HOXA5

Summary

HOXA5 (homeobox A5, HGNC:5106) is a protein-coding gene on chromosome 7p15.2, encoding Homeobox protein Hox-A5 (P20719). 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. Methylation of this gene may result in the loss of its expression and, since the encoded protein upregulates the tumor suppressor p53, this protein may play an important role in tumorigenesis.

Source: NCBI Gene 3202 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 1 total
• Transcription factor: yes — 18 downstream targets (CollecTRI)
• MANE Select transcript: NM_019102

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5106
Approved symbol	HOXA5
Name	homeobox A5
Location	7p15.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000106004
Ensembl biotype	protein_coding
OMIM	142952
Entrez	3202

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000222726, ENST00000520854

RefSeq mRNA: 1 — MANE Select: NM_019102 NM_019102

CCDS: CCDS5406

Canonical transcript exons

ENST00000222726 — 2 exons

Exon	Start	End
ENSE00000674260	27143046	27143681
ENSE00001012494	27141052	27142085

Expression profiles

Bgee: expression breadth ubiquitous, 203 present calls, max score 95.01.

FANTOM5 (CAGE): breadth broad, TPM avg 2.6691 / max 98.0452, expressed in 689 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83293	0.9295	405
83294	0.8941	422
83289	0.2613	117
83292	0.2217	106
83295	0.1848	90
83290	0.0651	23
83288	0.0619	22
83291	0.0507	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	95.01	gold quality
caput epididymis	UBERON:0004358	94.66	gold quality
corpus epididymis	UBERON:0004359	94.54	gold quality
renal medulla	UBERON:0000362	94.46	gold quality
left uterine tube	UBERON:0001303	94.44	gold quality
adrenal cortex	UBERON:0001235	93.74	gold quality
right adrenal gland cortex	UBERON:0035827	93.67	gold quality
left adrenal gland cortex	UBERON:0035825	93.42	gold quality
right adrenal gland	UBERON:0001233	93.34	gold quality
adrenal gland	UBERON:0002369	93.19	gold quality
left adrenal gland	UBERON:0001234	92.97	gold quality
mucosa of transverse colon	UBERON:0004991	92.17	gold quality
metanephros cortex	UBERON:0010533	91.67	gold quality
ileal mucosa	UBERON:0000331	91.58	gold quality
right uterine tube	UBERON:0001302	90.81	gold quality
lower lobe of lung	UBERON:0008949	90.37	gold quality
transverse colon	UBERON:0001157	89.76	gold quality
right lung	UBERON:0002167	88.18	gold quality
nipple	UBERON:0002030	87.56	gold quality
mammary duct	UBERON:0001765	87.25	gold quality
lung	UBERON:0002048	87.12	gold quality
visceral pleura	UBERON:0002401	87.12	gold quality
epithelium of mammary gland	UBERON:0003244	87.11	gold quality
mucosa of stomach	UBERON:0001199	86.85	gold quality
spinal cord	UBERON:0002240	86.84	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.81	gold quality
peritoneum	UBERON:0002358	86.74	gold quality
omental fat pad	UBERON:0010414	86.74	gold quality
upper lobe of lung	UBERON:0008948	86.71	gold quality
adipose tissue of abdominal region	UBERON:0007808	86.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-10485	yes	664.75
E-ANND-3	yes	7.61

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

18 targets.

Target	Regulation
ARHGEF1	Activation
DST	Unknown
HOXA4	Repression
HOXA5
IGFBP1
KDR
LHX2
MLH1
PAX1	Unknown
PGR	Activation
PTN	Activation
SLC6A2	Repression
TH	Unknown
THBS2	Activation
TNC	Activation
TP53	Activation
VIM
ZEB1	Activation

JASPAR motifs

Motif	Name	Family
MA0158.1	HOXA5	HOX
MA0158.2	HOXA5	HOX

JASPAR matrix evidence (PMIDs): PMID:17916232, PMID:18585359

Upstream regulators (CollecTRI, top): BCOR, FOXO1, FOXO3, HOXA4, HOXA5, KDM6A, NOTCH1, RARB

miRNA regulators (miRDB)

142 targeting HOXA5, 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-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1252-5P	100.00	69.80	2774
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-5692A	100.00	74.40	6850
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
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-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-12133	99.92	71.82	2006

Literature-anchored findings (GeneRIF, showing 40)

• engineered a p53-mutant breast cancer cell line, Hs578T, to inducibly express HOXA5. Expression of HOXA5 can induce apoptosis through an apoptotic mechanism mediated by caspases 2 and 8. (PMID:14701762)
• loss of HOXA5 expression could lead to the functional activation of Twist resulting in aberrant cell cycle regulation and promoting breast carcinogenesis (PMID:15545268)
• analysis of transcriptional targets of HOXA5 by microarray hybridization (PMID:15757903)
• Hox A5 expression is inconsistent with an angiogenic phenotype; expression of Hox A5 may help to maintain existing vessels in a quiescent, differentiated state. (PMID:16379594)
• HOXA5 is a transcriptional regulator of hMLH1 in breast cancer cells (PMID:16756717)
• HOXA5 expression was maintained at stable levels at different reproductive stages of a woman’s life, except during lactation. HOXA5 protein expression levels in breast carcinomas inversely co-relates with Epidermal Growth Factor Receptor expression. (PMID:17167183)
• Study identified hypermethylation and gene inactivation of HOXA4 and HOXA5 was frequently observed (26-79%) in all types of leukemias studied. (PMID:17785556)
• HOXA5 acts directly downstream of RARbeta and may contribute to retinoid-induced anticancer and chemopreventive effects. (PMID:17804711)
• miR-130a is a regulator of the angiogenic phenotype of vascular endothelial cells largely through its ability to modulate the expression of GAX and HOXA5 (PMID:17957028)
• The promoter methylation status of a panel of critical growth regulatory genes, RASSF1A, RARbeta2, BRCA1 and HOXA5, in 54 breast cancers and 5 distant normal breast tissues of Indian patients, was analyzed. (PMID:18538349)
• Epigenetic inactivation of Homeobox A5 gene is associated with nonsmall cell lung cancer. (PMID:19554572)
• HOXA5 is hypermethylated in clear cell renal cell carcinoma. (PMID:20846263)
• The methylation percentage of HOXA5 in AML patients was higher than that of HOXA5 in control patients. (PMID:20890077)
• Androgen receptor mutations are associated with altered epigenomic programming as evidenced by HOXA5 methylation. (PMID:21311178)
• Studies suggest that HOXA4, HOXA5 and HOXB4 provide the spatial information needed to restrict the response to signals from the notochord, and not up regulated in pancreatic cancer. (PMID:21546695)
• since lower levels of HOXA5 predict poor prognosis, this gene may be a novel candidate for development of therapeutic strategies in OSCC. (PMID:22227861)
• HOXA5 can suppress keratinocytes growth and epidermal formation. (PMID:22464764)
• Our analysis showed that miR-196a suppressed the expression of HOXA5 both at the mRNA and protein levels; knockdown of HOXA5 expression in A549 cells using RNAi was shown to promote NSCLC cell proliferation, migration and invasion. (PMID:22876840)
• Our findings present that decreased HOXA5 could be identified as a poor prognostic biomarker in nonsmall cell lung cancer and regulate cell proliferation and invasion (PMID:25549794)
• The NK AML patients with NPM1 mutations exhibited elevated HOXA4 methylation and expression levels of HOXA5 and MEIS1 compared with the NPM1 wildtype patients. (PMID:25585874)
• Ectopic expression of HOXA5 in highly invasive cancer cells suppressed cell migration, invasion, and filopodia formation in vitro and inhibited metastatic potential in vivo. (PMID:25875824)
• Among the mechanosensitive genes, the two transcription factors, HoxA5 and Klf3, contain cAMP-response-elements methylation of which could serve as a mechanosensitive master switch in gene expression in atherosclerosis. (Review) (PMID:25979369)
• Increased expression of HOXA5 is associated with acute myeloid leukemia. (PMID:25987065)
• HOXA5-induced apoptosis was p53-independent. (PMID:26219418)
• Downregulation of HOXA5 by shRNA may trigger apoptosis and overcome drug resistance in leukemia cells. (PMID:26397212)
• In colon cancer, HOXA5 is downregulated, and its re-expression induces loss of the cancer stem cell phenotype, preventing tumor progression and metastasis. (PMID:26678341)
• high expression levels of HOXA5 mRNA and protein in children with ALL indicate that HOXA5 is closely associated with childhood ALL. (PMID:26846409)
• ATRA may inhibit the proliferation of K562 cells and promote apoptosis by upregulating the HOXA5 mRNA and protein expression. (PMID:27052693)
• loss of HOXA5 in mammary cells leads to loss of epithelial traits, an increase in stemness and cell plasticity, and the acquisition of more aggressive phenotypes. (PMID:27157614)
• lung cancer stem-like cells have plasticity under a condition of oxidative stress, and HOAX5 has a critical role in dedifferentiation (PMID:27418136)
• Knockdown of HOXA5 suppressed the proliferation and metastasis of esophageal squamous cell cancer cells. (PMID:27960137)
• HOXA5 could bind in the promoter of linc00312 and up-regulated the expression of it. (PMID:28338293)
• HOXA5 was identified as a tumor suppressor gene, which inhibited non-small-cell lung cancer metastasis by regulating cytoskeletal remodeling. Its expression is repressed by linc00673 through binding with EZH2. (PMID:28423732)
• The present study demonstrates that HOXA5 can be silenced in the psoriatic stratum corneum due to DNA methylation of the CGI located in the 5’ region of HOXA5. (PMID:28482119)
• Research demonstrated that depletion of HOXA5 inhibited osteogenic differentiation and repressed cell proliferation by arresting cell cycle progression at the S phase via p16(INK4A) , p18(INK4C) , and Cyclin A in SCAPs, indicating that HOXA5 has a significant role in maintaining the proliferation and differentiation potential of dental-tissue-derived MSCs. (PMID:28833816)
• homeobox A5 and signal transducer and activator of transcription 3 were physically associated and appeared interdependent in activating PD-L1 transcription. Functional studies showed that HDAC8-mediated regulation of PD-L1 expression participated in modulating anti-melanoma T-cell responses. (PMID:29174371)
• The study demonstrated that MPP8 was associated with non-small cell lung cancer cell proliferation through regulation of HOXA5. (PMID:29412790)
• HOXA5, HOXB6, and GLTP were direct target genes of MIR196B in CRC cells. (PMID:29532406)
• study implicates HOXA5 as a chromosome 7-associated gene-level locus that promotes selection for gain of whole chromosome 7 and an aggressive phenotype in glioblastoma. (PMID:29632085)
• Low HOXA5 expression is associated with Gastric cancer. (PMID:30015922)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	hoxa5a	ENSDARG00000102501
mus_musculus	Hoxa5	ENSMUSG00000038253
rattus_norvegicus	LOC103692127	ENSRNOG00000047951

Paralogs (42): HOXA11 (ENSG00000005073), HOXC8 (ENSG00000037965), HOXA1 (ENSG00000105991), HOXA2 (ENSG00000105996), HOXA3 (ENSG00000105997), HOXA6 (ENSG00000106006), HOXA13 (ENSG00000106031), TLX1 (ENSG00000107807), HOXB6 (ENSG00000108511), TLX2 (ENSG00000115297), HOXB8 (ENSG00000120068), HOXB5 (ENSG00000120075), HOXB3 (ENSG00000120093), HOXB1 (ENSG00000120094), HOXA7 (ENSG00000122592), HOXC13 (ENSG00000123364), HOXC11 (ENSG00000123388), HOXC12 (ENSG00000123407), HOXD1 (ENSG00000128645), HOXD3 (ENSG00000128652), HOXD9 (ENSG00000128709), HOXD10 (ENSG00000128710), HOXD11 (ENSG00000128713), HOXD13 (ENSG00000128714), PDX1 (ENSG00000139515), HOXB13 (ENSG00000159184), TLX3 (ENSG00000164438), HOXD4 (ENSG00000170166), HOXD12 (ENSG00000170178), HOXB9 (ENSG00000170689), HOXC5 (ENSG00000172789), HOXB2 (ENSG00000173917), HOXD8 (ENSG00000175879), GSX2 (ENSG00000180613), HOXC9 (ENSG00000180806), HOXC10 (ENSG00000180818), HOXB4 (ENSG00000182742), HOXA4 (ENSG00000197576), HOXC6 (ENSG00000197757), HOXC4 (ENSG00000198353)

Protein

Protein identifiers

Homeobox protein Hox-A5 — P20719 (reviewed: P20719)

Alternative names: Homeobox protein Hox-1C

All UniProt accessions (1): P20719

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. Also binds to its own promoter. Binds specifically to the motif 5’-CYYNATTA[TG]Y-3'.

Subunit / interactions. Forms a DNA-binding heterodimer with transcription factor PBX1.

Subcellular location. Nucleus.

Similarity. Belongs to the Antp homeobox family.

RefSeq proteins (1): NP_061975* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR001827	Homeobox_Antennapedia_CS	Conserved_site
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR017995	Homeobox_antennapedia	Family
IPR020479	HD_metazoa	Domain
IPR050296	Antp_homeobox	Family

Pfam: PF00046

UniProt features (8 total): compositionally biased region 3, chain 1, DNA-binding region 1, region of interest 1, short sequence motif 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20719-F1	64.02	0.26

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 362 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_MYELOID_CELL_DIFFERENTIATION, VALK_AML_WITH_FLT3_ITD, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, AHRARNT_01, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, RRAGTTGT_UNKNOWN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, MULLIGHAN_NPM1_SIGNATURE_3_UP, ACTACCT_MIR196A_MIR196B, GOBP_LUNG_EPITHELIUM_DEVELOPMENT

GO Biological Process (36): respiratory system process (GO:0003016), regulation of transcription by RNA polymerase II (GO:0006357), anterior/posterior pattern specification (GO:0009952), positive regulation of gene expression (GO:0010628), cell migration (GO:0016477), negative regulation of angiogenesis (GO:0016525), thyroid gland development (GO:0030878), regulation of mammary gland epithelial cell proliferation (GO:0033599), multicellular organism growth (GO:0035264), positive regulation of apoptotic process (GO:0043065), positive regulation of myeloid cell differentiation (GO:0045639), negative regulation of erythrocyte differentiation (GO:0045647), positive regulation of transcription by RNA polymerase II (GO:0045944), lung alveolus development (GO:0048286), embryonic skeletal system morphogenesis (GO:0048704), bronchiole development (GO:0060435), epithelial tube branching involved in lung morphogenesis (GO:0060441), lung goblet cell differentiation (GO:0060480), lung-associated mesenchyme development (GO:0060484), trachea cartilage morphogenesis (GO:0060535), intestinal epithelial cell maturation (GO:0060574), mesenchymal-epithelial cell signaling (GO:0060638), mammary gland epithelial cell differentiation (GO:0060644), mammary gland alveolus development (GO:0060749), cell-cell signaling involved in mammary gland development (GO:0060764), skeletal system development (GO:0001501), morphogenesis of an epithelium (GO:0002009), regulation of DNA-templated transcription (GO:0006355), pattern specification process (GO:0007389), respiratory gaseous exchange by respiratory system (GO:0007585), lung development (GO:0030324), mammary gland development (GO:0030879), embryonic skeletal system development (GO:0048706), trachea morphogenesis (GO:0060439), lobar bronchus epithelium development (GO:0060481), cartilage morphogenesis (GO:0060536)

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

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lung development	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
system process	1
respiratory gaseous exchange by respiratory system	1
regionalization	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
cell motility	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
endocrine system development	1
gland development	1
mammary gland epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
multicellular organismal process	1
developmental growth	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
myeloid cell differentiation	1
positive regulation of cell differentiation	1
regulation of myeloid cell differentiation	1
erythrocyte differentiation	1
negative regulation of myeloid cell differentiation	1
regulation of erythrocyte differentiation	1
positive regulation of DNA-templated transcription	1
anatomical structure development	1
embryonic organ morphogenesis	1
skeletal system morphogenesis	1
embryonic skeletal system development	1
respiratory tube development	1
branching morphogenesis of an epithelial tube	1
lung morphogenesis	1
lobar bronchus epithelium development	1
lung secretory cell differentiation	1

Protein interactions and networks

STRING

1395 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HOXA5	HDAC8	Q9BY41	709
HOXA5	PBX1	P40424	628
HOXA5	HAND2	P61296	619
HOXA5	MYO18A	O95411	616
HOXA5	MEIS1	O00470	599
HOXA5	GATA2	P23769	571
HOXA5	CD34	P28906	570
HOXA5	ETS1	P14921	548
HOXA5	STAT3	P40763	533
HOXA5	ZNF354C	Q86Y25	529
HOXA5	GATA3	P23771	527
HOXA5	HOXD10	P28358	490
HOXA5	HOXD9	P28356	481
HOXA5	LCOR	Q96JN0	477
HOXA5	HOXA10	P31260	474

IntAct

63 interactions, top by confidence:

A	B	Type	Score
HOXA5	CTBP2	psi-mi:“MI:0915”(physical association)	0.560
HOXA5	PICK1	psi-mi:“MI:0915”(physical association)	0.560
HOXA5	DVL3	psi-mi:“MI:0915”(physical association)	0.560
HOXA5	PBX2	psi-mi:“MI:0915”(physical association)	0.560
HOXA5	APBB2	psi-mi:“MI:0915”(physical association)	0.560
HOXA5		psi-mi:“MI:0915”(physical association)	0.560
HOXA5	HTT	psi-mi:“MI:0915”(physical association)	0.560
ERP44	MEX3A	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
HEATR3	SLC27A2	psi-mi:“MI:0914”(association)	0.530
HOXA5	GTF2A1L	psi-mi:“MI:0915”(physical association)	0.370
DDIT3	HOXA5	psi-mi:“MI:0915”(physical association)	0.370
HOXA5	SMAD1	psi-mi:“MI:0915”(physical association)	0.370
HOXA5	ZNF408	psi-mi:“MI:0915”(physical association)	0.370
HOXA5	PRMT6	psi-mi:“MI:0915”(physical association)	0.370
k8	RGL2	psi-mi:“MI:0914”(association)	0.350
BCL2L14		psi-mi:“MI:0914”(association)	0.350
IFITM3	STX12	psi-mi:“MI:0914”(association)	0.350

BioGRID (104): HOXA5 (Affinity Capture-MS), HOXA5 (Affinity Capture-MS), HOXA5 (Affinity Capture-MS), HOXA5 (Affinity Capture-MS), HOXA5 (Affinity Capture-MS), HOXA5 (Affinity Capture-MS), HOXA5 (Reconstituted Complex), HOXA5 (Affinity Capture-MS), HOXA5 (Affinity Capture-MS), HOXA5 (Affinity Capture-MS), FOXA2 (Reconstituted Complex), HOXA5 (Affinity Capture-MS), HOXA5 (Affinity Capture-MS), HOXA5 (Two-hybrid), DVL3 (Two-hybrid)

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: A1L2P5, A1YER7, A1YF08, A1YFD8, A1YFY3, A1YG85, A2D4P8, A2D5I1, A2D5K9, A2D5Y4, A2T6X6, A2T756, A8DT10, A9L937, B0VXK3, O13074, O42365, O42367, O42368, O42370, O43364, O43365, O57374, O93353, P02830, P02831, P06798, P09013, P09014, P09016, P09019, P09020, P09021, P09026, P09027, P09067, P09070, P09074, P09079, P09080

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
NOTCH1	“up-regulates quantity by expression”	HOXA5	“transcriptional regulation”
KDM6A	“up-regulates quantity by expression”	HOXA5	“transcriptional regulation”
BCOR	“down-regulates quantity by repression”	HOXA5	“transcriptional regulation”

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

311 predictions. Top by Δscore:

Variant	Effect	Δscore
7:27142082:TTGT:T	acceptor_gain	1.0000
7:27142083:TGT:T	acceptor_gain	1.0000
7:27142083:TGTCT:T	acceptor_loss	1.0000
7:27142084:GTC:G	acceptor_loss	1.0000
7:27142086:C:A	acceptor_loss	1.0000
7:27142086:C:CC	acceptor_gain	1.0000
7:27142081:GTTGT:G	acceptor_gain	0.9900
7:27142084:GT:G	acceptor_gain	0.9900
7:27142091:A:AC	acceptor_gain	0.9900
7:27143040:CTTTA:C	donor_loss	0.9900
7:27143041:TTTA:T	donor_loss	0.9900
7:27143042:TTAC:T	donor_loss	0.9900
7:27143043:TA:T	donor_loss	0.9900
7:27143044:ACCAT:A	donor_loss	0.9900
7:27143054:A:AC	donor_gain	0.9900
7:27143054:ATGTG:A	donor_gain	0.9900
7:27143055:T:C	donor_gain	0.9900
7:27142089:C:CT	acceptor_gain	0.9800
7:27142083:TGTC:T	acceptor_gain	0.9700
7:27142084:GTCT:G	acceptor_gain	0.9700
7:27143044:A:AC	donor_gain	0.9700
7:27143045:C:CC	donor_gain	0.9700
7:27142082:TTGTC:T	acceptor_gain	0.9600
7:27142085:TCT:T	acceptor_gain	0.9600
7:27142086:C:G	acceptor_gain	0.9600
7:27142090:A:T	acceptor_gain	0.9600
7:27142087:T:A	acceptor_gain	0.9500
7:27143045:CCA:C	donor_gain	0.9400
7:27142662:AGC:A	donor_gain	0.9200
7:27142667:T:TA	donor_gain	0.8800

AlphaMissense

1796 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:27141892:T:A	K252N	1.000
7:27141892:T:G	K252N	1.000
7:27141893:T:A	K252I	1.000
7:27141894:T:C	K252E	1.000
7:27141895:T:A	K251N	1.000
7:27141895:T:G	K251N	1.000
7:27141896:T:A	K251I	1.000
7:27141897:T:C	K251E	1.000
7:27141900:A:G	W250R	1.000
7:27141900:A:T	W250R	1.000
7:27141901:C:A	K249N	1.000
7:27141901:C:G	K249N	1.000
7:27141903:T:C	K249E	1.000
7:27141904:C:A	M248I	1.000
7:27141904:C:G	M248I	1.000
7:27141904:C:T	M248I	1.000
7:27141905:A:C	M248R	1.000
7:27141905:A:G	M248T	1.000
7:27141905:A:T	M248K	1.000
7:27141907:T:A	R247S	1.000
7:27141907:T:G	R247S	1.000
7:27141908:C:A	R247I	1.000
7:27141908:C:G	R247T	1.000
7:27141909:T:C	R247G	1.000
7:27141911:C:A	R246L	1.000
7:27141911:C:G	R246P	1.000
7:27141912:G:A	R246W	1.000
7:27141912:G:C	R246G	1.000
7:27141913:G:C	N245K	1.000
7:27141913:G:T	N245K	1.000

dbSNP variants (sampled 300 via entrez): RS1001081480 (7:27145492 G>T), RS1001169296 (7:27141784 A>C), RS1001169495 (7:27141541 T>C), RS1001305429 (7:27141799 C>A,T), RS1004517423 (7:27143827 T>C,G), RS1004631376 (7:27144881 G>C), RS1005749622 (7:27141040 A>G), RS1006456513 (7:27145107 G>A), RS1007421047 (7:27142702 A>G,T), RS1007628772 (7:27145416 C>A,T), RS1008452212 (7:27142377 G>A,C), RS1009102996 (7:27144352 G>A), RS1009957315 (7:27141111 T>A), RS1010106055 (7:27141477 C>T), RS1010774775 (7:27144382 G>T)

Disease associations

OMIM: gene MIM:142952 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004343_3	Chronic venous disease	3.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases expression, affects cotreatment	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Estradiol	decreases expression, increases expression	2
Nickel	decreases expression	2
Tretinoin	affects cotreatment, increases expression	2
geraniol	increases expression	1
trichostatin A	affects cotreatment, increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
cupric chloride	decreases expression	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
isoginkgetin	affects reaction, decreases reaction, increases expression, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
Chir 99021	affects cotreatment, increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate	decreases reaction, increases expression, affects reaction	1
MRK 003	decreases expression	1
bisphenol S	decreases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
3-(4-pyridyl)-1H-indole	affects cotreatment, increases 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
Temozolomide	increases expression	1
Decitabine	affects cotreatment, increases expression	1
Arsenic Trioxide	decreases expression	1
Air Pollutants	affects methylation, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A2X3	SEES3-1V human HOXA5, clone1	Embryonic stem cell	Male
CVCL_A2X4	SEES3-1V human HOXA5, clone2	Embryonic stem cell	Male
CVCL_A2X5	SEES3-1V human HOXA5, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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