FAM107B (family with sequence similarity 107, member B)
2015-01-01 Hideo Nakajima , Keita Koizumi AffiliationIdentity
HGNC
LOCATION
10p13
LOCUSID
ALIAS
C10orf45,HITS
FUSION GENES
Abstract
FAM107 members contain an N-terminal domain of unknown function (DUF1151) that is conserved across species. Mammals have two genes, FAM107A and FAM107B, which expressions are strong in neural cells, whereas their expressions are mostly down-regulated in cancer cells. Both proteins appear to alter cytoskeleton rearrangements and are involved in cell migration and invasion. The molecular mechanisms underlying the diverse biological functions of FAM107 remain unclear, while it shows functional similarity with heat-shock proteins (HSPs) as well as reactions to cellular stress.
DNA/RNA
Description
FAM107B gene is located on the minus strand of chromosome 10, p13, which is on the short arm of the chromosome.
Transcription
FAM107B has ten transcript variants. Variant 1 and 3 through 10 encode the same isoform (a: 131 aa) with coding DNA sequence consisting of 396 bps on three exons. Variant 2 lacks an exon and initiates translation at an alternate start codon, which encodes longer isoform (b: 306 aa) with a distinct N-terminus.
Proteins
Note
FAM107 members contain an N-terminal domain of unknown function (DUF1151) that is conserved across species, including mammalian, xenopus, fish, and drosophila, and show no homologous matches to other functionally conserved domains. Mammals have two genes, FAM107A and FAM107B, which encode for proteins of 144 amino acids (aa) and 131 aa, respectively.
Description
131 amino acids, 15.6 kDa. FAM107B protein includes an N-terminal (aa 1-66) conserved domain DUF1151, a nuclear localization signal (NLS) and a C-terminal (aa 61-112) variable coiled-coil domain (Nakajima et al., 2010; Nakajima et al., 2014).
Expression
FAM107B is expressed in most tissues and found in all stages of human development. FAM107B gene has a promoter region with heat-shock transcription factor 1 (HSF1) binding sites, and FAM107B expression is increased after heat-shock or hyperthermia treatment (Nakajima et al., 2010).
Localisation
Nucleus (Nakajima et al., 2010)
Function
FAM107B is regarded as a candidate tumor suppressor gene because a loss of FAM107B expression was observed to be a common phenomenon in cancers of various organs, resulting in tumor development and proliferation. Forced expression of FAM107B inhibited cancer cell proliferation in response to growth factors in vitro and tumor xenograft growth in vivo (Nakajima et al., 2010; Nakajima et al., 2012).
Homology
FAM107B protein sequence is nearly 98% identical with mouse and rat homologues. FAM107A and FAM107B proteins have 65% sequence similarity in their DUF1151 regions (Nakajima et al., 2010; Nakajima et al., 2014).
Mutations
Note
A point mutation in the C-terminal region (chromosome 10:14603968 CïG?TïA transition) is frequently observed in basal-like breast cancer (Ding et al., 2010).
Implicated in
Entity name
Breast cancer
Note
A point mutation in the C-terminal region was frequently observed in basal-like breast cancer (Ding et al., 2010), and mutated amino acid sequence of FAM107B in breast cancer was identified as a unique tumor antigen predicted to bind to HLA-A2 (Li et al., 2011). Copy number aberrations (CNA) of FAM107B are found specifically in basal-like breast cancer (Weigman et al., 2012). In addition, genome-wide DNA methylation study was performed to identify differentially methylated sites between monozygotic twins discordant for breast cancer. FAM107B was identified as a hypermethylated region in breast cancer blood samples (Heyn et al., 2013). In analysis for FAM107B expression and the clinico-pathological parameters, FAM107B expression intensity was positively correlated with the expressions of HER2 and Ki-67, but it was inversely correlated with PR expression. Accordingly, FAM107B expression was mostly lost in HER2 negative, Ki-67 negative, PR positive, and desmoplastic reaction-negative type breast cancer, which is believed to be a non-aggressive or indolent phenotype (Nakajima et al., 2012).
