PBX3

Summary

PBX3 (PBX homeobox 3, HGNC:8634) is a protein-coding gene on chromosome 9q33.3, encoding Pre-B-cell leukemia transcription factor 3 (P40426). Transcriptional activator that binds the sequence 5’-ATCAATCAA-3'.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in several processes, including embryonic organ development; eye development; and nervous system development. Predicted to act upstream of or within several processes, including adult locomotory behavior; dorsal spinal cord development; and regulation of respiratory gaseous exchange by nervous system process. Predicted to be located in chromatin. Predicted to be part of transcription regulator complex. Biomarker of esophagus squamous cell carcinoma.

Source: NCBI Gene 5090 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 40 total — 3 likely-pathogenic
• MANE Select transcript: NM_006195

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8634
Approved symbol	PBX3
Name	PBX homeobox 3
Location	9q33.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000167081
Ensembl biotype	protein_coding
OMIM	176312
Entrez	5090

Gene structure

Transcript identifiers

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

ENST00000342287, ENST00000373482, ENST00000373487, ENST00000373489, ENST00000373492, ENST00000428092, ENST00000447726, ENST00000491160, ENST00000491787, ENST00000492314, ENST00000497091, ENST00000538998, ENST00000672674, ENST00000673571, ENST00000970833

RefSeq mRNA: 4 — MANE Select: NM_006195 NM_001134778, NM_001330782, NM_001411009, NM_006195

CCDS: CCDS48021, CCDS6865, CCDS83416, CCDS94482

Canonical transcript exons

ENST00000373489 — 9 exons

Exon	Start	End
ENSE00001152144	125747373	125747653
ENSE00003492493	125962102	125962214
ENSE00003597093	125963012	125963101
ENSE00003680381	125965831	125967377
ENSE00003689267	125748550	125748623
ENSE00003695962	125915686	125915927
ENSE00003699340	125935472	125935607
ENSE00003701966	125960684	125960849
ENSE00003788154	125929655	125929845

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 96.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.3979 / max 182.2200, expressed in 1667 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98521	4.7877	1373
98520	1.3688	831
98519	0.8578	517
98524	0.6829	375
98523	0.4596	244
98522	0.4131	230
98534	0.4101	179
98533	0.2357	80
98518	0.1821	83

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ovary	UBERON:0002119	96.30	gold quality
right adrenal gland cortex	UBERON:0035827	95.85	gold quality
right adrenal gland	UBERON:0001233	95.59	gold quality
adrenal cortex	UBERON:0001235	95.58	gold quality
right ovary	UBERON:0002118	95.58	gold quality
left adrenal gland cortex	UBERON:0035825	95.48	gold quality
left adrenal gland	UBERON:0001234	95.44	gold quality
adrenal gland	UBERON:0002369	94.24	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.11	gold quality
ovary	UBERON:0000992	93.65	gold quality
right atrium auricular region	UBERON:0006631	93.43	gold quality
cardiac atrium	UBERON:0002081	93.32	gold quality
medial globus pallidus	UBERON:0002477	92.34	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.31	gold quality
gall bladder	UBERON:0002110	92.26	gold quality
spinal cord	UBERON:0002240	92.01	gold quality
vena cava	UBERON:0004087	91.08	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.99	gold quality
globus pallidus	UBERON:0001875	90.96	gold quality
calcaneal tendon	UBERON:0003701	90.96	gold quality
ectocervix	UBERON:0012249	90.95	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.88	gold quality
heart	UBERON:0000948	90.87	gold quality
lower esophagus	UBERON:0013473	90.87	gold quality
superior vestibular nucleus	UBERON:0007227	90.85	gold quality
cardiac muscle of right atrium	UBERON:0003379	90.75	gold quality
mucosa of stomach	UBERON:0001199	90.54	gold quality
nucleus accumbens	UBERON:0001882	90.44	gold quality
heart left ventricle	UBERON:0002084	90.44	gold quality
islet of Langerhans	UBERON:0000006	90.40	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	15.33
E-ANND-3	yes	4.94
E-MTAB-7249	no	780.75

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
FGF8	Unknown
TLX3

JASPAR motifs

Motif	Name	Family
MA1114.1	PBX3	TALE-type homeo domain factors
MA1114.2	PBX3	TALE-type homeo domain factors

JASPAR matrix evidence (PMIDs): PMID:10082572

Upstream regulators (CollecTRI, top): TOP2B

miRNA regulators (miRDB)

