ARID4A

Summary

ARID4A (AT-rich interaction domain 4A, HGNC:9885) is a protein-coding gene on chromosome 14q23.1, encoding AT-rich interactive domain-containing protein 4A (P29374). DNA-binding protein which modulates activity of several transcription factors including RB1 (retinoblastoma-associated protein) and AR (androgen receptor).

The protein encoded by this gene is a ubiquitously expressed nuclear protein. It binds directly, with several other proteins, to retinoblastoma protein (pRB) which regulates cell proliferation. pRB represses transcription by recruiting the encoded protein. This protein, in turn, serves as a bridging molecule to recruit HDACs and, in addition, provides a second HDAC-independent repression function. The encoded protein possesses transcriptional repression activity. Multiple alternatively spliced transcripts have been observed for this gene, although not all transcript variants have been fully described.

Source: NCBI Gene 5926 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 166 total — 1 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_002892

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9885
Approved symbol	ARID4A
Name	AT-rich interaction domain 4A
Location	14q23.1
Locus type	gene with protein product
Status	Approved
Aliases	RBP1, RBP-1
Ensembl gene	ENSG00000032219
Ensembl biotype	protein_coding
OMIM	180201
Entrez	5926

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000348476, ENST00000355431, ENST00000395168, ENST00000417477, ENST00000424658, ENST00000431317, ENST00000431612, ENST00000445108, ENST00000466065, ENST00000469635, ENST00000553355, ENST00000941390

RefSeq mRNA: 3 — MANE Select: NM_002892 NM_002892, NM_023000, NM_023001

CCDS: CCDS45114, CCDS9732, CCDS9733

Canonical transcript exons

ENST00000355431 — 24 exons

Exon	Start	End
ENSE00000658052	58329528	58329604
ENSE00000658061	58360901	58361042
ENSE00000658064	58365518	58365622
ENSE00000867394	58301580	58301690
ENSE00000902444	58318542	58318621
ENSE00000902445	58318711	58318805
ENSE00000902446	58323485	58323617
ENSE00000902447	58328237	58328316
ENSE00000902454	58351073	58351323
ENSE00001094609	58347020	58347117
ENSE00001094616	58346411	58346505
ENSE00001094617	58347647	58347878
ENSE00001255076	58366024	58366230
ENSE00001424790	58299798	58299860
ENSE00001871355	58298555	58298700
ENSE00001883608	58371886	58373876
ENSE00003505137	58366883	58367029
ENSE00003527257	58306022	58306112
ENSE00003576959	58344695	58344767
ENSE00003641464	58304944	58305009
ENSE00003650982	58353658	58353855
ENSE00003683486	58359132	58359216
ENSE00003787128	58364170	58365300
ENSE00003789788	58330003	58330169

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 96.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.7041 / max 1995.1524, expressed in 1708 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139817	11.0875	1699
139820	1.5003	124
139819	0.8748	145
139818	0.5736	268
139824	0.4588	184
207235	0.2092	46

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	96.34	gold quality
sural nerve	UBERON:0015488	95.44	gold quality
buccal mucosa cell	CL:0002336	94.80	gold quality
colonic epithelium	UBERON:0000397	93.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.35	gold quality
tendon	UBERON:0000043	93.15	gold quality
cortical plate	UBERON:0005343	92.15	gold quality
monocyte	CL:0000576	91.11	gold quality
mononuclear cell	CL:0000842	90.77	gold quality
ventricular zone	UBERON:0003053	90.53	gold quality
bone marrow cell	CL:0002092	90.40	gold quality
leukocyte	CL:0000738	90.09	gold quality
tendon of biceps brachii	UBERON:0008188	89.72	silver quality
ganglionic eminence	UBERON:0004023	88.32	gold quality
tonsil	UBERON:0002372	88.04	gold quality
bone marrow	UBERON:0002371	87.81	gold quality
corpus callosum	UBERON:0002336	86.49	gold quality
superficial temporal artery	UBERON:0001614	85.85	gold quality
secondary oocyte	CL:0000655	85.50	gold quality
mammary duct	UBERON:0001765	85.36	gold quality
rectum	UBERON:0001052	85.32	gold quality
corpus epididymis	UBERON:0004359	85.27	gold quality
caput epididymis	UBERON:0004358	85.22	gold quality
cauda epididymis	UBERON:0004360	85.08	gold quality
adrenal tissue	UBERON:0018303	84.89	gold quality
medial globus pallidus	UBERON:0002477	84.72	gold quality
right lung	UBERON:0002167	84.69	gold quality
epithelium of mammary gland	UBERON:0003244	84.55	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.44	gold quality
mucosa of stomach	UBERON:0001199	84.33	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
ARID4A
BRMS1
DLST
GNAS
RB1	Repression
RUNX2	Unknown
SIN3A

