DUXB

Summary

DUXB (double homeobox B, HGNC:33345) is a protein-coding gene on chromosome 16q23.1, encoding Double homeobox protein B (A0A1W2PPF3).

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 transcription by RNA polymerase II. Predicted to be located in nucleoplasm. Predicted to be active in nucleus.

Source: NCBI Gene 100033411 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 5 total
• MANE Select transcript: NM_001351307

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33345
Approved symbol	DUXB
Name	double homeobox B
Location	16q23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000282757
Ensembl biotype	protein_coding
OMIM	618698
Entrez	100033411

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000633875

RefSeq mRNA: 2 — MANE Select: NM_001351307 NM_001351307, NM_001351309

CCDS: CCDS86542

Canonical transcript exons

ENST00000633875 — 5 exons

Exon	Start	End
ENSE00003776065	75695961	75696115
ENSE00003777418	75693893	75694525
ENSE00003783668	75700015	75700169
ENSE00003783937	75696838	75696943
ENSE00003811083	75701394	75701461

Expression profiles

Bgee: expression breadth broad, 55 present calls, max score 63.11.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0564 / max 19.1172, expressed in 22 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158185	0.0564	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	63.11	gold quality
corpus callosum	UBERON:0002336	58.16	gold quality
sural nerve	UBERON:0015488	54.05	silver quality
bone marrow cell	CL:0002092	47.67	gold quality
right lobe of thyroid gland	UBERON:0001119	46.40	gold quality
colonic epithelium	UBERON:0000397	45.88	silver quality
left lobe of thyroid gland	UBERON:0001120	45.19	gold quality
thyroid gland	UBERON:0002046	45.12	gold quality
blood	UBERON:0000178	44.95	gold quality
skeletal muscle tissue	UBERON:0001134	44.66	gold quality
right lung	UBERON:0002167	43.19	silver quality
tonsil	UBERON:0002372	42.78	gold quality
apex of heart	UBERON:0002098	41.42	silver quality
lower esophagus mucosa	UBERON:0035834	40.95	silver quality
muscle tissue	UBERON:0002385	40.57	gold quality
kidney	UBERON:0002113	40.28	silver quality
vagina	UBERON:0000996	39.95	silver quality
uterine cervix	UBERON:0000002	39.74	silver quality
tibial nerve	UBERON:0001323	39.55	silver quality
monocyte	CL:0000576	39.25	silver quality
ovary	UBERON:0000992	39.02	silver quality
muscle of leg	UBERON:0001383	38.97	silver quality
right ovary	UBERON:0002118	38.87	silver quality
left ovary	UBERON:0002119	38.60	silver quality
gastrocnemius	UBERON:0001388	38.38	silver quality
leukocyte	CL:0000738	38.20	silver quality
skin of leg	UBERON:0001511	37.95	silver quality
endometrium	UBERON:0001295	37.80	gold quality
spleen	UBERON:0002106	37.62	silver quality
ectocervix	UBERON:0012249	37.18	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.45

Regulation

Is transcription factor: no

Cross-species orthologs

0 orthologs

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

Double homeobox protein B — A0A1W2PPF3 (reviewed: A0A1W2PPF3)

All UniProt accessions (1): A0A1W2PPF3

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Similarity. Belongs to the paired homeobox family.

RefSeq proteins (2): NP_001338236, NP_001338238 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR051306	Homeobox_regulator	Family

Pfam: PF00046

UniProt features (8 total): sequence conflict 3, DNA-binding region 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0A1W2PPF3-F1	58.91	0.22

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9819196	Zygotic genome activation (ZGA)

MSigDB gene sets: 8 (showing top): MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, chr16q23, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, GOMF_DNA_BINDING_TRANSCRIPTION_FACTOR_ACTIVITY, REACTOME_MATERNAL_TO_ZYGOTIC_TRANSITION_MZT, REACTOME_ZYGOTIC_GENOME_ACTIVATION_ZGA, GOMF_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), 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): nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Maternal to zygotic transition (MZT)	1

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
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
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

306 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DUXB	DPRX	A6NFQ7	808
DUXB	TPRX1	Q8N7U7	768
DUXB	ARGFX	A6NJG6	730
DUXB	LEUTX	A8MZ59	727
DUXB	NANOGNB	Q7Z5D8	609
DUXB	PLAC9	Q5JTB6	608
DUXB	ADAT1	Q9BUB4	561
DUXB	HESX1	Q9UBX0	529
DUXB	ANHX	E9PGG2	513
DUXB	MBD3L3	A6NE82	503
DUXB	RHOXF2B	P0C7M4	490
DUXB	MBD3L5	A6NJ08	471
DUXB	MBD3L2	Q8NHZ7	471
DUXB	TERF2IP	Q9NYB0	460
DUXB	ZSCAN4	Q8NAM6	451

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A1W2PPF3, A0A1W2PPM1, A1A546, A1YGI6, A2T763, A5YC49, A6NFQ7, A6NJG6, D2HQI1, G3X9P6, O42173, O57374, P09632, P0C7M4, P10242, P14837, P17278, P31272, P31538, Q1KKS8, Q28ET4, Q28G02, Q3LTE0, Q3UT54, Q4JM65, Q4KL20, Q5TM83, Q5TM84, Q5W1J6, Q68EH7, Q6NSW7, Q80Z64, Q8IUE1, Q8JH55, Q8JIT7, Q8JJ26, Q8MIB7, Q8MIB8, Q8MIE9, Q91685

Diamond homologs: A0A1W2PPF3, A1YEY5, A1YFI3, A1YG57, A2T733, A2T7P4, A6NLW8, A6NNA5, F1NEA7, G5EBU4, G5EDS1, O18381, O35137, O35160, O42250, O43186, O43316, O43812, O54751, O70137, O73917, O75360, O75364, O95076, P09088, P0CJ85, P0CJ86, P0CJ87, P0CJ88, P0CJ89, P0CJ90, P21711, P22810, P26367, P26630, P29454, P32242, P32243, P34764, P34765

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

232 predictions. Top by Δscore:

Variant	Effect	Δscore
16:75694523:CAT:C	acceptor_gain	0.9900
16:75695959:A:AC	donor_gain	0.9900
16:75695960:C:CC	donor_gain	0.9900
16:75696112:TATT:T	acceptor_gain	0.9900
16:75696114:TT:T	acceptor_gain	0.9900
16:75696116:C:CC	acceptor_gain	0.9900
16:75700009:GCCTA:G	donor_loss	0.9900
16:75700010:CCTAC:C	donor_loss	0.9900
16:75700011:CTA:C	donor_loss	0.9900
16:75700013:ACCT:A	donor_loss	0.9900
16:75700014:C:CA	donor_loss	0.9900
16:75694521:CACAT:C	acceptor_gain	0.9800
16:75694526:C:CC	acceptor_gain	0.9800
16:75696115:TC:T	acceptor_loss	0.9800
16:75696116:C:CA	acceptor_loss	0.9800
16:75696117:T:G	acceptor_loss	0.9800
16:75694524:ATC:A	acceptor_loss	0.9700
16:75694525:TC:T	acceptor_loss	0.9700
16:75694526:C:A	acceptor_loss	0.9700
16:75695954:AACTT:A	donor_loss	0.9700
16:75695955:ACTTA:A	donor_loss	0.9700
16:75695956:CT:C	donor_loss	0.9700
16:75695957:TTA:T	donor_loss	0.9700
16:75695958:TACTT:T	donor_loss	0.9700
16:75696111:GTATT:G	acceptor_gain	0.9700
16:75696942:ACCTA:A	acceptor_loss	0.9500
16:75696943:CCT:C	acceptor_loss	0.9500
16:75695953:GAACT:G	donor_loss	0.9400
16:75696939:CAAAC:C	acceptor_gain	0.9300
16:75694522:ACATC:A	acceptor_gain	0.9200

AlphaMissense

2299 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:75696935:A:C	F63L	0.992
16:75696935:A:T	F63L	0.992
16:75696937:A:G	F63L	0.992
16:75694517:A:C	F150L	0.990
16:75694517:A:T	F150L	0.990
16:75694519:A:G	F150L	0.990
16:75700093:A:C	F34L	0.985
16:75700093:A:T	F34L	0.985
16:75700095:A:G	F34L	0.985
16:75700050:C:G	A49P	0.983
16:75700106:A:T	L30H	0.981
16:75696936:A:G	F63S	0.980
16:75700049:G:T	A49D	0.978
16:75700106:A:G	L30P	0.974
16:75696940:A:G	W62R	0.973
16:75696940:A:T	W62R	0.973
16:75696039:A:C	F121L	0.971
16:75696039:A:T	F121L	0.971
16:75696041:A:G	F121L	0.971
16:75700117:T:A	Q26H	0.970
16:75700117:T:G	Q26H	0.970
16:75700052:A:G	L48P	0.968
16:75700060:T:A	R45S	0.968
16:75700060:T:G	R45S	0.968
16:75695996:C:G	A136P	0.963
16:75694518:A:G	F150S	0.961
16:75700049:G:A	A49V	0.961
16:75696923:T:A	R67S	0.955
16:75696923:T:G	R67S	0.955
16:75700094:A:G	F34S	0.954

dbSNP variants (sampled 300 via entrez): RS1000071723 (16:75700275 C>T), RS1000153072 (16:75700665 C>A,T), RS1000274471 (16:75700828 T>G), RS1000292185 (16:75697904 G>A,T), RS1000873441 (16:75699745 T>G), RS1000929917 (16:75694367 G>A,C), RS1001556514 (16:75699568 T>C), RS1002004937 (16:75703121 G>A), RS1002018632 (16:75696617 T>C,G), RS1002116340 (16:75701772 G>A), RS1002178652 (16:75701501 G>A,C), RS1002279638 (16:75698491 A>G), RS1002369433 (16:75696864 T>C), RS1002634837 (16:75694203 A>C,G), RS1002881335 (16:75697234 C>G,T)

Disease associations

OMIM: gene MIM:618698 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

1 total (human), top 1 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
abrine	increases expression	1

Clinical trials (associated diseases)

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