ARID5B

Summary

ARID5B (AT-rich interaction domain 5B, HGNC:17362) is a protein-coding gene on chromosome 10q21.2, encoding AT-rich interactive domain-containing protein 5B (Q14865). Transcription coactivator that binds to the 5’-AATA[CT]-3’ core sequence and plays a key role in adipogenesis and liver development.

This gene encodes a member of the AT-rich interaction domain (ARID) family of DNA binding proteins. The encoded protein forms a histone H3K9Me2 demethylase complex with PHD finger protein 2 and regulates the transcription of target genes involved in adipogenesis and liver development. This gene also plays a role in cell growth and differentiation of B-lymphocyte progenitors, and single nucleotide polymorphisms in this gene are associated with acute lymphoblastic leukemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 84159 — RefSeq curated summary.

At a glance

• Gene–disease (curated): isolated cleft palate (No Known Disease Relationship, GenCC)
• GWAS associations: 85
• Clinical variants (ClinVar): 151 total
• MANE Select transcript: NM_032199

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17362
Approved symbol	ARID5B
Name	AT-rich interaction domain 5B
Location	10q21.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21150, MRF2
Ensembl gene	ENSG00000150347
Ensembl biotype	protein_coding
OMIM	608538
Entrez	84159

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000279873, ENST00000309334, ENST00000644638, ENST00000647323, ENST00000681100

RefSeq mRNA: 2 — MANE Select: NM_032199 NM_001244638, NM_032199

CCDS: CCDS31208, CCDS58082

Canonical transcript exons

ENST00000279873 — 10 exons

Exon	Start	End
ENSE00000994546	62059243	62059295
ENSE00000994549	62069700	62069797
ENSE00000994550	62085702	62085900
ENSE00001179143	61940183	61940408
ENSE00001179149	61902159	61902413
ENSE00001274844	62050888	62051000
ENSE00001274882	62057117	62057318
ENSE00001274896	62000091	62000321
ENSE00001461591	62090862	62096944
ENSE00001879709	61901699	61901730

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 98.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 77.2989 / max 3669.2128, expressed in 1771 samples.

FANTOM5 promoters (26 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105088	23.7544	1533
105056	22.8415	1713
105085	10.9222	1283
105100	10.3612	1452
105086	2.5861	865
105089	2.2795	988
105087	0.9140	498
105084	0.5825	317
105092	0.4732	165
105099	0.3290	157

Top tissues by expression

302 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	98.83	gold quality
saphenous vein	UBERON:0007318	98.58	gold quality
pericardium	UBERON:0002407	98.47	gold quality
vena cava	UBERON:0004087	98.39	gold quality
urethra	UBERON:0000057	98.12	gold quality
parietal pleura	UBERON:0002400	98.00	gold quality
decidua	UBERON:0002450	97.73	gold quality
mucosa of urinary bladder	UBERON:0001259	97.46	gold quality
mammary duct	UBERON:0001765	97.38	gold quality
pleura	UBERON:0000977	97.32	gold quality
superficial temporal artery	UBERON:0001614	97.05	gold quality
epithelium of mammary gland	UBERON:0003244	96.93	gold quality
diaphragm	UBERON:0001103	96.74	gold quality
cervix epithelium	UBERON:0004801	96.39	gold quality
epithelium of nasopharynx	UBERON:0001951	96.22	gold quality
nipple	UBERON:0002030	96.21	gold quality
nasopharynx	UBERON:0001728	96.20	gold quality
cardia of stomach	UBERON:0001162	96.16	gold quality
visceral pleura	UBERON:0002401	96.12	gold quality
penis	UBERON:0000989	96.07	gold quality
mammalian vulva	UBERON:0000997	95.63	gold quality
cauda epididymis	UBERON:0004360	95.50	gold quality
gluteal muscle	UBERON:0002000	95.43	gold quality
germinal epithelium of ovary	UBERON:0001304	95.35	gold quality
thoracic mammary gland	UBERON:0005200	95.26	gold quality
mammary gland	UBERON:0001911	95.24	gold quality
cervix squamous epithelium	UBERON:0006922	95.19	gold quality
esophagus squamous epithelium	UBERON:0006920	95.08	gold quality
superior surface of tongue	UBERON:0007371	95.05	gold quality
synovial joint	UBERON:0002217	95.01	gold quality

Single-cell (SCXA)

Detected in 23 experiment(s), a significant marker in 19.

Experiment	Marker?	Max mean expression
E-MTAB-7051	yes	2943.13
E-MTAB-8142	yes	91.24
E-MTAB-10287	yes	49.25
E-HCAD-8	yes	46.09
E-HCAD-10	yes	44.09
E-CURD-112	yes	38.60
E-CURD-122	yes	37.23
E-HCAD-4	yes	37.07
E-GEOD-135922	yes	31.75
E-CURD-46	yes	28.83
E-MTAB-6701	yes	18.54
E-HCAD-1	yes	16.01
E-GEOD-125970	yes	13.24
E-MTAB-9388	yes	12.51
E-MTAB-6678	yes	9.72

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

9 targets.