Upstream regulators (CollecTRI, top): ARID4A

miRNA regulators (miRDB)

222 targeting ARID4A, 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-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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-12136	99.98	72.81	5713
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775

Literature-anchored findings (GeneRIF, showing 10)

• RBP1 and the mSin3 histone deacetylase complex bind to BRMS1 and repress transcription (PMID:14581478)
• there is an E2-dependent, ER isoform-specific transcriptional activation of the RBBP1 gene, which in part, is explained by the differential activity of ER AF1 and enhancer element binding (PMID:16873370)
• Alterations of BRMS1-ARID4A interaction modify gene expression but still suppress metastasis in human breast cancer cells. (PMID:18211900)
• chromobarrel domain of RBBP1 is responsible for recognizing methylated histone tails in chromatin remodeling and epigenetic regulation (PMID:22247551)
• ARID4a (AT-rich interacting domain 4a, also known as RBP1) and CCL5 (C-C motif ligand 5) are targets for miR-302. (PMID:22732186)
• The RBBP1 Tudor domain binds both double- and single-stranded DNA with an affinity of 10-100 muM; no apparent DNA sequence specificity was detected. (PMID:24379399)
• Consistently, our ITC assays also showed that DNA does not significantly enhance the histone binding ability of the chromo barrel domain of RBBP1. (PMID:29408527)
• ARID4A and ARID4B may play the role as tumor suppressor gene in prostate cancer by inhibiting cell proliferation, migration, and invasion. Moreover, co-downregulation of ARID4A and ARID4B can predict poorer prognosis in prostate cancer, suggesting they might be the novel marker of prognosis and potential therapeutic targets for prostate cancer in human. (PMID:29797600)
• Structural Insight into Chromatin Recognition by Multiple Domains of the Tumor Suppressor RBBP1. (PMID:34506790)
• A novel heterozygous missense variant of the ARID4A gene identified in Han Chinese families with schizophrenia-diagnosed siblings that interferes with DNA-binding activity. (PMID:35365808)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	arid4a	ENSDARG00000043873
mus_musculus	Arid4a	ENSMUSG00000048118
rattus_norvegicus	Arid4a	ENSRNOG00000026239
drosophila_melanogaster	htk	FBGN0085451
caenorhabditis_elegans		WBGENE00044689

Paralogs (3): ARID4B (ENSG00000054267), ARID5B (ENSG00000150347), ARID5A (ENSG00000196843)

Protein

Protein identifiers

AT-rich interactive domain-containing protein 4A — P29374 (reviewed: P29374)

Alternative names: Retinoblastoma-binding protein 1

All UniProt accessions (5): C9J1W3, C9JIF4, P29374, F8WAR5, H7C485

UniProt curated annotations — full annotation on UniProt →

Function. DNA-binding protein which modulates activity of several transcription factors including RB1 (retinoblastoma-associated protein) and AR (androgen receptor). May function as part of an mSin3A repressor complex. Has no intrinsic transcriptional activity. Plays a role in the regulation of epigenetic modifications at the PWS/AS imprinting center near the SNRPN promoter, where it might function as part of a complex with RB1 and ARID4B. Involved in spermatogenesis, together with ARID4B, where it acts as a transcriptional coactivator for AR and enhances expression of genes required for sperm maturation. Regulates expression of the tight junction protein CLDN3 in the testis, which is important for integrity of the blood-testis barrier. Plays a role in myeloid homeostasis where it regulates the histone methylation state of bone marrow cells and expression of various genes involved in hematopoiesis. May function as a leukemia suppressor.

