ARID1A

Summary

ARID1A (AT-rich interaction domain 1A, HGNC:11110) is a protein-coding gene on chromosome 1p36.11, encoding AT-rich interactive domain-containing protein 1A (O14497). Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). In precision oncology, ARID1A Loss OR ARID1A Wildtype confers sensitivity to Dasatinib in Ovarian Clear Cell Carcinoma (CIViC Level B); 6 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 17.2% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the SWI/SNF family, whose members have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. It possesses at least two conserved domains that could be important for its function. First, it has a DNA-binding domain that can specifically bind an AT-rich DNA sequence known to be recognized by a SNF/SWI complex at the beta-globin locus. Second, the C-terminus of the protein can stimulate glucocorticoid receptor-dependent transcriptional activation. It is thought that the protein encoded by this gene confers specificity to the SNF/SWI complex and may recruit the complex to its targets through either protein-DNA or protein-protein interactions. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 8289 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Coffin-Siris syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 36
• Clinical variants (ClinVar): 1,925 total — 85 pathogenic, 53 likely-pathogenic
• Phenotypes (HPO): 89
• Druggable target: yes
• Precision-oncology evidence (CIViC): 7 curated variant–drug associations
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 38 cancer types
• Cancer dependency (DepMap): dependent in 17.2% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 11 downstream targets (CollecTRI)
• MANE Select transcript: NM_006015

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11110
Approved symbol	ARID1A
Name	AT-rich interaction domain 1A
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Aliases	B120, P270, C10rf4, BAF250, BAF250a
Ensembl gene	ENSG00000117713
Ensembl biotype	protein_coding
OMIM	603024
Entrez	8289

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 8 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000324856, ENST00000374152, ENST00000430291, ENST00000430799, ENST00000457599, ENST00000466382, ENST00000524572, ENST00000532781, ENST00000636072, ENST00000636110, ENST00000636219, ENST00000636422, ENST00000636794, ENST00000636958, ENST00000637465, ENST00000637788, ENST00000850904

RefSeq mRNA: 2 — MANE Select: NM_006015 NM_006015, NM_139135

CCDS: CCDS285, CCDS44091

Canonical transcript exons

ENST00000324856 — 20 exons

Exon	Start	End
ENSE00000761096	26766221	26766366
ENSE00000872621	26771119	26771326
ENSE00000902180	26731152	26731604
ENSE00001157462	26762973	26763285
ENSE00001227767	26772812	26772987
ENSE00001227772	26772500	26772632
ENSE00001227857	26732676	26732792
ENSE00001349739	26774329	26775220
ENSE00001349752	26767790	26767999
ENSE00001349753	26766457	26766566
ENSE00001349760	26762152	26762319
ENSE00001349761	26761384	26761473
ENSE00001349762	26760856	26761096
ENSE00001883917	26779023	26782104
ENSE00001907429	26696015	26697540
ENSE00003460238	26773802	26773898
ENSE00003471930	26729651	26729863
ENSE00003552035	26775577	26775707
ENSE00003589420	26773580	26773717
ENSE00003672172	26773346	26773496

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 96.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.4830 / max 311.6793, expressed in 1823 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1644	15.0304	1790
1642	9.6760	1744
1646	2.7932	1261
1648	1.1314	398
1645	0.9896	607
1641	0.8709	574
1650	0.8405	489
1647	0.6997	458
1643	0.4513	267

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	96.39	gold quality
ventricular zone	UBERON:0003053	96.34	gold quality
embryo	UBERON:0000922	96.24	gold quality
colonic epithelium	UBERON:0000397	96.01	gold quality
ileal mucosa	UBERON:0000331	95.83	gold quality
cortical plate	UBERON:0005343	95.76	gold quality
ganglionic eminence	UBERON:0004023	95.46	gold quality
caput epididymis	UBERON:0004358	95.05	gold quality
corpus epididymis	UBERON:0004359	94.87	gold quality
sural nerve	UBERON:0015488	94.87	gold quality
trabecular bone tissue	UBERON:0002483	94.78	gold quality
adult organism	UBERON:0007023	94.36	gold quality
nipple	UBERON:0002030	94.30	gold quality
pigmented layer of retina	UBERON:0001782	94.26	gold quality
pylorus	UBERON:0001166	94.10	gold quality
nasal cavity epithelium	UBERON:0005384	94.03	gold quality
tonsil	UBERON:0002372	93.83	gold quality
lower lobe of lung	UBERON:0008949	93.69	gold quality
cauda epididymis	UBERON:0004360	93.35	gold quality
mammary duct	UBERON:0001765	93.31	gold quality
oocyte	CL:0000023	93.28	gold quality
cardia of stomach	UBERON:0001162	93.16	gold quality
mammalian vulva	UBERON:0000997	93.15	gold quality
epithelium of mammary gland	UBERON:0003244	92.99	gold quality
seminal vesicle	UBERON:0000998	92.86	gold quality
upper leg skin	UBERON:0004262	92.75	gold quality
tibialis anterior	UBERON:0001385	92.67	gold quality
thymus	UBERON:0002370	92.63	gold quality
superficial temporal artery	UBERON:0001614	92.61	gold quality
leukocyte	CL:0000738	92.37	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.35
E-GEOD-137537	no	607.28
E-GEOD-100618	no	590.86

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

11 targets.

