ARID5B (AT rich interactive domain 5B (MRF1-like))

2013-08-01 Heng Xu , Jun J Yang Affiliation

Department of Pharmaceutical Sciences, St. Jude Childrens Research Hospital, 262 DannyThomas Place, MS 313, Memphis, TN 38105-2794, USA

Identity

HGNC

ARID5B

LOCATION

10q21.2

LOCUSID

84159

ALIAS

DESRT,MRF-2,MRF2

FUSION GENES

Show Gene Fusions

DNA/RNA

Illustration of transcriptions of human ARID5B gene.

Description

The ARID5B gene is composed of 10 exons spanning ~200 kb on chr 10q21.2. Two alternative splicing variants have been identified. Both transcripts share exons 5 to 10 but the short isoform (7032 bp) lacks a portion of the 5 coding region of the long transcript (7948 bp).

Proteins

Expression

ARID5B is expressed is in a variety of tissues and cell types, particularly in uterus, smooth muscle, placenta, and CD19+ B cells.

Localisation

ARID5B contains nuclei location signal (NLS) and may primarily function as a transcription regulator within the nucleus.

Function

ARID5B was identified as one of the intermediate early effector genes of the platelet-derived growth factor (PDGF). It forms a histone H3K9Me2 demethylase complex with PHD finger protein 2 and regulates the transcription of target genes involved in adipogenesis and liver development. ARID5B also plays a role in hematopoietic cell development and differentiation, plausibly as a transcription factor.

Implicated in

Entity name

Acute lymphoblastic leukemia (ALL)

Note

Single nucleotide polymorphisms (SNPs) in this gene (e.g., rs10821936) are strongly associated with susceptibility to childhood ALL, particularly hyperdiploid B-lineage ALL. Also, ARID5B SNPs were also related to ALL relapse, with the disease susceptibility alleles always linked to poorer treatment outcome. However, the molecular mechanisms of how ARID5B contributes to leukemogenesis and relapse remain unclear.

Entity name

Endometrial carcinoma

Note

Recurrent somatic mutations in ARID5B have also been described in endometrial carcinoma and is particularly enriched in the MSI subtype (23,1%).

Entity name

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)

Note

SNPs in this gene (e.g., rs10821944 in RA and rs4948496 in SLE) are associated with RA and SLE, both of which are autoimmune diseases but with distinct clinical characteristics.

Bibliography

Pubmed ID	Last Year	Title	Authors
21532585	2011	PKA-dependent regulation of the histone lysine demethylase complex PHF2-ARID5B.	Baba A et al
23636398	2013	Integrated genomic characterization of endometrial carcinoma.	Kandoth C et al
11483573	2001	Gene targeting of Desrt, a novel ARID class DNA-binding protein, causes growth retardation and abnormal development of reproductive organs.	Lahoud MH et al
21241896	2011	Densely interconnected transcriptional circuits control cell states in human hematopoiesis.	Novershtern N et al
22446963	2012	Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population.	Okada Y et al
19684604	2009	Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia.	Papaemmanuil E et al
15640446	2005	DNA-binding properties of ARID family proteins.	Patsialou A et al
17143286	2007	PDGF signaling specificity is mediated through multiple immediate early genes.	Schmahl J et al
19684603	2009	Germline genomic variants associated with childhood acute lymphoblastic leukemia.	Treviño LR et al
22971728	2012	Associations of variations in the MRF2/ARID5B gene with susceptibility to type 2 diabetes in the Japanese population.	Wang G et al
22291082	2012	ARID5B genetic polymorphisms contribute to racial disparities in the incidence and treatment outcome of childhood acute lymphoblastic leukemia.	Xu H et al
23512250	2013	Novel susceptibility variants at 10p12.31-12.2 for childhood acute lymphoblastic leukemia in ethnically diverse populations.	Xu H et al
23273568	2013	Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians.	Yang W et al
9808040	1998	A novel DNA-binding motif shares structural homology to DNA replication and repair nucleases and polymerases.	Yuan YC et al

Other Information

Locus ID:

NCBI: 84159
MIM: 608538
HGNC: 17362
Ensembl: ENSG00000150347

Variants:

dbSNP: 84159
ClinVar: 84159
TCGA: ENSG00000150347
COSMIC: ARID5B

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000150347	ENST00000279873	Q14865
ENSG00000150347	ENST00000309334	Q14865
ENSG00000150347	ENST00000644638	A0A2R8Y5F2

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

Pathways

Pathway	Source	External ID
Chromatin organization	REACTOME	R-HSA-4839726
Chromatin modifying enzymes	REACTOME	R-HSA-3247509
HDMs demethylate histones	REACTOME	R-HSA-3214842

Protein levels (Protein atlas)

Not detected

Low

Medium

High

PharmGKB

Entity ID	Name	Type	Evidence	Association	PK	PMIDs
PA446155	Precursor Cell Lymphoblastic Leukemia-Lymphoma	Disease	ClinicalAnnotation	associated	PK	24712521
PA449841	haloperidol	Chemical	MultilinkAnnotation	associated		27023437
PA450428	methotrexate	Chemical	ClinicalAnnotation	associated	PK	24712521

References

Pubmed ID	Year	Title	Citations
19684603	2009	Germline genomic variants associated with childhood acute lymphoblastic leukemia.	166
19684603	2009	Germline genomic variants associated with childhood acute lymphoblastic leukemia.	166
19684604	2009	Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia.	159
22291082	2012	ARID5B genetic polymorphisms contribute to racial disparities in the incidence and treatment outcome of childhood acute lymphoblastic leukemia.	51
20042726	2010	Verification of the susceptibility loci on 7p12.2, 10q21.2, and 14q11.2 in precursor B-cell acute lymphoblastic leukemia of childhood.	49
24561991	2014	Neonatal genome-wide methylation patterns in relation to birth weight in the Norwegian Mother and Child Cohort.	40
22660188	2012	Genetic polymorphisms and childhood acute lymphoblastic leukemia: GWAS of the ESCALE study (SFCE).	32
20054350	2010	ARID5B SNP rs10821936 is associated with risk of childhood acute lymphoblastic leukemia in blacks and contributes to racial differences in leukemia incidence.	30
20054350	2010	ARID5B SNP rs10821936 is associated with risk of childhood acute lymphoblastic leukemia in blacks and contributes to racial differences in leukemia incidence.	30
20460642	2010	Replication analysis confirms the association of ARID5B with childhood B-cell acute lymphoblastic leukemia.	29

Citation

Heng Xu ; Jun J Yang

ARID5B (AT rich interactive domain 5B (MRF1-like))

Atlas Genet Cytogenet Oncol Haematol. 2013-08-01

Online version: http://atlasgeneticsoncology.org/gene/51529/arid5b-(at-rich-interactive-domain-5b-(mrf1-like))