157 targeting PBX3, 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-4262	100.00	73.26	3931
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
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-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-9983-3P	99.94	71.48	3631

Literature-anchored findings (GeneRIF, showing 40)

• our results seem to discard the role of the previously described polymorphisms in SERPINE2, PPP6C and PBX3 in celiac disease susceptibility. (PMID:19626039)
• PBX3 is up-regulated in prostate cancer and post- transcriptionally regulated by androgen through Let-7d. (PMID:21548940)
• Data show that up-regulation of the HOXA7, HOXA9, HOXA11, and PBX3 resulting from the down-regulation of miR-181 family members probably contribute to the poor prognosis of patients with nonfavorable cytogenetically abnormal AML (CA-AML). (PMID:22251480)
• The Pbx3 Ala136Val variant is a modifier or risk allele for congenital heart defects. (PMID:22426282)
• Increased expression of PBX3 is associated with pilocytic astrocytoma. (PMID:23161775)
• Collectively, our data suggest that PBX3 is a critical cofactor of HOXA9 in leukemogenesis. (PMID:23264595)
• An intermediate-risk group of acute myeloid leukemia patients compared to a group with a favorable risk reduces to a four-gene signature of HOXA6, HOXA9, PBX3 and MEIS1 by iterative analysis of independent platforms. (PMID:23539541)
• matrigel invasion assay showed that PBX3 transfection also increased cell-invading ability (PMID:24375258)
• we report a novel hypomethylation pattern, specific to CBFB-MYH11 fusion resulting from inv(16) rearrangement in acute myeloid leukemia the expression of which correlated with PBX3 differential methylation (PMID:25266220)
• PBX3 induces invasion and metastasis of colorectal caner cells partially through activation of the MAPK/ERK signaling pathway. (PMID:25561793)
• Pbx3 contributes to Hoxa9 leukemogenesis through stabilization of the Meis1 protein. (PMID:26130510)
• let-7c, miR-200b, miR-222 and miR-424 target PBX3, which is necessary for the acquisition and maintenance of liver tumour-initiating cells properties. (PMID:26420065)
• Studies implicate PBX3/MEIS1 interaction as a driver of cell transformation and leukemogenesis, and that this axis may play a critical role in the regulation of the core transcriptional programs activated in MLL-rearranged and HOX-overexpressing AML. (PMID:26747896)
• Our findings collectively indicate that miR-320a inhibits cell proliferation and induces apoptosis in MM cells by directly targeting PBX3, supporting its utility as a novel and potential therapeutic agent for miRNA-based MM therapy. (PMID:27086852)
• Patients undergoing radical prostatectomy, with high levels of PBX3 mRNA, had improved prostate cancer specific survival compared to patients expressing low levels. (PMID:27273830)
• miR-33a-3p suppressed the malignant phenotype while also inhibiting PBX3 expression in hepatocellular cancer (PMID:27285759)
• results suggest that miR-144-3p suppresses GC progression by inhibiting EMT through targeting PBX3 (PMID:28111340)
• Silencing PBX3 inhibited the migratory and invasive capacities of glioma cells. (PMID:28124208)
• Results found that PBX3 is epigenetically aberrant in leukemia stem cell maintenance of MLL-rearranged AML and is essential for leukemia development. (PMID:28411381)
• Results show that PBX3 expression is increased in both human glioma tissues and cell lines. Furthermore, silencing of PBX3 remarkably reduced glioma cell proliferation and induced apoptosis, while PBX3 overexpression dramatically increased glioma cell proliferation. Finally, PBX3 promoted glioma cell proliferation by modulating cell cycle progression. (PMID:28856521)