Target	Regulation
CEBPA	Activation
GATA3	Activation
LEP	Repression
MYB	Activation
MYC	Activation
PHF2
PPARG	Activation
RUNX1	Activation
TAL1	Activation

Upstream regulators (CollecTRI, top): ESR1

miRNA regulators (miRDB)

178 targeting ARID5B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753

Literature-anchored findings (GeneRIF, showing 40)

• NMR spectroscopy studies of Mrf-2 in complex with DNA suggest that two flexible interhelical loops, the flexible C-terminal tail, and one alpha-helix are involved in DNA recognition, indicating the importance of protein dynamics in DNA binding. (PMID:11478881)
• The results implicate possible disease relevance of the polymorphisms in the Mrf-2 gene with susceptibility to CAD (PMID:18612189)
• The ARID5B single nucleotide polymorphisms distinguished B-hyperdiploid ALL from other subtypes in an independent validation cohort and were associated with methotrexate accumulation and gene expression patterns in leukemic lymphoblasts. (PMID:19684603)
• ARID5B SNP rs10821936 is associated with risk of childhood acute lymphoblastic leukemia in blacks and contributes to racial differences in leukemia incidence. (PMID:20054350)
• confirmed the association of 5 SNPs [rs7073837 (P=4.2 x 10(-4)), rs10994982 (P=3.8 x 10(-4)), rs10740055 (P=1.6 x 10(-5)), rs10821936 (P=1.7 x 10(-7)) and rs7089424 (P=3.6 x 10(-7))] in the ARID5B gene with childhood acute lymphoblastic leukemia (PMID:20460642)
• Single nucleotide polymorphism in ARID5B gene is associated with childhood acute lymphoblastic leukemia. (PMID:21889209)
• ARID5B polymorphisms are important determinants of childhood ALL susceptibility and treatment outcome, and they contribute to racial disparities in this disease. (PMID:22291082)
• Single Nucleotide Polymorphism in ARID5B gene is associated with childhood acute lymphoblastic leukemia. (PMID:22660188)
• ARID5B polymorphisms are associated with childhood acute myeloblastic leukemia. (PMID:22922568)
• variants of rs2893880, rs10740055, rs7087507 and rs10761600 on the ARID5B gene were associated with susceptibility to type 2 diabetes (PMID:22971728)
• Although germ-line SNPs in ARID5B, CEBPE, IKZF1 and CDKN2A are associated with the incidence of ALL in children, authors found no significant association between adult ALL cases and controls. (PMID:23016962)
• Association of the autoimmune thyroid disease phenotype (both Graves disease and Hashimoto’s thyroiditis) with SNP rs6479778 located within the ARID5B gene. (PMID:23118423)
• ARID5B single nucleotide polymorphism rs10821936 is associated with an increased risk of childhood acute lymphoblastic leukemia in Chinese population. (PMID:23608171)
• Data indicate associations between childhood acute lymphoblastic leukemia (ALL) and ARID5B and IKZF1 SNPs. (PMID:23692655)
• study found that previously identified childhood acute lymphoblastic leukemia susceptibility loci in ARID5B and CEBPE show consistent risk effects across both Hispanic and non-Hispanic White populations, providing compelling supportive evidence for susceptibility at these loci (PMID:23836053)
• ARID5B genetic polymorphism was associated with the increased risk of ALL. (PMID:23975371)
• The intron 3 of ARID5B gene was found to be strongly associated with B-ALL risk in the Spanish population examined. (PMID:24013273)
• We found that rs7073837 in ARID5B correlated with a risk for childhood B lineage ALL. (PMID:24200646)
• Germline variants in IKZF1, ARID5B, and CEBPE as risk factors for adult-onset acute lymphoblastic leukemia: an analysis from the GMALL study group. (PMID:24497567)
• In an epigenome-wide methylation Norwegian Mother-Baby cohort study 2 ARID5B CpGs were identified in cord blood DNA as having an inverse association with birth weight (higher methylation fraction associated with lower birth weight). (PMID:24561991)
• ARID5B polymorphism confers an increased risk to acquire specific MLL rearrangements in early childhood leukemia. (PMID:24564228)
• Our findings confirm the association of novel genetic variations in folate-related and ARID5B genes with the serum MTX levels and acute toxicity. (PMID:24712521)
• Data indicate no significant associations of transcription factors rs4132601 (IKZF1), rs7089424 (ARID5B) and rs2239633 (CEBPE) with risk of pediatric non-Hodgkin lymphoma (NHL). (PMID:25005032)
• Single nucleotide polymorphisms rs10994982 and rs7089424 in ARID5B gene are associated with increased risk of childhood acute lymphoblastic leukemia. (PMID:25124600)
• These results evidence that interaction of genetic variants in ARID5B and IKZF1 and environmental exposures may further alter risk of childhood acute lymphoblastic leukemia. (PMID:25310577)
• variants within IKZF1, ARID5B, and CEBPE were associated with increased acute lymphoblastic leukemia (ALL) risk, and the effects for ARID5B and CEBPE were most prominent in high-hyperdiploid ALL subtype in the California Hispanic population (PMID:25761407)
• Interactions between rs10740055 in ARID5B or rs4132601 in IKZF1 and each of the suspected non-genetic factors were tested. (PMID:25806972)
• This study showed that rs4948496 in ARID5B is associated with several subphenotypes of systemic lupus erythematosus and this gene may cause the complicacy of clinical features. (PMID:25808444)
• Non-coding variant rs10821936 in ARID5B was strongly associated with childhood B-cell acute lymphoblastic leukemia. No coding variants were associated with B-ALL susceptibility. (PMID:26104880)
• variants within IKZF1, ARID5B, and CEBPE were associated with pediatric ALL risks. (PMID:27184773)
• Results identified a novel hotspot in the terminal exon of ARID5B.The ARID5B indel mutations were seen in both mismatch repair (MMR)-deficient and MMR-normal tumors, suggesting biologic selection in endometrial neoplasm. (PMID:27346418)
• Genotypic and allelic frequencies differed significantly between cases and controls at IKZF1-rs4132601 (p=0.039, p=0.015) and ARID5B-rs10821936 (p=0.028, p=0.026). (PMID:27644650)
• ARID5B variants are associated with acute lymphoblastic leukemia in Yemeni children with several gender biases of ARID5B single nucleotide polymorphisms reported. (PMID:28381164)
• The present results identified MRF2/ARID5B as a potential susceptibility gene for new-onset T2DM in a Northern Chinese population, while the rs7087507 SNP was associated with HDL-C levels. Further larger studies are required to validate these findings. (PMID:28469100)
• Associations between ALL and rs10821936 and rs7089424 ARID5B SNPs were found (PMID:28476190)
• Our results confirmed the role of ARID5B in childhood ALL susceptibility among Hispanics; however, our assessment did not reveal any strong novel inherited genetic risks for acute lymphoblastic leukemia among this ethnic group. (PMID:28817678)
• Differential methylation and expression of ARID5B to be associated with human atherosclerosis. (PMID:28855511)
• We systematically screened 6 potentially functional SNPs in ARID5B and IKZF1 genes. (PMID:29292192)
• ARID5B reinforces the oncogenic transcriptional program by positively regulating the TAL1-induced regulatory circuit and MYC in T-ALL, thereby contributing to T-cell leukemogenesis. (PMID:29326336)
• Our study revealed that AR transcription is positively regulated by ARID5B through H3K4me3 recruitment in the AR promoter. (PMID:30027545)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Arid5b	ENSMUSG00000019947
rattus_norvegicus	Arid5b	ENSRNOG00000000635
drosophila_melanogaster	htk	FBGN0085451
caenorhabditis_elegans		WBGENE00044689