Subunit / interactions. Identified in mSin3A corepressor complexes together with SIN3A, SIN3B, RBBP4, RBBP7, SAP30, BRMS1, HDAC1 and HDAC2. Interacts with BRMS1. Interacts with RB1. Interacts with ARID4B. Interacts with AR.

Subcellular location. Nucleus.

Domain organisation. The function of the Tudor-knot domain, also named chromodomain-like, is uncertain. One study suggests that it mediates binding to lysine-methylated histone tails, with strongest affinity for H4K20me3 and H3K36me3. However, another study failed to find any interaction between this domain and histone H4K20me3 peptide.

Isoforms (3)

UniProt ID	Names	Canonical?
P29374-1	I	yes
P29374-2	II
P29374-3	III

RefSeq proteins (3): NP_002883, NP_075376, NP_075377 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000953	Chromo/chromo_shadow_dom	Domain
IPR001606	ARID_dom	Domain
IPR002999	Tudor	Domain
IPR012603	ARID4A/B_PWWP	Domain
IPR016197	Chromo-like_dom_sf	Homologous_superfamily
IPR025995	Tudor-knot	Domain
IPR036431	ARID_dom_sf	Homologous_superfamily
IPR047472	Tudor_ARID4A_rpt1	Domain
IPR047473	CBD_RBP1-like	Domain
IPR051232	ARID/SWI1_ChromRemod	Family

Pfam: PF01388, PF08169, PF11717

UniProt features (100 total): strand 21, helix 18, compositionally biased region 16, region of interest 11, modified residue 5, cross-link 5, mutagenesis site 5, sequence conflict 5, turn 5, splice variant 3, sequence variant 3, domain 2, chain 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
6BPH	X-RAY DIFFRACTION	1.85
7V8N	X-RAY DIFFRACTION	2.05
7SMC	X-RAY DIFFRACTION	2.7
2LCC	SOLUTION NMR
2MAM	SOLUTION NMR
2YRV	SOLUTION NMR
6L87	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29374-F1	56.77	0.21

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 (10): 676, 716, 864, 1109, 1145, 481, 513, 718, 738, 759

Mutagenesis-validated functional residues (5):

Position	Phenotype
583	no effect on binding to trimethylated lysines.
592	significantly reduces affinity for trimethylated lysines.
612	abolishes binding to trimethylated lysines.
615	abolishes binding to trimethylated lysines.
619	abolishes binding to trimethylated lysines.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-3214815	HDACs deacetylate histones
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-1643685	Disease
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-5663205	Infectious disease
R-HSA-9679506	SARS-CoV Infections
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 631 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_NK_CELL_VS_CD8_TCELL_UP, E2F_Q4, MODULE_52, E2F_Q4_01, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, FREAC2_01, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_DN, JI_RESPONSE_TO_FSH_UP, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_MYELOID_CELL_HOMEOSTASIS, E2F4DP1_01, GOBP_MYELOID_CELL_DEVELOPMENT, KAAB_FAILED_HEART_ATRIUM_DN

GO Biological Process (16): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), spermatogenesis (GO:0007283), negative regulation of cell migration (GO:0030336), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), erythrocyte development (GO:0048821), genomic imprinting (GO:0071514), establishment of Sertoli cell barrier (GO:0097368), negative regulation of stem cell population maintenance (GO:1902455), positive regulation of stem cell population maintenance (GO:1902459), chromatin organization (GO:0006325), regulation of DNA-templated transcription (GO:0006355), cell differentiation (GO:0030154)

