GBX1

Summary

GBX1 (gastrulation brain homeobox 1, HGNC:4185) is a protein-coding gene on chromosome 7q36.1, encoding Homeobox protein GBX-1 (Q14549).

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of nervous system development and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within adult walking behavior; neuron differentiation; and proprioception. Predicted to be located in chromatin. Predicted to be active in nucleus.

Source: NCBI Gene 2636 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 58 total
• MANE Select transcript: NM_001098834

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4185
Approved symbol	GBX1
Name	gastrulation brain homeobox 1
Location	7q36.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000164900
Ensembl biotype	protein_coding
OMIM	603354
Entrez	2636

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000297537, ENST00000475831

RefSeq mRNA: 1 — MANE Select: NM_001098834 NM_001098834

CCDS: CCDS43682

Canonical transcript exons

ENST00000297537 — 2 exons

Exon	Start	End
ENSE00001088391	151148009	151149142
ENSE00001527802	151167011	151167694

Expression profiles

Bgee: expression breadth broad, 57 present calls, max score 80.35.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0917 / max 9.7873, expressed in 35 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86876	0.0878	33
86877	0.0039	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	80.35	gold quality
secondary oocyte	CL:0000655	80.05	gold quality
left testis	UBERON:0004533	79.26	gold quality
testis	UBERON:0000473	76.32	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	75.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	75.23	gold quality
skeletal muscle tissue	UBERON:0001134	74.95	gold quality
sperm	CL:0000019	74.92	gold quality
muscle of leg	UBERON:0001383	73.73	gold quality
gastrocnemius	UBERON:0001388	73.40	gold quality
biceps brachii	UBERON:0001507	71.70	gold quality
quadriceps femoris	UBERON:0001377	71.05	gold quality
oocyte	CL:0000023	70.97	silver quality
vastus lateralis	UBERON:0001379	70.48	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	70.37	gold quality
muscle tissue	UBERON:0002385	69.00	gold quality
nasal cavity epithelium	UBERON:0005384	68.66	gold quality
superficial temporal artery	UBERON:0001614	67.81	gold quality
metanephric glomerulus	UBERON:0004736	67.61	gold quality
endometrium epithelium	UBERON:0004811	66.09	gold quality
heart right ventricle	UBERON:0002080	65.33	gold quality
mucosa of paranasal sinus	UBERON:0005030	64.85	gold quality
cerebellar vermis	UBERON:0004720	64.18	gold quality
epithelium of nasopharynx	UBERON:0001951	64.07	gold quality
deltoid	UBERON:0001476	63.90	gold quality
apex of heart	UBERON:0002098	63.85	gold quality
cardiac ventricle	UBERON:0002082	63.82	gold quality
heart left ventricle	UBERON:0002084	63.81	gold quality
jejunal mucosa	UBERON:0000399	61.51	gold quality
mammary duct	UBERON:0001765	61.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.63

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA0889.1	GBX1	HOX
MA0889.2	GBX1	HOX

JASPAR matrix evidence (PMIDs): PMID:18585359

Literature-anchored findings (GeneRIF, showing 2)

• Study reveals the preferential expression of GBX1 by germinal vesicle (GV) oocytes. (PMID:16597639)
• Dynamic local polymorphisms in the Gbx1 homeodomain induced by DNA binding have been reported. (PMID:27396829)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gbx1	ENSDARG00000071418
mus_musculus	Gbx1	ENSMUSG00000067724
rattus_norvegicus	Gbx1	ENSRNOG00000013369
drosophila_melanogaster	unpg	FBGN0015561

Paralogs (1): GBX2 (ENSG00000168505)

Protein

Protein identifiers

Homeobox protein GBX-1 — Q14549 (reviewed: Q14549)

Alternative names: Gastrulation and brain-specific homeobox protein 1

All UniProt accessions (1): Q14549

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

RefSeq proteins (1): NP_001092304* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR020479	HD_metazoa	Domain
IPR042982	GBX-1/2	Family

Pfam: PF00046

UniProt features (13 total): compositionally biased region 4, helix 3, region of interest 2, chain 1, DNA-binding region 1, sequence variant 1, strand 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2M34	SOLUTION NMR
2ME0	SOLUTION NMR
2ME6	SOLUTION NMR
2N8G	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14549-F1	60.75	0.17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 63 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_BEHAVIOR, GOBP_ADULT_BEHAVIOR, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_ADULT_LOCOMOTORY_BEHAVIOR, GOBP_CELL_DIFFERENTIATION_IN_SPINAL_CORD, GOBP_SPINAL_CORD_MOTOR_NEURON_DIFFERENTIATION, GOBP_VENTRAL_SPINAL_CORD_DEVELOPMENT, GOBP_CENTRAL_NERVOUS_SYSTEM_NEURON_DIFFERENTIATION, GOBP_SENSORY_PERCEPTION, GOBP_NEUROMUSCULAR_PROCESS_CONTROLLING_POSTURE, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_NEURON_FATE_COMMITMENT, GOBP_NEUROMUSCULAR_PROCESS

GO Biological Process (8): regulation of transcription by RNA polymerase II (GO:0006357), adult walking behavior (GO:0007628), proprioception (GO:0019230), spinal cord motor neuron differentiation (GO:0021522), neuron fate commitment (GO:0048663), regulation of nervous system development (GO:0051960), sensory neuron axon guidance (GO:0097374), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (3): 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 (GO:0003677)

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
adult locomotory behavior	1
walking behavior	1
sensory perception	1
neuromuscular process controlling posture	1
cell differentiation in spinal cord	1
ventral spinal cord development	1
central nervous system neuron differentiation	1
neuron differentiation	1
cell fate commitment	1
nervous system development	1
regulation of multicellular organismal development	1
axon guidance	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription cis-regulatory region binding	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
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

574 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GBX1	LHX8	Q68G74	897
GBX1	SOHLH1	Q5JUK2	825
GBX1	DRC11L	A6NCM1	543
GBX1	LHX6	Q9UPM6	472
GBX1	ZNF879	B4DU55	392
GBX1	NPAS1	Q99742	389
GBX1	ENTREP2	O60320	384
GBX1	PAX2	Q02962	366
GBX1	ZNF391	Q9UJN7	358
GBX1	ISL1	P20663	356
GBX1	C7orf33	Q8WU49	348
GBX1	LHX5	Q9H2C1	346
GBX1	Q05D86	Q05D86	340
GBX1	EN2	P19622	337
GBX1	RNF212	Q495C1	335

IntAct

3 interactions, top by confidence:

A	B	Type	Score
GBX1	DNAJC6	psi-mi:“MI:0914”(association)	0.350
GBX2	FHL3	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): PKMYT1 (Affinity Capture-MS), TRIM11 (Affinity Capture-MS), GBX1 (Affinity Capture-MS), GABPA (Affinity Capture-MS), DNAJC6 (Affinity Capture-MS), GRN (Affinity Capture-MS), QPRT (Affinity Capture-MS), NAALAD2 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A1W2PQ73, A1YF16, A1YG93, A2RU54, A5PKG8, O02786, O14813, O15353, O35602, O43638, O57601, P13297, P19419, P28360, P35548, P41969, P42580, P43687, P49640, P50223, P50548, P52946, P52950, P63156, P63157, P70459, P78413, Q03358, Q14549, Q2VL78, Q2VL79, Q2VL82, Q2VL83, Q2VL84, Q2VL85, Q2VL86, Q2VL87, Q2VL88, Q5NSW5, Q61575

Diamond homologs: A1YER7, A1YF08, A1YFD8, A1YFY3, A1YG85, A1YGA4, A2D4P8, A2D5I1, A2D5K9, A2D5Y4, A2T6X6, A2T756, A2T779, A2T7T2, F1Q4R9, M0R6D8, O13074, O42230, O42365, O42367, O42506, O57374, P06798, P07548, P09016, P09017, P09019, P09020, P09021, P09067, P09070, P09074, P0C1T1, P10178, P10284, P10628, P14652, P14837, P14838, P14840

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

303 predictions. Top by Δscore:

Variant	Effect	Δscore
7:151167004:CACTT:C	donor_loss	0.9900
7:151167005:ACTTA:A	donor_loss	0.9900
7:151167006:CTTAC:C	donor_loss	0.9900
7:151167007:TTAC:T	donor_loss	0.9900
7:151167008:TACCG:T	donor_loss	0.9900
7:151167009:A:AC	donor_gain	0.9900
7:151167009:A:AG	donor_loss	0.9900
7:151167010:C:CC	donor_gain	0.9900
7:151167010:CCGGG:C	donor_gain	0.9900
7:151167010:CCGG:C	donor_gain	0.9800
7:151149140:CTG:C	acceptor_gain	0.9700
7:151149160:CCAA:C	acceptor_gain	0.9700
7:151149161:CAA:C	acceptor_gain	0.9700
7:151149162:A:T	acceptor_gain	0.9700
7:151149163:A:AC	acceptor_gain	0.9700
7:151149163:A:C	acceptor_gain	0.9700
7:151149167:A:C	acceptor_gain	0.9700
7:151149138:CTCTG:C	acceptor_gain	0.9600
7:151149167:A:AC	acceptor_gain	0.9600
7:151167009:AC:A	donor_gain	0.9600
7:151167010:CC:C	donor_gain	0.9600
7:151167010:CCG:C	donor_gain	0.9600
7:151149143:C:CC	acceptor_gain	0.9300
7:151149139:TCTG:T	acceptor_loss	0.9200
7:151149142:GCTGT:G	acceptor_loss	0.9200
7:151149143:CTGTG:C	acceptor_loss	0.9200
7:151149144:T:G	acceptor_loss	0.9200
7:151149154:A:T	acceptor_gain	0.9200
7:151149141:TG:T	acceptor_gain	0.9100
7:151149145:G:C	acceptor_gain	0.9100

AlphaMissense

2307 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:151148659:A:C	I341R	1.000
7:151148659:A:G	I341T	1.000
7:151148659:A:T	I341K	1.000
7:151148665:A:T	V339D	1.000
7:151148668:A:T	V338D	1.000
7:151148671:A:C	I337S	1.000
7:151148728:C:G	R318P	1.000
7:151148729:G:A	R318C	1.000
7:151148729:G:T	R318S	1.000
7:151148730:C:A	K317N	1.000
7:151148730:C:G	K317N	1.000
7:151148732:T:C	K317E	1.000
7:151148733:C:A	W316C	1.000
7:151148733:C:G	W316C	1.000
7:151148735:A:G	W316R	1.000
7:151148735:A:T	W316R	1.000
7:151148736:C:A	K315N	1.000
7:151148736:C:G	K315N	1.000
7:151148737:T:A	K315M	1.000
7:151148738:T:C	K315E	1.000
7:151148738:T:G	K315Q	1.000
7:151148740:G:T	A314D	1.000
7:151148741:C:G	A314P	1.000
7:151148743:C:G	R313P	1.000
7:151148744:G:A	R313W	1.000
7:151148744:G:C	R313G	1.000
7:151148746:C:A	R312L	1.000
7:151148746:C:G	R312P	1.000
7:151148747:G:C	R312G	1.000
7:151148748:A:C	N311K	1.000

dbSNP variants (sampled 300 via entrez): RS1000016666 (7:151147577 G>A,T), RS1000084655 (7:151149211 T>C,G), RS1000138844 (7:151157122 C>G), RS1000418276 (7:151160909 G>T), RS1000447064 (7:151162224 C>T), RS1000614080 (7:151166117 A>G), RS1000696647 (7:151155374 T>C), RS1000705895 (7:151149489 C>G,T), RS1000747435 (7:151155736 T>G), RS1000756906 (7:151149127 T>C), RS1001159869 (7:151159251 A>C), RS1001182716 (7:151161241 G>A), RS1001304788 (7:151154207 G>A), RS1001399654 (7:151168256 C>A,T), RS1001454093 (7:151160589 T>C)

Disease associations

OMIM: gene MIM:603354 | 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
GCST003476_9	Eyebrow thickness	7.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
bisphenol A	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression, decreases reaction	1
abrine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Lipopolysaccharides	increases expression, decreases reaction	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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