VENTX

Summary

VENTX (VENT homeobox, HGNC:13639) is a protein-coding gene on chromosome 10q26.3, encoding Homeobox protein VENTX (O95231). May be involved in ventralization.

This gene encodes a member of the Vent family of homeodomain proteins. The encoded protein may function as a transcriptional repressor and be involved in mesodermal patterning and hemopoietic stem cell maintenance. Multiple pseudogenes exist for this gene. A transcribed pseudogene located on chromosome X may lead to antigen production in certain melanomas.

Source: NCBI Gene 27287 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 59 total
• MANE Select transcript: NM_014468

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13639
Approved symbol	VENTX
Name	VENT homeobox
Location	10q26.3
Locus type	gene with protein product
Status	Approved
Aliases	HPX42B
Ensembl gene	ENSG00000151650
Ensembl biotype	protein_coding
OMIM	607158
Entrez	27287

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000325980, ENST00000928836, ENST00000949222

RefSeq mRNA: 1 — MANE Select: NM_014468 NM_014468

CCDS: CCDS7675

Canonical transcript exons

ENST00000325980 — 3 exons

Exon	Start	End
ENSE00001000841	133239676	133239836
ENSE00001152946	133239932	133241928
ENSE00001248518	133237855	133238155

Expression profiles

Bgee: expression breadth ubiquitous, 149 present calls, max score 82.60.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2178 / max 56.6723, expressed in 64 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107767	0.1664	55
107768	0.0514	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	82.60	gold quality
monocyte	CL:0000576	81.92	gold quality
mononuclear cell	CL:0000842	81.63	gold quality
leukocyte	CL:0000738	81.47	gold quality
endometrium epithelium	UBERON:0004811	77.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.08	gold quality
right coronary artery	UBERON:0001625	75.72	gold quality
tibial nerve	UBERON:0001323	73.22	gold quality
type B pancreatic cell	CL:0000169	71.64	gold quality
blood	UBERON:0000178	71.20	gold quality
subcutaneous adipose tissue	UBERON:0002190	70.76	gold quality
right lung	UBERON:0002167	70.61	gold quality
left coronary artery	UBERON:0001626	69.94	gold quality
spleen	UBERON:0002106	69.90	gold quality
upper lobe of left lung	UBERON:0008952	69.78	gold quality
thoracic aorta	UBERON:0001515	69.46	gold quality
descending thoracic aorta	UBERON:0002345	69.42	gold quality
ascending aorta	UBERON:0001496	69.09	gold quality
left adrenal gland cortex	UBERON:0035825	68.92	gold quality
coronary artery	UBERON:0001621	68.79	gold quality
apex of heart	UBERON:0002098	68.65	gold quality
left adrenal gland	UBERON:0001234	68.64	gold quality
paraflocculus	UBERON:0005351	68.48	gold quality
Brodmann (1909) area 10	UBERON:0013541	68.45	gold quality
right adrenal gland cortex	UBERON:0035827	68.37	gold quality
omental fat pad	UBERON:0010414	68.19	gold quality
peritoneum	UBERON:0002358	68.11	gold quality
adipose tissue of abdominal region	UBERON:0007808	67.93	gold quality
right adrenal gland	UBERON:0001233	67.89	gold quality
frontal pole	UBERON:0002795	67.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.40

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
CDKN1A	Activation
CDKN2A	Activation
IL6
RB1
TP53

JASPAR motifs

Motif	Name	Family
MA0724.1	VENTX	NK

JASPAR matrix evidence (PMIDs): PMID:18585360

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

41 targeting VENTX, 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-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3924	100.00	72.09	2394
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-4533	100.00	69.48	2758
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-2276-3P	98.76	67.75	1384

Literature-anchored findings (GeneRIF, showing 10)

