DBX2

Summary

DBX2 (developing brain homeobox 2, HGNC:33186) is a protein-coding gene on chromosome 12q12, encoding Homeobox protein DBX2 (Q6ZNG2).

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including G2/M transition of mitotic cell cycle; epidermal growth factor receptor signaling pathway; and neural precursor cell proliferation. Predicted to be located in chromatin.

Source: NCBI Gene 440097 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 70 total
• MANE Select transcript: NM_001004329

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33186
Approved symbol	DBX2
Name	developing brain homeobox 2
Location	12q12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ16139
Ensembl gene	ENSG00000185610
Ensembl biotype	protein_coding
OMIM	620706
Entrez	440097

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000332700

RefSeq mRNA: 1 — MANE Select: NM_001004329 NM_001004329

CCDS: CCDS31781

Canonical transcript exons

ENST00000332700 — 4 exons

Exon	Start	End
ENSE00001296229	45014672	45016618
ENSE00001329801	45023707	45023894
ENSE00001382840	45050525	45051099
ENSE00001485971	45036019	45036114

Expression profiles

Bgee: expression breadth broad, 57 present calls, max score 81.22.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2528 / max 27.2415, expressed in 98 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130542	0.1516	73
130541	0.0843	45
130540	0.0169	7

Top tissues by expression

113 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	81.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.87	gold quality
substantia nigra	UBERON:0002038	68.08	gold quality
hypothalamus	UBERON:0001898	66.80	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	66.73	gold quality
amygdala	UBERON:0001876	65.64	gold quality
temporal lobe	UBERON:0001871	65.49	gold quality
anterior cingulate cortex	UBERON:0009835	64.47	gold quality
prefrontal cortex	UBERON:0000451	64.44	gold quality
putamen	UBERON:0001874	63.84	gold quality
Ammon’s horn	UBERON:0001954	63.04	gold quality
frontal cortex	UBERON:0001870	63.02	gold quality
nucleus accumbens	UBERON:0001882	62.92	gold quality
cerebral cortex	UBERON:0000956	62.54	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	62.25	gold quality
Brodmann (1909) area 9	UBERON:0013540	62.20	gold quality
right frontal lobe	UBERON:0002810	61.35	gold quality
superior frontal gyrus	UBERON:0002661	60.53	gold quality
primary visual cortex	UBERON:0002436	60.34	gold quality
caudate nucleus	UBERON:0001873	58.91	gold quality
brain	UBERON:0000955	57.59	gold quality
corpus callosum	UBERON:0002336	54.83	gold quality
omental fat pad	UBERON:0010414	51.10	gold quality
right hemisphere of cerebellum	UBERON:0014890	49.20	gold quality
cerebellum	UBERON:0002037	48.40	gold quality
cerebellar cortex	UBERON:0002129	48.29	gold quality
right coronary artery	UBERON:0001625	48.21	gold quality
cerebellar hemisphere	UBERON:0002245	48.19	gold quality
skin of leg	UBERON:0001511	48.04	gold quality
thoracic mammary gland	UBERON:0005200	46.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.93

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

67 targeting DBX2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-494-3P	99.70	71.45	2795

Literature-anchored findings (GeneRIF, showing 1)

• DBX2 is obviously upregulated in hepatocellular carcinoma (HCC) tissues and strongly correlated with tumor size. Subsequently, both gain and loss of function assays indicated that DBX2 promoted HCC migration, invasion, and proliferation by facilitating the transition from G1 to S phase and attenuating apoptosis in vitro and in vivo. (PMID:30833799)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000105053
mus_musculus	Dbx2	ENSMUSG00000045608
rattus_norvegicus	Dbx2	ENSRNOG00000006885

Paralogs (3): DBX1 (ENSG00000109851), HLX (ENSG00000136630), LEUTX (ENSG00000213921)

Protein

Protein identifiers

Homeobox protein DBX2 — Q6ZNG2 (reviewed: Q6ZNG2)

Alternative names: Developing brain homeobox protein 2

All UniProt accessions (1): Q6ZNG2

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Similarity. Belongs to the H2.0 homeobox family.

RefSeq proteins (1): NP_001004329* (*=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
IPR051662	H2.0_Homeobox_NeuralPatt	Family

Pfam: PF00046

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZNG2-F1	58.74	0.17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 39 (showing top): GOBP_CELL_CYCLE_PHASE_TRANSITION, chr12q12, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION, GOBP_ERBB_SIGNALING_PATHWAY, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOBP_MITOTIC_CELL_CYCLE, GOBP_CELL_CYCLE_G2_M_PHASE_TRANSITION, GOBP_CELL_SURFACE_RECEPTOR_PROTEIN_TYROSINE_KINASE_SIGNALING_PATHWAY, GOBP_CELL_CYCLE_PROCESS, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, GOBP_ENZYME_LINKED_RECEPTOR_PROTEIN_SIGNALING_PATHWAY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, MIR4659A_3P_MIR4659B_3P, MIR545_3P

GO Biological Process (6): G2/M transition of mitotic cell cycle (GO:0000086), regulation of transcription by RNA polymerase II (GO:0006357), epidermal growth factor receptor signaling pathway (GO:0007173), gene expression (GO:0010467), neural precursor cell proliferation (GO:0061351), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (3): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), 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
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G2/M phase transition	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
ERBB signaling pathway	1
macromolecule biosynthetic process	1
cell population proliferation	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