Entity name
Stomach Cancer
Note
FAM107B expression is decreased in intestinal-type gastric adenocarcinomas but not in diffuse type or mucinous adenocarcinomas (Nakajima et al., 2010).
Entity name
Colon Cancer
Note
FAM107B expression is decreased during the processes in the colorectal adenoma-to-carcinoma transition (Nakajima et al., 2010).
Entity name
Uterine Cervical Cancer
Note
In uterine cervical diseases, FAM107B expression is lost in invasive squamous cell carcinoma but not in cervical intraepithelial neoplasia (CIN) (Nakajima et al., 2012).
Entity name
Autism Spectrum Disorder
Note
Six genome-wide association studies (GWASs) were integrated to figures out genetic networks of candidate genes associated with autism spectrum disorders (ASD). SNP close to FAM107B is mentioned as one of the ASD associated candidates (Poelmans et al., 2013).
Entity name
Major Depression
Note
Genome-wide DNA methylation study using post mortem frontal cortex of healthy and major depression subjects figured out FAM107B region is differentially methylated in neural cells of major depression (Guintivano et al., 2013).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 20393555 | 2010 | Genome remodelling in a basal-like breast cancer metastasis and xenograft. | Ding L et al |
| 23426267 | 2013 | A cell epigenotype specific model for the correction of brain cellular heterogeneity bias and its application to age, brain region and major depression. | Guintivano J et al |
| 23054610 | 2013 | DNA methylation profiling in breast cancer discordant identical twins identifies DOK7 as novel epigenetic biomarker. | Heyn H et al |
| 24213133 | 2011 | Cancer genome sequencing and its implications for personalized cancer vaccines. | Li L et al |
| 24748967 | 2014 | Family with sequence similarity 107: A family of stress responsive small proteins with diverse functions in cancer and the nervous system (Review). | Nakajima H et al |
| 23756379 | 2013 | AKAPs integrate genetic findings for autism spectrum disorders. | Poelmans G et al |
| 22048815 | 2012 | Basal-like Breast cancer DNA copy number losses identify genes involved in genomic instability, response to therapy, and patient survival. | Weigman VJ et al |
Other Information
Locus ID:
NCBI: 83641
HGNC: 23726
Ensembl: ENSG00000065809
Variants:
dbSNP: 83641
ClinVar: 83641
TCGA: ENSG00000065809
COSMIC: FAM107B
RNA/Proteins
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 28675500 | 2017 | FAM107B is regulated by S100A4 and mediates the effect of S100A4 on the proliferation and migration of MGC803 gastric cancer cells. | 4 |
| 28675500 | 2017 | FAM107B is regulated by S100A4 and mediates the effect of S100A4 on the proliferation and migration of MGC803 gastric cancer cells. | 4 |
| 22825356 | 2012 | Loss of HITS (FAM107B) expression in cancers of multiple organs: tissue microarray analysis. | 4 |
| 22825356 | 2012 | Loss of HITS (FAM107B) expression in cancers of multiple organs: tissue microarray analysis. | 4 |
| 20379614 | 2010 | Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. | 78 |
| 20628086 | 2010 | Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. | 15 |
| 20379614 | 2010 | Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. | 78 |
| 20628086 | 2010 | Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. | 15 |
| 19913121 | 2009 | Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. | 105 |
| 19913121 | 2009 | Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. | 105 |
| 16385451 | 2006 | A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease. | 83 |
| 16385451 | 2006 | A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease. | 83 |
Citation
Hideo Nakajima ; Keita Koizumi
FAM107B (family with sequence similarity 107, member B)
Atlas Genet Cytogenet Oncol Haematol. 2015-01-01
Online version: http://atlasgeneticsoncology.org/gene/53778/fam107b-(family-with-sequence-similarity-107-member-b)
