DUXA

Summary

DUXA (double homeobox A, HGNC:32179) is a protein-coding gene on chromosome 19q13.43, encoding Double homeobox protein A (A6NLW8). Transcription factor that acts as a repressor.

Homeobox genes encode DNA-binding proteins, many of which are thought to be involved in early embryonic development. Homeobox genes encode a DNA-binding domain of 60 to 63 amino acids referred to as the homeodomain. This gene is a member of the DUXA homeobox gene family. Evidence of mRNA expression has not yet been found for this gene. Multiple, related processed pseudogenes have been found which are thought to reflect expression of this gene in the germ line or embryonic cells.

Source: NCBI Gene 503835 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_001012729

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32179
Approved symbol	DUXA
Name	double homeobox A
Location	19q13.43
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000258873
Ensembl biotype	protein_coding
OMIM	611168
Entrez	503835

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000554048

RefSeq mRNA: 1 — MANE Select: NM_001012729 NM_001012729

CCDS: CCDS33126

Canonical transcript exons

ENST00000554048 — 6 exons

Exon	Start	End
ENSE00001469905	57155267	57155372
ENSE00001469909	57158328	57158473
ENSE00001469913	57159167	57159278
ENSE00001469917	57160643	57160797
ENSE00002445070	57154021	57154482
ENSE00002471883	57167419	57167485

Expression profiles

Bgee: expression breadth broad, 20 present calls, max score 47.28.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	47.28	gold quality
left coronary artery	UBERON:0001626	42.52	gold quality
sural nerve	UBERON:0015488	41.67	silver quality
descending thoracic aorta	UBERON:0002345	41.32	gold quality
cortical plate	UBERON:0005343	40.52	silver quality
thoracic aorta	UBERON:0001515	39.43	gold quality
apex of heart	UBERON:0002098	39.20	silver quality
ascending aorta	UBERON:0001496	38.89	gold quality
right coronary artery	UBERON:0001625	37.76	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
corpus callosum	UBERON:0002336	37.09	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
tibial artery	UBERON:0007610	36.40	gold quality
popliteal artery	UBERON:0002250	36.39	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	34.99	gold quality
mucosa of stomach	UBERON:0001199	33.78	gold quality
muscle tissue	UBERON:0002385	33.34	gold quality
bone marrow	UBERON:0002371	32.98	gold quality
blood	UBERON:0000178	32.68	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
gall bladder	UBERON:0002110	31.43	silver quality
liver	UBERON:0002107	31.40	gold quality
monocyte	CL:0000576	31.39	silver quality
leukocyte	CL:0000738	31.04	silver quality
subcutaneous adipose tissue	UBERON:0002190	30.16	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.77	gold quality
placenta	UBERON:0001987	29.58	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.29

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA0884.1	DUXA	Paired-related HD factors
MA0884.2	DUXA	Paired-related HD factors

JASPAR matrix evidence (PMIDs): PMID:24278031

miRNA regulators (miRDB)

109 targeting DUXA, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514

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 A — A6NLW8 (reviewed: A6NLW8)

All UniProt accessions (1): A6NLW8

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that acts as a repressor.

Subcellular location. Nucleus.

Tissue specificity. Expressed in embryonic stem cells.

Similarity. Belongs to the paired homeobox family.

RefSeq proteins (1): NP_001012747* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000047	HTH_motif	Conserved_site
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR051306	Homeobox_regulator	Family

Pfam: PF00046

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NLW8-F1	76.04	0.52

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 25 (showing top): GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, MIR513A_3P_MIR513C_3P, MIR3606_3P, MIR548L, MIR4291, MIR1207_5P, MIR4524A_3P, MIR4703_5P, MIR6778_3P, MIR142_3P, MIR4766_3P, MIR4691_3P, MIR4693_5P

GO Biological Process (1): regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (4): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677)

GO Cellular Component (3): chromatin (GO:0000785), 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
cellular anatomical structure	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	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
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

380 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DUXA	LEUTX	A8MZ59	721
DUXA	TPRX1	Q8N7U7	705
DUXA	ARGFX	A6NJG6	693
DUXA	ZSCAN4	Q8NAM6	579
DUXA	NANOGNB	Q7Z5D8	548
DUXA	MBD3L3	A6NE82	507
DUXA	ADAT1	Q9BUB4	482
DUXA	PLAC9	Q5JTB6	449
DUXA	RHOXF2B	P0C7M4	448
DUXA	ANHX	E9PGG2	433
DUXA	PRAMEF5	Q5TYX0	432
DUXA	ANXA11	P50995	416
DUXA	TERF2IP	Q9NYB0	410
DUXA	PRAMEF1	O95521	398
DUXA	DPRX	A6NFQ7	396
DUXA	MBD3L2	Q8NHZ7	396

IntAct

0 interactions, top by confidence:

BioGRID (11): SMARCA5 (Proximity Label-MS), TOP2A (Proximity Label-MS), SMARCA1 (Proximity Label-MS), MKI67 (Proximity Label-MS), BPTF (Proximity Label-MS), MDC1 (Proximity Label-MS), ZNF512B (Proximity Label-MS), ARID3A (Proximity Label-MS), BAZ1A (Proximity Label-MS), CHD7 (Proximity Label-MS), BAZ1B (Proximity Label-MS)

ESM2 similar proteins: A0A1W2PPF3, A1YGA2, A1YGI6, A2T777, A6NLW8, E9Q3T6, G5E8B9, O43167, O88436, O97670, P09075, P09076, P09532, P09634, P10178, P14150, P14839, P18863, P18866, P20269, P21523, P23459, P31261, P31538, P49925, P50209, P50210, P51783, P87393, Q05007, Q05095, Q28598, Q28601, Q28J15, Q3B725, Q3UL53, Q61658, Q6P2A1, Q804R0, Q80X44

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

666 predictions. Top by Δscore:

Variant	Effect	Δscore
19:57154480:CAC:C	acceptor_gain	1.0000
19:57154483:C:CC	acceptor_gain	1.0000
19:57155368:CAAAT:C	acceptor_gain	1.0000
19:57155373:C:CC	acceptor_gain	1.0000
19:57158325:CACTT:C	donor_loss	1.0000
19:57158326:A:AC	donor_gain	1.0000
19:57158326:ACT:A	donor_loss	1.0000
19:57158327:C:CT	donor_gain	1.0000
19:57158470:CTAC:C	acceptor_gain	1.0000
19:57158474:C:CC	acceptor_gain	1.0000
19:57158474:CT:C	acceptor_loss	1.0000
19:57159165:A:AC	donor_gain	1.0000
19:57159166:C:CC	donor_gain	1.0000
19:57159168:TTGAA:T	donor_gain	1.0000
19:57160638:CTTA:C	donor_loss	1.0000
19:57160639:TTAC:T	donor_loss	1.0000
19:57160640:TACCT:T	donor_loss	1.0000
19:57160641:A:T	donor_loss	1.0000
19:57160642:C:CT	donor_loss	1.0000
19:57160793:CATCT:C	acceptor_gain	1.0000
19:57160794:ATCT:A	acceptor_gain	1.0000
19:57160796:CT:C	acceptor_gain	1.0000
19:57160797:TC:T	acceptor_loss	1.0000
19:57160798:C:CC	acceptor_gain	1.0000
19:57160798:C:CG	acceptor_loss	1.0000
19:57160799:T:A	acceptor_loss	1.0000
19:57160809:T:TC	acceptor_gain	1.0000
19:57155372:TC:T	acceptor_loss	0.9900
19:57155373:CT:C	acceptor_loss	0.9900
19:57155374:T:G	acceptor_loss	0.9900

AlphaMissense

1341 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:57155364:G:C	F149L	0.998
19:57155364:G:T	F149L	0.998
19:57155366:A:G	F149L	0.998
19:57158406:A:C	F120L	0.997
19:57158406:A:T	F120L	0.997
19:57158408:A:G	F120L	0.997
19:57159270:A:C	F63L	0.997
19:57159270:A:T	F63L	0.997
19:57159272:A:G	F63L	0.997
19:57155352:T:A	R153S	0.995
19:57155352:T:G	R153S	0.995
19:57155365:A:G	F149S	0.995
19:57158332:A:T	V145D	0.995
19:57159258:T:A	R67S	0.995
19:57159258:T:G	R67S	0.995
19:57155369:A:G	W148R	0.994
19:57155369:A:T	W148R	0.994
19:57158373:T:A	R131S	0.994
19:57158373:T:G	R131S	0.994
19:57159271:A:G	F63S	0.994
19:57159275:A:G	W62R	0.994
19:57159275:A:T	W62R	0.994
19:57160721:G:C	F34L	0.994
19:57160721:G:T	F34L	0.994
19:57160723:A:G	F34L	0.994
19:57155353:C:G	R153T	0.993
19:57158362:G:T	A135D	0.993
19:57158419:A:G	L116P	0.991
19:57158363:C:G	A135P	0.990
19:57155356:C:G	R152P	0.989

dbSNP variants (sampled 300 via entrez): RS1000149076 (19:57153750 C>T), RS1000158882 (19:57153978 G>A), RS1000284050 (19:57169203 C>T), RS1000300830 (19:57159789 A>T), RS1000491347 (19:57163733 T>G), RS1000580912 (19:57168995 C>G,T), RS1000790728 (19:57158610 G>T), RS1000982260 (19:57156141 G>T), RS1000992140 (19:57155789 C>T), RS1001285319 (19:57166291 A>G,T), RS1001311034 (19:57159750 C>A,T), RS1001631644 (19:57163465 A>G), RS1001787486 (19:57168453 T>C), RS1002059636 (19:57157257 A>C,T), RS1002709906 (19:57164612 G>C,T)

Disease associations

OMIM: gene MIM:611168 | 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
GCST001144_10	Dupuytren’s disease	7.000000e-14
GCST004858_25	Dupuytren’s disease	2.000000e-17
GCST010396_251	Gut microbiota (bacterial taxa, hurdle binary method)	2.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004229	Dupuytren Contracture
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation	1
ferrous chloride	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Cisplatin	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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