Target	Regulation
AR	Activation
BMP10
CDH1
CDH17
CDKN1A	Unknown
IL10
SLU7
SMAD3	Unknown
SMARCA1
SMARCA2
TNFRSF11A

miRNA regulators (miRDB)

186 targeting ARID1A, 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-12118	100.00	65.88	1270
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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-557	99.96	70.01	1640

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 17.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• largest subunits of SWI/SNF participate in promoting transcriptional activation by the steroid hormone receptors (PMID:12200431)
• BAF250 chromatin-remodeling complexes contain a mixed-lineage leukemia chromosomal translocation partner. (PMID:12665591)
• ARID1B is associated with SWI/SNF-related complexes and indicates that ARID1A and ARID1B, similar to the ATPase subunits BRG1 and hBRM, are alternative, mutually exclusive subunits of the complexes (PMID:15170388)
• Levels of ARID1A are frequently deficient in renal cell carcinoma samples. (PMID:15382044)
• The noncatalytic subunits of mammalian SWI/SNF complexes include p270/ARID1A. p270-containing complexes are functionally distinct from ARID1B-containing complexes and a deficiency of p270 is suggested to play a causative role in carcinogenesis. (PMID:16230384)
• The subset of SWI/SNF complexes containing ARID1A have an associated histone deacetylase (HDAC) activity. (PMID:17255939)
• in the primary breast carcinoma, transforming ARID1A sequence was an antisense cDNA, and was the product of a genomic rearrangement; identified a lung adenocarcinoma cell line with a highly localized homozygous genomic deletion in the 5’ end of ARID1A (PMID:17492758)
• ARID1A/BAF250A was identified as a new HIC1 partner. (PMID:19486893)
• Results report that BAF250b complexes purified from mammalian cells contain elongin C (Elo C), a BC box binding component of an E3 ubiquitin ligase. (PMID:20086098)
• genes mutated in ovarian clear cell carcinoma(OCCC);data suggest PPP2R1A functions as an oncogene and ARID1A as tumor-suppressor gene; in 42 OCCCs, 7% had mutations in PPP2R1A and 57% in ARID1A; suggests aberrant chromatin remodeling contributes to OCCC (PMID:20826764)
• These data implicate ARID1A as a tumor-suppressor gene frequently disrupted in ovarian clear-cell and endometrioid carcinomas. (PMID:20942669)
• uterine low-grade endometrioid carcinoma is the predominant tumor type harboring ARID1A mutations and frequent loss of ARID1A expression (PMID:21412130)
• These data suggest that low ARID1A expression is frequent in breast cancers;Low ARID1A expression was a predictor, not an independent, of overall survival (PMID:21889920)
• we show that low ARID1A RNA or nuclear protein expression is associated with more aggressive breast cancer phenotypes (PMID:21892209)
• ARID1A is a bona fide tumor suppressor that collaborates with p53 to regulate CDKN1A and SMAD3 transcription and tumor growth in gynecologic cancers. (PMID:21900401)
• The aberrant chromatin remodeling consequent to ARID1A inactivation contributes to a variety of different types of neoplasms. (PMID:22009941)
• The mutation spectrum for ARID1A differs between molecular subtypes of gastric cancer, and mutation prevalence is negatively associated with mutations in TP53 (PMID:22037554)
• loss of ARID1A in ovarian clear cell carcinoma is a negative prognostic factor in patients treated with platinum-based chemotherapy (PMID:22101352)
• Loss of ARID1A protein expression occurs as a very early event in ovarian clear-cell carcinoma development and frequently coexists (not mutually exclusive) with PIK3CA mutations. (PMID:22157930)
• Data confirm that loss of the ARID1A-encoded protein BAF250a is a frequent event in the genesis of clear cell and endometrioid ovarian cancers. Loss of BAF250a was not associated with clinical or epidemiologic characteristics. (PMID:22193641)
• the current study examined the prognostic significance of loss of ARID1A expression in cervical cancer by investigating the relationship between ARID1A immunohistochemical expression and various clinicopathological variables in cervical cancer. (PMID:22274316)
• The loss of expression of the tumor-suppressor protein ARID1A/BAF250a in some endometriomas possibly indicates a risk of malignant transformation. (PMID:22301703)
• Recurrent somatic mutations in ARID1A gene is associated with gastric adenocarcinoma. (PMID:22484628)
• The loss of expression of ARID1A and the presence of inactivating mutations of the ARID1A gene further link this tumor to endometrioid and clear cell tumors, as does the frequent association with endometriosis. (PMID:22653341)
• ARID1A may play an important role in gastric cancer. (PMID:22808142)
• No associations were detected for ARID1A polymorphisms and endometriosis in Caucasian women. (PMID:22910690)
• Loss of ARID1A has different and pathway-dependent roles in gastric carcinoma. (PMID:22915242)
• No significant differences between positive and negative cases of AT-rich interactive domain 1A are observed with respect to any clinicopathologic features or patient survival. (PMID:22939958)
• Loss of ARID1A expression is an early molecular event in tumor progression from ovarian endometriotic cyst to clear cell and endometrioid carcinoma. (PMID:22976498)
• data presented suggest that somatic mutation may be a main event in ARID1A inactivation in the gastric, colorectal and prostate cancers and that loss of ARID1A expression without ARID1A mutation may not be a main event (PMID:23030592)
• Loss of ARID1A appears to be an early event in the carcinogenesis of endometrioid uterine carcinomas and the association with deep myometrial infiltration may suggest an importance for invasiveness. (PMID:23080032)
• study demonstrates that in-frame indel mutations of ARID1A, are associated with the loss of ability to suppress cellular proliferation and activate CDKN1A (p21) transcription (PMID:23097632)
• Identification of recurrent somatic mutations in the chromatin-remodeling gene ARID1A in the childhood cancer neuroblastoma. (PMID:23202128)
• Inactivating mutations of the ARID1A tumor suppressor gene are the most common in endometriosis related ovarian neoplasms. (PMID:23232571)
• Data indicate enhanced cell growth, proliferation and invasion were observed on ARID1A knockdown in esophageal adenocarcinoma (EAC) cells. (PMID:23318448)
• Data indicate that promoter hypermethylation was the main culprit for ARID1A mRNA low expression in invasive ductal carcinomas. (PMID:23349767)
• both the protein and mRNA levels of ARID1A are statistically significant prognostic markers for clear cell renal cell carcinoma. (PMID:23416164)
• The loss of ARID1A/BAF250a expression is linked to tumor progression and adverse prognosis in cervical cancer. (PMID:23427874)
• Loss of BAF250a expression has no prognostic significance in endometrial clear cell carcinomas (PMID:23524907)
• ARID1A inactivation is a key player in bladder carcinogenesis occurring predominantly in FGFR3 wild type tumors. (PMID:23650517)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	arid1aa	ENSDARG00000101710
danio_rerio	arid1ab	ENSDARG00000101891
mus_musculus	Arid1a	ENSMUSG00000007880
rattus_norvegicus	Arid1a	ENSRNOG00000006137
drosophila_melanogaster	osa	FBGN0261885
caenorhabditis_elegans	let-526	WBGENE00002717