GO Molecular Function (3): transcription cis-regulatory region binding (GO:0000976), DNA binding (GO:0003677), double-stranded DNA binding (GO:0003690)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), plasma membrane (GO:0005886), transcription repressor complex (GO:0017053), Sin3-type complex (GO:0070822)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Chromatin modifying enzymes	1
SARS-CoV Infections	1
Chromatin organization	1
Disease	1
Viral Infection Pathways	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	3
DNA-templated transcription	3
regulation of transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
stem cell population maintenance	2
regulation of stem cell population maintenance	2
negative regulation of DNA-templated transcription	1
developmental process involved in reproduction	1
male gamete generation	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
negative regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
erythrocyte differentiation	1
myeloid cell development	1
germ cell development	1
epigenetic programming of gene expression	1
Sertoli cell development	1
negative regulation of developmental process	1
negative regulation of multicellular organismal process	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
cellular component organization	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular developmental process	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
nucleic acid binding	1
DNA binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
membrane	1
cell periphery	1
transcription regulator complex	1

Protein interactions and networks

STRING

3124 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARID4A	BRMS1L	Q5PSV4	986
ARID4A	BRMS1	Q9HCU9	976
ARID4A	SUDS3	Q9H7L9	932
ARID4A	SAP30	O75446	921
ARID4A	ING1	Q9UK53	879
ARID4A	HDAC1	Q13547	830
ARID4A	SIN3A	Q96ST3	817
ARID4A	ING2	Q9H160	798
ARID4A	SIN3B	O75182	776
ARID4A	HDAC2	Q92769	767
ARID4A	KDM5A	P29375	743
ARID4A	RBBP6	Q7Z6E9	687
ARID4A	RB1	P06400	680
ARID4A	SON	P18583	587
ARID4A	KDM5B	Q9UGL1	585

IntAct

62 interactions, top by confidence:

A	B	Type	Score
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
HDAC1	TNRC18	psi-mi:“MI:0914”(association)	0.790
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
HDAC1	ZNF609	psi-mi:“MI:0914”(association)	0.730
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730
FOXK2	DVL2	psi-mi:“MI:0914”(association)	0.640
MLLT1	ELL2	psi-mi:“MI:0914”(association)	0.640
SINHCAF	TNRC18	psi-mi:“MI:0914”(association)	0.640
ZNF704	SAP30	psi-mi:“MI:0914”(association)	0.640
ARID4A	BRMS1	psi-mi:“MI:0915”(physical association)	0.550
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530
SIN3B	TNRC18	psi-mi:“MI:0914”(association)	0.530
RBBP7	SMARCA5	psi-mi:“MI:0914”(association)	0.530
RBBP7	EPOP	psi-mi:“MI:0914”(association)	0.530
SAP30	TNRC18	psi-mi:“MI:0914”(association)	0.530
ARID4A	PROCR	psi-mi:“MI:0915”(physical association)	0.400
SAP30	BRMS1	psi-mi:“MI:0914”(association)	0.350
FOXK1	AP5Z1	psi-mi:“MI:0914”(association)	0.350
FOXK2	PHF20L1	psi-mi:“MI:0914”(association)	0.350
FOXK1	PHKG2	psi-mi:“MI:0914”(association)	0.350
HDAC1		psi-mi:“MI:0914”(association)	0.350
HDAC2		psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (125): ARID4A (Affinity Capture-MS), ARID4A (Affinity Capture-MS), SIN3A (Co-fractionation), BRMS1 (Affinity Capture-Western), ARID4A (Affinity Capture-Western), ARID4A (Proximity Label-MS), ARID4A (Affinity Capture-MS), ARID4A (Affinity Capture-MS), ARID4A (Affinity Capture-MS), ARID4A (Affinity Capture-MS), ARID4A (Affinity Capture-MS), ARID4A (Affinity Capture-MS), ARID4A (Affinity Capture-MS), ARID4A (Affinity Capture-MS), ARID4A (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GR68, A2CG63, E6ZGB4, F7AQ22, F8VPQ2, G3V8T1, O75151, O75376, O75475, O88974, O96028, P29374, Q0VEE6, Q0VGB7, Q15047, Q2TB10, Q3TYA6, Q4KKX4, Q4LE39, Q5F363, Q5HYC2, Q5JSH3, Q5R9U6, Q5XJV7, Q5XXA9, Q5ZMU6, Q60974, Q62315, Q66T72, Q6DCQ0, Q6INA9, Q6NVE8, Q6P7W0, Q6P949, Q6P964, Q812D1, Q8BVE8, Q8MJG1, Q8QG78, Q8VBW5

