DBX1

Summary

DBX1 (developing brain homeobox 1, HGNC:33185) is a protein-coding gene on chromosome 11p15.1, encoding Homeobox protein DBX1 (A6NMT0). Could have a role in patterning the central nervous system during embryogenesis.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in cell differentiation in spinal cord and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within ventral spinal cord interneuron specification. Predicted to be located in chromatin.

Source: NCBI Gene 120237 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tourette syndrome (No Known Disease Relationship, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_001029865

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33185
Approved symbol	DBX1
Name	developing brain homeobox 1
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000109851
Ensembl biotype	protein_coding
OMIM	619830
Entrez	120237

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000524983

RefSeq mRNA: 1 — MANE Select: NM_001029865 NM_001029865

CCDS: CCDS31443

Canonical transcript exons

ENST00000524983 — 4 exons

Exon	Start	End
ENSE00000707492	20159191	20159292
ENSE00001308058	20157037	20157239
ENSE00002143316	20156155	20156573
ENSE00002159044	20159958	20160475

Expression profiles

Bgee: expression breadth tissue_specific, 5 present calls, max score 81.98.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1437 / max 38.6243, expressed in 45 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119004	0.1437	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.98	silver quality
bone marrow cell	CL:0002092	38.47	gold quality
lower esophagus mucosa	UBERON:0035834	38.21	gold quality
sural nerve	UBERON:0015488	37.76	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	35.03	gold quality
bone marrow	UBERON:0002371	34.12	gold quality
liver	UBERON:0002107	33.07	gold quality
pituitary gland	UBERON:0000007	32.50	silver quality
muscle tissue	UBERON:0002385	32.27	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
right testis	UBERON:0004534	31.83	silver quality
tonsil	UBERON:0002372	29.96	gold quality
testis	UBERON:0000473	29.91	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
left testis	UBERON:0004533	29.55	silver quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
right lobe of liver	UBERON:0001114	28.33	gold quality
duodenum	UBERON:0002114	28.14	gold quality
blood	UBERON:0000178	28.09	gold quality
descending thoracic aorta	UBERON:0002345	28.08	gold quality
urinary bladder	UBERON:0001255	27.77	gold quality
lymph node	UBERON:0000029	27.57	gold quality
primary visual cortex	UBERON:0002436	27.53	gold quality
right coronary artery	UBERON:0001625	27.01	gold quality
transverse colon	UBERON:0001157	26.93	gold quality
right lobe of thyroid gland	UBERON:0001119	26.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.98

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
DBX1

Upstream regulators (CollecTRI, top): DBX1

Literature-anchored findings (GeneRIF, showing 1)

• Dbx1-derived neurons are essential for the transgenic expression and generation of respiratory behavior both in vitro and in vivo. (PMID:21048147)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dbx1b	ENSDARG00000001859
danio_rerio	dbx1a	ENSDARG00000086393
mus_musculus	Dbx1	ENSMUSG00000030507
rattus_norvegicus	Dbx1	ENSRNOG00000014706
drosophila_melanogaster	Dbx	FBGN0261723

Paralogs (3): HLX (ENSG00000136630), DBX2 (ENSG00000185610), LEUTX (ENSG00000213921)

Protein

Protein identifiers

Homeobox protein DBX1 — A6NMT0 (reviewed: A6NMT0)

Alternative names: Developing brain homeobox protein 1

All UniProt accessions (1): A6NMT0

UniProt curated annotations — full annotation on UniProt →

Function. Could have a role in patterning the central nervous system during embryogenesis. Has a key role in regulating the distinct phenotypic features that distinguish two major classes of ventral interneurons, V0 and V1 neurons. Regulates the transcription factor profile, neurotransmitter phenotype, intraspinal migratory path and axonal trajectory of V0 neurons, features that differentiate them from an adjacent set of V1 neurons.

Subcellular location. Nucleus.

Similarity. Belongs to the H2.0 homeobox family.

RefSeq proteins (1): NP_001025036* (*=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 (6 total): region of interest 2, compositionally biased region 2, chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NMT0-F1	63.03	0.17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 34 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_NEUROGENESIS, GOBP_CELL_DIFFERENTIATION_IN_SPINAL_CORD, GOBP_DORSAL_VENTRAL_PATTERN_FORMATION, SHEPARD_BMYB_MORPHOLINO_DN, GOBP_VENTRAL_SPINAL_CORD_DEVELOPMENT, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, GOBP_NEURON_FATE_SPECIFICATION, GOBP_CENTRAL_NERVOUS_SYSTEM_NEURON_DIFFERENTIATION, GOBP_SPINAL_CORD_PATTERNING, GOBP_VENTRAL_SPINAL_CORD_INTERNEURON_DIFFERENTIATION, GOBP_NEURON_FATE_COMMITMENT, GOBP_CELL_FATE_SPECIFICATION, GOBP_CELL_FATE_COMMITMENT, SHEPARD_BMYB_TARGETS

