ARID3A

Summary

ARID3A (AT-rich interaction domain 3A, HGNC:3031) is a protein-coding gene on chromosome 19p13.3, encoding AT-rich interactive domain-containing protein 3A (Q99856). Transcription factor which may be involved in the control of cell cycle progression by the RB1/E2F1 pathway and in B-cell differentiation.

This gene encodes a member of the ARID (AT-rich interaction domain) family of DNA binding proteins. It was found by homology to the Drosophila dead ringer gene, which is important for normal embryogenesis. Other ARID family members have roles in embryonic patterning, cell lineage gene regulation, cell cycle control, transcriptional regulation, and possibly in chromatin structure modification.

Source: NCBI Gene 1820 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 138 total — 3 pathogenic
• Transcription factor: yes — 10 downstream targets (CollecTRI)
• MANE Select transcript: NM_005224

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3031
Approved symbol	ARID3A
Name	AT-rich interaction domain 3A
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	BRIGHT
Ensembl gene	ENSG00000116017
Ensembl biotype	protein_coding
OMIM	603265
Entrez	1820

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000263620, ENST00000457152, ENST00000585733, ENST00000585895, ENST00000587532, ENST00000590749, ENST00000592216, ENST00000852898, ENST00000937801, ENST00000937802

RefSeq mRNA: 1 — MANE Select: NM_005224 NM_005224

CCDS: CCDS12050

Canonical transcript exons

ENST00000263620 — 9 exons

Exon	Start	End
ENSE00000769032	932418	932742
ENSE00000769035	964833	965080
ENSE00000769037	966572	966868
ENSE00000892195	929262	929896
ENSE00001366881	926035	926059
ENSE00001710382	971878	975939
ENSE00003668103	964248	964431
ENSE00003691519	968405	968503
ENSE00003696955	960092	960164

Expression profiles

Bgee: expression breadth ubiquitous, 187 present calls, max score 88.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.8109 / max 342.1206, expressed in 1743 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172808	6.1169	1455
172809	3.4276	1084
172807	2.6360	1016
172810	0.9813	548
172814	0.2628	129
172815	0.2211	96
172812	0.1164	23
172811	0.0245	9
172813	0.0242	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	88.99	gold quality
mononuclear cell	CL:0000842	88.38	gold quality
blood	UBERON:0000178	88.36	gold quality
leukocyte	CL:0000738	87.97	gold quality
placenta	UBERON:0001987	86.19	gold quality
bone marrow cell	CL:0002092	86.07	gold quality
left testis	UBERON:0004533	85.73	gold quality
right testis	UBERON:0004534	85.61	gold quality
stromal cell of endometrium	CL:0002255	84.92	gold quality
buccal mucosa cell	CL:0002336	82.93	silver quality
granulocyte	CL:0000094	82.84	gold quality
testis	UBERON:0000473	82.29	gold quality
sural nerve	UBERON:0015488	81.56	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.50	gold quality
amniotic fluid	UBERON:0000173	80.78	gold quality
bone marrow	UBERON:0002371	79.53	gold quality
trabecular bone tissue	UBERON:0002483	78.24	gold quality
bone element	UBERON:0001474	78.21	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.08	silver quality
right hemisphere of cerebellum	UBERON:0014890	76.63	gold quality
cerebellar hemisphere	UBERON:0002245	76.42	gold quality
cerebellar cortex	UBERON:0002129	76.37	gold quality
spleen	UBERON:0002106	76.35	gold quality
right lung	UBERON:0002167	75.88	gold quality
upper lobe of left lung	UBERON:0008952	75.77	gold quality
upper lobe of lung	UBERON:0008948	75.48	gold quality
decidua	UBERON:0002450	75.12	silver quality
mucosa of stomach	UBERON:0001199	75.04	gold quality
cerebellum	UBERON:0002037	74.81	gold quality
vermiform appendix	UBERON:0001154	74.75	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	677.71
E-MTAB-6701	yes	80.45
E-MTAB-6678	yes	16.21
E-MTAB-9467	yes	13.58
E-MTAB-9067	yes	12.86
E-CURD-112	yes	12.51
E-ANND-3	yes	7.91
E-MTAB-8060	no	774.97

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

10 targets.