Paralogs (3): ARID4A (ENSG00000032219), ARID4B (ENSG00000054267), ARID5A (ENSG00000196843)

Protein

Protein identifiers

AT-rich interactive domain-containing protein 5B — Q14865 (reviewed: Q14865)

Alternative names: MRF1-like protein, Modulator recognition factor 2

All UniProt accessions (3): Q14865, A0A2R8Y5F2, A0A7P0TAD2

UniProt curated annotations — full annotation on UniProt →

Function. Transcription coactivator that binds to the 5’-AATA[CT]-3’ core sequence and plays a key role in adipogenesis and liver development. Acts by forming a complex with phosphorylated PHF2, which mediates demethylation at Lys-336, leading to target the PHF2-ARID5B complex to target promoters, where PHF2 mediates demethylation of dimethylated ‘Lys-9’ of histone H3 (H3K9me2), followed by transcription activation of target genes. The PHF2-ARID5B complex acts as a coactivator of HNF4A in liver. Required for adipogenesis: regulates triglyceride metabolism in adipocytes by regulating expression of adipogenic genes. Overexpression leads to induction of smooth muscle marker genes, suggesting that it may also act as a regulator of smooth muscle cell differentiation and proliferation. Represses the cytomegalovirus enhancer.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed, including in liver (at protein level).

Post-translational modifications. Methylation at Lys-336 prevents DNA-binding. Demethylation by PHF2 promotes recruitment of the PHF2-ARID5B complex to promoters.

Disease relevance. Defects in ARID5B may be a cause of susceptibility to coronary atherosclerosis in the Japanese population. Leukemia, acute lymphoblastic (ALL) [MIM:613065] A subtype of acute leukemia, a cancer of the white blood cells. ALL is a malignant disease of bone marrow and the most common malignancy diagnosed in children. The malignant cells are lymphoid precursor cells (lymphoblasts) that are arrested in an early stage of development. The lymphoblasts replace the normal marrow elements, resulting in a marked decrease in the production of normal blood cells. Consequently, anemia, thrombocytopenia, and neutropenia occur to varying degrees. The lymphoblasts also proliferate in organs other than the marrow, particularly the liver, spleen, and lymphnodes. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Domain organisation. The ARID domain mediates the interaction with DNA.