Paralogs (1): ARID1B (ENSG00000049618)

Protein

Protein identifiers

AT-rich interactive domain-containing protein 1A — O14497 (reviewed: O14497)

Alternative names: B120, BRG1-associated factor 250, BRG1-associated factor 250a, Osa homolog 1, SWI-like protein, SWI/SNF complex protein p270, SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily F member 1, hELD

All UniProt accessions (7): A0A1B0GTU5, A0A1B0GVT5, E9PQW6, O14497, H0Y488, H0YCU6, H0YEW5

UniProt curated annotations — full annotation on UniProt →

Function. Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Binds DNA non-specifically. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth.

Subunit / interactions. Component of SWI/SNF chromatin remodeling complexes, in some of which it can be mutually exclusive with ARID1B/BAF250B. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific. Component of the BAF (SWI/SNF-A) complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C. In muscle cells, the BAF complex also contains DPF3. Component of neural progenitors-specific chromatin remodeling complex (npBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, PHF10/BAF45A, ACTL6A/BAF53A and actin. Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin. Component of a SWI/SNF-like EBAFa complex, at least composed of SMARCA4/BRG1/BAF190A, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCC1/BAF155, SMARCC2/BAF170, BAF250A and MLLT1/ENL. Interacts through its C-terminus with SMARCA2/BRM/BAF190B and SMARCA4/BRG1/BAF190A. Interacts with SMARCC1/BAF155. Interacts with FOS, FOSB isoform 1 and 2, FOSL1 and FOSL2.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon, and PBL, and at a much lower level in heart, brain, placenta, lung, liver, skeletal muscle, kidney, and pancreas.

Disease relevance. Coffin-Siris syndrome 2 (CSS2) [MIM:614607] A form of Coffin-Siris syndrome, a congenital multiple malformation syndrome with broad phenotypic and genetic variability. Cardinal features are intellectual disability, coarse facial features, hypertrichosis, and hypoplastic or absent fifth digit nails or phalanges. Additional features include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Sucking/feeding difficulties, poor growth, ophthalmologic abnormalities, hearing impairment, and spinal anomalies are common findings. Both autosomal dominant and autosomal recessive inheritance patterns have been reported. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
O14497-1	1	yes
O14497-2	2
O14497-3	3

RefSeq proteins (2): NP_006006, NP_624361 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001606	ARID_dom	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR021906	BAF250/Osa	Family
IPR030094	ARID1A_ARID_BRIGHT_DNA-bd	Domain
IPR033388	BAF250_C	Domain
IPR036431	ARID_dom_sf	Homologous_superfamily