Target	Regulation
ATP11C
CDC6	Unknown
CDK1	Unknown
CDKN1A	Unknown
CR2	Unknown
E2F1	Unknown
IGHV1-69	Unknown
IGHV3-23	Unknown
PML	Activation
RBL1	Unknown

Upstream regulators (CollecTRI, top): BCOR, CBX8, TP53

miRNA regulators (miRDB)

75 targeting ARID3A, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
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-1252-5P	100.00	69.80	2774
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-202-3P	99.84	71.41	1290

Literature-anchored findings (GeneRIF, showing 39)

• Results show that DRIL1 disrupts cellular protection against RAS(V12)-induced proliferation downstream of the p19(ARF)/p53 pathway. (PMID:11812999)
• role in p53 regulatory pathway.(E2FBP1) (PMID:12136662)
• Variations in Bright binding and matrix attachment region activity contribute to localized control of accessibility and therefore nonrandom gene use during V(D)J recombination. (PMID:12193717)
• a putative p53-binding site was found, which specifically responded to p53, in the second intron of the E2FBP1/DRIL1 gene (PMID:12692263)
• E2FBP1 modulates cell growth through down-regulation of promyelocytic leukemia bodies. (PMID:15017387)
• Bright is not expressed in all human B lymphocyte subpopulations. (PMID:15203319)
• TFII-I directly interacts with Bright through amino acids in Bright’s protein interaction domain (PMID:16738337)
• identify Bright as a contributor to accessibility of the IgH enhancer (PMID:17386101)
• Id1 inhibited DNA binding by Dril1, and the two proteins co-localized in vitro and in vivo, providing a potential mechanism for suppression of fibrosis by Id1 through inhibition of the profibrotic function of Dril1. (PMID:18583319)
• A palmitoylated pool of Bright is diverted to lipid rafts of resting B cells where it associates with signalosome components. (PMID:19214191)
• Solution NMR structure of the ARID domain of human ARID3A. (PMID:20455271)
• Bright/ARID3a inhibition causes increased developmental plasticity in mouse and human cells. (PMID:20680960)
• report that E2FBP1 inhibits accumulation of ICP0 RNA and, at the same time, is degraded via ICP0’s herpes ubiquitin ligase 2 (HUL-2) activity upon HSV-1 infection. (PMID:21248039)
• functions as a critical antagonist to the p16(INK4A)-Rb tumor suppressor machinery by regulating promyelocytic leukemia protein stability (PMID:22010578)
• These results indicate both cooperative and interdependent roles for ARID3A and p53 in the transcriptional activation of p21(WAF1) in response to DNA damage. (PMID:22172947)
• These findings support the hypothesis that Epstein-Barr virus EBNA1 initiates transcription at the C promoter via interactions between multiple EBNA1 homodimers and cellular transcription such as E2F1, ARID3A and Oct-2. (PMID:22302879)
• miR-125b can act as an oncogene in B-cell acute lymphoblastic leukemia by targeting ARID3a and mediating its repression. (PMID:22469780)
• Systemic lupus erythematosus (SLE) patients had increased ARID3a+ B cells compared to healthy controls. ARID3a was not expressed in naive B cells of controls, but was abundant in SLE patients. Number of ARID3a+ B cells correlated with disease activity. (PMID:25185498)
• These data reveal new functions for ARID3a in early hematopoiesis and suggest that knowledge regarding ARID3a levels in HSPCs could be informative for applications requiring transplantation of those cells. (PMID:25535283)
• results suggest that appropriate regulation of ARID3a is critical for normal development of both myeloid and B lineage pathways. (PMID:26685208)
• Data indicate ARID3a(+) B cells as a type of effector B cell, and link ARID3a expression in B lymphocytes to interferon alpha (IFNa)-associated inflammatory responses in systemic lupus erythematosus (SLE). (PMID:27522115)
• these data identify ARID3a as a potential transcription regulator of IFNalpha-related inflammatory responses and other pathways important for systemic lupus erythematosus disease activity (PMID:30297159)
• Study demonstrated that ARID3A overexpression is an independent prognostic factor for cancer-specific survival in patients with surgically resected residual rectal cancer after neoadjuvant chemoradiotherapy and plays an important role in rectal cancer. (PMID:31177122)
• The associations of ARID3a expression with increased disease severity in Systemic Lupus Erythematosus (SLE), suggest that it, or its downstream targets, may provide new therapeutic targets for SLE. [review] (PMID:31554207)
• ARID3A was verified as a direct target gene of miR-574-5p and decreased level of ARID3A forced fibroblast-to-myofibroblast differentiation of TGF-beta-induced human cardiac fibroblasts. (PMID:31672272)
• Study provides a comprehensive list of genes and pathways regulated by ARID3A and ARID3B in ovarian cancer cells. (PMID:32061921)
• Long noncoding RNA ERICD interacts with ARID3A via E2F1 and regulates migration and proliferation of osteosarcoma cells. (PMID:32749762)
• TLR engagement induces ARID3a in human blood hematopoietic progenitors and modulates IFNalpha production. (PMID:32979763)
• ARID3A promotes the development of colorectal cancer by upregulating AURKA. (PMID:33165575)
• Distinct and overlapping roles of ARID3A and ARID3B in regulating E2Fdependent transcription via direct binding to E2F target genes. (PMID:33649863)
• The megakaryocytic transcription factor ARID3A suppresses leukemia pathogenesis. (PMID:34570885)
• Deficiencies in the DNA Binding Protein ARID3a Alter Chromatin Structures Important for Early Human Erythropoiesis. (PMID:34663594)
• ARID3A regulates autophagy related gene BECN1 expression and inhibits proliferation of osteosarcoma cells. (PMID:34801937)
• MiR-361-3p promotes tumorigenesis of osteosarcoma cells via targeting ARID3A. (PMID:35219069)
• ARID3A promotes the chemosensitivity of colon cancer by inhibiting AKR1C3. (PMID:35257428)
• Hepatic ARID3A facilitates liver cancer malignancy by cooperating with CEP131 to regulate an embryonic stem cell-like gene signature. (PMID:36008383)
• Several genetic variants associated with systemic sclerosis in a Chinese Han population. (PMID:36301368)
• A regulatory variant at 19p13.3 is associated with primary biliary cholangitis risk and ARID3A expression. (PMID:36977669)
• ARID3A variant and the risk of primary biliary cholangitis in a Central European cohort. (PMID:38036008)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	arid3a	ENSDARG00000070843
mus_musculus	Arid3a	ENSMUSG00000019564
rattus_norvegicus	Arid3a	ENSRNOG00000026435
drosophila_melanogaster	retn	FBGN0004795
caenorhabditis_elegans	cfi-1	WBGENE00000476

