ARID4B

Summary

ARID4B (AT-rich interaction domain 4B, HGNC:15550) is a protein-coding gene on chromosome 1q42.3, encoding AT-rich interactive domain-containing protein 4B (Q4LE39). Acts as a transcriptional repressor.

This gene encodes a protein with sequence similarity to retinoblastoma-binding protein-1. The encoded protein is a subunit of the histone deacetylase-dependant SIN3A transcriptional corepressor complex, which functions in diverse cellular processes including proliferation, differentiation, apoptosis, oncogenesis, and cell fate determination. The gene product is recognized by IgG antibody isolated from a breast cancer patient and appears to be a molecular marker associated with a broad range of human malignancies. Alternate transcriptional splice variants encoding different isoforms have been characterized.

Source: NCBI Gene 51742 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 180 total — 3 pathogenic
• Transcription factor: yes — 12 downstream targets (CollecTRI)
• MANE Select transcript: NM_016374

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15550
Approved symbol	ARID4B
Name	AT-rich interaction domain 4B
Location	1q42.3
Locus type	gene with protein product
Status	Approved
Aliases	BCAA, BRCAA1, SAP180
Ensembl gene	ENSG00000054267
Ensembl biotype	protein_coding
OMIM	609696
Entrez	51742

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 7 protein_coding, 5 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000264183, ENST00000349213, ENST00000366603, ENST00000418304, ENST00000421364, ENST00000444620, ENST00000462969, ENST00000466653, ENST00000471257, ENST00000474401, ENST00000474953, ENST00000491632, ENST00000494543, ENST00000938135, ENST00000960476

RefSeq mRNA: 3 — MANE Select: NM_016374 NM_001206794, NM_016374, NM_031371

CCDS: CCDS31060, CCDS31061

Canonical transcript exons

ENST00000264183 — 24 exons

Exon	Start	End
ENSE00003469293	235213769	235214026
ENSE00003476826	235219793	235219968
ENSE00003504447	235260642	235260752
ENSE00003504753	235234413	235234492
ENSE00003508300	235240313	235240451
ENSE00003512214	235181585	235182793
ENSE00003531254	235194013	235194211
ENSE00003547015	235252730	235252809
ENSE00003564874	235177800	235177913
ENSE00003571485	235246420	235246511
ENSE00003582049	235224703	235224775
ENSE00003598363	235175184	235175399
ENSE00003603085	235255660	235255750
ENSE00003603903	235326914	235326968
ENSE00003608366	235223166	235223260
ENSE00003609443	235231113	235231189
ENSE00003611150	235229231	235229385
ENSE00003619864	235257160	235257225
ENSE00003651637	235220302	235220545
ENSE00003665014	235196031	235196115
ENSE00003685336	235172618	235172764
ENSE00003689714	235221565	235221662
ENSE00003805423	235166902	235168652
ENSE00003849115	235327769	235328179

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 98.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.4527 / max 1031.2089, expressed in 1807 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18138	22.0025	1807
18131	1.5362	524
18130	0.4580	140
18137	0.4560	186

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
choroid plexus epithelium	UBERON:0003911	98.27	gold quality
sperm	CL:0000019	98.03	gold quality
parietal pleura	UBERON:0002400	97.65	gold quality
visceral pleura	UBERON:0002401	97.60	gold quality
epithelium of nasopharynx	UBERON:0001951	97.53	gold quality
nasopharynx	UBERON:0001728	97.51	gold quality
tibia	UBERON:0000979	97.46	gold quality
pleura	UBERON:0000977	97.41	gold quality
calcaneal tendon	UBERON:0003701	97.11	gold quality
germinal epithelium of ovary	UBERON:0001304	97.00	gold quality
sural nerve	UBERON:0015488	96.83	gold quality
male germ cell	CL:0000015	96.53	gold quality
buccal mucosa cell	CL:0002336	96.47	gold quality
corpus callosum	UBERON:0002336	95.96	gold quality
palpebral conjunctiva	UBERON:0001812	95.95	gold quality
tendon	UBERON:0000043	95.40	gold quality
eye	UBERON:0000970	95.34	gold quality
amniotic fluid	UBERON:0000173	95.26	gold quality
esophagus squamous epithelium	UBERON:0006920	95.14	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	95.01	gold quality
superficial temporal artery	UBERON:0001614	94.95	gold quality
seminal vesicle	UBERON:0000998	94.42	gold quality
inferior olivary complex	UBERON:0002127	94.42	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.33	gold quality
epithelium of mammary gland	UBERON:0003244	94.25	gold quality
tonsil	UBERON:0002372	94.15	gold quality
mammary duct	UBERON:0001765	93.99	gold quality
caput epididymis	UBERON:0004358	93.97	gold quality
gingival epithelium	UBERON:0001949	93.74	gold quality
bone marrow	UBERON:0002371	93.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-4	no	28.82
E-HCAD-13	no	3.34
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

