghmani el H, Steltenpool J, Ferrer M, Fontaine C, de Groot J, Rooimans MA, Scheper RJ, Meetei AR, Wang W, Joenje H, de Winter JP
Blood 2006 Sep 15;108(6):2072-80
PMID 16720839
Ketamine depresses myocardial contractility as evaluated by the preload recruitable stroke work relationship in chronically instrumented dogs with autonomic nervous system blockade
Pagel PS, Kampine JP, Schmeling WT, Warltier DC
Anesthesiology 1992 Apr;76(4):564-72
PMID 1550282
The genetic and biochemical basis of FANCD2 monoubiquitination
Rajendra E, Oestergaard VH, Langevin F, Wang M, Dornan GL, Patel KJ, Passmore LA
Mol Cell 2014 Jun 5;54(5):858-69
PMID 24905007
The FA Core Complex Contains a Homo-dimeric Catalytic Module for the Symmetric Mono-ubiquitination of FANCI-FANCD2
Swuec P, Renault L, Borg A, Shah F, Murphy VJ, van Twest S, Snijders AP, Deans AJ, Costa A
Cell Rep 2017 Jan 17;18(3):611-623
PMID 27986592
Mechanism of Ubiquitination and Deubiquitination in the Fanconi Anemia Pathway
van Twest S, Murphy VJ, Hodson C, Tan W, Swuec P, O'Rourke JJ, Heierhorst J, Crismani W, Deans AJ
Mol Cell 2017 Jan 19;65(2):247-259
PMID 27986371
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Fanconi Anemia Research Fund, Inc; 2014.


This paper should be referenced as such :
Sylvie van Twest, Andrew Deans
FANCB (FA complementation group B)
Atlas Genet Cytogenet Oncol Haematol. 2020;24(1):18-21.
Free journal version : [ pdf ]   [ DOI ]

Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 2 ]
  Fanconi anemia Familial Myeloproliferative Disorders

External links


HGNC (Hugo)FANCB   3583
LRG (Locus Reference Genomic)LRG_496
Atlas Explorer : (Salamanque)FANCB
Entrez_Gene (NCBI)FANCB    FA complementation group B
AliasesFA2; FAAP90; FAAP95; FAB; 
GeneCards (Weizmann)FANCB
Ensembl hg19 (Hinxton)ENSG00000181544 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000181544 [Gene_View]  ENSG00000181544 [Sequence]  chrX:14843407-14873069 [Contig_View]  FANCB [Vega]
ICGC DataPortalENSG00000181544
Genatlas (Paris)FANCB
Genetics Home Reference (NIH)FANCB
Genomic and cartography
GoldenPath hg38 (UCSC)FANCB  -     chrX:14843407-14873069 -  Xp22.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)FANCB  -     Xp22.2   [Description]    (hg19-Feb_2009)
GoldenPathFANCB - Xp22.2 [CytoView hg19]  FANCB - Xp22.2 [CytoView hg38]
Genome Data Viewer NCBIFANCB [Mapview hg19]  
OMIM300514   300515   314390   
Gene and transcription
Genbank (Entrez)AK091383 BC043596 BC055411 BC136558 BC136560
RefSeq transcript (Entrez)NM_001018113 NM_001324162 NM_152633
Consensus coding sequences : CCDS (NCBI)FANCB
Gene Expression Viewer (FireBrowse)FANCB [ Firebrowse - Broad ]
GenevisibleExpression of FANCB in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)2187
GTEX Portal (Tissue expression)FANCB
Human Protein AtlasENSG00000181544-FANCB [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8NB91   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ8NB91  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8NB91
Domains : Interpro (EBI)FANCB   
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)FANCB
AlphaFold pdb e-kbQ8NB91   
Human Protein Atlas [tissue]ENSG00000181544-FANCB [tissue]
Protein Interaction databases
IntAct (EBI)Q8NB91
Ontologies - Pathways
Ontology : AmiGOchromatin  protein binding  nucleoplasm  protein monoubiquitination  Fanconi anaemia nuclear complex  Fanconi anaemia nuclear complex  positive regulation of double-strand break repair via homologous recombination  replication-born double-strand break repair via sister chromatid exchange  negative regulation of double-strand break repair via homologous recombination  
Ontology : EGO-EBIchromatin  protein binding  nucleoplasm  protein monoubiquitination  Fanconi anaemia nuclear complex  Fanconi anaemia nuclear complex  positive regulation of double-strand break repair via homologous recombination  replication-born double-strand break repair via sister chromatid exchange  negative regulation of double-strand break repair via homologous recombination  
REACTOMEQ8NB91 [protein]
REACTOME PathwaysR-HSA-6783310 [pathway]   
Atlas of Cancer Signalling NetworkFANCB
Wikipedia pathwaysFANCB
Orthology - Evolution
GeneTree (enSembl)ENSG00000181544
Phylogenetic Trees/Animal Genes : TreeFamFANCB
Homologs : HomoloGeneFANCB
Homology/Alignments : Family Browser (UCSC)FANCB
Gene fusions - Rearrangements
Fusion : FusionHubCDKAL1--FANCB    MOSPD2--FANCB    SERPINA1--FANCB   
Fusion : QuiverFANCB
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerFANCB [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)FANCB
Exome Variant ServerFANCB
GNOMAD BrowserENSG00000181544
Varsome BrowserFANCB
ACMGFANCB variants
Genomic Variants (DGV)FANCB [DGVbeta]
DECIPHERFANCB [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisFANCB 
ICGC Data PortalFANCB 
TCGA Data PortalFANCB 
Broad Tumor PortalFANCB
OASIS PortalFANCB [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICFANCB  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DFANCB
Mutations and Diseases : HGMDFANCB
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)FANCB
DoCM (Curated mutations)FANCB
CIViC (Clinical Interpretations of Variants in Cancer)FANCB
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM300514    300515    314390   
Orphanet634    3007   
Genetic Testing Registry FANCB
NextProtQ8NB91 [Medical]
Target ValidationFANCB
Huge Navigator FANCB [HugePedia]
ClinGenFANCB (curated)
Clinical trials, drugs, therapy
Protein Interactions : CTDFANCB
Pharm GKB GenePA27996
Clinical trialFANCB
DataMed IndexFANCB
PubMed45 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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