GSX1

Summary

GSX1 (GS homeobox 1, HGNC:20374) is a protein-coding gene on chromosome 13q12.2, encoding GS homeobox 1 (Q9H4S2). Probable transcription factor that binds to the DNA sequence 5’-GC[TA][AC]ATTA[GA]-3'.

Enables sequence-specific double-stranded DNA binding activity. Acts upstream of or within positive regulation of transcription by RNA polymerase II. Predicted to be located in chromatin. Predicted to be active in nucleus.

Source: NCBI Gene 219409 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 49 total
• MANE Select transcript: NM_145657

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20374
Approved symbol	GSX1
Name	GS homeobox 1
Location	13q12.2
Locus type	gene with protein product
Status	Approved
Aliases	Gsh-1
Ensembl gene	ENSG00000169840
Ensembl biotype	protein_coding
OMIM	616542
Entrez	219409

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000302945

RefSeq mRNA: 1 — MANE Select: NM_145657 NM_145657

CCDS: CCDS9326

Canonical transcript exons

ENST00000302945 — 2 exons

Exon	Start	End
ENSE00001157670	27793566	27794768
ENSE00001157677	27792483	27793102

Expression profiles

Bgee: expression breadth broad, 18 present calls, max score 62.27.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1134 / max 12.6374, expressed in 49 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
134537	0.1134	49

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
superficial temporal artery	UBERON:0001614	62.27	gold quality
buccal mucosa cell	CL:0002336	60.84	gold quality
epithelium of nasopharynx	UBERON:0001951	60.55	gold quality
amniotic fluid	UBERON:0000173	59.59	gold quality
gingival epithelium	UBERON:0001949	57.32	gold quality
germinal epithelium of ovary	UBERON:0001304	55.59	gold quality
gingiva	UBERON:0001828	55.05	gold quality
mucosa of paranasal sinus	UBERON:0005030	54.85	gold quality
Brodmann (1909) area 23	UBERON:0013554	53.77	gold quality
hypothalamus	UBERON:0001898	52.50	gold quality
middle temporal gyrus	UBERON:0002771	52.17	gold quality
trabecular bone tissue	UBERON:0002483	50.66	gold quality
corpus epididymis	UBERON:0004359	50.57	gold quality
cauda epididymis	UBERON:0004360	50.13	gold quality
caput epididymis	UBERON:0004358	50.08	gold quality
inferior vagus X ganglion	UBERON:0005363	48.02	gold quality
heart right ventricle	UBERON:0002080	47.93	gold quality
ventral tegmental area	UBERON:0002691	47.74	gold quality
skin of hip	UBERON:0001554	47.59	silver quality
vastus lateralis	UBERON:0001379	47.03	gold quality
quadriceps femoris	UBERON:0001377	46.87	gold quality
subthalamic nucleus	UBERON:0001906	45.90	gold quality
cardia of stomach	UBERON:0001162	45.56	gold quality
saphenous vein	UBERON:0007318	44.47	gold quality
medulla oblongata	UBERON:0001896	44.31	gold quality
dorsal plus ventral thalamus	UBERON:0001897	43.95	gold quality
pigmented layer of retina	UBERON:0001782	43.75	gold quality
trigeminal ganglion	UBERON:0001675	43.64	gold quality
trachea	UBERON:0003126	43.54	gold quality
medial globus pallidus	UBERON:0002477	43.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.46

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
GCLC
GHRH	Activation
GSX1
INS

Upstream regulators (CollecTRI, top): GSX1

Literature-anchored findings (GeneRIF, showing 1)

• the study ruled out microdeletions on the critical region as a common cause of Moebius syndrome and excluded GSH1 gene (PMID:19460469)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gsx1	ENSDARG00000035735
mus_musculus	Gsx1	ENSMUSG00000053129
rattus_norvegicus	Gsx1	ENSRNOG00000000952
caenorhabditis_elegans		WBGENE00012584
caenorhabditis_elegans		WBGENE00044032

Paralogs (1): NOTO (ENSG00000214513)

Protein

Protein identifiers

GS homeobox 1 — Q9H4S2 (reviewed: Q9H4S2)

Alternative names: Homeobox protein GSH-1

All UniProt accessions (1): Q9H4S2

UniProt curated annotations — full annotation on UniProt →

Function. Probable transcription factor that binds to the DNA sequence 5’-GC[TA][AC]ATTA[GA]-3’. Activates the transcription of the GHRH gene. Plays an important role in pituitary development.

Subcellular location. Nucleus.

Similarity. Belongs to the Antp homeobox family.

RefSeq proteins (1): NP_663632* (*=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
IPR042191	GSH1/2	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-Q9H4S2-F1	65.45	0.23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 109 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, AHRARNT_01, RRAGTTGT_UNKNOWN, BENPORATH_ES_WITH_H3K27ME3, GOBP_PITUITARY_GLAND_DEVELOPMENT, GOBP_NEUROGENESIS, GGGTGGRR_PAX4_03, GOBP_CELL_DIFFERENTIATION_IN_SPINAL_CORD, GOBP_FOREBRAIN_DEVELOPMENT, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, GOBP_HYPOTHALAMUS_DEVELOPMENT, NKX62_Q2, FREAC3_01, NF1_Q6_01, OCT1_03

GO Biological Process (10): transcription by RNA polymerase II (GO:0006366), central nervous system development (GO:0007417), brain development (GO:0007420), spinal cord association neuron differentiation (GO:0021527), hypothalamus development (GO:0021854), adenohypophysis development (GO:0021984), neuron differentiation (GO:0030182), positive regulation of transcription by RNA polymerase II (GO:0045944), neuron fate commitment (GO:0048663), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (8): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), 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
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
DNA-templated transcription	2
anatomical structure development	2
regulation of transcription by RNA polymerase II	2
nervous system development	1
system development	1
central nervous system development	1
animal organ development	1
head development	1
cell differentiation in spinal cord	1
dorsal spinal cord development	1
central nervous system neuron differentiation	1
diencephalon development	1
limbic system development	1
pituitary gland development	1
cell differentiation	1
generation of neurons	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
neuron differentiation	1
cell fate commitment	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
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
DNA binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
regulation of DNA-templated transcription	1
transcription regulator activity	1
binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

816 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GSX1	ASCL1	P50553	634
GSX1	LHX6	Q9UPM6	579
GSX1	TBR1	Q16650	542
GSX1	LHX8	Q68G74	510
GSX1	SP8	Q8IXZ3	483
GSX1	PTF1A	Q7RTS3	456
GSX1	NEUROG2	Q9H2A3	456
GSX1	OLIG2	Q13516	452
GSX1	CUX1	P39880	425
GSX1	SP9	P0CG40	409
GSX1	NEUROG1	Q92886	391
GSX1	LHX5	Q9H2C1	380
GSX1	ZNF503	Q96F45	379
GSX1	TSHZ1	Q6ZSZ6	367
GSX1	GAD1	Q99259	365

IntAct

5 interactions, top by confidence:

A	B	Type	Score
KRTAP19-7	GSX1	psi-mi:“MI:0915”(physical association)	0.560
GSX1	YKT6	psi-mi:“MI:0914”(association)	0.350
GSX1	KRTAP19-7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (46): KRTAP19-7 (Two-hybrid), PSMG4 (Affinity Capture-MS), CYB5R3 (Affinity Capture-MS), HIBCH (Affinity Capture-MS), PDCD10 (Affinity Capture-MS), STXBP2 (Affinity Capture-MS), DHRS4 (Affinity Capture-MS), BCS1L (Affinity Capture-MS), PPID (Affinity Capture-MS), AK4 (Affinity Capture-MS), NDUFAF7 (Affinity Capture-MS), EEF1A2 (Affinity Capture-MS), NAA50 (Affinity Capture-MS), ZMPSTE24 (Affinity Capture-MS), EFHD2 (Affinity Capture-MS)

ESM2 similar proteins: A0A8V0YY16, A0JPN1, A7MB54, A8MTJ6, O35762, O42115, O57601, O88181, O95096, P09065, P23683, P28356, P31311, P31315, P32443, P39020, P42581, P42586, P43697, P48031, P49640, P50222, P50476, P52951, P52954, P52955, P78426, P81067, P81068, P97334, Q14549, Q14774, Q1KKY1, Q1XID0, Q2NKI2, Q2VL76, Q2VL80, Q4V5A3, Q5SQQ9, Q60554

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

245 predictions. Top by Δscore:

Variant	Effect	Δscore
13:27793174:G:GT	donor_gain	1.0000
13:27793558:A:AG	acceptor_gain	1.0000
13:27793559:C:G	acceptor_gain	1.0000
13:27793562:CCAG:C	acceptor_loss	1.0000
13:27793563:CA:C	acceptor_loss	1.0000
13:27793564:A:AG	acceptor_gain	1.0000
13:27793564:AGACA:A	acceptor_loss	1.0000
13:27793565:G:GT	acceptor_gain	1.0000
13:27793565:GA:G	acceptor_gain	1.0000
13:27793565:GAC:G	acceptor_gain	1.0000
13:27793565:GACA:G	acceptor_gain	1.0000
13:27793098:TGTGG:T	donor_loss	0.9900
13:27793099:GTGG:G	donor_gain	0.9900
13:27793101:GG:G	donor_gain	0.9900
13:27793102:GG:G	donor_gain	0.9900
13:27793102:GGTAA:G	donor_loss	0.9900
13:27793103:G:GC	donor_loss	0.9900
13:27793104:T:TC	donor_loss	0.9900
13:27793554:T:TA	acceptor_gain	0.9900
13:27793103:G:GG	donor_gain	0.9800
13:27793105:AA:A	donor_loss	0.9800
13:27793563:CAGA:C	acceptor_gain	0.9800
13:27793564:AGAC:A	acceptor_gain	0.9800
13:27793080:G:GT	donor_gain	0.9700
13:27793171:G:GT	donor_gain	0.9700
13:27793562:CCAGA:C	acceptor_gain	0.9700
13:27793565:GACAG:G	acceptor_gain	0.9700
13:27793679:C:G	acceptor_gain	0.9700
13:27793153:G:GT	donor_gain	0.9600
13:27793181:G:T	donor_gain	0.9600

AlphaMissense

1686 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:27792703:T:C	F5L	1.000
13:27792705:C:A	F5L	1.000
13:27792705:C:G	F5L	1.000
13:27793595:A:G	K148E	1.000
13:27793597:G:C	K148N	1.000
13:27793597:G:T	K148N	1.000
13:27793599:G:T	R149M	1.000
13:27793600:G:C	R149S	1.000
13:27793600:G:T	R149S	1.000
13:27793604:C:A	R151S	1.000
13:27793604:C:G	R151G	1.000
13:27793604:C:T	R151C	1.000
13:27793605:G:A	R151H	1.000
13:27793611:C:A	A153D	1.000
13:27793613:T:A	F154I	1.000
13:27793613:T:C	F154L	1.000
13:27793613:T:G	F154V	1.000
13:27793614:T:C	F154S	1.000
13:27793614:T:G	F154C	1.000
13:27793615:C:A	F154L	1.000
13:27793615:C:G	F154L	1.000
13:27793617:C:T	T155I	1.000
13:27793626:A:G	Q158R	1.000
13:27793627:G:C	Q158H	1.000
13:27793627:G:T	Q158H	1.000
13:27793629:T:A	L159Q	1.000
13:27793629:T:C	L159P	1.000
13:27793632:T:C	L160P	1.000
13:27793638:T:A	L162Q	1.000
13:27793638:T:C	L162P	1.000

dbSNP variants (sampled 300 via entrez): RS1000477680 (13:27792568 G>A), RS1001072649 (13:27791172 C>T), RS1001491358 (13:27791394 C>T), RS1001819248 (13:27795213 A>G), RS1001925354 (13:27795196 C>A), RS1003041464 (13:27794164 C>G,T), RS1003756564 (13:27792290 C>G,T), RS1003830011 (13:27792515 T>A,C), RS1006147791 (13:27790530 A>T), RS1006208102 (13:27791425 A>G), RS1006990354 (13:27794806 A>C), RS1007996001 (13:27793336 G>C,T), RS1008224776 (13:27794372 C>A,G), RS1008698565 (13:27792859 G>A,C,T), RS1008773115 (13:27791950 C>T)

Disease associations

OMIM: gene MIM:616542 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000253_2	Attention deficit hyperactivity disorder and conduct disorder	9.000000e-06
GCST001996_3	Adverse response to chemotherapy (neutropenia/leucopenia) (epirubicin)	5.000000e-06
GCST002553_1	Pancreatic cancer	2.000000e-09
GCST005951_4	Body mass index	2.000000e-08
GCST006431_6	Plasma parathyroid hormone levels	2.000000e-06
GCST90011898_20	Alanine aminotransferase levels	4.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Progesterone	increases expression	1

Clinical trials (associated diseases)

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