Pfam: PF01388, PF12031

UniProt features (157 total): compositionally biased region 34, helix 30, modified residue 27, sequence conflict 24, strand 9, turn 6, region of interest 6, sequence variant 6, short sequence motif 5, mutagenesis site 5, splice variant 2, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
6LTH	ELECTRON MICROSCOPY	3
9RL4	ELECTRON MICROSCOPY	3.5
6LTJ	ELECTRON MICROSCOPY	3.7
9RN2	ELECTRON MICROSCOPY	4.1
9RMC	ELECTRON MICROSCOPY	4.2
9RN1	ELECTRON MICROSCOPY	5.9
1RYU	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14497-F1	47.81	0.17

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 (27): 2, 58, 79, 233, 286, 301, 363, 382, 429, 604, 696, 698, 702, 730, 764, 772, 1184, 1235, 1276, 1604 …

Mutagenesis-validated functional residues (5):

Position	Phenotype
1073	partial loss of dna-binding activity. complete loss of activity; when associated with a-1096.
1096	partial loss of dna-binding activity. complete loss of activity; when associated with a-1073.
1370–1371	displays nucleocytoplasmic localization and increased stability; when associated with t-1383.
1383	displays nucleocytoplasmic localization and increased stability; when associated with 1370-t-t-1371.
1656–1658	no effect on subcellular localization.

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-3214858	RMTs methylate histone arginines
R-HSA-8939243	RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known
R-HSA-9764790	Positive Regulation of CDH1 Gene Transcription
R-HSA-9824585	Regulation of MITF-M-dependent genes involved in pigmentation
R-HSA-9845323	Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)
R-HSA-9933937	Formation of the canonical BAF (cBAF) complex
R-HSA-9933946	Formation of the embryonic stem cell BAF (esBAF) complex
R-HSA-9934037	Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)
R-HSA-1266738	Developmental Biology
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-212436	Generic Transcription Pathway
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878171	Transcriptional regulation by RUNX1
R-HSA-9730414	MITF-M-regulated melanocyte development
R-HSA-9842860	Regulation of endogenous retroelements
R-HSA-9856651	MITF-M-dependent gene expression

MSigDB gene sets: 701 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CHROMOSOME_ORGANIZATION, MODULE_52, TAATAAT_MIR126, MYOGENIN_Q6, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, LFA1_Q6, GCM_ZNF198, GOBP_CELL_CYCLE_PHASE_TRANSITION, MAZ_Q6, AP4_Q6, MODULE_16, AAAYRNCTG_UNKNOWN

GO Biological Process (16): nucleosome disassembly (GO:0006337), chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), nervous system development (GO:0007399), regulation of mitotic metaphase/anaphase transition (GO:0030071), positive regulation of T cell differentiation (GO:0045582), positive regulation of cell differentiation (GO:0045597), positive regulation of myoblast differentiation (GO:0045663), transcription initiation-coupled chromatin remodeling (GO:0045815), positive regulation of DNA-templated transcription (GO:0045893), regulation of G0 to G1 transition (GO:0070316), positive regulation of stem cell population maintenance (GO:1902459), regulation of G1/S transition of mitotic cell cycle (GO:2000045), positive regulation of double-strand break repair (GO:2000781), regulation of nucleotide-excision repair (GO:2000819), chromatin organization (GO:0006325)

GO Molecular Function (5): DNA binding (GO:0003677), transcription coactivator activity (GO:0003713), nuclear receptor binding (GO:0016922), protein binding (GO:0005515), nucleosome binding (GO:0031491)

GO Cellular Component (8): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), SWI/SNF complex (GO:0016514), brahma complex (GO:0035060), npBAF complex (GO:0071564), nBAF complex (GO:0071565), bBAF complex (GO:0140092)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
SWI/SNF chromatin remodelers	3
Gene expression (Transcription)	2
Chromatin modifying enzymes	1
Transcriptional regulation by RUNX1	1
Regulation of CDH1 Gene Transcription	1
MITF-M-dependent gene expression	1
Regulation of endogenous retroelements	1
RNA Polymerase II Transcription	1
Chromatin organization	1
Generic Transcription Pathway	1
Developmental Biology	1
Epigenetic regulation of gene expression	1
MITF-M-regulated melanocyte development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
SWI/SNF superfamily-type complex	5
regulation of DNA-templated transcription	2
regulation of mitotic cell cycle phase transition	2
positive regulation of developmental process	2
cellular anatomical structure	2
protein-DNA complex disassembly	1
nucleosome organization	1
chromatin organization	1
transcription by RNA polymerase II	1
system development	1
metaphase/anaphase transition of mitotic cell cycle	1
regulation of metaphase/anaphase transition of cell cycle	1
T cell differentiation	1
regulation of T cell differentiation	1
positive regulation of lymphocyte differentiation	1
positive regulation of T cell activation	1
cell differentiation	1
regulation of cell differentiation	1
positive regulation of cellular process	1
myoblast differentiation	1
positive regulation of cell differentiation	1
regulation of myoblast differentiation	1
transcription initiation at RNA polymerase II promoter	1
positive regulation of gene expression, epigenetic	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
regulation of cell cycle process	1
G0 to G1 transition	1
stem cell population maintenance	1
positive regulation of multicellular organismal process	1
regulation of stem cell population maintenance	1
G1/S transition of mitotic cell cycle	1
regulation of cell cycle G1/S phase transition	1
double-strand break repair	1
positive regulation of DNA repair	1
regulation of double-strand break repair	1
regulation of DNA repair	1
nucleotide-excision repair	1
cellular component organization	1
nucleic acid binding	1