12 targets.

Target	Regulation
ACTG2	Repression
AKT1	Repression
ALB	Activation
GSK3B	Repression
HOXB3	Repression
HOXB5	Repression
HOXB6	Repression
HOXB8	Repression
IGF1	Repression
IGF1R	Repression
IGF2	Repression
PTGS2	Repression

miRNA regulators (miRDB)

213 targeting ARID4B, 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-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-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4514	99.99	67.10	1870
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-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-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3065-5P	99.97	71.56	3281

Literature-anchored findings (GeneRIF, showing 8)

• Immunohistochemistry analysis showed that the antigen epitope exhibited positive expression in 65% (39 of 60) breast cancer specimens and negative expression in 60 non-cancerous tissues. A novel breast cancer antigen epitope, SSKKQKRSHK, is identified (PMID:15247124)
• Consistent with our genetic analysis and in vivo experiments in our mouse model system, ARID4B expression was also an independent predictor of distant metastasis-free survival in breast cancer patients with ER+ tumors (PMID:22693453)
• ARID4B was significantly elevated in the serum of excessive alcohol users. (PMID:25704570)
• ARID4B overexpression presented in most of primary brain tumors, rather than non-neoplastic brain tissue, and correlated with WHO grades in meningiomas and gliomas. (PMID:27451434)
• our results suggest that ARID4B acts as an oncogene in hepatocellular carcinoma and can therefore serve as a biomarker for the prognoses of patients with hepatocellular carcinoma (PMID:29288040)
• miR-519b-3p directly binds to the 3’ UTR of ARID4B mRNA whose expression was inversely correlated with miR-519b-3p expression. (PMID:29477868)
• 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)
• Circ-SMARCA5 suppresses colorectal cancer progression via downregulating miR-39-3p and upregulating ARID4B. (PMID:32807692)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	arid4b	ENSDARG00000090656
mus_musculus	Arid4b	ENSMUSG00000039219
rattus_norvegicus	Arid4b	ENSRNOG00000016391
drosophila_melanogaster	htk	FBGN0085451
caenorhabditis_elegans		WBGENE00044689

Paralogs (3): ARID4A (ENSG00000032219), ARID5B (ENSG00000150347), ARID5A (ENSG00000196843)

Protein

Protein identifiers

AT-rich interactive domain-containing protein 4B — Q4LE39 (reviewed: Q4LE39)

Alternative names: 180 kDa Sin3-associated polypeptide, Breast cancer-associated antigen BRCAA1, Histone deacetylase complex subunit SAP180, Retinoblastoma-binding protein 1-like 1

All UniProt accessions (4): Q4LE39, H0Y7Y8, H7C5R6, X6RCR8

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional repressor. May function in the assembly and/or enzymatic activity of the Sin3A corepressor complex or in mediating interactions between the complex and other regulatory complexes. 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 ARID4A. Involved in spermatogenesis, together with ARID4A, where it functions as a transcriptional coactivator for AR (androgen receptor) 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. Component of a Sin3A corepressor complex consisting of SIN3A, SAP130, SUDS3/SAP45, SAP180, HDAC1 and HDAC2. Interacts with ARID4A. Interacts with AR.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Highly expressed in the testis and in breast, lung, colon, pancreatic and ovarian cancers. Expressed at low levels in the thymus, prostate and ovary.

Domain organisation. The C-terminus mediates interaction with mSin3A corepressor complex. The N-terminus is involved in transcriptional repression by HDAC-independent mechanisms. The ARID domain is involved in stabilizing the mSin3A corepressor complex on DNA.