810 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DBX2	IRX3	P78415	644
DBX2	IRX6	P78412	592
DBX2	OLIG2	Q13516	554
DBX2	OLIG3	Q7RTU3	484
DBX2	SHH	Q15465	442
DBX2	MRO	Q9BYG7	437
DBX2	M0QYG6	M0QYG6	420
DBX2	ISL2	Q96A47	412
DBX2	RNF220	Q5VTB9	396
DBX2	TMEM117	Q9H0C3	390
DBX2	LHX5	Q9H2C1	377
DBX2	RANBP3L	Q86VV4	376
DBX2	ZC4H2	Q9NQZ6	372
DBX2	RBPJ	Q06330	371
DBX2	KIAA1755	Q5JYT7	370

IntAct

3 interactions, top by confidence:

A	B	Type	Score
DBX2	STT3B	psi-mi:“MI:0915”(physical association)	0.400
DBX2	ANKRD17	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): STT3B (Proximity Label-MS), DBX2 (Affinity Capture-MS), PPP1R10 (Affinity Capture-MS), ANKRD17 (Affinity Capture-MS), ANKHD1 (Affinity Capture-MS), ANKHD1-EIF4EBP3 (Affinity Capture-MS), ZC3H4 (Affinity Capture-MS), DBX2 (Cross-Linking-MS (XL-MS))

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

Diamond homologs: 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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

465 predictions. Top by Δscore:

Variant	Effect	Δscore
12:45023902:C:CT	acceptor_gain	1.0000
12:45023903:G:T	acceptor_gain	1.0000
12:45028825:T:A	donor_gain	1.0000
12:45023691:T:TA	donor_gain	0.9900
12:45023701:TAGTA:T	donor_loss	0.9900
12:45023702:AGTAC:A	donor_loss	0.9900
12:45023703:GTACC:G	donor_loss	0.9900
12:45023704:TA:T	donor_loss	0.9900
12:45023706:CC:C	donor_loss	0.9900
12:45023714:T:TA	donor_gain	0.9900
12:45023892:CTC:C	acceptor_gain	0.9900
12:45023893:TCCTA:T	acceptor_loss	0.9900
12:45023895:C:CC	acceptor_gain	0.9900
12:45023895:CTAG:C	acceptor_loss	0.9900
12:45023896:T:C	acceptor_loss	0.9900
12:45036017:A:AC	donor_gain	0.9900
12:45036018:C:CC	donor_gain	0.9900
12:45036115:C:CC	acceptor_gain	0.9900
12:45050520:CTCA:C	donor_loss	0.9900
12:45050521:TCACC:T	donor_loss	0.9900
12:45050522:CACCT:C	donor_loss	0.9900
12:45050523:ACC:A	donor_loss	0.9900
12:45050524:C:T	donor_loss	0.9900
12:45023707:C:G	donor_loss	0.9800
12:45023890:TTCTC:T	acceptor_gain	0.9800
12:45050519:GCTCA:G	donor_loss	0.9800
12:45023893:TC:T	acceptor_gain	0.9700
12:45023894:CC:C	acceptor_gain	0.9700
12:45036111:GGTG:G	acceptor_gain	0.9700
12:45036113:TG:T	acceptor_gain	0.9700

AlphaMissense

2159 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:45016592:C:A	R238S	1.000
12:45016592:C:G	R238S	1.000
12:45016593:C:A	R238M	1.000
12:45016593:C:G	R238T	1.000
12:45016595:C:A	R237S	1.000
12:45016595:C:G	R237S	1.000
12:45016596:C:A	R237M	1.000
12:45016596:C:G	R237T	1.000
12:45016598:G:C	N236K	1.000
12:45016598:G:T	N236K	1.000
12:45016599:T:A	N236I	1.000
12:45016599:T:C	N236S	1.000
12:45016599:T:G	N236T	1.000
12:45016600:T:C	N236D	1.000
12:45016601:C:A	Q235H	1.000
12:45016601:C:G	Q235H	1.000
12:45016604:A:C	F234L	1.000
12:45016604:A:T	F234L	1.000
12:45016605:A:C	F234C	1.000
12:45016605:A:G	F234S	1.000
12:45016606:A:C	F234V	1.000
12:45016606:A:G	F234L	1.000
12:45016606:A:T	F234I	1.000
12:45016607:C:A	W233C	1.000
12:45016607:C:G	W233C	1.000
12:45016609:A:G	W233R	1.000
12:45016609:A:T	W233R	1.000
12:45016613:T:A	K231N	1.000
12:45016613:T:G	K231N	1.000
12:45023720:A:G	L225P	1.000

dbSNP variants (sampled 300 via entrez): RS1000070887 (12:45051783 TG>T), RS1000208778 (12:45047080 T>G), RS1000423175 (12:45034306 C>T), RS1000446757 (12:45039015 T>A,C), RS1000577855 (12:45042457 A>C), RS1000598915 (12:45045552 T>C), RS1000634989 (12:45048036 T>C), RS1000692633 (12:45042675 A>G), RS1000741137 (12:45051175 T>A), RS1000751143 (12:45050955 G>A,C,T), RS1000921151 (12:45047779 G>C), RS1000949693 (12:45045808 C>T), RS1001000196 (12:45029903 T>TAAATAAATAAAA), RS1001051688 (12:45023611 A>C), RS1001116683 (12:45024124 G>C)

Disease associations

OMIM: gene MIM:620706 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation	1
arsenite	increases methylation	1
bisphenol S	increases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Valproic Acid	decreases methylation	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A0W2	SEES3-1V human DBX2, clone1	Embryonic stem cell	Male
CVCL_A0W3	SEES3-1V human DBX2, clone2	Embryonic stem cell	Male
CVCL_A0W4	SEES3-1V human DBX2, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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