Protein interactions and networks

STRING

2774 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARID1A	SMARCA4	P51532	997
ARID1A	SMARCB1	Q12824	997
ARID1A	PBRM1	Q86U86	997
ARID1A	SMARCC1	Q92922	996
ARID1A	SMARCA2	P51531	996
ARID1A	SMARCE1	Q969G3	996
ARID1A	SMARCC2	Q8TAQ2	995
ARID1A	SMARCD1	Q96GM5	994
ARID1A	ACTL6A	O96019	993
ARID1A	DPF2	Q92785	989
ARID1A	ARID2	Q68CP9	989
ARID1A	ARID1B	Q8NFD5	983
ARID1A	DPF1	Q92782	983
ARID1A	MSH2	P43246	970
ARID1A	BRD7	Q9NPI1	962

IntAct

201 interactions, top by confidence:

A	B	Type	Score
ARID1A	SMARCA4	psi-mi:“MI:0914”(association)	0.940
SMARCA4	ARID1A	psi-mi:“MI:0914”(association)	0.940
SMARCA4	ARID1A	psi-mi:“MI:0915”(physical association)	0.940
ARID1A	SMARCA4	psi-mi:“MI:0915”(physical association)	0.940
SMARCB1	ARID1A	psi-mi:“MI:0914”(association)	0.860
SMARCE1	ARID1A	psi-mi:“MI:0914”(association)	0.840

BioGRID (501): ARID1A (Affinity Capture-RNA), ARID1A (Affinity Capture-RNA), ARID1A (Affinity Capture-RNA), ARID1A (Affinity Capture-MS), ARID1A (Affinity Capture-MS), ARID1A (Affinity Capture-MS), ARID1A (Affinity Capture-MS), ARID1A (Affinity Capture-MS), ARID1A (Affinity Capture-MS), ARID1A (Affinity Capture-RNA), ARID1A (Co-fractionation), ARID1A (Co-fractionation), ARID1A (Co-fractionation), ARID1A (Co-fractionation), ARID1A (Co-fractionation)

ESM2 similar proteins: A1YFU7, A2AJK6, A2BH40, B2RWS6, D3YWE6, E9Q4N7, M9NEY8, O00512, O14497, O35126, O42368, O43365, O57401, P02831, P02833, P22810, P23441, P23512, P25822, P32182, P34545, P35582, P35583, P43698, P43699, P50220, P50901, P54258, P54259, P54269, P55317, Q06A37, Q08DG7, Q08E31, Q09472, Q0VCT9, Q10571, Q1KKX7, Q24248, Q24645

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

8 interactions.

A	Effect	B	Mechanism
ARID1A	“form complex”	“SWI/SNF complex”	binding
ARID1A	“form complex”	“SWI/SNF ACTL6A-ARID1A-SMARCA2 variant”	binding
ARID1A	“form complex”	“Neural progenitor-specific SWI/SNF”	binding
ARID1A	“form complex”	“Muscle cell-specific SWI/SNF ARID1A variant”	binding
ARID1A	“form complex”	“Muscle cell-specific SWI/SNF SMARCA4 variant”	binding
ARID1A	“form complex”	“Brain-specific SWI/SNF SMARCA2 variant”	binding
ARID1A	“form complex”	“Brain-specific SWI/SNF SMARCA4 variant”	binding
ARID1A	“form complex”	“Embryonic stem cell-specific SWI/SNF”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 148 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
Formation of the canonical BAF (cBAF) complex	16	93.1×	4e-29
Formation of the non-canonical BAF (ncBAF) complex	13	80.1×	6e-22
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	19	79.6×	8e-32
Formation of the embryonic stem cell BAF (esBAF) complex	14	77.2×	4e-23
Formation of the polybromo-BAF (pBAF) complex	13	75.7×	2e-21
Regulation of MITF-M-dependent genes involved in pigmentation	21	51.2×	1e-29
Regulation of endogenous retroelements	15	50.7×	4e-21
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	12	33.1×	3e-14

GO biological processes:

GO term	Partners	Fold	FDR
regulation of G0 to G1 transition	17	86.2×	3e-28
regulation of nucleotide-excision repair	17	76.9×	3e-27
regulation of mitotic metaphase/anaphase transition	17	63.4×	3e-25
nucleosome disassembly	9	54.3×	2e-12
positive regulation of T cell differentiation	13	44.5×	8e-17
positive regulation of double-strand break repair	17	44.0×	6e-22
positive regulation of myoblast differentiation	15	41.3×	7e-19
regulation of G1/S transition of mitotic cell cycle	17	39.2×	5e-21

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 38 cancer types — BL, BLCA, BRCA, CCRCC, CESC, CHOL, CLLSLL, COAD, COADREAD, DLBCLNOS, EGC, ESCA…(+26 more).