• a potential role of VentX in the clinical behavior of hematopoietic malignancies. (PMID:20028861)
• these data extend our insights into the function of embryonic mesodermal factors in human postnatal hematopoiesis and indicate a role for VENTX in normal and malignant myelopoiesis. (PMID:20833819)
• Data show that VentX is a direct transcriptional activator of p53-p21 and p16ink4a-Rb tumor suppression pathways. (PMID:21325273)
• Results provide mechanistic insight into the crucial roles of VentX in macrophage differentiation and proinflammatory activation and suggest that dysregulation of VentX may play a role in the pathogenesis of autoimmune diseases. (PMID:21670496)
• VentX regulates critical cell cycle regulators and Wnt downstream genes previously implicated in HSC/MPP proliferation and expansion. (PMID:22791709)
• Data suggest that homeobox transcription factor VentX may be a target to modulate Dendritic cells (DCs) functions and manage inflammatory diseases. (PMID:24706756)
• VentX induces apoptosis of cancer cells in a p53-independent manner (PMID:27175592)
• VENTX impairs expression of genes involved in erythroid differentiation and is highly expressed in patients with acute erythroid leukemia. (PMID:27888632)
• Findings suggest potential applications of homeobox protein VentX (VentX)-regulated tumor-associated macrophages (TAMs) in cancer immunotherapy. (PMID:29872044)
• VentX expression in tumor-associated macrophages promotes phagocytosis and immunity against pancreatic cancers. (PMID:32573491)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bsx	ENSDARG00000068976
danio_rerio	vent	ENSDARG00000100483
drosophila_melanogaster	Dll	FBGN0000157
caenorhabditis_elegans		WBGENE00000463

Paralogs (9): DLX6 (ENSG00000006377), DLX3 (ENSG00000064195), DLX5 (ENSG00000105880), DLX4 (ENSG00000108813), NANOG (ENSG00000111704), DLX2 (ENSG00000115844), DLX1 (ENSG00000144355), BSX (ENSG00000188909), NANOGP8 (ENSG00000255192)

Protein

Protein identifiers

Homeobox protein VENTX — O95231 (reviewed: O95231)

Alternative names: VENT homeobox homolog, VENT-like homeobox protein 2

All UniProt accessions (1): O95231

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in ventralization.

Subcellular location. Nucleus.

Tissue specificity. Expressed in bone marrow of patients recovering from chemotherapy. Also expressed in an erythroleukemia cell line.

RefSeq proteins (1): NP_055283* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR050848	Homeobox_TF	Family

Pfam: PF00046

UniProt features (10 total): sequence variant 5, region of interest 2, chain 1, DNA-binding region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95231-F1	65.22	0.24

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
R-HSA-8853884	Transcriptional Regulation by VENTX

MSigDB gene sets: 57 (showing top): MODULE_16, MODULE_13, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MODULE_41, GOBP_POSITIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOMF_DNA_BINDING_TRANSCRIPTION_ACTIVATOR_ACTIVITY, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, REACTOME_SENESCENCE_ASSOCIATED_SECRETORY_PHENOTYPE_SASP, REACTOME_CELLULAR_SENESCENCE, REACTOME_CELLULAR_RESPONSES_TO_STIMULI, PDGF_UP.V1_DN, KRAS.AMP.LUNG_UP.V1_UP, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, REACTOME_TRANSCRIPTIONAL_REGULATION_BY_VENTX, IGLV5_37_TARGET_GENES

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), cell differentiation (GO:0030154), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355)

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), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cellular Senescence	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
regulation of DNA-templated transcription	1
cellular developmental process	1
positive regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	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
DNA binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

482 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VENTX	ARGFX	A6NJG6	590
VENTX	GLIS2	Q9BZE0	479
VENTX	LEUTX	A8MZ59	463
VENTX	NKX6-3	A6NJ46	432
VENTX	PRDM16	Q9HAZ2	394
VENTX	UTF1	Q5T230	390
VENTX	PLAC9	Q5JTB6	387
VENTX	CIBAR1	A1XBS5	380
VENTX	DUXB	A0A1W2PPF3	377
VENTX	KNDC1	Q76NI1	376
VENTX	DUXA	A6NLW8	375
VENTX	ZSCAN29	Q8IWY8	370
VENTX	NANOGNB	Q7Z5D8	367
VENTX	DPRX	A6NFQ7	364
VENTX	TPRX1	Q8N7U7	331

IntAct

300 interactions, top by confidence:

A	B	Type	Score
VENTX	KRTAP12-2	psi-mi:“MI:0915”(physical association)	0.720
VENTX	TBX22	psi-mi:“MI:0915”(physical association)	0.720
KRTAP12-2	VENTX	psi-mi:“MI:0915”(physical association)	0.720
VENTX	DAB1	psi-mi:“MI:0915”(physical association)	0.670
VENTX	KRTAP12-4	psi-mi:“MI:0915”(physical association)	0.670
C1orf94	VENTX	psi-mi:“MI:0915”(physical association)	0.670
VENTX	RBPMS	psi-mi:“MI:0915”(physical association)	0.670
TBX15	VENTX	psi-mi:“MI:0915”(physical association)	0.670
KRTAP12-4	VENTX	psi-mi:“MI:0915”(physical association)	0.670
VENTX	C1orf94	psi-mi:“MI:0915”(physical association)	0.670
RBPMS	VENTX	psi-mi:“MI:0915”(physical association)	0.670
VENTX	TBX15	psi-mi:“MI:0915”(physical association)	0.670
DAB1	VENTX	psi-mi:“MI:0915”(physical association)	0.670
KRT34	VENTX	psi-mi:“MI:0915”(physical association)	0.600
VENTX	KRTAP6-1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (112): VENTX (Two-hybrid), VENTX (Two-hybrid), VENTX (Two-hybrid), VENTX (Two-hybrid), TBX22 (Two-hybrid), C1orf94 (Two-hybrid), KRTAP12-2 (Two-hybrid), KRTAP12-4 (Two-hybrid), AES (Affinity Capture-MS), TLE4 (Affinity Capture-MS), TLE1 (Affinity Capture-MS), TLE3 (Affinity Capture-MS), RBPMS (Two-hybrid), VENTX (Two-hybrid), VENTX (Two-hybrid)

ESM2 similar proteins: A0A5F9ZHS7, A1YGK1, A2T7E6, A8MZG2, O08574, O43593, O60393, O75593, O88621, O95231, P0C1T1, P0CG20, P20428, P97609, Q04667, Q17QR5, Q2KIS6, Q2M1V0, Q2T9Q7, Q32LE6, Q497V6, Q5JUK2, Q5M844, Q5RJB0, Q5TGS1, Q61645, Q61657, Q6ZMY3, Q6ZN32, Q6ZNG2, Q7RTU1, Q8BZW2, Q8CGW9, Q8IWN7, Q8IXT2, Q8IZ20, Q8N1L9, Q8N7G0, Q8N944, Q8N9Y4

Diamond homologs: A1YG92, A1YGA4, A2T763, A2T779, A7Y7W3, A8XJD0, D2KQB0, E7FDX5, G5EE18, O02491, O08686, O35767, O60479, O88181, O95231, P02836, P09015, P09145, P20009, P22544, P31533, P32443, P39020, P40764, P50222, P50574, P50576, P50577, P52730, P52954, P52955, P53770, P53771, P53772, P53773, P53774, P53775, P54655, P56177, P56178

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 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
Keratinization	17	22.6×	3e-17

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

490 predictions. Top by Δscore:

Variant	Effect	Δscore
10:133239722:A:AG	acceptor_gain	1.0000
10:133239723:G:GG	acceptor_gain	1.0000
10:133239723:GC:G	acceptor_gain	1.0000
10:133239837:GT:G	donor_loss	1.0000
10:133239927:TACA:T	acceptor_loss	1.0000
10:133239929:CA:C	acceptor_loss	1.0000
10:133239930:A:AG	acceptor_gain	1.0000
10:133239931:G:GG	acceptor_gain	1.0000
10:133239931:GAT:G	acceptor_gain	1.0000
10:133239931:GATA:G	acceptor_gain	1.0000
10:133239931:GATAA:G	acceptor_gain	1.0000
10:133238151:GGCCG:G	donor_gain	0.9900
10:133238152:GCCGG:G	donor_gain	0.9900
10:133238153:CCGG:C	donor_loss	0.9900
10:133238156:G:GA	donor_loss	0.9900
10:133238156:G:GG	donor_gain	0.9900
10:133238157:T:A	donor_loss	0.9900
10:133239675:GGGTT:G	acceptor_gain	0.9900
10:133239721:C:G	acceptor_gain	0.9900
10:133239723:GCC:G	acceptor_gain	0.9900
10:133239837:G:GG	donor_gain	0.9900
10:133239931:GA:G	acceptor_gain	0.9900
10:133238152:GCCG:G	donor_gain	0.9800
10:133239718:GCACA:G	acceptor_loss	0.9800
10:133239720:ACAG:A	acceptor_loss	0.9800
10:133239722:AGC:A	acceptor_loss	0.9800
10:133239723:G:A	acceptor_loss	0.9800
10:133239723:GCCTT:G	acceptor_gain	0.9800
10:133239812:G:GT	donor_gain	0.9800
10:133239832:TCCAG:T	donor_gain	0.9800

AlphaMissense

1644 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:133239726:T:C	F98L	0.998
10:133239728:C:A	F98L	0.998
10:133239728:C:G	F98L	0.998
10:133239944:T:C	F139L	0.998
10:133239946:T:A	F139L	0.998
10:133239946:T:G	F139L	0.998
10:133239762:T:C	F110L	0.997
10:133239764:C:A	F110L	0.997
10:133239764:C:G	F110L	0.997
10:133239727:T:C	F98S	0.994
10:133239945:T:C	F139S	0.994
10:133239950:A:G	N141D	0.994
10:133239727:T:G	F98C	0.992
10:133239951:A:G	N141S	0.992
10:133239954:G:C	R142P	0.992
10:133239956:C:A	R143S	0.992
10:133239970:A:C	K147N	0.992
10:133239970:A:T	K147N	0.992
10:133239751:T:C	L106S	0.991
10:133239937:A:C	K136N	0.991
10:133239937:A:T	K136N	0.991
10:133239945:T:G	F139C	0.991
10:133239763:T:C	F110S	0.990
10:133239941:T:A	W138R	0.989
10:133239941:T:C	W138R	0.989
10:133239951:A:C	N141T	0.989
10:133239763:T:G	F110C	0.988
10:133239949:G:C	Q140H	0.988
10:133239949:G:T	Q140H	0.988
10:133239952:T:A	N141K	0.988

dbSNP variants (sampled 300 via entrez): RS1000354641 (10:133241669 G>A), RS1000678864 (10:133238560 G>C), RS1001342267 (10:133235864 G>A), RS1001846022 (10:133238289 C>G,T), RS1002891944 (10:133239143 T>C), RS1003016440 (10:133236862 C>T), RS1003116345 (10:133237205 G>A,C), RS1004136076 (10:133239490 G>GC), RS1004141535 (10:133236529 G>A,C), RS1004172682 (10:133236306 C>A,T), RS1004866753 (10:133238859 A>C), RS1005107168 (10:133238642 A>G), RS1005909754 (10:133237901 C>G,T), RS1006162452 (10:133242168 G>C), RS1006546050 (10:133242419 G>A)

Disease associations

OMIM: gene MIM:607158 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	3
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Nickel	increases expression	2
benzo(e)pyrene	increases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
MT19c compound	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzene	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Folic Acid	decreases expression	1
Methapyrilene	increases methylation	1
Ozone	affects expression, increases abundance	1
Tretinoin	increases expression	1
Asbestos, Crocidolite	decreases methylation	1
Asbestos, Amosite	decreases methylation	1

Clinical trials (associated diseases)

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