Paralogs (2): ARID3B (ENSG00000179361), ARID3C (ENSG00000205143)

Protein

Protein identifiers

AT-rich interactive domain-containing protein 3A — Q99856 (reviewed: Q99856)

Alternative names: B-cell regulator of IgH transcription, Dead ringer-like protein 1, E2F-binding protein 1

All UniProt accessions (3): Q99856, H0YFY1, K7EJ04

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor which may be involved in the control of cell cycle progression by the RB1/E2F1 pathway and in B-cell differentiation.

Subunit / interactions. Homodimer. Heterodimer with ARID3B. Interacts with E2F1. Interacts with GTF2I and BTK.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Widely expressed, with highest expression in skeletal muscle, thalamus, and colon.

Induction. By p53/TP53 following DNA damage.

RefSeq proteins (1): NP_005215* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001606	ARID_dom	Domain
IPR023334	REKLES_domain	Domain
IPR036431	ARID_dom_sf	Homologous_superfamily
IPR045147	ARI3A/B/C	Family

Pfam: PF01388

UniProt features (48 total): helix 9, modified residue 8, region of interest 7, mutagenesis site 7, compositionally biased region 6, cross-link 4, sequence variant 3, domain 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4LJX	X-RAY DIFFRACTION	2.21
2KK0	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99856-F1	62.23	0.22

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 (12): 77, 81, 88, 98, 101, 119, 353, 362, 398, 399, 452, 462

Mutagenesis-validated functional residues (7):

Position	Phenotype
325	abolishes dna-binding.
461	abolishes nuclear targeting.
527	impairs dna-binding but not self-association.
530	impairs dna-binding but not self-association.
530	no effect on dna-binding.
532	impairs dna-binding.
534	impairs dna-binding.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-6804116	TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-6791312	TP53 Regulates Transcription of Cell Cycle Genes
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 156 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, MODULE_45, MODULE_16, PATIL_LIVER_CANCER, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A5, MODULE_205, DER_IFN_BETA_RESPONSE_UP, MORF_PRKDC, BOYAULT_LIVER_CANCER_SUBCLASS_G1_UP, PID_P53_DOWNSTREAM_PATHWAY, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_UP, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, MODULE_98, MODULE_38, DURCHDEWALD_SKIN_CARCINOGENESIS_DN

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (5): DNA binding (GO:0003677), chromatin binding (GO:0003682), transcription coregulator activity (GO:0003712), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), membrane raft (GO:0045121), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
TP53 Regulates Transcription of Cell Cycle Genes	1
RNA Polymerase II Transcription	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
transcription by RNA polymerase II	2
binding	2
regulation of DNA-templated transcription	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
nucleic acid binding	1
transcription regulator activity	1
protein binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
membrane microdomain	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARID3A	IGHV4-38-2	P0DP08	644
ARID3A	BTK	Q06187	617
ARID3A	GTF2I	P78347	614
ARID3A	PRRX2	Q99811	563
ARID3A	TEAD4	Q15561	550
ARID3A	RBL2	Q08999	548
ARID3A	TP53	P04637	547
ARID3A	E2F1	Q01094	540
ARID3A	LIN28B	Q6ZN17	538
ARID3A	SP100	P23497	530
ARID3A	GATA2	P23769	528
ARID3A	KDM4C	Q9H3R0	520
ARID3A	NANOG	Q9H9S0	513
ARID3A	ARID5A	Q03989	503
ARID3A	KLF4	P78338	497

IntAct

123 interactions, top by confidence:

A	B	Type	Score
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
TTC32	ARID3A	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	ARID3A	psi-mi:“MI:0915”(physical association)	0.560
ARID3A	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
KRT31	ARID3A	psi-mi:“MI:0915”(physical association)	0.560
ARID3A	MORF4L1	psi-mi:“MI:0915”(physical association)	0.560
MORF4L2	ARID3A	psi-mi:“MI:0915”(physical association)	0.560
MAGEB4	ARID3A	psi-mi:“MI:0915”(physical association)	0.560
MAGEB2	ARID3A	psi-mi:“MI:0915”(physical association)	0.560
TIMM8A	ARID3A	psi-mi:“MI:0915”(physical association)	0.560
XPA	ARID3A	psi-mi:“MI:0915”(physical association)	0.560
ARID3A	ANKRD11	psi-mi:“MI:0915”(physical association)	0.560
REP15	ARID3A	psi-mi:“MI:0915”(physical association)	0.560
ARID3A	BTK	psi-mi:“MI:0915”(physical association)	0.560
LCN15	POTEF	psi-mi:“MI:0914”(association)	0.530
ARID3A	ARID3C	psi-mi:“MI:0914”(association)	0.530
FAM200C	CRLF3	psi-mi:“MI:0914”(association)	0.530
FOS	MYO1C	psi-mi:“MI:2364”(proximity)	0.480
IGHM	CD19	psi-mi:“MI:0914”(association)	0.480
EN1	NFIB	psi-mi:“MI:2364”(proximity)	0.470
ARID3A	IGHM	psi-mi:“MI:0403”(colocalization)	0.460
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
FOXB1	DDX39A	psi-mi:“MI:0914”(association)	0.350

BioGRID (362): TTC32 (Two-hybrid), NOTCH2NL (Two-hybrid), ARID3A (Affinity Capture-MS), ARID3A (Affinity Capture-MS), ARID3A (Affinity Capture-MS), ARID3A (Affinity Capture-MS), ARID3A (Affinity Capture-MS), ARID3C (Affinity Capture-MS), ARID3B (Affinity Capture-MS), ARID3A (Affinity Capture-MS), HERC2 (Affinity Capture-MS), ARID3A (Affinity Capture-MS), ARID3A (Affinity Capture-MS), ARID3A (Affinity Capture-MS), ARID3A (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JTZ2, A0A8I3PQN6, A1L1N5, A2BEA6, A4IFD2, A8WWH5, B3DM43, O02326, O15409, P0CF24, P24350, P31368, P31369, P40645, P40647, P58462, P58463, P70062, P70063, Q20733, Q24573, Q24705, Q2LE08, Q498D1, Q4H3P5, Q4VYR7, Q4VYS1, Q58NQ4, Q5QL03, Q5W1J5, Q5XGD9, Q62431, Q6GL68, Q6GQD7, Q800Q5, Q8HZ00, Q8IVW6, Q8MJ97, Q8MJ98, Q8MJ99

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

3 interactions.