Clinical variants and AI predictions

ClinVar

1925 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	85
Likely pathogenic	53
Uncertain significance	762
Likely benign	540
Benign	192

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1065491	NM_006015.6(ARID1A):c.175G>T (p.Glu59Ter)	Pathogenic
1120179	NM_006015.6(ARID1A):c.5940_6000del (p.Val1982fs)	Pathogenic
1177329	NM_006015.6(ARID1A):c.166C>T (p.Gln56Ter)	Pathogenic
1177330	NM_006015.6(ARID1A):c.1708_1766del (p.Pro570fs)	Pathogenic
1177343	NM_006015.6(ARID1A):c.2914del (p.Asp972fs)	Pathogenic
1323396	NM_006015.6(ARID1A):c.1850C>A (p.Ser617Ter)	Pathogenic
1323404	NM_006015.6(ARID1A):c.2122C>T (p.Gln708Ter)	Pathogenic
1338402	NM_006015.6(ARID1A):c.666C>G (p.Tyr222Ter)	Pathogenic
1675353	NM_006015.6(ARID1A):c.1642C>T (p.Gln548Ter)	Pathogenic
1693158	NM_006015.6(ARID1A):c.6625C>T (p.Gln2209Ter)	Pathogenic
1699033	NM_006015.6(ARID1A):c.3058A>T (p.Arg1020Trp)	Pathogenic
1701098	NM_006015.6(ARID1A):c.148_149delinsTA (p.Met50Ter)	Pathogenic
1735301	NM_006015.6(ARID1A):c.3826C>T (p.Arg1276Ter)	Pathogenic
1746859	NM_006015.6(ARID1A):c.5329G>T (p.Glu1777Ter)	Pathogenic
1760779	NM_006015.6(ARID1A):c.1251C>G (p.Tyr417Ter)	Pathogenic
2097717	NM_006015.6(ARID1A):c.4563del (p.Ala1522fs)	Pathogenic
210259	NM_006015.6(ARID1A):c.394del (p.Val132fs)	Pathogenic
225842	NM_006015.6(ARID1A):c.5965C>T (p.Arg1989Ter)	Pathogenic
225843	NM_006015.6(ARID1A):c.1113del (p.Gln372fs)	Pathogenic
225844	NM_006015.6(ARID1A):c.3679G>T (p.Glu1227Ter)	Pathogenic
235660	NM_006015.6(ARID1A):c.1207C>T (p.Gln403Ter)	Pathogenic
2412701	NM_006015.6(ARID1A):c.4087C>T (p.Gln1363Ter)	Pathogenic
2425459	NC_000001.10:g.(?27092692)(27094510_?)del	Pathogenic
2442347	NM_006015.6(ARID1A):c.1015del (p.Ala339fs)	Pathogenic
2443219	NM_006015.6(ARID1A):c.1397del (p.Gly466fs)	Pathogenic
2446550	NM_006015.6(ARID1A):c.3185G>T (p.Gly1062Val)	Pathogenic
2576602	NM_006015.6(ARID1A):c.284del (p.Gly95fs)	Pathogenic
2582238	NM_006015.6(ARID1A):c.511C>T (p.Gln171Ter)	Pathogenic
2582239	NM_006015.6(ARID1A):c.1813C>T (p.Gln605Ter)	Pathogenic
2582240	NM_006015.6(ARID1A):c.2434C>T (p.Gln812Ter)	Pathogenic

SpliceAI

2653 predictions. Top by Δscore:

Variant	Effect	Δscore
1:26729754:GACA:G	donor_gain	1.0000
1:26731148:ACAG:A	acceptor_loss	1.0000
1:26731149:CAGAT:C	acceptor_loss	1.0000
1:26731150:A:AG	acceptor_gain	1.0000
1:26731150:A:T	acceptor_loss	1.0000
1:26731151:G:GA	acceptor_gain	1.0000
1:26731604:GGTAA:G	donor_loss	1.0000
1:26731605:GTAAG:G	donor_loss	1.0000
1:26731606:T:A	donor_loss	1.0000
1:26732670:TTGTA:T	acceptor_loss	1.0000
1:26732671:TGTA:T	acceptor_loss	1.0000
1:26732672:GTA:G	acceptor_loss	1.0000
1:26732673:TA:T	acceptor_loss	1.0000
1:26732789:GCCT:G	donor_gain	1.0000
1:26732790:CCTG:C	donor_loss	1.0000
1:26732791:CTG:C	donor_loss	1.0000
1:26732792:TGT:T	donor_loss	1.0000
1:26732793:G:GC	donor_loss	1.0000
1:26732793:G:GG	donor_gain	1.0000
1:26732794:TG:T	donor_loss	1.0000
1:26732796:A:AC	donor_loss	1.0000
1:26760954:GA:G	donor_gain	1.0000
1:26760965:C:G	donor_gain	1.0000
1:26761372:T:TA	acceptor_gain	1.0000
1:26761376:T:TA	acceptor_gain	1.0000
1:26761382:AGGC:A	acceptor_loss	1.0000
1:26761472:AGGT:A	donor_loss	1.0000
1:26761474:GTGAG:G	donor_loss	1.0000
1:26761475:T:A	donor_loss	1.0000
1:26766207:A:AG	acceptor_gain	1.0000