Diamond homologs: A0A0K3AXH1, A2CG63, F8VPQ2, P29374, Q4LE39, Q9JKB5, A2BEA6, A2BH40, A6NKF2, A6PWV5, E1BLP6, E2R9X2, E7F888, E9Q4N7, O02326, O14497, O74365, P29375, P41229, P41230, Q03214, Q03989, Q14865, Q24573, Q30DN6, Q38JA7, Q3SWY1, Q3U108, Q3UXZ9, Q4H3P5, Q5F3R2, Q5XGD9, Q5XUN4, Q5ZJ69, Q62431, Q6GQD7, Q6IQX0, Q8BM75, Q8IN94, Q8IVW6

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CDK2	down-regulates	ARID4A	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 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
Regulation of TP53 Activity through Acetylation	5	50.8×	3e-06
NuRD complex assembly	7	21.9×	3e-06
HDACs deacetylate histones	8	21.4×	7e-07
Deposition of new CENPA-containing nucleosomes at the centromere	6	21.1×	1e-05
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	6	20.3×	1e-05
Interaction of NuRD complexes with transcription factors	7	19.7×	3e-06
Negative Regulation of CDH1 Gene Transcription	7	18.7×	4e-06
PRC2 methylates histones and DNA	5	16.9×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of stem cell population maintenance	9	121.0×	5e-15
positive regulation of stem cell population maintenance	9	54.3×	1e-11
negative regulation of transforming growth factor beta receptor signaling pathway	9	27.4×	4e-09
negative regulation of cell migration	10	19.6×	7e-09
nucleosome assembly	6	14.8×	1e-04
chromatin remodeling	7	9.0×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	132
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1458692	NC_000014.8:g.(?58711639)(59014694_?)del	Pathogenic
800352	NM_002892.4(ARID4A):c.2614G>T (p.Glu872Ter)	Likely pathogenic

SpliceAI

4863 predictions. Top by Δscore:

Variant	Effect	Δscore
14:58299795:T:G	acceptor_gain	1.0000
14:58299796:A:AG	acceptor_gain	1.0000
14:58299797:G:GG	acceptor_gain	1.0000
14:58299856:TGAAG:T	donor_gain	1.0000
14:58299857:GAAG:G	donor_gain	1.0000
14:58299857:GAAGG:G	donor_gain	1.0000
14:58299858:AAGG:A	donor_loss	1.0000
14:58299859:AG:A	donor_gain	1.0000
14:58299859:AGG:A	donor_loss	1.0000
14:58299860:GG:G	donor_gain	1.0000
14:58299860:GGTA:G	donor_loss	1.0000
14:58299861:G:GG	donor_gain	1.0000
14:58299861:GT:G	donor_loss	1.0000
14:58301575:A:AG	acceptor_gain	1.0000
14:58301576:C:G	acceptor_gain	1.0000
14:58301576:CCA:C	acceptor_loss	1.0000
14:58301576:CCAG:C	acceptor_gain	1.0000
14:58301577:CAG:C	acceptor_gain	1.0000
14:58301578:A:AG	acceptor_gain	1.0000
14:58301578:AGG:A	acceptor_gain	1.0000
14:58301578:AGGC:A	acceptor_gain	1.0000
14:58301579:G:GG	acceptor_gain	1.0000
14:58301579:GGC:G	acceptor_gain	1.0000
14:58301579:GGCG:G	acceptor_gain	1.0000
14:58301680:TGA:T	donor_gain	1.0000
14:58301686:T:G	donor_gain	1.0000
14:58301686:TTAAG:T	donor_loss	1.0000
14:58301687:TAAG:T	donor_loss	1.0000
14:58301689:AGG:A	donor_loss	1.0000
14:58301690:GGT:G	donor_loss	1.0000