• PBX3 is a novel indicator of EMT in colorectal cancer, part of an EMT regulatory network, and a promising prognostic predictor that may aid in therapeutic decision making for patients with colorectal cancer. (PMID:29391352)
• the present study indicates that PBX 3’UTR may induce inflammatory responses and sepsis via acting as a competing endogenous RNA for HMGB1. (PMID:29484406)
• These data indicate that NPMc+ leukemic cell survival requires upregulation of PBX3 and HOXA9. (PMID:30214626)
• In response to treatment with si-lncRNA HOST2, si-PBX3, and let-7b mimic, glioma cell lines exhibited decreased cell viability, suppressed cell migration, invasion, and reduced colony formation of glioma cells. This was accompanied by an attenuated tumor formation with smaller volume and weight in nude mice, suggesting that down-regulated HOST2 could inhibit the tumorigenicity of glioma cells (PMID:30290058)
• miR-302a inhibits human HepG2 and SMMC-7721 cells proliferation and promotes apoptosis by targeting MAP3K2 and PBX3. (PMID:30765768)
• miR-526b was decreased in CC cells and CC clinical specimens, especially in CC specimens with stromal invasion, pelvic lymph node metastasis and deficiency vaginal involvement. Moreover, it was proved that the character of miR-526b in CC was dependent on controlling the PBX3-mediated EMT process. (PMID:30859853)
• EWSR1-PBX3 fusions occur in most (and possibly all) cases of cutaneous syncytial myoepithelioma. (PMID:31135487)
• PBL PBX3 hypermethylation is positively associated with better prognosis of CRC, especially for the UICC stage III CRC patients and colon cancer patients. (PMID:31140752)
• PBX3 Promotes Tumor Growth and Angiogenesis via Activation of AT1R/VEGFR2 Pathway in Papillary Thyroid Carcinoma. (PMID:32047817)
• Compared with negative methylation (Nm), DLEC1-positive methylation (Pm) was associated with increased GC risk in PS (OR 2.083, 95% CI 1.220-3.558, P = 0.007), but PBX3 Pm was not associated with GC risk. (PMID:32144534)
• MiR-4458/human antigen R (HuR) modulates PBX3 mRNA stability in melanoma tumorigenesis. (PMID:32157373)
• SNHG10/DDX54/PBX3 Feedback Loop Contributes to Gastric Cancer Cell Growth. (PMID:32712782)
• MiR-144 inhibits colorectal cancer cell migration and invasion by regulating PBX3. (PMID:33015777)
• MiR-320a inhibits malignant phenotype of melanoma cells via targeting PBX3. (PMID:33099955)
• MiR-655-3p inhibits growth and invasiveness of trophoblasts via targeting PBX3 and thus deteriorates preeclampsia. (PMID:33155190)
• Knockdown of lncRNA HCG11 suppresses cell progression in ovarian cancer by modulating miR-144-3p/PBX3. (PMID:33215418)
• The transcription factor PBX3 promotes tumor cell growth through transcriptional suppression of the tumor suppressor p53. (PMID:33526870)
• Circular RNA circ_0032962 promotes trophoblast cell progression as ceRNA to target PBX3 via sponging miR-326 in preeclampsia. (PMID:34742151)
• Long non-coding RNA DSCAM-AS1 promotes pancreatic cancer progression via regulating the miR-136-5p/PBX3 axis. (PMID:35142595)
• USF1-ATRAP-PBX3 Axis Promote Breast Cancer Glycolysis and Malignant Phenotype by Activating AKT/mTOR Signaling. (PMID:35414770)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	pbx3b	ENSDARG00000013615
mus_musculus	Pbx3	ENSMUSG00000038718
rattus_norvegicus	Pbx3	ENSRNOG00000022162
drosophila_melanogaster	exd	FBGN0000611
drosophila_melanogaster	hth	FBGN0001235
drosophila_melanogaster	vis	FBGN0033748
drosophila_melanogaster	achi	FBGN0033749
caenorhabditis_elegans		WBGENE00000443
caenorhabditis_elegans		WBGENE00006796
caenorhabditis_elegans		WBGENE00017690