Isoforms (4)

UniProt ID	Names	Canonical?
Q4LE39-1	1	yes
Q4LE39-2	2
Q4LE39-3	3
Q4LE39-4	4

RefSeq proteins (3): NP_001193723, NP_057458, NP_112739 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001606	ARID_dom	Domain
IPR002999	Tudor	Domain
IPR012603	ARID4A/B_PWWP	Domain
IPR016197	Chromo-like_dom_sf	Homologous_superfamily
IPR025995	Tudor-knot	Domain
IPR028853	ARID4B_ARID/BRIGHT	Domain
IPR036431	ARID_dom_sf	Homologous_superfamily
IPR047474	Tudor_ARID4B_rpt2	Domain
IPR047476	Tudor_ARID4B_rpt1	Domain
IPR051232	ARID/SWI1_ChromRemod	Family

Pfam: PF01388, PF08169, PF11717

UniProt features (98 total): sequence conflict 23, compositionally biased region 19, modified residue 18, region of interest 9, strand 9, splice variant 6, cross-link 5, domain 2, coiled-coil region 2, turn 2, helix 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7DM4	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4LE39-F1	56.28	0.20

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 (23): 276, 295, 296, 483, 666, 675, 717, 778, 790, 793, 1014, 1026, 1029, 1150, 1152, 1153, 1155, 1159, 429, 440 …

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-3214815	HDACs deacetylate histones
R-HSA-427413	NoRC negatively regulates rRNA expression
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-1643685	Disease
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-5250941	Negative epigenetic regulation of rRNA expression
R-HSA-5663205	Infectious disease
R-HSA-74160	Gene expression (Transcription)
R-HSA-9679506	SARS-CoV Infections
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 360 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, AAGCAAT_MIR137, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPITHELIAL_CELL_DEVELOPMENT, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_SERTOLI_CELL_DEVELOPMENT, GCM_ZNF198, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GTTAAAG_MIR302B, GOBP_MALE_GAMETE_GENERATION, PATIL_LIVER_CANCER, CAGCAGG_MIR370, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN

GO Biological Process (12): 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), positive regulation of transcription by RNA polymerase II (GO:0045944), 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)

GO Molecular Function (3): transcription cis-regulatory region binding (GO:0000976), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), cytosol (GO:0005829), Sin3-type complex (GO:0070822), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Negative epigenetic regulation of rRNA expression	1
SARS-CoV Infections	1
Gene expression (Transcription)	1
Chromatin organization	1
Epigenetic regulation of gene expression	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
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
stem cell population maintenance	2
regulation of stem cell population maintenance	2
intracellular membrane-bounded organelle	2
cytoplasm	2
negative regulation of DNA-templated transcription	1
regulation of DNA-templated transcription	1
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
positive regulation of DNA-templated transcription	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
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
nucleic acid binding	1
binding	1
nuclear lumen	1
histone deacetylase complex	1
nuclear chromosome	1
chromatin	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3353 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARID4B	SUDS3	Q9H7L9	981
ARID4B	SAP30	O75446	939
ARID4B	SIN3A	Q96ST3	937
ARID4B	HDAC2	Q92769	930
ARID4B	HDAC1	Q13547	912
ARID4B	ING1	Q9UK53	876
ARID4B	BRMS1L	Q5PSV4	869
ARID4B	SIN3B	O75182	866
ARID4B	BRMS1	Q9HCU9	842
ARID4B	RBBP4	P31149	785
ARID4B	SAP18	O00422	771
ARID4B	KDM5A	P29375	735
ARID4B	RBBP7	Q16576	648
ARID4B	SINHCAF	Q9NP50	605
ARID4B	SNRPN	P14648	591

IntAct

133 interactions, top by confidence:

A	B	Type	Score
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
HDAC1	TNRC18	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
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
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
YAF2	E2F6	psi-mi:“MI:0914”(association)	0.640
SNX5	SNX2	psi-mi:“MI:0914”(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
CTSK	CTSV	psi-mi:“MI:0914”(association)	0.530
DDX41	NOS1AP	psi-mi:“MI:0914”(association)	0.530
LACC1	DUSP14	psi-mi:“MI:0914”(association)	0.530
RBBP7	EPOP	psi-mi:“MI:0914”(association)	0.530

BioGRID (269): ARID4B (Affinity Capture-Western), ARID4B (Affinity Capture-Western), CUL4B (Affinity Capture-Western), DDB1 (Affinity Capture-Western), ARID4B (Affinity Capture-MS), ARID4B (Affinity Capture-MS), ARID4B (Affinity Capture-MS), ARID4B (Affinity Capture-MS), ARID4B (Affinity Capture-MS), ARID4B (Co-fractionation), ARID4B (Co-fractionation), SAP130 (Co-fractionation), SAP30 (Co-fractionation), SIN3A (Co-fractionation), ARID4B (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GR68, A2CG63, E9Q9M8, F7AQ22, G3V8T1, O75152, O75376, P49140, P51826, P97432, Q13625, Q14596, Q17R98, Q1LY51, Q3TYA6, Q4KKX4, Q4LE39, Q4R6F6, Q501R9, Q505G8, Q5F3Z9, Q5HYC2, Q5RC94, Q5XJV7, Q60974, Q68FE8, Q69Z61, Q6A098, Q6NXK2, Q6NZF1, Q6PJT7, Q6ZNC4, Q86YI8, Q8BFU3, Q8BJ05, Q8CCH7, Q8CG79, Q8CHY6, Q8K2W6, Q8ND24

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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 146 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
Transcription of E2F targets under negative control by DREAM complex	5	25.9×	1e-04
Regulation of TP53 Activity through Acetylation	5	21.8×	2e-04
Transcriptional Regulation by E2F6	6	16.7×	1e-04
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	5	14.7×	6e-04
Deactivation of the beta-catenin transactivating complex	6	13.3×	2e-04
HDACs deacetylate histones	11	12.6×	6e-07
NOTCH1 Intracellular Domain Regulates Transcription	5	11.3×	1e-03
Constitutive Signaling by NOTCH1 PEST Domain Mutants	6	11.2×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of stem cell population maintenance	10	55.1×	1e-13
neuron fate specification	5	25.3×	1e-04
positive regulation of stem cell population maintenance	10	24.7×	1e-09
chondrocyte differentiation	6	13.0×	4e-04
negative regulation of transforming growth factor beta receptor signaling pathway	10	12.5×	1e-06
somatic stem cell population maintenance	6	10.7×	1e-03
positive regulation of miRNA transcription	5	10.4×	4e-03
DNA replication	8	9.5×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	134
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2577840	NC_000001.11:g.(233502994_233518999)_(236093155_236105019)del	Pathogenic
3242280	GRCh37/hg19 1q42.2-42.3(chr1:234117880-236536349)x1	Pathogenic
4820101	NC_000001.11:g.234258308_236349718del	Pathogenic

SpliceAI

7049 predictions. Top by Δscore:

Variant	Effect	Δscore
1:235131996:TT:T	acceptor_gain	1.0000
1:235131998:C:CC	acceptor_gain	1.0000
1:235131998:CT:C	acceptor_loss	1.0000
1:235135647:CATAC:C	donor_loss	1.0000
1:235135648:ATAC:A	donor_loss	1.0000
1:235135649:TACC:T	donor_loss	1.0000
1:235135650:A:C	donor_loss	1.0000
1:235135651:C:A	donor_loss	1.0000
1:235135685:G:A	donor_gain	1.0000
1:235135768:CTT:C	acceptor_gain	1.0000
1:235135769:TT:T	acceptor_gain	1.0000
1:235135771:C:CC	acceptor_gain	1.0000
1:235135778:C:CT	acceptor_gain	1.0000
1:235135779:A:T	acceptor_gain	1.0000
1:235136032:A:AC	donor_gain	1.0000
1:235136033:C:CC	donor_gain	1.0000
1:235137869:CTACT:C	donor_loss	1.0000
1:235137870:TACTT:T	donor_loss	1.0000
1:235137871:ACTTA:A	donor_loss	1.0000
1:235137873:TTA:T	donor_loss	1.0000
1:235137874:T:TG	donor_loss	1.0000
1:235137875:A:AC	donor_gain	1.0000
1:235137875:A:AG	donor_loss	1.0000
1:235137876:C:CG	donor_gain	1.0000
1:235137876:CA:C	donor_gain	1.0000
1:235137876:CAG:C	donor_gain	1.0000
1:235137936:CATTT:C	acceptor_gain	1.0000
1:235137938:TTT:T	acceptor_gain	1.0000
1:235137939:TT:T	acceptor_gain	1.0000
1:235137939:TTCTG:T	acceptor_loss	1.0000