Similarity. Belongs to the ARID5B family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q14865-1	1	yes
Q14865-2	2
Q14865-3	3

RefSeq proteins (2): NP_001231567, NP_115575* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001606	ARID_dom	Domain
IPR030408	ARID5B_ARID/BRIGHT_DNA-bd	Domain
IPR036431	ARID_dom_sf	Homologous_superfamily
IPR051232	ARID/SWI1_ChromRemod	Family

Pfam: PF01388

UniProt features (53 total): cross-link 17, helix 7, region of interest 6, compositionally biased region 4, modified residue 4, splice variant 4, sequence conflict 3, turn 3, strand 2, chain 1, domain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1IG6	SOLUTION NMR
2OEH	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14865-F1	51.00	0.14

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (21): 264, 336, 1032, 1133, 130, 445, 494, 496, 767, 774, 803, 810, 893, 916, 920, 935, 988, 1000, 1013, 1055 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
336	abolishes methylation and fsk-dependent dna-binding of the phf2-arid5b complex to promoters.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

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

MSigDB gene sets: 432 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_BODY_MORPHOGENESIS, BROWNE_HCMV_INFECTION_6HR_DN, BENPORATH_ES_WITH_H3K27ME3, GGTGTGT_MIR329, ZHAN_MULTIPLE_MYELOMA_PR_DN, KANG_FLUOROURACIL_RESISTANCE_UP, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_RESPONSE_TO_PEPTIDE, FISCHER_G1_S_CELL_CYCLE, GOZGIT_ESR1_TARGETS_DN, AAGCCAT_MIR135A_MIR135B, GOBP_GROWTH

GO Biological Process (23): negative regulation of transcription by RNA polymerase II (GO:0000122), kidney development (GO:0001822), liver development (GO:0001889), regulation of transcription by RNA polymerase II (GO:0006357), male gonad development (GO:0008584), female gonad development (GO:0008585), post-embryonic development (GO:0009791), fibroblast migration (GO:0010761), adrenal gland development (GO:0030325), multicellular organism growth (GO:0035264), fat cell differentiation (GO:0045444), negative regulation of DNA-templated transcription (GO:0045892), platelet-derived growth factor receptor signaling pathway (GO:0048008), cell development (GO:0048468), muscle organ morphogenesis (GO:0048644), skeletal system morphogenesis (GO:0048705), obsolete positive regulation of DNA-binding transcription factor activity (GO:0051091), roof of mouth development (GO:0060021), face morphogenesis (GO:0060325), adipose tissue development (GO:0060612), fat pad development (GO:0060613), cellular response to leukemia inhibitory factor (GO:1990830), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (4): transcription cis-regulatory region binding (GO:0000976), DNA binding (GO:0003677), transcription coactivator activity (GO:0003713), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Chromatin organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
animal organ development	2
gland development	2
regulation of DNA-templated transcription	2
gonad development	2
multicellular organismal process	2
cell differentiation	2
anatomical structure development	2
animal organ morphogenesis	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
renal system development	1
hepaticobiliary system development	1
development of primary male sexual characteristics	1
development of primary female sexual characteristics	1
multicellular organism development	1
ameboidal-type cell migration	1
endocrine system development	1
developmental growth	1
DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular developmental process	1
muscle organ development	1
skeletal system development	1
anatomical structure morphogenesis	1
head morphogenesis	1
face development	1
connective tissue development	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
nucleic acid binding	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1624 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARID5B	CEBPE	Q15744	917
ARID5B	PHF2	O75151	774
ARID5B	PIP4K2A	P48426	694
ARID5B	ARID1A	O14497	690
ARID5B	SMARCB1	Q12824	683
ARID5B	ARID2	Q68CP9	667
ARID5B	KDM5C	P41229	647
ARID5B	IRX5	P78411	644
ARID5B	IKZF1	Q13422	611
ARID5B	IRX1	P78414	610
ARID5B	IRX6	P78412	607
ARID5B	IRX3	P78415	606
ARID5B	PBRM1	Q86U86	565
ARID5B	RBL2	Q08999	550
ARID5B	SMARCA4	P51532	535

IntAct

64 interactions, top by confidence:

A	B	Type	Score
HDAC1	ARID5B	psi-mi:“MI:0403”(colocalization)	0.870
HDAC1	ARID5B	psi-mi:“MI:0915”(physical association)	0.870
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
HDAC1	TNRC18	psi-mi:“MI:0914”(association)	0.790
H2AZ1	ZNHIT1	psi-mi:“MI:0914”(association)	0.770
HDAC1	ZNF609	psi-mi:“MI:0914”(association)	0.730
SRP9	SRP72	psi-mi:“MI:0914”(association)	0.730
H2BC1	PPM1G	psi-mi:“MI:0914”(association)	0.640
C16orf87	CDC27	psi-mi:“MI:0914”(association)	0.640
Smc3	RAD21	psi-mi:“MI:0914”(association)	0.600
H2BC26	PPM1G	psi-mi:“MI:0914”(association)	0.530
NR1H4	PHF2	psi-mi:“MI:0914”(association)	0.520
ARID5B	PHF2	psi-mi:“MI:0407”(direct interaction)	0.440
ARID5B	EPB41L2	psi-mi:“MI:0915”(physical association)	0.400
ARID5B	TCERG1	psi-mi:“MI:0915”(physical association)	0.400
Kat8	HCFC1	psi-mi:“MI:0914”(association)	0.350
CHORDC1	SSR3	psi-mi:“MI:0914”(association)	0.350
RACGAP1	STX18	psi-mi:“MI:0914”(association)	0.350
Kctd5		psi-mi:“MI:0914”(association)	0.350
PARD6A		psi-mi:“MI:0914”(association)	0.350

BioGRID (90): ARID5B (Affinity Capture-MS), ARID5B (Affinity Capture-MS), ARID5B (Affinity Capture-MS), ARID5B (Affinity Capture-MS), ARID5B (Affinity Capture-MS), ARID5B (Affinity Capture-MS), ARID5B (Affinity Capture-MS), ARID5B (Affinity Capture-MS), ARID5B (Affinity Capture-MS), ARID5B (Affinity Capture-MS), ARID5B (Affinity Capture-MS), ARID5B (Affinity Capture-MS), ARID5B (Affinity Capture-MS), ARID5B (Affinity Capture-MS), ARID5B (Affinity Capture-MS)

ESM2 similar proteins: A5GFT6, A5X7A0, A7XYH5, A7XYI6, A7XYJ6, A8MW92, B3DJM5, D3ZKB9, E1BLP6, E2R9X2, E7F888, O15014, O35914, O73590, P14404, Q01954, Q0P5V2, Q14865, Q2HNT1, Q2HNT2, Q4V9H5, Q566I1, Q5DTH5, Q5ZJ69, Q61412, Q63HK5, Q68FE9, Q6ZPY5, Q6ZSZ6, Q76L83, Q7YR76, Q86UP3, Q8BHZ4, Q8BM75, Q8BZ32, Q8BZ47, Q8C0Q2, Q8CCH7, Q8CCJ9, Q8CGV9

Diamond homologs: A2BEA6, A2BH40, A2CG63, A6NKF2, A6PWV5, E1BLP6, E2R9X2, E7F888, E9Q4N7, F8VPQ2, O02326, O14497, O74365, P29374, P29375, P41229, P41230, Q03214, Q03989, Q14865, Q24573, Q30DN6, Q38JA7, Q3SWY1, Q3U108, Q3UXZ9, Q4H3P5, Q4LE39, Q5F3R2, Q5XGD9, Q5XUN4, Q5ZJ69, Q62431, Q6GQD7, Q6IQX0, Q8BM75, Q8IN94, Q8IVW6, Q8MQH7, Q8NFD5

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
ARID5B	“up-regulates quantity by expression”	MYC	“transcriptional regulation”
ARID5B	“up-regulates quantity by expression”	TAL1	“transcriptional regulation”
ARID5B	“up-regulates quantity by expression”	GATA3	“transcriptional regulation”
ARID5B	“up-regulates quantity by expression”	RUNX1	“transcriptional regulation”
ARID5B	“up-regulates quantity by expression”	MYB	“transcriptional regulation”
PHF2	“up-regulates activity”	ARID5B	binding
ARID5B	“up-regulates activity”	PHF2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 75 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
NuRD complex assembly	6	16.0×	8e-04
Interaction of NuRD complexes with transcription factors	5	12.0×	3e-03
Transcriptional regulation of granulopoiesis	5	11.8×	3e-03
Formation of the beta-catenin:TCF transactivating complex	5	11.3×	3e-03
HDACs deacetylate histones	5	11.3×	3e-03
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	5	11.3×	3e-03
Negative Regulation of CDH1 Gene Transcription	5	11.3×	3e-03
NoRC negatively regulates rRNA expression	5	9.9×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
chromatin remodeling	7	7.7×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

151 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	119
Likely benign	14
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

2258 predictions. Top by Δscore:

Variant	Effect	Δscore
10:61940168:A:AG	acceptor_gain	1.0000
10:61940169:A:G	acceptor_gain	1.0000
10:61940172:A:AG	acceptor_gain	1.0000
10:61940173:C:G	acceptor_gain	1.0000
10:61940178:T:A	acceptor_gain	1.0000
10:61940178:TGTAG:T	acceptor_loss	1.0000
10:61940179:GTAGG:G	acceptor_loss	1.0000
10:61940180:TAGGA:T	acceptor_loss	1.0000
10:61940181:AG:A	acceptor_gain	1.0000
10:61940181:AGGAT:A	acceptor_gain	1.0000
10:61940182:GG:G	acceptor_gain	1.0000
10:61940182:GGAT:G	acceptor_gain	1.0000
10:61940182:GGATG:G	acceptor_gain	1.0000
10:61940406:TGGG:T	donor_loss	1.0000
10:61940407:GGGT:G	donor_loss	1.0000
10:61940409:GTA:G	donor_loss	1.0000
10:61940410:T:A	donor_loss	1.0000
10:62000085:GTCTA:G	acceptor_loss	1.0000
10:62000087:CTAGG:C	acceptor_loss	1.0000
10:62000088:TAG:T	acceptor_loss	1.0000
10:62000089:A:AG	acceptor_gain	1.0000
10:62000089:AG:A	acceptor_gain	1.0000
10:62000089:AGG:A	acceptor_gain	1.0000
10:62000090:G:GA	acceptor_gain	1.0000
10:62000090:GG:G	acceptor_gain	1.0000
10:62000090:GGG:G	acceptor_gain	1.0000
10:62000090:GGGGA:G	acceptor_gain	1.0000
10:62000301:A:T	donor_gain	1.0000
10:62000317:GTTTG:G	donor_gain	1.0000
10:62000319:TTGG:T	donor_loss	1.0000

AlphaMissense

7844 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:61902313:T:C	L59P	1.000
10:61902318:T:A	W61R	1.000
10:61902318:T:C	W61R	1.000
10:62057240:T:C	F324L	1.000
10:62057241:T:C	F324S	1.000
10:62057242:C:A	F324L	1.000
10:62057242:C:G	F324L	1.000
10:62057253:T:A	L328H	1.000
10:62057253:T:C	L328P	1.000
10:62057265:T:C	M332T	1.000
10:62057266:G:A	M332I	1.000
10:62057266:G:C	M332I	1.000
10:62057266:G:T	M332I	1.000
10:62057286:T:A	I339K	1.000
10:62057286:T:G	I339R	1.000
10:62057295:T:A	I342K	1.000
10:62057298:C:A	P343H	1.000
10:62057304:T:C	L345S	1.000
10:62057306:G:C	G346R	1.000
10:62057306:G:T	G346C	1.000
10:62057307:G:A	G346D	1.000
10:62057307:G:T	G346V	1.000
10:62057309:T:A	F347I	1.000
10:62057309:T:C	F347L	1.000
10:62057309:T:G	F347V	1.000
10:62057310:T:C	F347S	1.000
10:62057310:T:G	F347C	1.000
10:62057311:T:A	F347L	1.000
10:62057311:T:G	F347L	1.000
10:62057314:A:C	K348N	1.000

dbSNP variants (sampled 300 via entrez): RS1000003891 (10:62073001 A>G), RS1000028938 (10:61989004 A>T), RS1000050866 (10:62083510 C>T), RS1000054674 (10:61949506 A>C), RS1000055017 (10:62037897 G>A), RS1000081426 (10:61956897 T>A), RS1000103627 (10:62033900 G>A), RS1000113853 (10:62079585 T>C), RS1000118693 (10:61995233 C>T), RS1000128090 (10:62037443 T>C), RS1000129749 (10:61985464 CT>C,CTT), RS1000130143 (10:61942821 A>C), RS1000135870 (10:62021103 G>A), RS1000169797 (10:62008450 G>A,T), RS1000176638 (10:61936402 G>C,T)

Disease associations

OMIM: gene MIM:608538 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
isolated cleft palate	No Known Disease Relationship	Unknown

Mondo (2): fetal growth restriction (MONDO:0005030), isolated cleft palate (MONDO:0007336)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

85 associations (top):