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), cell differentiation in spinal cord (GO:0021515), ventral spinal cord interneuron specification (GO:0021521), 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
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
spinal cord development	1
cell differentiation	1
neuron fate specification	1
cell fate specification involved in pattern specification	1
ventral spinal cord interneuron fate commitment	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

756 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DBX1	OLIG2	Q13516	636
DBX1	LHX6	Q9UPM6	616
DBX1	LHX2	P50458	596
DBX1	SHH	Q15465	592
DBX1	NEUROG2	Q9H2A3	587
DBX1	IRX3	P78415	580
DBX1	OLIG3	Q7RTU3	571
DBX1	LHX5	Q9H2C1	552
DBX1	TBR1	Q16650	547
DBX1	SLC6A5	Q9Y345	543
DBX1	ATOH1	Q92858	538
DBX1	SIM1	P81133	533
DBX1	IRX6	P78412	528
DBX1	SLC17A6	Q9P2U8	527
DBX1	LHX9	Q9NQ69	520

IntAct

3 interactions, top by confidence:

A	B	Type	Score
	DBX1	psi-mi:“MI:0915”(physical association)	0.370
TNFSF14	DBX1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (2): APOC1 (Two-hybrid), DBX1 (Positive Genetic)

ESM2 similar proteins: A0A1W2PPF3, A1A546, A1YGA4, A2T779, A2T7T2, A5YC49, A6NFQ7, A6NMT0, A6NNA5, F1Q4R9, O08686, O42173, O42358, P17278, P17482, P20615, P31272, P43688, P52950, P70368, P70436, P97436, P97458, Q01703, Q28ET4, Q2M1V0, Q3LU38, Q3LU39, Q3LU40, Q5NSW5, Q5TIS6, Q5TM83, Q61658, Q62798, Q80Z64, Q8BYH0, Q8JJ26, Q8MJI9, Q91926, Q92988

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

285 predictions. Top by Δscore:

Variant	Effect	Δscore
11:20156585:C:CT	acceptor_gain	1.0000
11:20156585:C:T	acceptor_gain	1.0000
11:20156586:G:T	acceptor_gain	1.0000
11:20156589:C:CT	acceptor_gain	1.0000
11:20156589:C:T	acceptor_gain	1.0000
11:20156590:G:T	acceptor_gain	1.0000
11:20156592:C:CT	acceptor_gain	1.0000
11:20156593:G:T	acceptor_gain	1.0000
11:20157032:CTCA:C	donor_loss	1.0000
11:20157033:TCACC:T	donor_loss	1.0000
11:20157034:CACC:C	donor_loss	1.0000
11:20157035:A:AC	donor_gain	1.0000
11:20157035:AC:A	donor_gain	1.0000
11:20157035:ACCTG:A	donor_gain	1.0000
11:20157036:C:CT	donor_gain	1.0000
11:20157036:CC:C	donor_gain	1.0000
11:20157036:CCT:C	donor_gain	1.0000
11:20157036:CCTG:C	donor_gain	1.0000
11:20157036:CCTGC:C	donor_gain	1.0000
11:20157235:GGAAG:G	acceptor_gain	1.0000
11:20157236:GAAG:G	acceptor_gain	1.0000
11:20157238:AG:A	acceptor_gain	1.0000
11:20157240:C:CC	acceptor_gain	1.0000
11:20157240:C:CG	acceptor_loss	1.0000
11:20157247:G:C	acceptor_gain	1.0000
11:20157247:G:GC	acceptor_gain	1.0000
11:20159315:C:CT	acceptor_gain	1.0000
11:20156569:TTCAC:T	acceptor_gain	0.9900
11:20156570:TCAC:T	acceptor_gain	0.9900
11:20156571:CAC:C	acceptor_gain	0.9900

AlphaMissense

2200 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:20156515:A:G	L244P	1.000
11:20156526:C:A	K240N	1.000
11:20156526:C:G	K240N	1.000
11:20156536:C:G	R237P	1.000
11:20156537:G:C	R237G	1.000
11:20156538:C:A	W236C	1.000
11:20156538:C:G	W236C	1.000
11:20156540:A:G	W236R	1.000
11:20156540:A:T	W236R	1.000
11:20156541:T:A	K235N	1.000
11:20156541:T:G	K235N	1.000
11:20156542:T:A	K235I	1.000
11:20156543:T:C	K235E	1.000
11:20156543:T:G	K235Q	1.000
11:20156544:C:A	M234I	1.000
11:20156544:C:G	M234I	1.000
11:20156544:C:T	M234I	1.000
11:20156545:A:C	M234R	1.000
11:20156545:A:G	M234T	1.000
11:20156545:A:T	M234K	1.000
11:20156548:C:G	R233P	1.000
11:20156548:C:T	R233H	1.000
11:20156549:G:A	R233C	1.000
11:20156549:G:C	R233G	1.000
11:20156549:G:T	R233S	1.000
11:20156551:C:A	R232L	1.000
11:20156551:C:G	R232P	1.000
11:20156552:G:C	R232G	1.000
11:20156553:G:C	N231K	1.000
11:20156553:G:T	N231K	1.000