AlphaMissense

14928 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:26760919:A:C	S662R	1.000
1:26760921:C:A	S662R	1.000
1:26760921:C:G	S662R	1.000
1:26760937:A:C	S668R	1.000
1:26760939:C:A	S668R	1.000
1:26760939:C:G	S668R	1.000
1:26760976:T:C	F681L	1.000
1:26760978:C:A	F681L	1.000
1:26760978:C:G	F681L	1.000
1:26767861:G:C	R1020S	1.000
1:26767861:G:T	R1020S	1.000
1:26767868:T:A	W1023R	1.000
1:26767868:T:C	W1023R	1.000
1:26767870:G:C	W1023C	1.000
1:26767870:G:T	W1023C	1.000
1:26767880:T:G	Y1027D	1.000
1:26767884:T:C	L1028P	1.000
1:26767889:T:C	F1030L	1.000
1:26767890:T:C	F1030S	1.000
1:26767891:C:A	F1030L	1.000
1:26767891:C:G	F1030L	1.000
1:26767926:C:A	P1042H	1.000
1:26767926:C:G	P1042R	1.000
1:26767929:C:A	A1043D	1.000
1:26767932:T:A	V1044E	1.000
1:26767934:G:C	G1045R	1.000
1:26767935:G:A	G1045D	1.000
1:26767953:T:A	L1051H	1.000
1:26767953:T:C	L1051P	1.000
1:26767962:T:A	L1054H	1.000

dbSNP variants (sampled 300 via entrez): RS1000007217 (1:26738731 G>A), RS1000056798 (1:26694965 C>A,T), RS1000077676 (1:26699100 T>C,G), RS1000085351 (1:26694238 C>G), RS1000102811 (1:26743812 T>C), RS1000127957 (1:26773294 A>G,T), RS1000138282 (1:26732440 C>CA), RS1000152818 (1:26742165 A>G), RS1000153041 (1:26699380 G>A), RS1000157153 (1:26713980 G>A,T), RS1000166629 (1:26743173 A>G), RS1000168612 (1:26705526 A>G), RS1000294869 (1:26710700 G>C), RS1000300865 (1:26732765 C>G,T), RS1000328468 (1:26734720 G>T)

Disease associations

OMIM: gene MIM:603024 | disease phenotypes: MIM:614607, MIM:135900, MIM:609943, MIM:614562, MIM:236750, MIM:182230, MIM:613861, MIM:109800, MIM:155255, MIM:213000, MIM:114500

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, autosomal dominant 14	Definitive	Autosomal dominant
Coffin-Siris syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Coffin-Siris syndrome	Definitive	AD

Mondo (20): intellectual disability, autosomal dominant 14 (MONDO:0013819), Coffin-Siris syndrome 1 (MONDO:0007617), neurodevelopmental disorder (MONDO:0700092), non-immune hydrops fetalis (MONDO:0009369), Coffin-Siris syndrome (MONDO:0015452), intellectual disability (MONDO:0001071), skeletal dysplasia (MONDO:0018230), septooptic dysplasia (MONDO:0008428), retinitis pigmentosa 59 (MONDO:0013468), endometrial carcinoma (MONDO:0002447), urinary bladder cancer (MONDO:0001187), obesity disorder (MONDO:0011122), astrocytoma (excluding glioblastoma) (MONDO:0019781), hepatoblastoma (MONDO:0018666), medulloblastoma (MONDO:0007959)

Orphanet (16): Coffin-Siris syndrome (Orphanet:1465), Non-immune hydrops fetalis (Orphanet:363999), Primary bone dysplasia (Orphanet:364526), Septo-optic dysplasia spectrum (Orphanet:3157), Retinitis pigmentosa (Orphanet:791), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), Hepatoblastoma (Orphanet:449), Medulloblastoma (Orphanet:616), Isolated cerebellar agenesis (Orphanet:1398), Cerebellar hypoplasia-tapetoretinal degeneration syndrome (Orphanet:2246), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Bladder cancer (Orphanet:157980), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399), NON RARE IN EUROPE: Periventricular leukomalacia (Orphanet:171676), NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667)

HPO phenotypes

89 total (30 of 89 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000085	Horseshoe kidney
HP:0000119	Abnormality of the genitourinary system
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000175	Cleft palate
HP:0000179	Thick lower lip vermilion
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000280	Coarse facial features
HP:0000289	Broad philtrum
HP:0000294	Low anterior hairline
HP:0000322	Short philtrum
HP:0000343	Long philtrum
HP:0000365	Hearing impairment
HP:0000377	Abnormal pinna morphology
HP:0000445	Wide nose
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000527	Long eyelashes
HP:0000545	Myopia
HP:0000574	Thick eyebrow
HP:0000684	Delayed eruption of teeth

GWAS associations

36 associations (top):

