SEBOX

Summary

SEBOX (SEBOX homeobox, HGNC:32942) is a protein-coding gene on chromosome 17q11.2, encoding Homeobox protein SEBOX (Q9HB31). Probable transcription factor involved in the control of specification of mesoderm and endoderm.

Homeodomain proteins, such as SEBOX, play a key role in coordinating gene expression during development (Cinquanta et al., 2000 [PubMed 10922053]).

Source: NCBI Gene 645832 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_001080837

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32942
Approved symbol	SEBOX
Name	SEBOX homeobox
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	OG9, OG9X
Ensembl gene	ENSG00000274529
Ensembl biotype	protein_coding
OMIM	610975
Entrez	645832

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000536498

RefSeq mRNA: 1 — MANE Select: NM_001080837 NM_001080837

CCDS: CCDS45634

Canonical transcript exons

ENST00000536498 — 3 exons

Exon	Start	End
ENSE00003625665	28364795	28364955
ENSE00003716982	28365121	28365199
ENSE00003789990	28363506	28364648

Expression profiles

Bgee: expression breadth broad, 37 present calls, max score 97.13.

Top tissues by expression

88 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	97.13	gold quality
right lobe of liver	UBERON:0001114	55.53	gold quality
liver	UBERON:0002107	48.15	gold quality
bone marrow cell	CL:0002092	46.79	gold quality
granulocyte	CL:0000094	46.63	silver quality
colonic epithelium	UBERON:0000397	41.80	gold quality
bone marrow	UBERON:0002371	39.89	gold quality
skeletal muscle tissue	UBERON:0001134	39.09	silver quality
blood	UBERON:0000178	39.05	silver quality
adrenal tissue	UBERON:0018303	37.58	silver quality
leukocyte	CL:0000738	37.38	silver quality
monocyte	CL:0000576	37.35	silver quality
muscle tissue	UBERON:0002385	36.72	silver quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
sural nerve	UBERON:0015488	35.84	gold quality
duodenum	UBERON:0002114	35.50	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
mucosa of stomach	UBERON:0001199	35.39	gold quality
urinary bladder	UBERON:0001255	34.84	gold quality
left adrenal gland cortex	UBERON:0035825	33.66	silver quality
right adrenal gland	UBERON:0001233	33.48	gold quality
adrenal gland	UBERON:0002369	32.95	silver quality
prefrontal cortex	UBERON:0000451	32.57	gold quality
right adrenal gland cortex	UBERON:0035827	32.56	silver quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
right uterine tube	UBERON:0001302	31.94	gold quality
superior frontal gyrus	UBERON:0002661	30.92	gold quality
lymph node	UBERON:0000029	30.82	silver quality
frontal cortex	UBERON:0001870	30.48	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.16

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• This publication reported the human SEBOX gene sequence and predicted amino acid sequence, in addition to mouse and rat Sebox gene sequences. (PMID:10922053)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sebox	ENSDARG00000042526
mus_musculus	Sebox	ENSMUSG00000001103
rattus_norvegicus	Sebox	ENSRNOG00000009979

Paralogs (50): ARX (ENSG00000004848), PAX6 (ENSG00000007372), PAX7 (ENSG00000009709), ALX4 (ENSG00000052850), GSC2 (ENSG00000063515), PITX1 (ENSG00000069011), PAX2 (ENSG00000075891), RHOXF1 (ENSG00000101883), CRX (ENSG00000105392), EVX1 (ENSG00000106038), PAX4 (ENSG00000106331), NOBOX (ENSG00000106410), PITX3 (ENSG00000107859), PHOX2B (ENSG00000109132), OTX1 (ENSG00000115507), PRRX1 (ENSG00000116132), VSX2 (ENSG00000119614), ESX1 (ENSG00000123576), PAX8 (ENSG00000125618), PAX1 (ENSG00000125813), RHOXF2 (ENSG00000131721), GSC (ENSG00000133937), RAX (ENSG00000134438), PAX3 (ENSG00000135903), ALX3 (ENSG00000156150), HESX1 (ENSG00000163666), PITX2 (ENSG00000164093), UNCX (ENSG00000164853), PHOX2A (ENSG00000165462), OTX2 (ENSG00000165588), DRGX (ENSG00000165606), PRRX2 (ENSG00000167157), SHOX2 (ENSG00000168779), OTP (ENSG00000171540), RAX2 (ENSG00000173976), EVX2 (ENSG00000174279), PROP1 (ENSG00000175325), ISX (ENSG00000175329), ALX1 (ENSG00000180318), MIXL1 (ENSG00000185155)

Protein

Protein identifiers

Homeobox protein SEBOX — Q9HB31 (reviewed: Q9HB31)

Alternative names: Homeobox OG-9, Skin-, embryo-, brain- and oocyte-specific homeobox

All UniProt accessions (1): Q9HB31

UniProt curated annotations — full annotation on UniProt →

Function. Probable transcription factor involved in the control of specification of mesoderm and endoderm.

Subcellular location. Nucleus.

Similarity. Belongs to the paired homeobox family.

RefSeq proteins (1): NP_001074306* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR042223	SEBOX	Family

Pfam: PF00046

UniProt features (7 total): region of interest 2, compositionally biased region 2, chain 1, DNA-binding region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HB31-F1	66.86	0.28

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 38 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_OOGENESIS, chr17q11, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_FEMALE_GAMETE_GENERATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_EMBRYO_DEVELOPMENT, LEIN_CEREBELLUM_MARKERS, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_QTL_TRANS, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, GSE10147_IL3_VS_IL3_AND_CPG_STIM_PDC_UP, GSE17721_POLYIC_VS_PAM3CSK4_6H_BMDC_UP, GSE17721_PAM3CSK4_VS_CPG_16H_BMDC_UP, GSE20715_0H_VS_48H_OZONE_LUNG_DN, GOBP_SEXUAL_REPRODUCTION

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), embryo development ending in birth or egg hatching (GO:0009792), oogenesis (GO:0048477), cell differentiation (GO:0030154)

GO Molecular Function (2): DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	1
embryo development	1
germ cell development	1
female gamete generation	1
cellular developmental process	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

530 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEBOX	LBX1	P52954	675
SEBOX	TMEM200A	Q86VY9	476
SEBOX	OOEP	A6NGQ2	459
SEBOX	SCGN	O76038	452
SEBOX	H1-8	Q8IZA3	420
SEBOX	NOBOX	O60393	418
SEBOX	MYH8	P13535	412
SEBOX	CA8	P35219	400
SEBOX	TLE6	Q9H808	389
SEBOX	MYH13	Q9UKX3	375
SEBOX	KIF13B	Q9NQT8	374
SEBOX	TARBP2	Q15633	357
SEBOX	VSTM2B	A6NLU5	357
SEBOX	BNC1	Q01954	352
SEBOX	RHOXF2B	P0C7M4	348

IntAct

0 interactions, top by confidence:

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: A1A546, A1YEV8, A1YG25, A2T711, A6NNA5, A6YP92, F1NEA7, G5EC89, L8E946, O14813, O35085, O35137, O35602, O35690, O42115, O42201, O42250, O42356, O42357, O42358, O42567, O43186, O54751, O70137, O73592, O75360, O95076, O97039, P06601, P09082, P09083, P0DMV5, P21711, P23759, P23760, P24610, P47239, P58304, P70368, P97458

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

414 predictions. Top by Δscore:

Variant	Effect	Δscore
17:28364952:CCGT:C	acceptor_gain	0.9900
17:28364953:CGTC:C	acceptor_gain	0.9900
17:28365106:C:A	donor_gain	0.9900
17:28364953:CGT:C	acceptor_gain	0.9800
17:28364956:C:CC	acceptor_gain	0.9800
17:28364964:C:CT	acceptor_gain	0.9700
17:28365105:T:TA	donor_gain	0.9700
17:28364790:CTCA:C	donor_loss	0.9600
17:28364791:TCACC:T	donor_loss	0.9600
17:28364792:CACC:C	donor_loss	0.9600
17:28364793:ACC:A	donor_loss	0.9600
17:28364794:C:CG	donor_loss	0.9600
17:28364793:A:T	donor_loss	0.9300
17:28364794:C:A	donor_loss	0.9300
17:28365115:GATCA:G	donor_loss	0.9300
17:28365116:ATCAC:A	donor_loss	0.9300
17:28365117:TCA:T	donor_loss	0.9300
17:28365118:CACCT:C	donor_loss	0.9300
17:28365119:A:G	donor_loss	0.9300
17:28365120:CC:C	donor_loss	0.9300
17:28365120:CCTG:C	donor_gain	0.9200
17:28364954:GTCTG:G	acceptor_loss	0.9100
17:28364955:TC:T	acceptor_loss	0.9100
17:28364956:C:CA	acceptor_loss	0.9100
17:28364957:T:A	acceptor_loss	0.9100
17:28364955:TCTG:T	acceptor_loss	0.9000
17:28364795:C:G	donor_loss	0.8600
17:28364795:CT:C	donor_loss	0.8600
17:28364647:AC:A	acceptor_loss	0.8500
17:28364649:CT:C	acceptor_loss	0.8500

AlphaMissense

1211 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:28364873:A:C	F38L	0.866
17:28364873:A:T	F38L	0.866
17:28364875:A:G	F38L	0.866
17:28364909:G:C	F26L	0.857
17:28364909:G:T	F26L	0.857
17:28364911:A:G	F26L	0.857
17:28364640:G:C	F67L	0.829
17:28364640:G:T	F67L	0.829
17:28364642:A:G	F67L	0.829
17:28364906:G:C	S27R	0.588
17:28364906:G:T	S27R	0.588
17:28364908:T:G	S27R	0.588

dbSNP variants (sampled 300 via entrez): RS1000063356 (17:28364109 G>C), RS1000664298 (17:28365300 G>A,T), RS1000732250 (17:28366554 C>G), RS1001202406 (17:28365581 C>T), RS1001896316 (17:28365968 C>A), RS1003918935 (17:28366020 G>T), RS1010302540 (17:28366580 G>C,T), RS1010616667 (17:28364047 G>A), RS1010856225 (17:28366930 C>T), RS1012744863 (17:28363179 T>C), RS1013459385 (17:28365635 G>A), RS1015276252 (17:28366217 G>A), RS1016227745 (17:28366022 G>A), RS1017281936 (17:28363714 C>T), RS1017861710 (17:28363553 G>A,C)

Disease associations

OMIM: gene MIM:610975 | 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
GCST002546_2	Osteoprotegerin levels	1.000000e-09

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
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Endosulfan	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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