dbSNP variants (sampled 300 via entrez): RS1000190330 (11:20160850 C>G), RS1000434461 (11:20156420 C>A,G,T), RS1000743757 (11:20156162 C>A,T), RS1001186326 (11:20157434 G>A), RS1002408184 (11:20158860 G>A), RS1003532920 (11:20158016 A>C), RS1004411945 (11:20158326 C>G,T), RS1004421788 (11:20158537 C>A), RS1004805355 (11:20159806 C>T), RS1006442150 (11:20159907 C>T), RS1006469699 (11:20160762 G>C), RS1006640114 (11:20156726 C>T), RS1006890302 (11:20161221 T>G), RS1007096830 (11:20157156 G>C), RS1008313663 (11:20157789 G>T)

Disease associations

OMIM: gene MIM:619830 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (1): Tourette syndrome (MONDO:0007661)

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002754_2	Response to inhaled glucocorticoid treatment in asthma (change in FEV1)	6.000000e-11
GCST004490_1	Cerebrospinal fluid t-tau:AB1-42 ratio	3.000000e-08
GCST006029_3	Fractional shortening	4.000000e-08
GCST007327_155	Smoking status (ever vs never smokers)	7.000000e-09
GCST008513_20	Health literacy	7.000000e-06
GCST009391_1742	Metabolite levels	6.000000e-06
GCST009391_2063	Metabolite levels	3.000000e-06

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0005921	FEV change measurement
EFO:0007708	t-tau:beta-amyloid 1-42 ratio measurement
EFO:0009285	fractional shortening
EFO:0004318	smoking behavior
EFO:0010104	health literacy measurement
EFO:0010348	cholesteryl ester 20:4 measurement
EFO:0010346	cholesteryl ester 18:3 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

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
Aflatoxin B1	decreases methylation, increases methylation	2
alpha phellandrene	increases expression	1
arsenite	increases methylation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases 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_A0V9	SEES3-1V human DBX1, clone1	Embryonic stem cell	Male
CVCL_A0W0	SEES3-1V human DBX1, clone2	Embryonic stem cell	Male
CVCL_A0W1	SEES3-1V human DBX1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT00004376	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323	PHASE3	COMPLETED	A Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336	PHASE3	COMPLETED	An Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00478842	PHASE3	COMPLETED	Pallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863	PHASE3	TERMINATED	Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695	PHASE3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT03087201	PHASE3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03487783	PHASE3	COMPLETED	Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291	PHASE3	TERMINATED	Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256	PHASE3	COMPLETED	A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT06021522	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT00004393	PHASE2	COMPLETED	Phase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652	PHASE2	COMPLETED	Phase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985	PHASE2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909	PHASE2	COMPLETED	Thalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308	PHASE2	COMPLETED	Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467	PHASE2	COMPLETED	Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549	PHASE2	TERMINATED	Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome
NCT01133353	PHASE2	WITHDRAWN	A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01475383	PHASE2	WITHDRAWN	Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome
NCT01647269	PHASE2	COMPLETED	A Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome
NCT01904773	PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette’s Disorder
NCT02102698	PHASE2	COMPLETED	Ecopipam Treatment of Tourette’s Syndrome in Subjects 7-17 Years
NCT02217007	PHASE2	WITHDRAWN	A Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of SNC-102 in Subjects With Tourette Syndrome
NCT02247206	PHASE2	COMPLETED	VoIP Delivered Behavior Therapy for Tourette Syndrome
NCT02581865	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome
NCT02619084	PHASE2	COMPLETED	Subthalamic Stimulation in Tourette’s Syndrome
NCT02679079	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome
NCT02879578	PHASE2	COMPLETED	Safety and Tolerability Study of NBI-98854 for the Treatment of Subjects With Tourette Syndrome
NCT03066193	PHASE2	COMPLETED	Efficacy of a Therapeutic Combination of Dronabinol and PEA for Tourette Syndrome
NCT03247244	PHASE2	TERMINATED	Safety and Efficacy of Cannabis in Tourette Syndrome
NCT03325010	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
NCT03444038	PHASE2	COMPLETED	Open-Label Safety and Tolerability Study of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome