BARX2

Summary

BARX2 (BARX homeobox 2, HGNC:956) is a protein-coding gene on chromosome 11q24.3, encoding Homeobox protein BarH-like 2 (Q9UMQ3). Transcription factor.

This gene encodes a member of the homeobox transcription factor family. A highly related protein in mouse has been shown to influence cellular processes that control cell adhesion and remodeling of the actin cytoskeleton in myoblast fusion and chondrogenesis. The encoded protein may also play a role in cancer progression.

Source: NCBI Gene 8538 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 48 total — 2 pathogenic
• Transcription factor: yes — 17 downstream targets (CollecTRI)
• MANE Select transcript: NM_003658

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:956
Approved symbol	BARX2
Name	BARX homeobox 2
Location	11q24.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000043039
Ensembl biotype	protein_coding
OMIM	604823
Entrez	8538

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000281437, ENST00000605151

RefSeq mRNA: 1 — MANE Select: NM_003658 NM_003658

CCDS: CCDS8481

Canonical transcript exons

ENST00000281437 — 4 exons

Exon	Start	End
ENSE00001128636	129436751	129437051
ENSE00001130961	129451136	129452279
ENSE00001130968	129375848	129376222
ENSE00002534530	129442835	129442919

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 97.72.

FANTOM5 (CAGE): breadth broad, TPM avg 6.3994 / max 341.5969, expressed in 360 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117576	3.0057	200
117573	2.6540	319
117575	0.2780	63
117577	0.1648	44
117574	0.1064	37
117579	0.1013	47
117578	0.0705	38
117584	0.0186	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.72	gold quality
esophagus mucosa	UBERON:0002469	95.49	gold quality
minor salivary gland	UBERON:0001830	95.46	gold quality
saliva-secreting gland	UBERON:0001044	93.60	gold quality
mouth mucosa	UBERON:0003729	92.85	gold quality
skin of abdomen	UBERON:0001416	88.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.61	gold quality
skin of leg	UBERON:0001511	85.56	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.93	gold quality
right uterine tube	UBERON:0001302	84.26	gold quality
mucosa of transverse colon	UBERON:0004991	84.16	gold quality
zone of skin	UBERON:0000014	83.29	gold quality
vagina	UBERON:0000996	83.07	gold quality
tonsil	UBERON:0002372	80.83	gold quality
parotid gland	UBERON:0001831	80.53	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.19	silver quality
pharyngeal mucosa	UBERON:0000355	77.68	gold quality
buccal mucosa cell	CL:0002336	77.20	gold quality
oral cavity	UBERON:0000167	77.15	gold quality
epithelium of esophagus	UBERON:0001976	75.88	silver quality
nasal cavity mucosa	UBERON:0001826	74.87	gold quality
body of tongue	UBERON:0011876	74.78	gold quality
esophagus squamous epithelium	UBERON:0006920	74.32	silver quality
rectum	UBERON:0001052	74.00	gold quality
gall bladder	UBERON:0002110	73.55	gold quality
tongue	UBERON:0001723	73.52	gold quality
islet of Langerhans	UBERON:0000006	73.51	gold quality
superior surface of tongue	UBERON:0007371	73.28	gold quality
duodenum	UBERON:0002114	73.25	gold quality
small intestine Peyer’s patch	UBERON:0003454	73.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-114	yes	19.00
E-ANND-3	yes	7.24

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

17 targets.

Target	Regulation
ACTA2	Activation
BARX2
CCND1	Activation
CDH6	Activation
EIF3K
ESR1	Unknown
FGF12	Activation
HSPA9	Unknown
L1CAM	Unknown
MMP9	Activation
MYOD1	Activation
NCAM1	Unknown
RBM15	Unknown
SMN1	Unknown
SOX5	Unknown
TIMP1
TIMP3

JASPAR motifs

Motif	Name	Family
MA1471.1	BARX2	NK
MA1471.2	BARX2	NK

JASPAR matrix evidence (PMIDs): PMID:10051657

Upstream regulators (CollecTRI, top): BARX2, MEF2A, MYOD1, MYOG, SRF

miRNA regulators (miRDB)

62 targeting BARX2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4307	99.82	70.45	3374

Literature-anchored findings (GeneRIF, showing 7)

• BARX2 can coordinate the expression of a network of genes that influence the growth of tumor cells (PMID:14744868)
• Down-regulation of Barx2 is associated with advanced clinical factors of colorectal cancer and predicts poor survival. (PMID:27453340)
• these findings indicate that reduction or loss of Barx2 dis-inhibits gastric cancer cell proliferation and invasion, and that reduction in Barx2 could serve as an independent prognostic biomarker for poor outcome in gastric cancer patients (PMID:27533254)
• These findings reveal that Barx2 serving as a tumor suppressor gene could decrease cell proliferation, migration, and aerobic glycolysis through inhibiting the Wnt/beta-catenin signaling pathway, and predicts a good prognosis in non-small cell lung carcinoma (PMID:29341468)
• BARX2 expression is downregulated by CpG island hypermethylation and is associated with suppressed cell proliferation and invasion of gastric cancer cells. (PMID:32236603)
• The miR-187 induced bone reconstruction and healing in a mouse model of osteoporosis, and accelerated osteoblastic differentiation of human multipotent stromal cells by targeting BARX2. (PMID:33550149)
• BarH-like homeobox 2 represses the transcription of keratin 16 and affects Ras signaling pathway to suppress nasopharyngeal carcinoma progression. (PMID:35037835)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	barx2	ENSDARG00000041098
mus_musculus	Barx2	ENSMUSG00000032033
rattus_norvegicus	Barx2	ENSRNOG00000008592
drosophila_melanogaster	B-H2	FBGN0004854
drosophila_melanogaster	B-H1	FBGN0011758
caenorhabditis_elegans		WBGENE00000451
caenorhabditis_elegans		WBGENE00000452

Paralogs (3): BARHL1 (ENSG00000125492), BARX1 (ENSG00000131668), BARHL2 (ENSG00000143032)

Protein

Protein identifiers

Homeobox protein BarH-like 2 — Q9UMQ3 (reviewed: Q9UMQ3)

All UniProt accessions (1): Q9UMQ3

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor. Binds optimally to the DNA consensus sequence 5’-YYTAATGRTTTTY-3’. May control the expression of neural adhesion molecules such as L1 or Ng-CAM during embryonic development of both the central and peripherical nervous system. May be involved in controlling adhesive processes in keratinizing epithelia.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in adult salivary gland and at much lower levels in mammary gland, kidney and placenta.

Similarity. Belongs to the BAR homeobox family.

RefSeq proteins (1): NP_003649* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000047	HTH_motif	Conserved_site
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR020479	HD_metazoa	Domain
IPR050848	Homeobox_TF	Family

Pfam: PF00046

UniProt features (7 total): compositionally biased region 3, region of interest 2, chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UMQ3-F1	65.88	0.20

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 122 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_CARTILAGE_DEVELOPMENT, MORF_MSH3, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GCANCTGNY_MYOD_Q6, MORF_BRCA1, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, MORF_ESR1, CAGCTG_AP4_Q5, MORF_RAD51L3, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_CELL_AGGREGATION, SANSOM_APC_TARGETS_DN

GO Biological Process (8): negative regulation of transcription by RNA polymerase II (GO:0000122), cartilage condensation (GO:0001502), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), myotube differentiation (GO:0014902), skeletal muscle cell differentiation (GO:0035914), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (9): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), 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), chromatin binding (GO:0003682), sequence-specific double-stranded DNA binding (GO:1990837), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), Golgi apparatus (GO:0005794), cytosol (GO:0005829), actin cytoskeleton (GO:0015629)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
cellular anatomical structure	3
regulation of DNA-templated transcription	2
DNA-templated transcription	2
transcription cis-regulatory region binding	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
negative regulation of DNA-templated transcription	1
skeletal system morphogenesis	1
cartilage development	1
cell aggregation	1
striated muscle cell differentiation	1
skeletal muscle tissue development	1
cell differentiation	1
positive regulation of DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
transcription regulator activity	1
DNA binding	1
chromosome	1
nuclear lumen	1
protein-containing complex	1
endomembrane system	1
cytoskeleton	1

Protein interactions and networks

STRING

810 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BARX2	L1CAM	P32004	662
BARX2	TBL1XR1	Q9BZK7	643
BARX2	TBL1X	O60907	635
BARX2	CCND1	P24385	471
BARX2	CREB1	P16220	401
BARX2	XPO7	Q9UIA9	398
BARX2	PROX1	Q92786	398
BARX2	XPO6	Q96QU8	396
BARX2	RANBP3	Q9H6Z4	396
BARX2	IPO4	Q8TEX9	393
BARX2	TBX6	O95947	387
BARX2	PPARD	Q03181	383
BARX2	PHOX2A	O14813	382
BARX2	SIM1	P81133	379
BARX2	NUP210	Q8TEM1	378

IntAct

7 interactions, top by confidence:

A	B	Type	Score
FHL2	BARX2	psi-mi:“MI:0915”(physical association)	0.560
FHL3	BARX2	psi-mi:“MI:0915”(physical association)	0.560
BARX2	FHL2	psi-mi:“MI:0915”(physical association)	0.000
BARX2	FHL3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): BARX2 (Synthetic Lethality), FHL2 (Two-hybrid), FHL3 (Two-hybrid)

ESM2 similar proteins: A0A1W2PPF3, A0A1W2PPM1, A1A546, A1YGI6, A2T763, A5YC49, A6NFQ7, A6NJG6, D2HQI1, G3X9P6, O42173, O57374, P09632, P0C7M4, P10242, P14837, P17278, P31272, P31538, Q1KKS8, Q28ET4, Q28G02, Q3LTE0, Q3UT54, Q4JM65, Q4KL20, Q5TM83, Q5TM84, Q5W1J6, Q68EH7, Q6NSW7, Q80Z64, Q8IUE1, Q8JH55, Q8JIT7, Q8JJ26, Q8MIB7, Q8MIB8, Q8MIE9, Q91685

Diamond homologs: A0JPN1, A1YG85, A5PKG8, A6NJ46, A6NMT0, A7MB54, A9L937, B0VXK3, D2KQB0, E7FDX5, M0R6D8, O08686, O13023, O35762, O42365, O43364, O43711, O55144, O88181, O93366, O93367, O93590, P0C1T1, P10035, P14652, P14837, P20009, P28468, P31245, P31246, P31261, P31314, P42583, P42584, P43120, P43345, P43688, P50219, P52945, P52950

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	37
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1808652	GRCh37/hg19 11q24.1-25(chr11:122975824-134938470)x1	Pathogenic
563879	GRCh37/hg19 11q24.3-25(chr11:129072293-134938470)x1	Pathogenic

SpliceAI

1289 predictions. Top by Δscore:

Variant	Effect	Δscore
11:129376220:CGGGT:C	donor_loss	1.0000
11:129376221:GG:G	donor_gain	1.0000
11:129376222:GG:G	donor_gain	1.0000
11:129376222:GGTAA:G	donor_loss	1.0000
11:129376223:G:GA	donor_loss	1.0000
11:129376224:T:A	donor_loss	1.0000
11:129442829:TTCTA:T	acceptor_loss	1.0000
11:129442830:TCTAG:T	acceptor_loss	1.0000
11:129442832:TAGG:T	acceptor_loss	1.0000
11:129442834:G:GC	acceptor_loss	1.0000
11:129442919:GGTAA:G	donor_loss	1.0000
11:129442920:G:GG	donor_gain	1.0000
11:129442920:GTAAG:G	donor_loss	1.0000
11:129442921:T:G	donor_loss	1.0000
11:129451132:GTA:G	acceptor_loss	1.0000
11:129451133:TAGGT:T	acceptor_loss	1.0000
11:129376223:G:GG	donor_gain	0.9900
11:129418079:G:GT	donor_gain	0.9900
11:129436745:TTCCA:T	acceptor_loss	0.9900
11:129436746:TCCAG:T	acceptor_loss	0.9900
11:129436747:CCAG:C	acceptor_loss	0.9900
11:129436748:CA:C	acceptor_loss	0.9900
11:129436749:A:AT	acceptor_loss	0.9900
11:129437028:G:GT	donor_gain	0.9900
11:129437047:GACAG:G	donor_gain	0.9900
11:129437048:ACAGG:A	donor_loss	0.9900
11:129437049:CAG:C	donor_loss	0.9900
11:129437051:GGTGA:G	donor_loss	0.9900
11:129437052:GT:G	donor_loss	0.9900
11:129437053:T:A	donor_loss	0.9900

AlphaMissense

1792 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:129436972:C:A	R137S	1.000
11:129436981:T:A	F140I	1.000
11:129436981:T:C	F140L	1.000
11:129436981:T:G	F140V	1.000
11:129436982:T:C	F140S	1.000
11:129436982:T:G	F140C	1.000
11:129436983:C:A	F140L	1.000
11:129436983:C:G	F140L	1.000
11:129436985:C:T	T141I	1.000
11:129436997:T:C	L145P	1.000
11:129437006:T:A	L148Q	1.000
11:129437006:T:C	L148P	1.000
11:129437017:T:A	F152I	1.000
11:129437017:T:C	F152L	1.000
11:129437017:T:G	F152V	1.000
11:129437018:T:C	F152S	1.000
11:129437018:T:G	F152C	1.000
11:129437019:C:A	F152L	1.000
11:129437019:C:G	F152L	1.000
11:129437032:T:C	Y157H	1.000
11:129437033:A:G	Y157C	1.000
11:129437036:T:C	L158S	1.000
11:129437036:T:G	L158W	1.000
11:129437051:G:T	R163M	1.000
11:129442835:G:C	R163S	1.000
11:129442835:G:T	R163S	1.000
11:129442846:C:A	A167D	1.000
11:129442855:T:C	L170P	1.000
11:129442861:T:A	L172H	1.000
11:129442861:T:C	L172P	1.000

dbSNP variants (sampled 300 via entrez): RS1000008292 (11:129391842 G>T), RS1000009695 (11:129433384 C>A,T), RS1000064457 (11:129430706 C>T), RS1000216046 (11:129394403 A>G), RS1000269925 (11:129394149 C>G), RS1000281419 (11:129447606 G>T), RS1000287925 (11:129397709 C>G), RS1000289350 (11:129378768 A>G), RS1000347522 (11:129442368 G>A), RS1000376798 (11:129447348 G>C), RS1000377126 (11:129400478 A>C), RS1000387439 (11:129428907 G>C), RS1000455586 (11:129448563 G>C), RS1000509390 (11:129396489 CTTAAA>C), RS1000513806 (11:129440141 GTGTT>G,GTGTTTGTT)

Disease associations

OMIM: gene MIM:604823 | 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
GCST001369_3	Type 2 diabetes	3.000000e-07
GCST001420_3	Breast cancer	5.000000e-07
GCST003445_4	Response to cyclophosphamide in systemic lupus erythematosus with lupus nephritis	1.000000e-06
GCST003542_66	Night sleep phenotypes	1.000000e-06
GCST008180_7	Spontaneous preterm birth with premature rupture of membranes	5.000000e-06
GCST010002_202	Refractive error	1.000000e-17
GCST011743_60	HDL cholesterol levels in HIV infection	5.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007827	nighttime rest measurement
EFO:0006917	spontaneous preterm birth
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
Fluorouracil	increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
sotorasib	affects cotreatment, decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
arsenite	decreases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	increases expression, decreases reaction	1
antimonite	decreases expression, increases abundance	1
abrine	increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Antimony Potassium Tartrate	decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Estradiol	affects cotreatment, decreases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1
S-Nitrosoglutathione	increases expression	1
Particulate Matter	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A0G6	SEES3-1V human BARX2, clone1	Embryonic stem cell	Male
CVCL_A0G7	SEES3-1V human BARX2, clone2	Embryonic stem cell	Male
CVCL_A0G8	SEES3-1V human BARX2, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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