FAM107B (family with sequence similarity 107, member B)

2015-01-01 Hideo Nakajima , Keita Koizumi Affiliation

Identity

HGNC

FAM107B

LOCATION

10p13

LOCUSID

83641

ALIAS

C10orf45,HITS

FUSION GENES

Show Gene Fusions

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).

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

Gene ID	Transcript ID	Uniprot
ENSG00000065809	ENST00000181796	Q9H098
ENSG00000065809	ENST00000378458	Q9H098
ENSG00000065809	ENST00000378462	Q9H098
ENSG00000065809	ENST00000378465	Q9H098
ENSG00000065809	ENST00000378467	Q9H098
ENSG00000065809	ENST00000378470	Q9H098
ENSG00000065809	ENST00000442012	X6RET8
ENSG00000065809	ENST00000452706	C9JW51
ENSG00000065809	ENST00000468492	A0A1C7CYX8
ENSG00000065809	ENST00000468747	Q9H098
ENSG00000065809	ENST00000472095	C9JYP1
ENSG00000065809	ENST00000475786	C9J3Q3
ENSG00000065809	ENST00000478076	Q9H098
ENSG00000065809	ENST00000479731	Q9H098
ENSG00000065809	ENST00000481209	F8WCJ2
ENSG00000065809	ENST00000482277	C9J6Y8
ENSG00000065809	ENST00000487335	F8WDH7
ENSG00000065809	ENST00000488576	C9JP05
ENSG00000065809	ENST00000489100	C9JQ40
ENSG00000065809	ENST00000494865	C9J6N5
ENSG00000065809	ENST00000496330	Q9H098
ENSG00000065809	ENST00000622567	Q9H098

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
19913121	2009	Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.	85
16385451	2006	A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.	69
20379614	2010	Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.	62
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.	11
22825356	2012	Loss of HITS (FAM107B) expression in cancers of multiple organs: tissue microarray analysis.	2
28675500	2017	FAM107B is regulated by S100A4 and mediates the effect of S100A4 on the proliferation and migration of MGC803 gastric cancer cells.	1

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