BSX

Summary

BSX (brain specific homeobox, HGNC:20450) is a protein-coding gene on chromosome 11q24.1, encoding Brain-specific homeobox protein homolog (Q3C1V8). DNA binding protein that function as transcriptional activator.

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in cell differentiation; regulation of transcription by RNA polymerase II; and stem cell population maintenance. Predicted to act upstream of or within several processes, including eating behavior; mammary gland involution; and positive regulation of transcription by RNA polymerase II. Predicted to be located in chromatin. Predicted to be part of transcription regulator complex.

Source: NCBI Gene 390259 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_001098169

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20450
Approved symbol	BSX
Name	brain specific homeobox
Location	11q24.1
Locus type	gene with protein product
Status	Approved
Aliases	BSX1
Ensembl gene	ENSG00000188909
Ensembl biotype	protein_coding
OMIM	611074
Entrez	390259

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000343035

RefSeq mRNA: 1 — MANE Select: NM_001098169 NM_001098169

CCDS: CCDS41728

Canonical transcript exons

ENST00000343035 — 3 exons

Exon	Start	End
ENSE00001369670	122979261	122979457
ENSE00001379779	122981410	122981834
ENSE00001381774	122977570	122977891

Expression profiles

Bgee: expression breadth tissue_specific, 4 present calls, max score 44.54.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5923 / max 356.0552, expressed in 37 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122874	0.4646	32
122875	0.1021	15
122876	0.0256	5

Top tissues by expression

125 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	44.54	silver quality
sural nerve	UBERON:0015488	44.53	gold quality
hypothalamus	UBERON:0001898	40.30	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
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
prefrontal cortex	UBERON:0000451	29.90	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
lymph node	UBERON:0000029	28.92	gold quality
liver	UBERON:0002107	28.81	gold quality
tonsil	UBERON:0002372	28.53	gold quality
duodenum	UBERON:0002114	28.14	gold quality
urinary bladder	UBERON:0001255	27.87	gold quality
leukocyte	CL:0000738	27.32	gold quality
monocyte	CL:0000576	27.29	gold quality
blood	UBERON:0000178	26.48	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality
right adrenal gland cortex	UBERON:0035827	25.31	gold quality
frontal cortex	UBERON:0001870	25.07	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality
gastrocnemius	UBERON:0001388	23.80	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)

4 targets.

Target	Regulation
AGRP	Unknown
APP
MT-ATP6
NPY	Unknown

JASPAR motifs

Motif	Name	Family
MA0876.1	BSX	NK
MA0876.2	BSX	NK

JASPAR matrix evidence (PMIDs): PMID:18585359

Upstream regulators (CollecTRI, top): REST, SP1

Literature-anchored findings (GeneRIF, showing 2)

• Data suggest that BSX is essential for global cognitive function and that haplo-insufficiency may cause severe mental retardation, and that deletion of Neurogranin (PMID:18855024)
• Genetic ablation of the Bsx homeodomain transcription factor in zebrafish: Impact on mature pineal gland morphology and circadian behavior. (PMID:35249239)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bsx	ENSMUSG00000054360
rattus_norvegicus	Bsx	ENSRNOG00000024438
drosophila_melanogaster	Dll	FBGN0000157
caenorhabditis_elegans		WBGENE00000463

Paralogs (9): DLX6 (ENSG00000006377), DLX3 (ENSG00000064195), DLX5 (ENSG00000105880), DLX4 (ENSG00000108813), NANOG (ENSG00000111704), DLX2 (ENSG00000115844), DLX1 (ENSG00000144355), VENTX (ENSG00000151650), NANOGP8 (ENSG00000255192)

Protein

Protein identifiers

Brain-specific homeobox protein homolog — Q3C1V8 (reviewed: Q3C1V8)

All UniProt accessions (1): Q3C1V8

UniProt curated annotations — full annotation on UniProt →

Function. DNA binding protein that function as transcriptional activator. Is essential for normal postnatal growth and nursing. Is an essential factor for neuronal neuropeptide Y and agouti-related peptide function and locomotory behavior in the control of energy balance.

Subcellular location. Nucleus.

Similarity. Belongs to the distal-less homeobox family.

RefSeq proteins (1): NP_001091639* (*=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
IPR050848	Homeobox_TF	Family

Pfam: PF00046

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3C1V8-F1	68.92	0.27

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 38 (showing top): GOBP_MAMMARY_GLAND_MORPHOGENESIS, GOBP_GLAND_MORPHOGENESIS, GOBP_BEHAVIOR, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EATING_BEHAVIOR, GOBP_MAMMARY_GLAND_DEVELOPMENT, GOBP_MAINTENANCE_OF_CELL_NUMBER, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, GOBP_FEEDING_BEHAVIOR, MATZUK_POSTIMPLANTATION_AND_POSTPARTUM, chr11q24, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_TISSUE_REMODELING, MIKKELSEN_MCV6_ICP_WITH_H3K27ME3, MIKKELSEN_MEF_ICP_WITH_H3K27ME3

GO Biological Process (8): regulation of transcription by RNA polymerase II (GO:0006357), locomotory behavior (GO:0007626), stem cell population maintenance (GO:0019827), cell differentiation (GO:0030154), eating behavior (GO:0042755), positive regulation of transcription by RNA polymerase II (GO:0045944), mammary gland involution (GO:0060056), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (5): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), transcription regulator complex (GO:0005667)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of DNA-templated transcription	1
behavior	1
multicellular organismal process	1
maintenance of cell number	1
cellular developmental process	1
feeding behavior	1
positive regulation of DNA-templated transcription	1
tissue remodeling	1
mammary gland morphogenesis	1
DNA-templated transcription	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
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
DNA binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

332 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BSX	AGRP	O00253	791
BSX	NPY	P01303	726
BSX	LEP	P41159	549
BSX	LHX9	Q9NQ69	430
BSX	ITPKA	P23677	425
BSX	LHX2	P50458	421
BSX	DMRTA1	Q5VZB9	412
BSX	PMCH	P20382	408
BSX	FEZF2	Q8TBJ5	401
BSX	FEZF1	A0PJY2	399
BSX	BANF1	O75531	397
BSX	SIM1	P81133	382
BSX	LHX4	Q969G2	376
BSX	NHLH2	Q02577	376
BSX	NR5A1	Q13285	362

IntAct

2 interactions, top by confidence:

A	B	Type	Score
BSX	NPM1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): BSX (Proximity Label-MS)

ESM2 similar proteins: A1YF16, A1YG93, A2RU54, A2T764, A2T7P4, O02786, O42115, O43711, O57601, P13297, P23410, P28360, P28362, P35548, P35993, P42580, P43120, P43687, P50223, P63156, P63157, P70354, Q01703, Q03014, Q03356, Q03358, Q04281, Q05502, Q0P4W6, Q0P5C3, Q2VL76, Q2VL77, Q2VL78, Q2VL79, Q2VL80, Q2VL82, Q2VL83, Q2VL84, Q2VL85, Q2VL86

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

343 predictions. Top by Δscore:

Variant	Effect	Δscore
11:122977899:C:CT	acceptor_gain	1.0000
11:122977892:C:CA	acceptor_loss	0.9900
11:122977892:C:CC	acceptor_gain	0.9900
11:122977900:G:T	acceptor_gain	0.9900
11:122979243:C:CA	donor_gain	0.9900
11:122979453:CATCC:C	acceptor_gain	0.9900
11:122979455:TCC:T	acceptor_gain	0.9900
11:122979456:CC:C	acceptor_gain	0.9900
11:122979456:CCC:C	acceptor_gain	0.9900
11:122979457:CC:C	acceptor_gain	0.9900
11:122979458:C:CC	acceptor_gain	0.9900
11:122979552:T:TA	donor_gain	0.9900
11:122979598:AAG:A	donor_gain	0.9900
11:122980352:A:AC	donor_gain	0.9900
11:122980352:AGGG:A	donor_gain	0.9900
11:122980353:G:C	donor_gain	0.9900
11:122981405:CTT:C	donor_loss	0.9900
11:122981407:TACCC:T	donor_loss	0.9900
11:122981408:A:AC	donor_gain	0.9900
11:122981408:AC:A	donor_gain	0.9900
11:122981409:C:CC	donor_gain	0.9900
11:122981409:CC:C	donor_gain	0.9900
11:122977887:TTCAC:T	acceptor_gain	0.9800
11:122977889:CAC:C	acceptor_gain	0.9800
11:122979255:GCCCA:G	donor_loss	0.9800
11:122979256:CCCAC:C	donor_loss	0.9800
11:122979257:CCA:C	donor_loss	0.9800
11:122979258:CACC:C	donor_loss	0.9800
11:122979259:AC:A	donor_loss	0.9800
11:122979260:CCTGC:C	donor_loss	0.9800

AlphaMissense

1501 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:122977853:T:A	K166N	1.000
11:122977853:T:G	K166N	1.000
11:122977854:T:A	K166I	1.000
11:122977855:T:C	K166E	1.000
11:122977859:C:A	K164N	1.000
11:122977859:C:G	K164N	1.000
11:122977861:T:C	K164E	1.000
11:122977862:C:A	M163I	1.000
11:122977862:C:G	M163I	1.000
11:122977862:C:T	M163I	1.000
11:122977863:A:G	M163T	1.000
11:122977863:A:T	M163K	1.000
11:122977867:G:C	R162G	1.000
11:122977869:C:G	R161P	1.000
11:122977870:G:C	R161G	1.000
11:122977871:G:C	N160K	1.000
11:122977871:G:T	N160K	1.000
11:122977872:T:A	N160I	1.000
11:122977872:T:C	N160S	1.000
11:122977872:T:G	N160T	1.000
11:122977873:T:C	N160D	1.000
11:122977873:T:G	N160H	1.000
11:122977874:C:A	Q159H	1.000
11:122977874:C:G	Q159H	1.000
11:122977875:T:G	Q159P	1.000
11:122977876:G:T	Q159K	1.000
11:122977877:G:C	F158L	1.000
11:122977877:G:T	F158L	1.000
11:122977878:A:C	F158C	1.000
11:122977878:A:G	F158S	1.000

dbSNP variants (sampled 300 via entrez): RS1000285800 (11:122977977 G>A,T), RS1001055045 (11:122979896 A>G), RS1001486079 (11:122980157 C>T), RS1001543553 (11:122983176 A>G), RS1002021142 (11:122983328 G>A,C,T), RS1002121740 (11:122978403 G>A), RS1002472688 (11:122978183 C>T), RS1002869672 (11:122979619 A>G), RS1003612183 (11:122978059 A>C), RS1004823505 (11:122983360 C>A), RS1004895848 (11:122981942 G>A), RS1004981303 (11:122977290 G>T), RS1005076155 (11:122977481 G>A,C), RS1005208958 (11:122977249 G>A), RS1005238943 (11:122981878 C>T)

Disease associations

OMIM: gene MIM:611074 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000880_40	Menarche (age at onset)	2.000000e-12
GCST002541_91	Menarche (age at onset)	3.000000e-26
GCST012227_633	Hip circumference adjusted for BMI	6.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0008039	BMI-adjusted hip circumference

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
Benzo(a)pyrene	affects methylation, increases methylation	2
Aflatoxin B1	decreases methylation	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Resveratrol	decreases expression, affects cotreatment	1
Cadmium	decreases expression, increases abundance	1
Phthalic Acids	decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Cyclosporine	decreases methylation	1
Asbestos, Crocidolite	decreases methylation	1
Asbestos, Amosite	decreases methylation	1

Clinical trials (associated diseases)

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