AlphaMissense

8731 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:235172646:T:A	R1261S	1.000
1:235172646:T:G	R1261S	1.000
1:235172653:C:G	R1259P	1.000
1:235172665:G:T	A1255D	1.000
1:235172676:T:A	K1251N	1.000
1:235172676:T:G	K1251N	1.000
1:235172677:T:A	K1251I	1.000
1:235172678:T:C	K1251E	1.000
1:235172710:A:G	L1240P	1.000
1:235172722:A:G	L1236P	1.000
1:235182116:A:G	W935R	1.000
1:235182116:A:T	W935R	1.000
1:235182137:A:G	W928R	1.000
1:235182137:A:T	W928R	1.000
1:235196086:A:C	I624R	1.000
1:235196086:A:G	I624T	1.000
1:235196086:A:T	I624K	1.000
1:235196101:A:C	I619S	1.000
1:235196101:A:T	I619N	1.000
1:235196103:C:A	W618C	1.000
1:235196103:C:G	W618C	1.000
1:235196104:C:G	W618S	1.000
1:235196105:A:G	W618R	1.000
1:235196105:A:T	W618R	1.000
1:235196110:T:A	D616V	1.000
1:235196111:C:A	D616Y	1.000
1:235196111:C:G	D616H	1.000
1:235213774:A:C	N612K	1.000
1:235213774:A:T	N612K	1.000
1:235213777:C:A	W611C	1.000

dbSNP variants (sampled 300 via entrez): RS1000029341 (1:235327792 C>A,G), RS1000031927 (1:235272747 A>G), RS1000061820 (1:235228377 C>A), RS1000090252 (1:235223525 C>T), RS1000107730 (1:235258507 T>G), RS1000131431 (1:235304676 G>C), RS1000141554 (1:235186266 C>T), RS1000185467 (1:235246351 A>G), RS1000188407 (1:235295150 T>C), RS1000196805 (1:235246748 GA>G), RS1000211747 (1:235329709 T>G), RS1000225177 (1:235205986 T>C), RS1000231521 (1:235295308 G>A), RS1000264307 (1:235288720 T>A), RS1000273484 (1:235249001 A>G)

Disease associations

OMIM: gene MIM:609696 | disease phenotypes: MIM:617765

GenCC curated gene-disease

Mondo (1): immunodeficiency, common variable, 14 (MONDO:0054691)

Orphanet (1): Common variable immunodeficiency phenotype due to IRF2BP2 deficiency (Orphanet:696904)

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003542_147	Night sleep phenotypes	8.000000e-07
GCST005212_7	Asthma	3.000000e-06
GCST90000025_860	Appendicular lean mass	1.000000e-14
GCST90002393_547	Monocyte count	2.000000e-09
GCST90002394_106	Monocyte percentage of white cells	3.000000e-17
GCST90002400_545	Plateletcrit	1.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	4
Tobacco Smoke Pollution	decreases methylation, increases expression	3
sodium arsenite	increases expression	2
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Air Pollutants	increases abundance, increases expression, decreases expression, affects cotreatment	2
Ozone	affects cotreatment, increases expression, increases abundance	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
bisphenol A	affects cotreatment, increases methylation, affects methylation	1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	affects cotreatment, decreases expression	1
cobaltous chloride	increases expression	1
coumarin	decreases phosphorylation	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
torcetrapib	increases expression	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
jinfukang	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Arsenic Trioxide	increases response to substance	1
Fulvestrant	increases methylation, affects cotreatment	1
Vorinostat	decreases expression	1
Leflunomide	increases expression	1
Benzo(a)pyrene	decreases expression, affects cotreatment	1

Clinical trials (associated diseases)

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