Study	Trait	p-value
GCST000394_2	Diastolic blood pressure	1.000000e-09
GCST000463_3	Acute lymphoblastic leukemia (childhood)	7.000000e-19
GCST000464_5	Acute lymphoblastic leukemia (childhood)	1.000000e-15
GCST001320_13	Acute lymphoblastic leukemia (childhood)	1.000000e-11
GCST001320_19	Acute lymphoblastic leukemia (childhood)	4.000000e-15
GCST001454_4	Rheumatoid arthritis	6.000000e-18
GCST001698_3	Serum total protein levels	2.000000e-06
GCST001795_4	Systemic lupus erythematosus	5.000000e-11
GCST001806_15	Corneal structure	6.000000e-10
GCST001912_2	Acute lymphoblastic leukemia (childhood)	6.000000e-46
GCST002158_3	Acute lymphoblastic leukemia (B-cell precursor)	5.000000e-54
GCST002318_133	Rheumatoid arthritis	5.000000e-22
GCST002318_134	Rheumatoid arthritis	3.000000e-15
GCST002318_135	Rheumatoid arthritis	1.000000e-08
GCST002465_1	Response to haloperidol in psychosis	1.000000e-06
GCST002657_1	Acute lymphoblastic leukemia (childhood)	2.000000e-09
GCST003155_10	Systemic lupus erythematosus	1.000000e-10
GCST003156_28	Systemic lupus erythematosus	2.000000e-07
GCST003622_36	Systemic lupus erythematosus	1.000000e-06
GCST004607_117	Plateletcrit	1.000000e-09
GCST004785_47	Vitiligo	7.000000e-09
GCST005170_42	Intraocular pressure	1.000000e-15
GCST005315_7	Acute lymphoblastic leukemia (childhood)	2.000000e-62
GCST005568_46	Rheumatoid arthritis (ACPA-positive)	4.000000e-10
GCST005569_20	Rheumatoid arthritis	1.000000e-08
GCST005580_199	Intraocular pressure	1.000000e-26
GCST005580_205	Intraocular pressure	1.000000e-25
GCST005667_20	Central corneal thickness	3.000000e-14
GCST005832_6	Acute lymphoblastic leukemia in childhood (B cell precursor)	2.000000e-73
GCST005860_1	Cholangiocarcinoma in primary sclerosing cholangitis (time to event)	3.000000e-06

EFO canonical traits (21, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0004536	total blood protein measurement
EFO:0004345	corneal topography
EFO:0007985	platelet crit
EFO:0004695	intraocular pressure measurement
EFO:0005213	central corneal thickness
EFO:0008393	reaction time measurement
EFO:0009270	heel bone mineral density
EFO:0004318	smoking behavior
EFO:0008579	risk-taking behaviour
EFO:0009933	Thyroid preparation use measurement
EFO:0010067	corneal resistance factor
EFO:0005670	smoking initiation
EFO:0004530	triglyceride measurement
EFO:0004531	urate measurement
EFO:0004980	appendicular lean mass
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D005317	Fetal Growth Retardation	C12.050.703.277.370; C16.300.390; C23.550.393.450

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

5 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10821936	Other	3	methotrexate	Acute lymphoblastic leukemia
rs10821936	Toxicity	3	glucarpidase	Nephrotoxicity
rs10994982	Metabolism/PK	3	methotrexate	Acute lymphoblastic leukemia
rs4948496	Metabolism/PK	3	methotrexate	Acute lymphoblastic leukemia
rs4948496	Toxicity	3	methotrexate	Acute lymphoblastic leukemia;Leukopenia

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4948496	ARID5B	3	1.50	2	methotrexate
rs10821936	ARID5B	3	1.50	2	methotrexate;glucarpidase
rs10994982	ARID5B	3	1.00	1	methotrexate

CTD chemical–gene interactions

82 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
sodium arsenite	affects cotreatment, decreases methylation, decreases expression, increases expression	4
Estradiol	decreases expression, decreases reaction, affects expression, affects cotreatment	4
trichostatin A	affects cotreatment, increases expression	3
Air Pollutants	decreases expression, increases abundance, increases expression	3
Cadmium Chloride	increases expression, decreases expression, increases abundance	3
Particulate Matter	decreases expression, increases abundance, increases expression, affects cotreatment	3
bisphenol A	increases methylation, increases expression, affects cotreatment	2
mercuric bromide	increases expression, affects cotreatment	2
Vorinostat	increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Arsenic	affects expression, increases methylation, decreases expression, increases abundance	2
Cisplatin	affects response to substance, affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
biochanin A	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
lead acetate	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
2-methyl-4-isothiazolin-3-one	increases expression	1
7-hydroxymethotrexate	affects abundance	1
arsenite	decreases reaction, affects binding	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
tobacco tar	decreases expression	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SD48	HAP1 ARID5B (-)	Cancer cell line	Male

Clinical trials (associated diseases)

224 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00347867	PHASE4	UNKNOWN	Viagra for the Treatment of IUGR
NCT00909974	PHASE4	COMPLETED	Effect of Prenatal Nutritional Supplementation on Birth Outcome in Hounde District, Burkina Faso
NCT01352234	PHASE4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01390051	PHASE4	COMPLETED	Can Low Molecular Weight Heparin During Pregnancy With Intrauterine Growth Restriction Increase Birth Weight?
NCT01695070	PHASE4	COMPLETED	Melatonin to Prevent Brain Injury in Unborn Growth Restricted Babies
NCT03674606	PHASE4	COMPLETED	Trial of Early Screening Test for Pre-eclampsia and Growth Restriction
NCT04051567	PHASE4	UNKNOWN	Low-dose Aspirin for Prevention of Adverse Pregnancy Outcomes in Twin Pregnancies
NCT05029778	PHASE4	UNKNOWN	Arginine + Citrulline as a Supplement for Weight Gain in Fetus With a Decrease in Their Growth Curve
NCT05800938	PHASE4	COMPLETED	The Effect of Oral Isosorbide Mononitrate Therapy on Umbilical Artery Doppler Resistance Index in Pregnancies With Intrauterine Growth Restriction: Prospective Randomized Control Trial
NCT07171086	PHASE4	NOT_YET_RECRUITING	AI-POCUS for Maternal and Neonatal Health in Ethiopia
NCT00174252	PHASE3	COMPLETED	Study Aimed At Improving Height With Genotonorm In Children Born Little And/Or Light With Growth Retardation At The Age
NCT00197340	PHASE3	COMPLETED	Antepartum Chronic Epidural Therapy (ACET) to Improve Blood Flow to the Uterus, Placenta and Baby in Pre-Eclampsia and Intrauterine Growth Restriction
NCT00452491	PHASE3	COMPLETED	MAXOMAT ® in the Treatment of Severe Early Onset Intrauterine Growth Retardation on Pre-pubertal Children
NCT01073605	PHASE3	COMPLETED	Genotropin Treatment in Short Prepubertal Children With Intra-Uterine Growth Retardation
NCT02336243	PHASE3	UNKNOWN	A Randomized Trial of Docosahexaenoic Acid Supplementation During Pregnancy to Prevent Deep Placentation Disorders
NCT02590536	PHASE3	COMPLETED	A Trial Evaluating the Role of Sildenafil in the Treatment of Fetal Growth Restriction
NCT02672566	PHASE3	COMPLETED	Low-molecular-weight Heparin in Constituted Vascular Intrauterine Growth Restriction
NCT03177824	PHASE3	UNKNOWN	Sildenafil Citrate for Treatment of Growth-restricted Fetuses
NCT03230162	PHASE3	UNKNOWN	Sildenafil Versus Low Molecular Weight Heparin in Fetal Growth Restriction Treatment
NCT03324139	PHASE3	COMPLETED	Treatment of Intrauterine Growth Restriction With Low Molecular Heparin.
NCT03669185	PHASE3	UNKNOWN	Pentaerithrityl Tetranitrate (PETN) for Secondary Prevention of Intrauterine Growth Restriction
NCT04084990	PHASE3	TERMINATED	Sleep Apnea and Fetal Growth Restriction
NCT04356326	PHASE3	RECRUITING	Chronic Hypertension and Acetyl Salicylic Acid in Pregnancy
NCT04557475	PHASE3	WITHDRAWN	Transplacental Aspirin Therapy for Early Onset Fetal Growth Restriction
NCT04762992	PHASE3	ENROLLING_BY_INVITATION	LMWH for Treatment of Early Fetal Growth Restriction (HepaGrowth)
NCT05253781	PHASE3	COMPLETED	Low Dose Aspirin for Preventing Intrauterine Growth Restriction and Preeclampsia in Sickle Cell Pregnancy (PIPSICKLE)
NCT05651347	PHASE3	RECRUITING	Antenatal Melatonin Supplementation for Neuroprotection in Fetal Growth Restriction
NCT05774236	PHASE3	COMPLETED	Cook´s Balloon Versus Dinoprostone for Labor Induction of Term Pregnancies With Fetal Growth Restriction
NCT06497959	PHASE3	RECRUITING	Study of Placental Vascularization Using Contrast Ultrasound
NCT02280031	PHASE2	COMPLETED	Effect of Low Dose Aspirin on Birthweight in Twins: The GAP Trial.
NCT02425436	PHASE2	COMPLETED	Role of Ginkgo Biloba Extract in IUGR
NCT02678221	PHASE2	UNKNOWN	Sildenafil Citrate for the Management of Asymmetrical Intrauterine Growth Restriction
NCT02696577	PHASE2	COMPLETED	The Effect of Omega 3 on Pregnancy Complicated by Asymmetrical Intrauterine Growth Restriction
NCT07098975	PHASE2	RECRUITING	Statin Intervention for Severe Early-Onset Placental Insufficiency. (STATIN-PRE Trial)
NCT04508751	PHASE1	COMPLETED	PED NEONAT 20-000599 Fetal Body Composition
NCT06565728	PHASE1	COMPLETED	Vitamin D Versus Sildenafil Citrate in Fetal Growth Restriction
NCT07549295	PHASE1	ENROLLING_BY_INVITATION	Melatonin and Perinatal Outcomes in MVM-Related Fetal Growth Restriction (MIMVMFGR)
NCT01107782	PHASE2/PHASE3	UNKNOWN	Sildenafil and Uteroplacental Perfusion
NCT02277132	PHASE2/PHASE3	TERMINATED	The Dutch STRIDER (Sildenafil TheRapy In Dismal Prognosis Early-onset Fetal Growth Restriction)
NCT02442492	PHASE2/PHASE3	TERMINATED	Sildenafil Therapy In Dismal Prognosis Early-Onset Intrauterine Growth Restriction