Study	Trait	p-value
GCST003245_7	White matter hyperintensities in ischemic stroke	2.000000e-06
GCST004608_3	Granulocyte percentage of myeloid white cells	2.000000e-12
GCST004609_173	Monocyte percentage of white cells	6.000000e-12
GCST005790_77	Rosacea symptom severity	1.000000e-06
GCST006288_252	Heel bone mineral density	1.000000e-09
GCST006288_600	Heel bone mineral density	4.000000e-11
GCST006979_870	Heel bone mineral density	2.000000e-25
GCST007611_16	Chronic obstructive pulmonary disease or high blood pressure (pleiotropy)	6.000000e-12
GCST008070_3	HDL cholesterol levels	2.000000e-07
GCST008070_99	HDL cholesterol levels	5.000000e-07
GCST008074_59	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-06
GCST008074_84	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-06
GCST008075_106	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-18
GCST008075_32	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-19
GCST008078_104	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-14
GCST008078_12	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-15
GCST008079_161	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4.000000e-13
GCST008079_19	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	7.000000e-14
GCST008083_126	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	7.000000e-07
GCST008083_52	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	1.000000e-06
GCST008084_105	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	7.000000e-156
GCST008084_145	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	4.000000e-154
GCST008085_161	HDL cholesterol levels in current drinkers	6.000000e-09
GCST008085_172	HDL cholesterol levels in current drinkers	4.000000e-08
GCST009602_9	Metabolic syndrome	2.000000e-12
GCST010241_185	Apolipoprotein A1 levels	2.000000e-28
GCST010242_469	HDL cholesterol levels	4.000000e-38
GCST010243_188	Apolipoprotein B levels	1.000000e-38
GCST010244_58	Triglyceride levels	4.000000e-35
GCST010245_167	LDL cholesterol levels	8.000000e-16

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0005665	white matter hyperintensity measurement
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0009180	rosacea severity measurement
EFO:0009270	heel bone mineral density
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0000195	metabolic syndrome
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004574	total cholesterol measurement
EFO:0004833	neutrophil count
EFO:0007985	platelet crit
EFO:0004309	platelet count

MeSH disease descriptors (10)

Descriptor	Name	Tree numbers
D001254	Astrocytoma	C04.557.465.625.600.380.080; C04.557.470.670.380.080; C04.557.580.625.600.380.080
D018197	Hepatoblastoma	C04.557.435.380
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D007969	Leukomalacia, Periventricular	C10.228.140.300.700; C10.228.140.461.550; C14.907.253.612; C16.614.521.450
D008527	Medulloblastoma	C04.557.465.625.600.380.515; C04.557.465.625.600.590.500; C04.557.470.670.380.515; C04.557.470.670.590.500; C04.557.580.625.600.380.515; C04.557.580.625.600.590.500
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D025962	Septo-Optic Dysplasia	C10.292.562.700.375.875; C10.500.034.937; C10.500.760.500; C11.590.436.400.875; C16.131.666.034.937; C16.131.666.763.500
C562568	Cerebellar Hypoplasia (supp.)
C536436	Coffin-Siris syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066172 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 7 predictive associations from 7 curated evidence items; also 3 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
ARID1A Loss OR ARID1A Wildtype	Dasatinib	Ovarian Clear Cell Carcinoma	Sensitivity/Response	CIViC B	EID11789
ARID1A Loss	Dasatinib	Ovarian Clear Cell Carcinoma	Sensitivity/Response	CIViC D	EID2982
ARID1A Loss	GSK126	Ovarian Clear Cell Carcinoma	Sensitivity/Response	CIViC D	EID2983
ARID1A Loss	Atezolizumab + Pembrolizumab + Nivolumab	Ovarian Cancer	Sensitivity/Response	CIViC D	EID6399
ARID1A Loss	Sorafenib	Liver Cancer	Sensitivity/Response	CIViC D	EID7328
ARID1A P1175FS*5	Dasatinib	Ovarian Clear Cell Carcinoma	Sensitivity/Response	CIViC D	EID4826
ARID1A Q456*	Dasatinib	Colorectal Cancer	Sensitivity/Response	CIViC D	EID4487

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
Fulvestrant	decreases response to substance, affects cotreatment, increases methylation, increases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
methylmercuric chloride	increases expression, affects cotreatment	2
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
Arsenic Trioxide	increases response to substance, increases sumoylation	2
Aflatoxin B1	decreases methylation	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
mivebresib	decreases expression	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
lasiocarpine	decreases expression, increases metabolic processing	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	increases abundance, decreases expression	1
coumarin	affects phosphorylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697246	Binding	Inhibition of ARID1A (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

63 cell lines: 56 cancer cell line, 3 spontaneously immortalized cell line, 2 transformed cell line, 2 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0017	U-698-M	Cancer cell line	Male
CVCL_0454	SNU-449	Cancer cell line	Male
CVCL_0505	RL95-2	Cancer cell line	Female
CVCL_0629	SK-LU-1	Cancer cell line	Female
CVCL_1121	ChaGo-K-1	Cancer cell line	Male
CVCL_1186	EB2 [Human Burkitt lymphoma]	Cancer cell line	Female
CVCL_1266	HCC2998	Cancer cell line	Sex unspecified
CVCL_1325	Karpas-422	Cancer cell line	Female
CVCL_1356	KYSE-70	Cancer cell line	Male
CVCL_1404	MES-SA	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays