HOXA6

Summary

HOXA6 (homeobox A6, HGNC:5107) is a protein-coding gene on chromosome 7p15.2, encoding Homeobox protein Hox-A6 (P31267). 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.

Source: NCBI Gene 3203 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_024014

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5107
Approved symbol	HOXA6
Name	homeobox A6
Location	7p15.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000106006
Ensembl biotype	protein_coding
OMIM	142951
Entrez	3203

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000222728, ENST00000521478

RefSeq mRNA: 1 — MANE Select: NM_024014 NM_024014

CCDS: CCDS5407

Canonical transcript exons

ENST00000222728 — 2 exons

Exon	Start	End
ENSE00000674261	27145396	27145917
ENSE00000674262	27147308	27147774

Expression profiles

Bgee: expression breadth ubiquitous, 114 present calls, max score 81.11.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left uterine tube	UBERON:0001303	81.11	gold quality
stromal cell of endometrium	CL:0002255	79.77	gold quality
metanephros cortex	UBERON:0010533	78.98	gold quality
transverse colon	UBERON:0001157	77.82	gold quality
body of uterus	UBERON:0009853	75.65	gold quality
tendon of biceps brachii	UBERON:0008188	75.43	silver quality
left adrenal gland cortex	UBERON:0035825	73.76	gold quality
right adrenal gland	UBERON:0001233	73.73	gold quality
right adrenal gland cortex	UBERON:0035827	73.48	gold quality
left adrenal gland	UBERON:0001234	73.45	gold quality
hindlimb stylopod muscle	UBERON:0004252	73.31	gold quality
adrenal cortex	UBERON:0001235	72.47	gold quality
small intestine Peyer’s patch	UBERON:0003454	72.26	gold quality
adrenal gland	UBERON:0002369	71.81	gold quality
muscle layer of sigmoid colon	UBERON:0035805	71.68	gold quality
colon	UBERON:0001155	71.18	gold quality
right uterine tube	UBERON:0001302	71.07	gold quality
large intestine	UBERON:0000059	70.11	gold quality
mucosa of transverse colon	UBERON:0004991	69.90	gold quality
muscle of leg	UBERON:0001383	69.83	gold quality
gastrocnemius	UBERON:0001388	69.71	gold quality
popliteal artery	UBERON:0002250	69.31	gold quality
tibial artery	UBERON:0007610	69.26	gold quality
intestine	UBERON:0000160	69.22	gold quality
adult mammalian kidney	UBERON:0000082	68.20	gold quality
small intestine	UBERON:0002108	67.95	gold quality
seminal vesicle	UBERON:0000998	67.48	silver quality
skin of abdomen	UBERON:0001416	67.30	gold quality
tibial nerve	UBERON:0001323	67.09	gold quality
muscle organ	UBERON:0001630	66.13	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.85

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA1497.1	HOXA6	HOX
MA1497.2	HOXA6	HOX

JASPAR matrix evidence (PMIDs): PMID:18585359

Literature-anchored findings (GeneRIF, showing 7)

• 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)
• Data indicate that genes with hypermethylated CpG islands in malignant meningiomas, such as HOXA6 and HOXA9, tend to coincide with the binding sites of polycomb repressive complexes (PRC) in early developmental stage. (PMID:23349797)
• HOXA6 is a signature gene involved in cell growth and sensitivity to chemotherapy in acute myeloid leukemia cells. (PMID:23539541)
• Results demonstrated thatHOXA6 is up-regulated in colorectal cancer (CRC) and promoted cell proliferation, migration and invasion, but inhibited apoptosis, whereas the downregulated expression of HOXA6 produced the opposite effects. HOXA6 regulated apoptosis through the Bcl-2 signaling pathway, and regulated migration and invasion through the EMT process. (PMID:29620285)
• Study revealed that the mRNA and protein expression levels of HOXA6 were suppressed in clear cell renal cell carcinoma (ccRCC) tissues. Its overexpression suppresses cell proliferation and promotes apoptosis, which may occur via inhibition of the PI3K/Akt/ERK cascade. (PMID:31081053)
• Coexpression of HOXA6 and PBX2 promotes metastasis in gastric cancer. (PMID:33535170)
• Next-generation sequencing identifies HOXA6 as a novel oncogenic gene in low grade glioma. (PMID:35349479)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hoxa6	ENSMUSG00000043219

Paralogs (42): HOXA11 (ENSG00000005073), HOXC8 (ENSG00000037965), HOXA1 (ENSG00000105991), HOXA2 (ENSG00000105996), HOXA3 (ENSG00000105997), HOXA5 (ENSG00000106004), 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-A6 — P31267 (reviewed: P31267)

Alternative names: Homeobox protein Hox-1B

All UniProt accessions (1): P31267

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.

Subcellular location. Nucleus.

Similarity. Belongs to the Antp homeobox family.

RefSeq proteins (1): NP_076919* (*=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 (6 total): region of interest 2, chain 1, DNA-binding region 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31267-F1	64.92	0.28

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9830364	Formation of the nephric duct

MSigDB gene sets: 89 (showing top): GGGACCA_MIR133A_MIR133B, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, MULLIGHAN_NPM1_SIGNATURE_3_UP, BENPORATH_ES_WITH_H3K27ME3, CCAWYNNGAAR_UNKNOWN, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, AP4_Q6, CAGCTG_AP4_Q5, MYOD_01, GOBP_ANTERIOR_POSTERIOR_PATTERN_SPECIFICATION, NF1_Q6_01, AACTTT_UNKNOWN, TGGNNNNNNKCCAR_UNKNOWN, GFI1_01

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), anterior/posterior pattern specification (GO:0009952), embryonic skeletal system development (GO:0048706), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (5): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear speck (GO:0016607)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Kidney development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
cellular anatomical structure	2
transcription by RNA polymerase II	1
regionalization	1
skeletal system development	1
chordate embryonic development	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
regulation of transcription by RNA polymerase II	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

658 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HOXA6	PRSS58	Q8IYP2	641
HOXA6	MEIS1	O00470	629
HOXA6	GALK1	P51570	555
HOXA6	PRSS1	P07477	549
HOXA6	HOXA3	O43365	469
HOXA6	HOXD9	P28356	461
HOXA6	HOXD10	P28358	460
HOXA6	HOXD8	P13378	452
HOXA6	HOXA5	P20719	403
HOXA6	IRF8	Q02556	391
HOXA6	PBX3	P40426	383
HOXA6	UPK3A	O75631	370
HOXA6	ELF2	Q15723	369
HOXA6	EGR4	Q05215	365
HOXA6	HOXC4	P09017	359

IntAct

22 interactions, top by confidence:

A	B	Type	Score
	HOXA6	psi-mi:“MI:0915”(physical association)	0.370
CCL5	HOXA6	psi-mi:“MI:0915”(physical association)	0.370
CXCL10	HOXA6	psi-mi:“MI:0915”(physical association)	0.370
IFNA7	HOXA6	psi-mi:“MI:0915”(physical association)	0.370
IFNL1	HOXA6	psi-mi:“MI:0915”(physical association)	0.370
IL15	HOXA6	psi-mi:“MI:0915”(physical association)	0.370
IL23A	HOXA6	psi-mi:“MI:0915”(physical association)	0.370
PPBP	HOXA6	psi-mi:“MI:0915”(physical association)	0.370
XCL2	HOXA6	psi-mi:“MI:0915”(physical association)	0.370
RNH1	DUSP11	psi-mi:“MI:0914”(association)	0.350

BioGRID (1): HOXA6 (Affinity Capture-MS)

ESM2 similar proteins: A1YEY5, A1YFA5, A1YFI3, A1YG57, A1YGK7, A2T733, A2T7F3, A2T7P4, A6NJ46, O43248, P02830, P02832, P04476, P09019, P09021, P09023, P09024, P09629, P09632, P15861, P17481, P17509, P18864, P23812, P24344, P31259, P31267, P31268, P31270, P31311, P35453, P53545, P56915, P70217, P97334, Q02591, Q1KKX1, Q1KKY1, Q1KKY3, Q1KKZ5

Diamond homologs: A1YER7, A1YFA5, A1YFD8, A1YFY3, A2D4P8, A2D5I1, A2D5K9, A2D5Y4, A2T6X6, A2T7F3, O13074, O42504, O57374, P02830, P02832, P02833, P04476, P06798, P07548, P09013, P09014, P09016, P09017, P09019, P09020, P09021, P09023, P09024, P09067, P09070, P09071, P09074, P09077, P09079, P09092, P09629, P09630, P10284, P10628, P10629

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 10 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
inflammatory response	5	18.9×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

95 predictions. Top by Δscore:

Variant	Effect	Δscore
7:27145925:C:CT	acceptor_gain	1.0000
7:27147303:CTTA:C	donor_loss	1.0000
7:27147305:TACC:T	donor_loss	1.0000
7:27147306:A:AC	donor_gain	1.0000
7:27147306:AC:A	donor_gain	1.0000
7:27147307:C:CC	donor_gain	1.0000
7:27147307:CC:C	donor_gain	1.0000
7:27147307:CCCG:C	donor_gain	1.0000
7:27147359:T:TA	donor_gain	1.0000
7:27145915:CAC:C	acceptor_gain	0.9900
7:27145918:C:A	acceptor_loss	0.9900
7:27145918:C:CC	acceptor_gain	0.9900
7:27145926:A:T	acceptor_gain	0.9900
7:27147306:ACC:A	donor_gain	0.9900
7:27147306:ACCCG:A	donor_gain	0.9900
7:27147307:CCC:C	donor_gain	0.9900
7:27147307:CCCGC:C	donor_gain	0.9900
7:27145914:GCAC:G	acceptor_gain	0.9800
7:27145915:CACC:C	acceptor_gain	0.9800
7:27145916:AC:A	acceptor_gain	0.9800
7:27145917:CC:C	acceptor_gain	0.9800
7:27145921:C:CT	acceptor_gain	0.9700
7:27145913:AGCAC:A	acceptor_gain	0.9500
7:27145922:G:T	acceptor_gain	0.9500
7:27147505:T:C	donor_gain	0.9400
7:27146802:T:TA	donor_gain	0.9000
7:27147530:A:AC	donor_gain	0.8900
7:27147531:C:CC	donor_gain	0.8900
7:27145915:CACCT:C	acceptor_gain	0.8600
7:27145916:ACC:A	acceptor_gain	0.8600

AlphaMissense

1523 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:27145727:T:A	K211N	1.000
7:27145727:T:G	K211N	1.000
7:27145733:C:A	K209N	1.000
7:27145733:C:G	K209N	1.000
7:27145735:T:C	K209E	1.000
7:27145736:C:A	M208I	1.000
7:27145736:C:G	M208I	1.000
7:27145736:C:T	M208I	1.000
7:27145737:A:C	M208R	1.000
7:27145737:A:G	M208T	1.000
7:27145737:A:T	M208K	1.000
7:27145740:C:G	R207P	1.000
7:27145741:G:C	R207G	1.000
7:27145741:G:T	R207S	1.000
7:27145743:C:G	R206P	1.000
7:27145744:G:C	R206G	1.000
7:27145744:G:T	R206S	1.000
7:27145745:G:C	N205K	1.000
7:27145745:G:T	N205K	1.000
7:27145746:T:A	N205I	1.000
7:27145746:T:C	N205S	1.000
7:27145746:T:G	N205T	1.000
7:27145747:T:C	N205D	1.000
7:27145747:T:G	N205H	1.000
7:27145748:C:A	Q204H	1.000
7:27145748:C:G	Q204H	1.000
7:27145749:T:G	Q204P	1.000
7:27145751:G:C	F203L	1.000
7:27145751:G:T	F203L	1.000
7:27145752:A:C	F203C	1.000

dbSNP variants (sampled 300 via entrez): RS1000241812 (7:27147143 C>G), RS1000312377 (7:27145740 C>A,T), RS1001081480 (7:27145492 G>T), RS1001745979 (7:27148014 A>C,G), RS1001779499 (7:27147829 T>C), RS1002015428 (7:27146207 G>A), RS1002083290 (7:27147506 C>G,T), RS1002516822 (7:27146482 G>A), RS1002687815 (7:27148845 A>T), RS1002785511 (7:27146558 A>G), RS1003190615 (7:27149193 G>T), RS1005749150 (7:27147136 A>G), RS1006456513 (7:27145107 G>A), RS1007007617 (7:27148317 G>A,T), RS1007628772 (7:27145416 C>A,T)

Disease associations

OMIM: gene MIM:142951 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004343_3	Chronic venous disease	3.000000e-07
GCST90002388_22	Lymphocyte count	4.000000e-17
GCST90002407_545	White blood cell count	5.000000e-09
GCST90020024_91	A body shape index	4.000000e-10
GCST90020025_739	Waist-to-hip ratio adjusted for BMI	2.000000e-10
GCST90020027_1341	Waist-hip index	5.000000e-11
GCST90020029_861	Waist circumference adjusted for body mass index	9.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte 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

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	2
Air Pollutants	increases abundance, increases expression, affects methylation	2
sodium arsenite	decreases expression	1
ferrous chloride	decreases expression	1
abrine	decreases expression	1
Atrazine	increases expression	1
Vehicle Emissions	affects methylation, increases abundance	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Nitrogen Dioxide	increases abundance, affects methylation	1
Phthalic Acids	increases methylation	1
Tretinoin	increases expression	1
Valproic Acid	decreases methylation	1
Asbestos, Crocidolite	decreases methylation	1
Asbestos, Amosite	decreases methylation	1
Particulate Matter	increases expression, increases abundance	1

Clinical trials (associated diseases)

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