AlphaMissense

8372 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:58301602:T:A	L10Q	1.000
14:58301602:T:C	L10P	1.000
14:58301602:T:G	L10R	1.000
14:58301610:G:A	G13R	1.000
14:58301610:G:C	G13R	1.000
14:58301611:G:A	G13E	1.000
14:58301611:G:T	G13V	1.000
14:58301620:T:A	V16D	1.000
14:58301622:A:C	S17R	1.000
14:58301624:T:A	S17R	1.000
14:58301624:T:G	S17R	1.000
14:58301625:G:C	A18P	1.000
14:58301626:C:A	A18D	1.000
14:58301628:A:G	K19E	1.000
14:58301630:G:C	K19N	1.000
14:58301630:G:T	K19N	1.000
14:58301631:T:A	Y20N	1.000
14:58301631:T:C	Y20H	1.000
14:58301631:T:G	Y20D	1.000
14:58301632:A:C	Y20S	1.000
14:58301632:A:G	Y20C	1.000
14:58301635:G:C	R21P	1.000
14:58301637:G:C	G22R	1.000
14:58301637:G:T	G22C	1.000
14:58301638:G:A	G22D	1.000
14:58301638:G:T	G22V	1.000
14:58301641:C:A	A23D	1.000
14:58301643:T:A	F24I	1.000
14:58301643:T:C	F24L	1.000
14:58301643:T:G	F24V	1.000

dbSNP variants (sampled 300 via entrez): RS1000019501 (14:58314697 A>G), RS1000071242 (14:58357315 A>C,T), RS1000103401 (14:58298215 G>T), RS1000154005 (14:58298069 G>A,T), RS1000212259 (14:58339146 TA>T), RS1000242701 (14:58347341 A>T), RS1000302568 (14:58351008 ATT>A,AT,ATTT), RS1000309765 (14:58327330 T>C), RS1000411110 (14:58360272 C>G), RS1000417342 (14:58370906 C>G), RS1000431195 (14:58327592 A>T), RS1000470212 (14:58309774 T>C), RS1000470285 (14:58354085 C>T), RS1000545548 (14:58323183 C>G), RS1000603455 (14:58363244 A>G)

Disease associations

OMIM: gene MIM:180201 | disease phenotypes: MIM:616490, MIM:616546, MIM:254500

GenCC curated gene-disease

Mondo (3): Joubert syndrome 23 (MONDO:0014664), short-rib thoracic dysplasia 14 with polydactyly (MONDO:0014688), plasma cell myeloma (MONDO:0009693)

Orphanet (4): Joubert syndrome with Jeune asphyxiating thoracic dystrophy (Orphanet:397715), Isolated Joubert syndrome (Orphanet:475), Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443)

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST004887_8	Alcohol consumption in current drinkers	4.000000e-08
GCST005195_111	Coronary artery disease	4.000000e-08
GCST007483_36	Waist-to-hip ratio adjusted for BMI (additive genetic model)	7.000000e-07
GCST007487_3	Waist-to-hip ratio adjusted for BMI (additive genetic model)	2.000000e-08
GCST007500_2	Waist-to-hip ratio adjusted for BMI (additive genetic model)	4.000000e-06
GCST007502_2	Waist-to-hip ratio adjusted for BMI (additive genetic model)	3.000000e-07
GCST008811_35	Alcohol consumption (drinks per week)	3.000000e-09
GCST009030_20	Venous thromboembolism	2.000000e-08
GCST010546_28	Problematic alcohol use	4.000000e-08
GCST010703_93	Brain morphology (MOSTest)	6.000000e-54
GCST010866_56	Coronary artery disease	1.000000e-08
GCST90000047_249	Age at first sexual intercourse	5.000000e-10
GCST90002392_451	Mean corpuscular volume	9.000000e-31
GCST90002395_199	Mean platelet volume	3.000000e-09
GCST90002397_75	Mean spheric corpuscular volume	5.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0009458	alcohol use disorder measurement
EFO:0004346	neuroimaging measurement
EFO:0009749	age at first sexual intercourse measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009101	Multiple Myeloma	C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3709855 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs61974485	Toxicity	3	ethanol	Alcohol abuse

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs61974485	ARID4A	3	1.50	1	ethanol

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Resveratrol	increases expression, decreases expression, affects cotreatment	3
Valproic Acid	decreases expression, decreases methylation	3
sodium arsenite	increases expression	2
perfluorooctane sulfonic acid	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
deguelin	decreases expression	1
thifluzamide	decreases expression	1
14-deoxy-11,12-didehydroandrographolide	increases expression	1
pyrachlostrobin	decreases expression	1
jinfukang	decreases expression	1
picoxystrobin	decreases expression	1
Irinotecan	decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	affects phosphorylation	1
Clorgyline	increases expression	1
Doxorubicin	decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	decreases expression	1
Menthol	increases expression	1
Mercury	affects expression	1
Methyl Methanesulfonate	increases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3859085	Binding	Binding affinity to RBBP1 (unknown origin) at 200 uM by DSF assay	Discovery of a Potent, Selective, and Cell-Active Dual Inhibitor of Protein Arginine Methyltransferase 4 and Protein Arginine Methyltransferase 6. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1737	TC-YIK	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00104104	PHASE4	COMPLETED	A Multiple Myeloma Trial in Patients With Bone Metastases
NCT00211211	PHASE4	COMPLETED	FREE Study - Fracture Reduction Evaluation
NCT00242528	PHASE4	WITHDRAWN	Open-label Study, to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Bone Lesions Secondary to Multiple Myeloma.
NCT00257114	PHASE4	COMPLETED	Evaluation of VELCADE Given as Retreatment to Multiple Myeloma Patients for Efficacy, Safety and Tolerability
NCT00352703	PHASE4	COMPLETED	PROMPT - Palifermin in Reduction of Oral Mucositis in PBSC Transplantation
NCT00361140	PHASE4	COMPLETED	Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)
NCT00622505	PHASE4	COMPLETED	Zoledronic Acid Treatment (Every 4 or 12 Weeks) to Prevent Skeletal Complications in Advanced Multiple Myeloma Participants
NCT00652041	PHASE4	COMPLETED	Bortezomib/Adriamycine/Melfalan/Prednisone (VAMP)/Thalidomide/Cyclophosphamide/Dexamethasone (TaCyDex) or Bortezomib/Melfalan/Prednisone (V-MP)/TaCyDex) in Refractary or Relapsed Multiple Myeloma
NCT00733538	PHASE4	COMPLETED	Stage I Multiple Myeloma Treatment
NCT01087008	PHASE4	COMPLETED	Zoledronic Acid in Patients With Multiple Myeloma and Asymptomatic Biochemical Relapse
NCT01249690	PHASE4	UNKNOWN	Efficacy Study of PAD and TAD in Newly Diagnosed Multiple Myeloma
NCT01410929	PHASE4	WITHDRAWN	Evaluation of Vertebral Compression Fracture Fixation With RF Kyphoplasty in Patients With Multiple Myeloma
NCT01731886	PHASE4	COMPLETED	Lenalidomide and Dexamethasone With/Without Stem Cell Transplant in Patients With Multiple Myeloma
NCT01868828	PHASE4	UNKNOWN	A Study of PAD Versus Velcade, Cyclophosphamide and Dexamethasone (VCD) Treatment in Subjects With Multiple Myeloma
NCT02268890	PHASE4	COMPLETED	A Pharmacokinetic Study of Bortezomib in Taiwanese Participants With Multiple Myeloma
NCT02286830	PHASE4	COMPLETED	Prolonged Protection From Bone Disease in Multiple Myeloma
NCT02559154	PHASE4	UNKNOWN	Modified Bortezomib-based Combination Therapy for Multiple Myeloma
NCT02577783	PHASE4	UNKNOWN	PDD vs PAD to Treat Initially Diagnosed MM
NCT02773550	PHASE4	TERMINATED	Treatment With a Scheme With Low Doses of Bortezomib / Melphalan / Prednisone (MPV) in Patients With Multiple Myeloma
NCT02958969	PHASE4	COMPLETED	Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
NCT03173092	PHASE4	TERMINATED	A Study of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) for the Treatment of Participants With Multiple Myeloma (MM)
NCT03619252	PHASE4	COMPLETED	Pneumococcal Vaccination of Multiple Myeloma Patients on Novel Agents
NCT03768960	PHASE4	COMPLETED	A Study of DARZALEX (Daratumumab) In Indian Participants With Relapsed and Refractory Multiple Myeloma, Whose Prior Therapy Included a Proteasome Inhibitor and an Immunomodulatory Agent
NCT03829371	PHASE4	ACTIVE_NOT_RECRUITING	STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA
NCT03908138	PHASE4	UNKNOWN	RDD Versus VDD in Newly Diagnosed Patients With Multiple Myeloma
NCT04217967	PHASE4	COMPLETED	Ixazomib, Lenalidomide, and Combination for Maintenance in NDMM Patients
NCT04952766	PHASE4	COMPLETED	Study Evaluating SARS-CoV-2 (COVID-19) Humoral Response After BNT162b2 Vaccine in Immunocompromised Adults Compared to Healthy Adults
NCT04989140	PHASE4	UNKNOWN	Study of Pomalidomide, Oral Dexamethasone and Ixazomib in Patients With Relapsed MM Who Have Received Lenalidomide
NCT05183139	PHASE4	WITHDRAWN	A Multicenter In-class Transition Study of Ixazomib Combined With Pomalidomide and Dexamethasone or With Lenalidomide and Dexamethasone in Adults With Relapsed/Refractory Multiple Myeloma
NCT05201781	PHASE4	RECRUITING	A Long-term Study for Participants Previously Treated With Ciltacabtagene Autoleucel
NCT05429515	PHASE4	NOT_YET_RECRUITING	Effect of HFR-SUPRA in the Treatment of Multiple Myeloma-related Acute Kidney Injury
NCT05511428	PHASE4	COMPLETED	Home Based Daratumumab Administration for Patients With Multiple Myeloma
NCT05545202	PHASE4	UNKNOWN	A Randomized, Comparative, Double-blind Trial of Pentaisomaltose and Dimethyl Sulphoxide for Cryoprotection of Hematopoietic Stem Cells in Subjects With Multiple Myeloma or Malignant Lymphoma With a Need for Autologous Transplantation
NCT05555329	PHASE4	COMPLETED	Alternative Dosing Scheme of Pomalidomide 4 mg Every Other Day Versus Pomalidomide 2 mg and 4 mg Every Day; the POMAlternative Study
NCT05722405	PHASE4	RECRUITING	Ixazomib Plus Low-dose Lenalidomide Versus Ixazomib Alone for Maintenance Treatment of High Risk Multiple Myeloma
NCT05855122	PHASE4	UNKNOWN	Safety and ASCT-related Symptom Burden Optimization of Tocilizumab in ASCT Following HD Melphalan Conditioning for Multiple Myeloma Patients
NCT05944783	PHASE4	NOT_YET_RECRUITING	Bioequivalence Studies of Dasatinib 100 Mg
NCT06057402	PHASE4	RECRUITING	Elranatamab Post Trial Access Study for Participants With Multiple Myeloma (MM)
NCT06251076	PHASE4	RECRUITING	Plan Development for Giving Teclistamab in the Outpatient Setting