Paralogs (13): MEIS3 (ENSG00000105419), PBX4 (ENSG00000105717), TGIF2 (ENSG00000118707), MEIS2 (ENSG00000134138), MEIS1 (ENSG00000143995), TGIF2LX (ENSG00000153779), PKNOX1 (ENSG00000160199), PKNOX2 (ENSG00000165495), TGIF2LY (ENSG00000176679), TGIF1 (ENSG00000177426), PBX1 (ENSG00000185630), MEIS3P2 (ENSG00000188013), PBX2 (ENSG00000204304)

Protein

Protein identifiers

Pre-B-cell leukemia transcription factor 3 — P40426 (reviewed: P40426)

Alternative names: Homeobox protein PBX3

All UniProt accessions (5): P40426, H0Y5D0, H3BLX0, Q5JS98, U3KQA2

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator that binds the sequence 5’-ATCAATCAA-3'.

Subunit / interactions. Interacts with PBXIP1.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitously expressed.

Similarity. Belongs to the TALE/PBX homeobox family.

Isoforms (5)

UniProt ID	Names	Canonical?
P40426-1	PBX3a	yes
P40426-2	PBX3b
P40426-3	PBX3c
P40426-4	PBX3d
P40426-5	5

RefSeq proteins (4): NP_001128250, NP_001317711, NP_001397938, NP_006186* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR005542	PBX_PBC_dom	Domain
IPR008422	KN_HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR050224	TALE_homeobox	Family

Pfam: PF03792, PF05920

UniProt features (17 total): region of interest 5, splice variant 4, compositionally biased region 3, sequence conflict 2, chain 1, domain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P40426-F1	71.37	0.33

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 347 (showing top): VALK_AML_WITH_FLT3_ITD, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_SPINAL_CORD_DEVELOPMENT, MODULE_516, MULLIGHAN_NPM1_SIGNATURE_3_UP, ACTACCT_MIR196A_MIR196B, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_BEHAVIOR, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GGGNRMNNYCAT_UNKNOWN, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, GOBP_ADULT_BEHAVIOR, GOBP_REGULATION_OF_RESPIRATORY_SYSTEM_PROCESS

GO Biological Process (13): eye development (GO:0001654), regulation of respiratory gaseous exchange by nervous system process (GO:0002087), anterior compartment pattern formation (GO:0007387), posterior compartment specification (GO:0007388), brain development (GO:0007420), respiratory gaseous exchange by respiratory system (GO:0007585), adult locomotory behavior (GO:0008344), animal organ morphogenesis (GO:0009887), dorsal spinal cord development (GO:0021516), embryonic organ development (GO:0048568), neuron development (GO:0048666), regulation of DNA-templated transcription (GO:0006355), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (7): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), transcription regulator complex (GO:0005667)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
compartment pattern specification	2
regulation of transcription by RNA polymerase II	2
sensory organ development	1
visual system development	1
respiratory gaseous exchange by respiratory system	1
regulation of respiratory system process	1
nervous system process	1
central nervous system development	1
head development	1
multicellular organismal process	1
locomotory behavior	1
adult behavior	1
anatomical structure morphogenesis	1
spinal cord development	1
anatomical structure development	1
embryo development	1
neuron differentiation	1
cell development	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
regulation of DNA-templated transcription	1
transcription regulator activity	1
binding	1
DNA binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1160 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PBX3	HOXA9	P31269	916
PBX3	AGPAT1	Q99943	810
PBX3	AGPAT2	O15120	711
PBX3	MEIS3	Q99687	596
PBX3	BCL3	P20749	590
PBX3	NOTCH4	Q99466	548
PBX3	ZNF444	Q8N0Y2	542
PBX3	HOXA7	P31268	507
PBX3	EWSR1	Q01844	504
PBX3	HOXA10	P31260	491
PBX3	TAL1	P17542	488
PBX3	HOXB6	P09068	485
PBX3	ZNF143	P52747	480
PBX3	NOTCH1	P46531	468
PBX3	HOXA5	P20719	465

IntAct

28 interactions, top by confidence:

A	B	Type	Score
MEIS2	PBX1	psi-mi:“MI:0914”(association)	0.660
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
PKNOX2	PBX1	psi-mi:“MI:0914”(association)	0.550
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
DNAAF8	CCDC85C	psi-mi:“MI:0914”(association)	0.530
C5orf24	MEIS1	psi-mi:“MI:0914”(association)	0.530
MAB21L1	MEIS1	psi-mi:“MI:0914”(association)	0.530
MAB21L2	MEIS1	psi-mi:“MI:0914”(association)	0.530
FAM222A	MEIS1	psi-mi:“MI:0914”(association)	0.530
MAGEA1	MAGEB3	psi-mi:“MI:0914”(association)	0.530
PBX3	FSD2	psi-mi:“MI:0915”(physical association)	0.370
PBX3	ZNHIT3	psi-mi:“MI:0915”(physical association)	0.370
CFTR	PBX3	psi-mi:“MI:0915”(physical association)	0.370
PBX3	ECE1	psi-mi:“MI:0915”(physical association)	0.370
ECE1	PBX3	psi-mi:“MI:0915”(physical association)	0.370
FOXE1	DDX39A	psi-mi:“MI:0914”(association)	0.350
LMX1B	POTEF	psi-mi:“MI:0914”(association)	0.350
MEIS2	MEIS1	psi-mi:“MI:0914”(association)	0.350
EN1	MEIS1	psi-mi:“MI:0914”(association)	0.350
MAP3K20	MEIS1	psi-mi:“MI:0914”(association)	0.350
TSHZ1	MEIS2	psi-mi:“MI:0914”(association)	0.350
VWA5A	GTPBP6	psi-mi:“MI:0914”(association)	0.350
MEIS2	LRPAP1	psi-mi:“MI:0914”(association)	0.350
PKNOX1	PBX3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (116): PBX3 (Two-hybrid), TPM3 (Two-hybrid), TRAF1 (Two-hybrid), ARL6IP1 (Two-hybrid), MAGEC2 (Two-hybrid), TRIM44 (Two-hybrid), AGTRAP (Two-hybrid), MAL2 (Two-hybrid), FSD2 (Two-hybrid), PBX3 (Affinity Capture-MS), PBX3 (Affinity Capture-MS), PBX3 (Affinity Capture-MS), PBX3 (Affinity Capture-MS), PBX3 (Affinity Capture-MS), AGTRAP (Two-hybrid)