A	Effect	B	Mechanism
ARID3A	“up-regulates quantity by expression”	“Immunoglobulin delta heavy chain”	“transcriptional regulation”
ARID3A	“up-regulates quantity by expression”	“Immunoglobulin mu heavy chain”	“transcriptional regulation”
GTF2I	“up-regulates activity”	ARID3A	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 110 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
RNA Polymerase III Transcription Termination	5	34.5×	9e-05
RNA Polymerase III Abortive And Retractive Initiation	5	19.3×	6e-04
Gastrulation	5	18.0×	6e-04
Deactivation of the beta-catenin transactivating complex	5	16.2×	9e-04
TCF dependent signaling in response to WNT	5	8.2×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
neuron fate specification	5	33.8×	5e-05
positive regulation of miRNA transcription	6	16.8×	2e-04
positive regulation of transcription initiation by RNA polymerase II	6	15.7×	2e-04
retina development in camera-type eye	5	12.3×	3e-03
response to wounding	5	10.7×	5e-03
anatomical structure morphogenesis	7	9.4×	7e-04
transcription by RNA polymerase II	13	8.8×	6e-07
neuron differentiation	8	7.7×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	108
Likely benign	8
Benign	5

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
145089	GRCh38/hg38 19p13.3(chr19:839492-995558)x1	Pathogenic
584004	NC_000019.9:g.(?852323)(1226652_?)del	Pathogenic
816518	GRCh37/hg19 19p13.3(chr19:260912-4384674)x3	Pathogenic

SpliceAI

1802 predictions. Top by Δscore:

Variant	Effect	Δscore
19:929256:CCTCA:C	acceptor_loss	1.0000
19:929257:CTCA:C	acceptor_loss	1.0000
19:929258:TCAG:T	acceptor_loss	1.0000
19:929259:CAGGT:C	acceptor_loss	1.0000
19:929261:G:A	acceptor_loss	1.0000
19:929892:GACAT:G	donor_gain	1.0000
19:929894:CATGT:C	donor_loss	1.0000
19:929895:ATG:A	donor_loss	1.0000
19:929896:TGTG:T	donor_loss	1.0000
19:929897:G:GG	donor_gain	1.0000
19:929897:GTGA:G	donor_loss	1.0000
19:960090:A:AG	acceptor_gain	1.0000
19:960091:G:GA	acceptor_gain	1.0000
19:960160:GCGAG:G	donor_gain	1.0000
19:960162:GAGGT:G	donor_loss	1.0000
19:960163:AGGT:A	donor_loss	1.0000
19:960164:GGTG:G	donor_loss	1.0000
19:960165:GTGAG:G	donor_loss	1.0000
19:960166:T:G	donor_loss	1.0000
19:964427:ACCCA:A	donor_gain	1.0000
19:964428:CCCA:C	donor_gain	1.0000
19:964429:CCA:C	donor_gain	1.0000
19:964430:CA:C	donor_gain	1.0000
19:964432:G:GG	donor_gain	1.0000
19:964433:T:G	donor_loss	1.0000
19:964434:GA:G	donor_loss	1.0000
19:964825:A:AG	acceptor_gain	1.0000
19:964829:ACAG:A	acceptor_loss	1.0000
19:964830:CA:C	acceptor_loss	1.0000
19:964831:A:AG	acceptor_gain	1.0000

AlphaMissense

3832 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:932734:T:C	F229L	1.000
19:932735:T:C	F229S	1.000
19:932736:T:A	F229L	1.000
19:932736:T:G	F229L	1.000
19:960093:T:A	L232H	1.000
19:960093:T:C	L232P	1.000
19:960120:G:C	R241T	1.000
19:960120:G:T	R241M	1.000
19:960121:G:C	R241S	1.000
19:960121:G:T	R241S	1.000
19:960128:T:C	F244L	1.000
19:960129:T:C	F244S	1.000
19:960129:T:G	F244C	1.000
19:960130:C:A	F244L	1.000
19:960130:C:G	F244L	1.000
19:960132:T:A	L245Q	1.000
19:960132:T:C	L245P	1.000
19:960141:T:C	L248S	1.000
19:960144:T:C	F249S	1.000
19:960149:T:C	F251L	1.000
19:960151:C:A	F251L	1.000
19:960151:C:G	F251L	1.000
19:960153:T:C	M252T	1.000
19:960154:G:A	M252I	1.000
19:960154:G:C	M252I	1.000
19:960154:G:T	M252I	1.000
19:960164:G:T	G256W	1.000
19:964257:T:A	V259E	1.000
19:964262:C:A	R261S	1.000
19:964262:C:G	R261G	1.000

dbSNP variants (sampled 300 via entrez): RS1000019167 (19:942412 G>C), RS1000081243 (19:965294 A>C,T), RS1000116738 (19:938420 G>A), RS1000139678 (19:973155 C>T), RS1000193009 (19:953598 T>C), RS1000200392 (19:927354 G>A), RS1000205594 (19:953593 C>A,T), RS1000227492 (19:928936 G>A,C), RS1000260480 (19:948915 G>A,T), RS1000313659 (19:968924 G>A), RS1000334688 (19:949235 C>A,G,T), RS1000398204 (19:957261 T>C), RS1000494618 (19:952852 G>A,C), RS1000508164 (19:952544 A>G), RS1000536846 (19:926653 C>T)

Disease associations

OMIM: gene MIM:603265 | disease phenotypes: MIM:175200

GenCC curated gene-disease

Mondo (1): Peutz-Jeghers syndrome (MONDO:0008280)

Orphanet (1): Peutz-Jeghers syndrome (Orphanet:2869)

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000700_4	Vertical cup-disc ratio	3.000000e-07
GCST004302_20	Primary biliary cholangitis	4.000000e-12
GCST004628_31	Immature fraction of reticulocytes	1.000000e-15
GCST005752_144	Systemic lupus erythematosus	6.000000e-06
GCST90002386_99	High light scatter reticulocyte percentage of red cells	2.000000e-11
GCST90002387_221	Immature fraction of reticulocytes	6.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D010580	Peutz-Jeghers Syndrome	C04.700.633; C06.405.469.578.750; C16.320.700.667; C17.800.621.430.530.550.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	3
Benzo(a)pyrene	increases expression, increases methylation, affects methylation	3
sodium arsenite	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	decreases expression, increases expression, increases methylation	2
Aflatoxin B1	increases expression, increases methylation	2
Vitamin K 3	affects expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
ginger extract	decreases expression, increases abundance	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
sulforaphane	increases expression	1
manganese chloride	increases abundance, increases expression	1
ochratoxin A	increases expression	1
benzo(e)pyrene	increases methylation	1
beta-methylcholine	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
erastin	increases expression, increases reaction	1
dorsomorphin	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	increases expression	1
Caffeine	increases phosphorylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Doxycycline	increases expression, increases reaction	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A0C1	SEES3-1V human ARID3A, clone1	Embryonic stem cell	Male
CVCL_A0C2	SEES3-1V human ARID3A, clone2	Embryonic stem cell	Male
CVCL_A0C3	SEES3-1V human ARID3A, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03781050	PHASE4	UNKNOWN	Efficacy of Rapamycin (Sirolimus) in the Treatment of Peutz-Jeghers Syndrome
NCT06001476	PHASE4	UNKNOWN	Cold Snare Polypectomy for Small Bowel Polyps in Patients With Peutz-Jeghers Syndrome
NCT02000089	PHASE3	RECRUITING	The Cancer of the Pancreas Screening-5 CAPS5)Study
NCT00811590	PHASE2	TERMINATED	Pilot Study of mTOR Inhibitor Therapy in Peutz-Jeghers Syndrome
NCT01178151	PHASE2	WITHDRAWN	Study of Everolimus in the Treatment of Advanced Malignancies in Patients With Peutz-Jeghers Syndrome
NCT00001452	Not specified	COMPLETED	Defining the Genetic Basis for the Development of Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and the Carney Complex
NCT00438906	Not specified	COMPLETED	Cancer of the Pancreas Screening Study (CAPS 3)
NCT00633607	Not specified	COMPLETED	Hereditary Colorectal and Associated Tumor Registry Study
NCT02206360	Not specified	ACTIVE_NOT_RECRUITING	Pancreatic Cancer Early Detection Program
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03806075	Not specified	UNKNOWN	Study of Accurate Diagnosis and Treatment of Peutz-Jeghers Syndrome
NCT04095195	Not specified	RECRUITING	Registry of Subjects at Risk of Pancreatic Cancer
NCT05692596	Not specified	ACTIVE_NOT_RECRUITING	The Pancreas Interception Center (PIC) for Early Detection, Prevention, and Novel Therapeutics
NCT06163365	Not specified	UNKNOWN	Inherited Cancer Early Diagnosis (ICED) Study
NCT06242457	Not specified	COMPLETED	Poorly Differentiated Adenocarcinoma of the Jejunum in a Patient With Peutz-Jeghers Syndrome: A Case Report
NCT06722534	Not specified	RECRUITING	Celecoxib for Prevention of Progression in Peutz-Jeghers Syndrome