HOXA9

Summary

HOXA9 (homeobox A9, HGNC:5109) is a protein-coding gene on chromosome 7p15.2, encoding Homeobox protein Hox-A9 (P31269). Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. This gene is highly similar to the abdominal-B (Abd-B) gene of Drosophila. A specific translocation event which causes a fusion between this gene and the NUP98 gene has been associated with myeloid leukemogenesis. Read-through transcription exists between this gene and the upstream homeobox A10 (HOXA10) gene.

Source: NCBI Gene 3205 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 1 total
• Transcription factor: yes — 41 downstream targets (CollecTRI)
• MANE Select transcript: NM_152739

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5109
Approved symbol	HOXA9
Name	homeobox A9
Location	7p15.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000078399
Ensembl biotype	protein_coding
OMIM	142956
Entrez	3205

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000343483, ENST00000396345, ENST00000465941, ENST00000487384, ENST00000489695, ENST00000497089, ENST00000673744, ENST00000673917

RefSeq mRNA: 1 — MANE Select: NM_152739 NM_152739

CCDS: CCDS5409

Canonical transcript exons

ENST00000343483 — 2 exons

Exon	Start	End
ENSE00001399299	27164878	27165537
ENSE00002711618	27162438	27163841

Expression profiles

Bgee: expression breadth ubiquitous, 205 present calls, max score 96.88.

FANTOM5 (CAGE): breadth broad, TPM avg 6.5202 / max 233.0522, expressed in 674 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83310	3.6279	624
83309	2.3279	555
83311	0.2146	129
83306	0.1117	42
83308	0.1109	42
83312	0.0973	44
83307	0.0301	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.88	silver quality
renal glomerulus	UBERON:0000074	96.64	gold quality
metanephric glomerulus	UBERON:0004736	96.43	gold quality
biceps brachii	UBERON:0001507	96.27	gold quality
nephron tubule	UBERON:0001231	95.68	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.54	gold quality
penis	UBERON:0000989	95.10	gold quality
kidney epithelium	UBERON:0004819	95.07	gold quality
tibia	UBERON:0000979	94.75	gold quality
metanephros	UBERON:0000081	93.84	gold quality
mammalian vulva	UBERON:0000997	93.13	gold quality
skin of hip	UBERON:0001554	93.08	gold quality
metanephros cortex	UBERON:0010533	92.68	gold quality
gluteal muscle	UBERON:0002000	92.56	gold quality
mucosa of transverse colon	UBERON:0004991	91.87	gold quality
cortex of kidney	UBERON:0001225	91.37	gold quality
deltoid	UBERON:0001476	91.07	gold quality
kidney	UBERON:0002113	90.99	gold quality
renal medulla	UBERON:0000362	90.94	gold quality
vastus lateralis	UBERON:0001379	90.92	gold quality
colonic mucosa	UBERON:0000317	90.58	gold quality
transverse colon	UBERON:0001157	90.54	gold quality
quadriceps femoris	UBERON:0001377	90.48	gold quality
cervix squamous epithelium	UBERON:0006922	90.45	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.40	gold quality
skin of abdomen	UBERON:0001416	90.30	gold quality
adult mammalian kidney	UBERON:0000082	90.06	gold quality
corpus epididymis	UBERON:0004359	90.04	gold quality
triceps brachii	UBERON:0001509	89.46	gold quality
urethra	UBERON:0000057	89.44	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	42.56
E-CURD-112	yes	7.39
E-ANND-3	yes	6.41

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

41 targets.

Target	Regulation
ARHGEF1	Activation
BRCA1	Unknown
CD34
CDH3	Unknown
CDH5	Activation
CREB1	Activation
CYBB
DACH1
EIF4E
EPHB4
FGF2	Activation
FLT3
HOXA10
HOXA9
HOXB4
ID2	Activation
IGF1	Activation
IGF1R	Activation
KDR
KRAS
MEF2C	Repression
MEIS1
MSI2	Activation
MYB	Unknown
MYCN	Activation
NFKB1	Repression
ODC1
PIM1	Activation
PKNOX1
PRDM16

JASPAR motifs

Motif	Name	Family
MA0594.2	HOXA9	HOX
MA0594.3	HOXA9	HOX

JASPAR matrix evidence (PMIDs): PMID:12923056

Upstream regulators (CollecTRI, top): ASCL1, ASXL1, BCOR, CDX1, CDX4, CREBBP, DNMT3A, DOT1L, EZH2, GFI1, HOXA10, HOXA9, KAT6A, KDM6A, KMT2A, MEN1, NFKB1, NFKB, NPM1, PHF1, SALL4, SETBP1, SUZ12, TET1, TFAP2A, TWIST1, VEZF1

miRNA regulators (miRDB)

165 targeting HOXA9, 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-5011-5P	100.00	83.46	5820
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-190A-3P	100.00	80.35	5520
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-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-186-5P	99.99	70.83	3707
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-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

Literature-anchored findings (GeneRIF, showing 40)

• the fusion gene NUP98-HOXA9 is an important gene in myeloid leukemogenesis. (PMID:11830496)
• Nup98-HoxA9 immortalizes myeloid progenitors, enforces expression of Hoxa9, Hoxa7 and Meis1, and alters cytokine-specific responses in a manner similar to that induced by retroviral co-expression of Hoxa9 and Meis1. (PMID:12082612)
• The HOXA9 cluster gene is frequently expressed in cell lines from acute myeloid leukemia cases with 11p15 translocations; in some cases HOX9 is not fused to NUP98. (PMID:12112533)
• The NUP98/HOXA9 FUSION transcript was detected by PC at exon A and not exon B of NUP98. (PMID:12138901)
• HOXA9 complexed with Pbx1 and DNA, so that the posterior Hox hexapeptide adopts an altered conformation. (PMID:12923056)
• Nup98-HOXA9 has a role in inducing gene transcription in myeloid cells (PMID:14561764)
• B-lineage development can proceed in t(4;11) leukemic blasts in the absence of HOX-A gene expression. (PMID:14562113)
• Hoxa9 and Hoxa7 as well as the Hox coregulators Meis1 and Pbx3 among the targets upregulated by MLL-ENL-ERtm in conditionally transformed cells (PMID:14701735)
• Lower expression of HOXA9 is associated with acute myeloid leukemia-M2 (PMID:14738146)
• HoxA9 binds to the EphB4 promoter & stimulates its expression resulting in an increase of endothelial cell migration and tube forming activity. Thus, modulation of EphB4 expression may contribute to the proangiogenic effect of HoxA9 in endothelial cells. (PMID:14764452)
• suggest that MLL aberrations may regulate MEIS1 and HOXA9 gene expression in ALL-derived cell lines, while AML-derived cell lines express these genes independently of the MLL status (PMID:15160920)
• HOXA9 nuclear transport is induced by thrombopoietin in immature hematopoietic cells (PMID:15254242)
• Dnalc4, Fcgr2b, Fcrl, and Con1 genes cooperated with NUP98-HOXA9 in transforming NIH 3T3 cells (PMID:15454493)
• advantage to Meis1-HoxA9 coexpressing cells in vivo, leading to leukemogenesis. (PMID:15479723)
• HOXA9, is a positive regulator of eIF4E. HOXA9 stimulates eIF4E-dependent export of cyclin D1 and ornithine decarboxylase (ODC) mRNAs in the nucleus, as well as increases the translation efficiency of ODC mRNA in the cytoplasm. (PMID:15657436)
• CYBB is a common target gene repressed by HoxA10 and activated by HoxA9, and Meis1 and Nup98-hoxA9 have roles in repressing myeloid-specific gene transcription (PMID:15681849)
• The HOXA9 protein expression was significantly downregulated in the MOF knockdown cells compared to control siRNA-treated cells. (PMID:15960975)
• 90% of meningioma 1-ets variant gene 6 +/HOXA9+ mice developed AML much more rapidly than control HOXA9+ mice (PMID:16105979)
• The relative HOXA9 expression was higher in patients in the accelerated phase of the disease (p<0.005). Interestingly, a patient with poorer prognosis (high Sokal’s score), showing the highest HOXA9/ABL ratio, quickly entered a blast crisis and died. (PMID:16630659)
• the expression of abd-b genes may be an imortant step involved in cervical cancer. (PMID:16803519)
• The t(7;11)(p15;p15) translocation, observed in acute myelogenous leukemia and myelodysplastic syndrome, generates a chimeric gene where the 5’ portion of the sequence encoding the human nucleoporin NUP98 protein is fused to the 3’ region of HOXA9. (PMID:17178874)
• Pim1 appears to be a direct transcriptional target of HOXA9 and a mediator of its antiapoptotic and proproliferative effects in early cells (PMID:17327400)
• HOXA9 participates in the transcriptional activation of SELE in endothelial cells. (PMID:17452460)
• HOXA9 inhibits endothelial cell activation downstream of NF-kappaB nuclear localization by interfering with NF-kappaB DNA binding, but not transactivation capacity (PMID:17586512)
• DNA hypermethylation of tumour suppressor genes seems to play an important role in ovarian carcinogenesis and HOXA9, HOXB5, SCGB3A1, and CRABP1 are identified as novel hypermethylated target genes in this tumour type (PMID:17623056)
• In this expt. mice with a compound deficiency in hoxa9, hoxb3 and hoxb4 (hoxa9/b3/b4) were investigated for evidence of synergy between these genes in hematopoiesis. (PMID:17761289)
• In hypertensive patients, downregulation of HOXA9 expression in peripheral CD34+ cells may have a role in the loss of circulating endothelial progenitor cells, potentially impairing postnatal neovascularization and vascular repair. (PMID:17885552)
• nuclear factor-kappaB (NF-kappaB) activation is an essential step for HOXA9 downregulation. And HOXA9 regulates its own expression by positive feedback mechanism. (PMID:18068911)
• HoxA9 overexpression induces IGF-1R expression and subsequently promotes leukemic cell growth (PMID:18337761)
• analysis of the role of deregulated PcG genes in acute myeloid leukemia, and the downstream PcG targets HOXA4, HOXA9 and MEIS1 (PMID:18410541)
• miR-126 may function in normal hematopoietic cells to modulate HOXA9 protein. (PMID:18474618)
• HOXA9 overexpression is associated with acute myeloid leukemias. (PMID:18668134)
• An important role for HOXA9 in human MLL-rearranged leukemias. (PMID:19056693)
• Enforced overexpression of HOXA6 or HOXA9 in FDCP-Mix resulted in increased proliferation and colony formation but had negligible effect on differentiation in early multipotential and later committed precursor cells (PMID:19157684)
• Gfi1 integrates 2 events during normal myeloid differentiation; the suppression of a HoxA9-Pbx1-Meis1 progenitor program and the induction of a granulopoietic transcription program. (PMID:19346496)
• CREB1 may mediate HOXA9 modulation of Meis1 expression. (PMID:19620287)
• effects of NUP98-HOXA9 on gene transcription and cell transformation are mediated by two distinct mechanisms: promoter binding through homeodomain with direct transcriptional activation, and another depending on NUP98 moiety not involving DNA binding (PMID:19696924)
• HOXA9 activation is a novel, independent, and negative prognostic marker in GBM that is reversible through a PI3K-associated epigenetic mechanism. Findings suggest a transcriptional pathway through which PI3K activates oncogenic HOXA expression. (PMID:20068170)
• Increased expression of HoxA9 is associated with chronic myeloid leukemia. (PMID:20141430)
• HOXA9 restricts breast tumor aggression by modulating expression of the tumor suppressor gene BRCA1 (PMID:20389018)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	hmx4	ENSDARG00000007941
mus_musculus	Hoxa9	ENSMUSG00000038227
rattus_norvegicus	Hoxa9	ENSRNOG00000064322

Paralogs (3): HMX3 (ENSG00000188620), HMX2 (ENSG00000188816), HMX1 (ENSG00000215612)

Protein

Protein identifiers

Homeobox protein Hox-A9 — P31269 (reviewed: P31269)

Alternative names: Homeobox protein Hox-1G

All UniProt accessions (4): P31269, A0A669K9T0, A0A669KBC8, A8MVF3

UniProt curated annotations — full annotation on UniProt →

Function. Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Required for induction of SELE/E-selectin and VCAM1 on the endothelial cells surface at sites of inflammation. Positively regulates EIF4E-mediated mRNA nuclear export and also increases the translation efficiency of ODC mRNA in the cytoplasm by competing with factors which repress EIF4E activity such as PRH.

Subunit / interactions. Transiently interacts with PRMT5 in TNF stimulated endothelial cells. Interacts with EIF4E.

Subcellular location. Nucleus. Cytoplasm.

Post-translational modifications. Methylated on Arg-140 by PRMT5; methylation is critical for E-selectin induction.

Disease relevance. A chromosomal aberration involving HOXA9 is found in a form of acute myeloid leukemia. Translocation t(7;11)(p15;p15) with NUP98. The chimera includes NUP98 intrinsic disordered regions which contribute to aberrant liquid-liquid phase separation puncta of the chimera in the nucleus. This phase-separation enhances the chimera genomic targeting and induces organization of aberrant three-dimensional chromatin structures leading to tumourous transformation. A chromosomal aberration involving HOXA9 may contribute to disease progression in chronic myeloid leukemia. Translocation t(7;17)(p15;q23) with MSI2.

Similarity. Belongs to the Abd-B homeobox family.

RefSeq proteins (1): NP_689952* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR006711	Hox9_activation_N	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017112	HXA9/HXB9/HXC9	Family
IPR017970	Homeobox_CS	Conserved_site
IPR020479	HD_metazoa	Domain

Pfam: PF00046, PF04617

UniProt features (11 total): sequence conflict 4, site 2, chain 1, DNA-binding region 1, region of interest 1, modified residue 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31269-F1	63.51	0.24

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 163–164 (breakpoint for translocation to form msi2/hoxa9 fusion protein); 163–164 (breakpoint for translocation to form the nup98-hoxa9 fusion protein)

Post-translational modifications (1): 140

Mutagenesis-validated functional residues (1):

Position	Phenotype
140	results in loss of methylation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 359 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, VALK_AML_WITH_FLT3_ITD, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GOBP_SINGLE_FERTILIZATION, FXR_IR1_Q6, E2F_Q4_01, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, MULLIGHAN_NPM1_SIGNATURE_3_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, BENPORATH_ES_WITH_H3K27ME3, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, LI_WILMS_TUMOR, CHIARETTI_T_ALL_REFRACTORY_TO_THERAPY

GO Biological Process (21): DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase II (GO:0006357), spermatogenesis (GO:0007283), single fertilization (GO:0007338), male gonad development (GO:0008584), anterior/posterior pattern specification (GO:0009952), proximal/distal pattern formation (GO:0009954), prostate gland development (GO:0030850), mammary gland development (GO:0030879), response to testosterone (GO:0033574), embryonic forelimb morphogenesis (GO:0035115), endothelial cell activation (GO:0042118), negative regulation of myeloid cell differentiation (GO:0045638), embryonic skeletal system morphogenesis (GO:0048704), uterus development (GO:0060065), definitive hemopoiesis (GO:0060216), regulation of DNA-templated transcription (GO:0006355), regulation of gene expression (GO:0010468), miRNA-mediated post-transcriptional gene silencing (GO:0035195), positive regulation of transcription by RNA polymerase II (GO:0045944), embryonic skeletal system development (GO:0048706)

GO Molecular Function (8): 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 transcription factor activity (GO:0003700), enzyme binding (GO:0019899), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737), RISC complex (GO:0016442)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
gene expression	2
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regionalization	2
reproductive structure development	2
gland development	2
regulation of transcription by RNA polymerase II	2
RNA biosynthetic process	1
developmental process involved in reproduction	1
male gamete generation	1
fertilization	1
gonad development	1
development of primary male sexual characteristics	1
urogenital system development	1
response to lipid	1
response to ketone	1
embryonic limb morphogenesis	1
forelimb morphogenesis	1
cell activation	1
myeloid cell differentiation	1
negative regulation of cell differentiation	1
regulation of myeloid cell differentiation	1
embryonic organ morphogenesis	1
skeletal system morphogenesis	1
embryonic skeletal system development	1
animal organ development	1
hemopoiesis	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of macromolecule biosynthetic process	1
regulatory ncRNA-mediated post-transcriptional gene silencing	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

Protein interactions and networks

STRING

1952 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HOXA9	MEIS1	O00470	996
HOXA9	PBX1	P40424	980
HOXA9	NUP98	P52948	965
HOXA9	MSI2	Q96DH6	916
HOXA9	PBX3	P40426	916
HOXA9	MLLT3	P42568	841
HOXA9	MLLT1	Q03111	819
HOXA9	MLLT10	P55197	768
HOXA9	AFF1	P51825	761
HOXA9	FCRLA	Q7L513	718
HOXA9	ASXL2	Q76L83	712
HOXA9	DDB1	Q16531	706
HOXA9	HOXA7	P31268	701
HOXA9	PBX2	P40425	687
HOXA9	PSIP1	O75475	685

IntAct

28 interactions, top by confidence:

A	B	Type	Score
HOXA9	TRIP6	psi-mi:“MI:0915”(physical association)	0.750
HOXA9	TRIP6	psi-mi:“MI:0914”(association)	0.750
HOXA9	KRTAP9-3	psi-mi:“MI:0915”(physical association)	0.560
	HOXA9	psi-mi:“MI:0915”(physical association)	0.560
PRMT5	HOXA9	psi-mi:“MI:0915”(physical association)	0.520
HOXA9	CCL2	psi-mi:“MI:0915”(physical association)	0.400
IFNA10	HOXA9	psi-mi:“MI:0915”(physical association)	0.370
HOXA9	RBPMS	psi-mi:“MI:0915”(physical association)	0.370
HOXA9	PLSCR1	psi-mi:“MI:0915”(physical association)	0.370
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
S100P	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CHCHD2	ZNF593	psi-mi:“MI:0914”(association)	0.350
HOXA9	FYN	psi-mi:“MI:0914”(association)	0.350
PTBP3		psi-mi:“MI:0914”(association)	0.350
HOXA9	HDAC1	psi-mi:“MI:2364”(proximity)	0.270
SUZ12	HOXA9	psi-mi:“MI:2364”(proximity)	0.270
KRTAP9-3	HOXA9	psi-mi:“MI:0915”(physical association)	0.000
	HOXA9	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (44): TRIP6 (Two-hybrid), RBPMS (Two-hybrid), PLSCR1 (Two-hybrid), TRIP6 (Affinity Capture-Western), HOXA9 (Synthetic Growth Defect), HOXA9 (Affinity Capture-RNA), HOXA9 (Phenotypic Enhancement), HOXA9 (Affinity Capture-MS), KRTAP9-3 (Two-hybrid), KRTAP10-1 (Two-hybrid), HOXA9 (Reconstituted Complex), HOXA9 (Reconstituted Complex), PBX1 (Reconstituted Complex), PBX3 (Reconstituted Complex), PBX2 (Reconstituted Complex)

ESM2 similar proteins: A1YEY5, A1YFA5, A1YFI3, A1YG57, A1YGK7, A2D5K9, A2D5Y4, A2T733, A2T748, A2T7F3, A2T7P4, O95096, P02830, P04476, P09021, P09024, P09067, P09629, P09631, P18864, P20719, P23459, P23463, P31268, P31269, P35453, P42586, P43697, P56915, P70217, P81068, P97334, Q02591, Q1KKX0, Q1KKX1, Q1KKY0, Q1KKY1, Q1KL17, Q2HJ67, Q5EU41

Diamond homologs: A1YFT7, A2D5V0, A2D635, A2T6F8, A2T7D1, A2T7H7, B5DFK3, O42502, O42503, O42506, O43248, P09013, P09014, P09023, P09025, P09067, P09079, P09087, P09631, P09632, P09633, P10179, P14838, P15861, P17481, P17482, P17509, P18863, P18866, P20615, P23459, P23813, P24340, P24341, P24342, P28356, P28357, P28358, P28359, P31257

SIGNOR signaling

23 interactions.

A	Effect	B	Mechanism
HOXA9	“up-regulates quantity by expression”	MSI2	“transcriptional regulation”
PRMT5	“up-regulates activity”	HOXA9	methylation
SETBP1	“up-regulates quantity by expression”	HOXA9	“transcriptional regulation”
HOXA9	“up-regulates quantity by expression”	IGF1	“transcriptional regulation”
HOXA9	“down-regulates quantity by repression”	MEF2C	“transcriptional regulation”
HOXA9	“up-regulates quantity by expression”	MYCN	“transcriptional regulation”
SALL4	“up-regulates quantity by expression”	HOXA9	“transcriptional regulation”
MLL-ENL	“up-regulates quantity by expression”	HOXA9	“transcriptional regulation”
HOXA9	down-regulates	Differentiation
“AEP complex”	“up-regulates quantity by expression”	HOXA9
MEN1	“up-regulates quantity by expression”	HOXA9	methylation
“Polycomb repressive complex 2”	“down-regulates quantity by repression”	HOXA9	“transcriptional regulation”
ASXL1	“down-regulates quantity by repression”	HOXA9	“transcriptional regulation”
DNMT3A	“down-regulates quantity by repression”	HOXA9	“transcriptional regulation”
DOT1L	“up-regulates quantity by expression”	HOXA9	“transcriptional regulation”
TET1	“up-regulates quantity by expression”	HOXA9	“transcriptional regulation”
KDM6A	“up-regulates quantity by expression”	HOXA9	“transcriptional regulation”
EZH2	“down-regulates quantity by repression”	HOXA9	“transcriptional regulation”
PHF1	“down-regulates quantity by repression”	HOXA9	“transcriptional regulation”
NPM1	“down-regulates quantity by repression”	HOXA9	“transcriptional regulation”
HOXA9	“up-regulates quantity by expression”	PIM1	“transcriptional regulation”
BCOR	“down-regulates quantity by repression”	HOXA9	“transcriptional regulation”
HOXA9	“up-regulates activity”	MEIS1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

698 predictions. Top by Δscore:

Variant	Effect	Δscore
7:27163837:GTTAT:G	acceptor_gain	1.0000
7:27163838:TTAT:T	acceptor_gain	1.0000
7:27163839:TAT:T	acceptor_gain	1.0000
7:27163840:AT:A	acceptor_gain	1.0000
7:27163842:C:CC	acceptor_gain	1.0000
7:27163843:T:G	acceptor_loss	1.0000
7:27164876:A:AC	donor_gain	1.0000
7:27164877:C:CC	donor_gain	1.0000
7:27164968:C:CC	acceptor_gain	1.0000
7:27172178:CA:C	acceptor_gain	1.0000
7:27172179:A:AC	acceptor_gain	1.0000
7:27172179:A:C	acceptor_gain	1.0000
7:27164877:C:CT	donor_gain	0.9900
7:27164965:CAA:C	acceptor_gain	0.9900
7:27165143:G:A	donor_gain	0.9900
7:27171928:C:CA	donor_gain	0.9900
7:27172170:TTGC:T	acceptor_gain	0.9900
7:27172171:TGC:T	acceptor_gain	0.9900
7:27172172:GCC:G	acceptor_loss	0.9900
7:27172174:C:CC	acceptor_gain	0.9900
7:27172175:T:A	acceptor_loss	0.9900
7:27172181:G:C	acceptor_gain	0.9900
7:27172181:G:GC	acceptor_gain	0.9900
7:27173343:GCTTA:G	donor_loss	0.9900
7:27173344:CTTAC:C	donor_loss	0.9900
7:27173345:TTACC:T	donor_loss	0.9900
7:27173346:TACC:T	donor_loss	0.9900
7:27173347:A:AC	donor_gain	0.9900
7:27173347:AC:A	donor_gain	0.9900
7:27173347:ACCC:A	donor_loss	0.9900

AlphaMissense

1776 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:27163635:T:C	K263E	1.000
7:27163636:C:A	K262N	1.000
7:27163636:C:G	K262N	1.000
7:27163638:T:C	K262E	1.000
7:27163642:T:A	K260N	1.000
7:27163642:T:G	K260N	1.000
7:27163643:T:A	K260I	1.000
7:27163644:T:C	K260E	1.000
7:27163644:T:G	K260Q	1.000
7:27163645:C:A	M259I	1.000
7:27163645:C:G	M259I	1.000
7:27163645:C:T	M259I	1.000
7:27163646:A:C	M259R	1.000
7:27163646:A:G	M259T	1.000
7:27163646:A:T	M259K	1.000
7:27163648:C:A	R258S	1.000
7:27163648:C:G	R258S	1.000
7:27163649:C:A	R258M	1.000
7:27163649:C:G	R258T	1.000
7:27163650:T:A	R258W	1.000
7:27163650:T:C	R258G	1.000
7:27163652:C:A	R257L	1.000
7:27163652:C:G	R257P	1.000
7:27163653:G:C	R257G	1.000
7:27163653:G:T	R257S	1.000
7:27163654:G:C	N256K	1.000
7:27163654:G:T	N256K	1.000
7:27163655:T:A	N256I	1.000
7:27163655:T:C	N256S	1.000
7:27163655:T:G	N256T	1.000

dbSNP variants (sampled 300 via entrez): RS1000950303 (7:27165162 G>A), RS1001052090 (7:27167291 G>A,T), RS1001381193 (7:27165360 C>A,G,T), RS1002348742 (7:27163080 C>T), RS1003015066 (7:27165521 T>C), RS1003350138 (7:27164346 T>C), RS1003795524 (7:27163965 G>A,C), RS1004188651 (7:27165728 C>A), RS1004461396 (7:27165713 A>G), RS1004492304 (7:27165967 G>A,T), RS1005118544 (7:27164416 T>G), RS1005236065 (7:27166547 G>A,C,T), RS1005980093 (7:27162201 C>G), RS1006132647 (7:27166810 G>A), RS1006165607 (7:27167029 C>T)

Disease associations

OMIM: gene MIM:142956 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST007706_27	Mean arterial pressure	2.000000e-12
GCST007707_30	Hypertension	1.000000e-08
GCST009066_10	Mosaic loss of chromosome Y (Y chromosome dosage)	2.000000e-13
GCST009067_12	Mosaic loss of chromosome Y (Y chromosome dosage)	9.000000e-25
GCST90002392_716	Mean corpuscular volume	4.000000e-12
GCST90002394_189	Monocyte percentage of white cells	6.000000e-10
GCST90002400_608	Plateletcrit	1.000000e-12
GCST90002402_15	Platelet count	4.000000e-09
GCST90002403_194	Red blood cell count	5.000000e-15
GCST90020024_90	A body shape index	3.000000e-16
GCST90020024_92	A body shape index	7.000000e-09
GCST90020024_93	A body shape index	2.000000e-08
GCST90020025_738	Waist-to-hip ratio adjusted for BMI	1.000000e-18
GCST90020025_740	Waist-to-hip ratio adjusted for BMI	6.000000e-12
GCST90020027_1340	Waist-hip index	1.000000e-19
GCST90020027_1342	Waist-hip index	2.000000e-12
GCST90020027_1343	Waist-hip index	4.000000e-08
GCST90020029_862	Waist circumference adjusted for body mass index	3.000000e-08
GCST90020029_863	Waist circumference adjusted for body mass index	2.000000e-13

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0006340	mean arterial pressure
EFO:0007783	mosaic loss of chromosome Y measurement
EFO:0007989	monocyte percentage of leukocytes
EFO:0007985	platelet crit
EFO:0004309	platelet count
EFO:0004305	erythrocyte count
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
Arsenic Trioxide	decreases expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
methylselenic acid	decreases expression	1
terbufos	increases methylation	1
hexamethylene bisacetamide	increases expression	1
cobaltous chloride	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
MRK 003	decreases expression	1
MK-8776	decreases expression	1
(+)-JQ1 compound	decreases expression	1
NSC668394	increases expression	1
EPZ004777	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Decitabine	increases expression	1
Air Pollutants	increases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	increases expression	1
Coal	increases expression, increases abundance	1
Diethylstilbestrol	increases expression	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Piroxicam	decreases expression	1
Silicon Dioxide	increases expression	1
Smoke	increases abundance, increases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Crocidolite	decreases methylation	1
Asbestos, Amosite	decreases methylation	1

Cellosaurus cell lines

13 cell lines: 7 transformed cell line, 3 cancer cell line, 2 embryonic stem cell, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A2X9	SEES3-1V human HOXA9, clone1	Embryonic stem cell	Male
CVCL_A2Y0	SEES3-1V human HOXA9, clone2	Embryonic stem cell	Male
CVCL_B1B0	Abcam HEK293 HOXA9 KO 1	Transformed cell line	Female
CVCL_B1B1	Abcam HEK293 HOXA9 KO 2	Transformed cell line	Female
CVCL_B7TY	CI-huFIB	Transformed cell line	Male
CVCL_B7U6	e-hMEC-1	Transformed cell line
CVCL_B7U8	e-hMEC-3	Transformed cell line
CVCL_B7UM	e-hUVEC-5	Transformed cell line
CVCL_B8HL	Abcam HCT 116 HOXA9 KO	Cancer cell line	Male
CVCL_B8WX	Abcam MCF-7 HOXA9 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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