ESM2 similar proteins: A3KMR8, A7Z017, B3DM47, B4R090, D3ZNT6, O35317, O35984, O42290, O57342, O75030, O75444, P10083, P23091, P25932, P40424, P40425, P40426, P41778, P54841, P54842, P54843, P54844, P56224, P57102, P61295, P61296, P79745, P79746, Q05192, Q0V9K1, Q27350, Q2PFS4, Q32NP8, Q4U1U2, Q504L8, Q61039, Q6DE84, Q6PFG8, Q789F3, Q7RTU3

Diamond homologs: A1YER0, A2D5H2, A6NDR6, A8K0S8, A8WL06, B3DM47, B4F6V6, O00470, O04134, O04135, O14770, O17894, O22299, O35317, O35984, O42406, O46339, O65034, O73916, O80416, O93307, O95343, O95475, P10842, P24345, P40424, P40425, P40426, P40427, P41778, P41779, P41817, P46608, P46609, P46639, P46640, P48731, P53147, P56661, P56662

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
HOXB8	“up-regulates activity”	PBX3	binding
TOP2B	“up-regulates quantity by expression”	PBX3	“transcriptional regulation”
NUP98-HOXA9	“up-regulates quantity by expression”	PBX3	“transcriptional regulation”
PBX3	“down-regulates quantity by repression”	FGF8	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 31 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.

GO biological processes:

GO term	Partners	Fold	FDR
eye development	5	65.0×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	31
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2430147	NM_006195.6(PBX3):c.945dup (p.Ala316fs)	Likely pathogenic
2430148	NM_006195.6(PBX3):c.946_947insTA (p.Ala316fs)	Likely pathogenic
2430149	NM_006195.6(PBX3):c.273del (p.Gly92fs)	Likely pathogenic

SpliceAI

3923 predictions. Top by Δscore:

Variant	Effect	Δscore
9:125747637:G:GT	donor_gain	1.0000
9:125747649:GCAAA:G	donor_gain	1.0000
9:125747669:T:G	donor_gain	1.0000
9:125747669:T:TG	donor_gain	1.0000
9:125748540:T:TA	acceptor_gain	1.0000
9:125748546:TTA:T	acceptor_loss	1.0000
9:125748547:TAG:T	acceptor_loss	1.0000
9:125748548:A:AG	acceptor_gain	1.0000
9:125748548:AG:A	acceptor_gain	1.0000
9:125748548:AGGAA:A	acceptor_loss	1.0000
9:125748549:G:GG	acceptor_gain	1.0000
9:125748549:GG:G	acceptor_gain	1.0000
9:125748549:GGA:G	acceptor_gain	1.0000
9:125748549:GGAA:G	acceptor_gain	1.0000
9:125748622:AGG:A	donor_loss	1.0000
9:125748624:GTAA:G	donor_loss	1.0000
9:125770096:G:GT	donor_gain	1.0000
9:125773429:T:TA	donor_gain	1.0000
9:125773430:A:AA	donor_gain	1.0000
9:125876498:G:GG	donor_gain	1.0000
9:125929654:GGCAT:G	acceptor_gain	1.0000
9:125935459:A:AG	acceptor_gain	1.0000
9:125935460:C:G	acceptor_gain	1.0000
9:125935467:CATAG:C	acceptor_loss	1.0000
9:125935468:ATAGA:A	acceptor_loss	1.0000
9:125935470:A:AG	acceptor_gain	1.0000
9:125935470:A:C	acceptor_loss	1.0000
9:125935470:AGAC:A	acceptor_gain	1.0000
9:125935471:G:GA	acceptor_gain	1.0000
9:125935471:GACG:G	acceptor_gain	1.0000

AlphaMissense

2869 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:125747602:T:A	L50H	1.000
9:125747602:T:C	L50P	1.000
9:125747608:A:C	Q52P	1.000
9:125747611:T:A	I53N	1.000
9:125747611:T:C	I53T	1.000
9:125747611:T:G	I53S	1.000
9:125747620:T:A	I56N	1.000
9:125747620:T:G	I56S	1.000
9:125747623:C:T	T57I	1.000
9:125747635:T:C	L61S	1.000
9:125747635:T:G	L61W	1.000
9:125747643:G:C	A64P	1.000
9:125747647:A:C	Q65P	1.000
9:125747649:G:C	A66P	1.000
9:125748551:A:G	K68E	1.000
9:125748552:A:T	K68I	1.000
9:125748553:A:C	K68N	1.000
9:125748553:A:T	K68N	1.000
9:125748561:T:A	L71Q	1.000
9:125748561:T:C	L71P	1.000
9:125748570:A:G	H74R	1.000
9:125748578:A:G	K77E	1.000
9:125748580:A:C	K77N	1.000
9:125748580:A:T	K77N	1.000
9:125748588:T:A	L80H	1.000
9:125748588:T:C	L80P	1.000
9:125748588:T:G	L80R	1.000
9:125748590:T:A	F81I	1.000
9:125748590:T:C	F81L	1.000
9:125748591:T:C	F81S	1.000

dbSNP variants (sampled 300 via entrez): RS1000027756 (9:125947899 A>G), RS1000035835 (9:125848270 G>A,T), RS1000044934 (9:125807463 G>A), RS1000049935 (9:125937009 C>T), RS1000076937 (9:125851852 T>G), RS1000080770 (9:125937296 T>C), RS1000101939 (9:125757974 A>G), RS1000123988 (9:125942262 A>G), RS1000125944 (9:125950707 C>T), RS1000147974 (9:125884008 A>G), RS1000148300 (9:125896005 C>G,T), RS1000159345 (9:125808282 A>T), RS1000173131 (9:125953453 C>T), RS1000183965 (9:125898551 A>T), RS1000197772 (9:125811054 C>G)

Disease associations

OMIM: gene MIM:176312 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): X-linked cone-rod dystrophy (MONDO:0021155)

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST002157_4	Response to mTOR inhibitor (everolimus)	5.000000e-06
GCST004750_23	Squamous cell lung carcinoma	9.000000e-06
GCST006624_99	Systolic blood pressure	1.000000e-22
GCST006914_3	Sleep duration	7.000000e-09
GCST007267_33	Systolic blood pressure	1.000000e-17
GCST007269_108	Pulse pressure	2.000000e-14
GCST007936_1	Medication use (opioids)	8.000000e-10
GCST008295_39	Number of decayed, missing and filled tooth surfaces or use of dentures	7.000000e-14
GCST008306_44	Dentures	3.000000e-13
GCST010002_280	Refractive error	1.000000e-13
GCST010138_5	Raw vegetable consumption	4.000000e-09
GCST010142_3	Fish- and plant-related diet	2.000000e-12
GCST010142_57	Fish- and plant-related diet	1.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005417	response to mTOR inhibitor
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0009937	Opioid use measurement
EFO:0010078	dentures
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	5
bisphenol F	increases methylation, affects cotreatment, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Tretinoin	decreases expression, increases expression	2
Cyclosporine	affects expression, decreases expression	2
methylmercuric chloride	decreases expression	1
uranyl acetate	affects expression	1
bisphenol A	increases methylation, affects cotreatment	1
trichostatin A	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
beta-methylcholine	affects expression	1
octa-2,4,6-trienoic acid	decreases expression	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, decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
LG 100815	decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Bortezomib	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Azathioprine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A5F3	SEES3-1V human PBX3, clone1	Embryonic stem cell	Male
CVCL_A5F4	SEES3-1V human PBX3, clone2	Embryonic stem cell	Male
CVCL_A5F5	SEES3-1V human PBX3, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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