DACT3

Summary

DACT3 (dishevelled binding antagonist of beta catenin 3, HGNC:30745) is a protein-coding gene on chromosome 19q13.32, encoding Dapper homolog 3 (Q96B18). May be involved in regulation of intracellular signaling pathways during development.

Predicted to enable delta-catenin binding activity; protein kinase A binding activity; and protein kinase C binding activity. Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of cell growth. Predicted to be active in cytoplasm.

Source: NCBI Gene 147906 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Clinical variants (ClinVar): 119 total
• GTEx eGene: eQTL in 9 tissues, sQTL in 4 (q < 0.05)
• Constraint (gnomAD): pLI 0.65 (intermediate), LOEUF 0.70 (unconstrained)
• MANE Select transcript: NM_145056
• Notable: 119 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30745
Approved symbol	DACT3
Name	dishevelled binding antagonist of beta catenin 3
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	MGC15476, DAPPER3
Ensembl gene	ENSG00000197380
Ensembl biotype	protein_coding
OMIM	611112
Entrez	147906

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

MANE Select: ENST00000391916

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 5: 1

ENST00000391916, ENST00000300875, ENST00000410105, ENST00001032978, ENST00001134391

RefSeq mRNA: 2 — MANE Select: NM_145056 NM_001301046, NM_145056

CCDS: CCDS12688, CCDS74402

Canonical transcript exons

ENST00000391916 — 4 exons

Exon	Start	End
ENSE00003540152	46647551	46649872
ENSE00003541849	46652660	46652812
ENSE00003690754	46652979	46653075
ENSE00003849607	46660816	46661182

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 96.93.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4415 / max 42.6396, expressed in 526 samples.

Highest expression (Bgee): popliteal artery, tibial artery, aorta, cardiac muscle of right atrium, inferior vagus X ganglion.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DACT3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 9 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

13 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Spleen	eqtl	2.5e-15	+0.43	19:46650822:G:T
Liver	eqtl	1.6e-04	+0.26	19:46650822:G:T
Nerve Tibial	eqtl	1.4e-02	-0.15	19:45920952:A:G
Colon Sigmoid	eqtl	1.7e-02	-0.13	19:46186505:T:C
Breast Mammary Tissue	eqtl	1.8e-02	-0.24	19:46436230:G:A
Esophagus Muscularis	eqtl	1.9e-02	-0.10	19:46779373:A:G
Adipose Visceral Omentum	eqtl	2.0e-02	-0.11	19:46563387:A:G
Artery Tibial	sqtl	2.1e-02	+0.26	19:46651176:A:G
Testis	sqtl	2.2e-02	-0.61	19:46660517:G:A
Pituitary	eqtl	2.6e-02	-0.48	19:47069018:G:C
Small Intestine Terminal Ileum	sqtl	3.2e-02	-1.63	19:45833847:C:T
Artery Aorta	sqtl	3.2e-02	-1.11	19:46639525:G:C
Artery Tibial	eqtl	4.1e-02	-0.10	19:45880957:G:T

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
181664	1.4226	521
181662	0.0189	11

Top tissues by expression

showing 100 of 251 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
popliteal artery	UBERON:0002250	96.93	gold quality
tibial artery	UBERON:0007610	96.93	gold quality
aorta	UBERON:0000947	96.33	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.18	gold quality
inferior vagus X ganglion	UBERON:0005363	96.08	gold quality
ascending aorta	UBERON:0001496	95.61	gold quality
thoracic aorta	UBERON:0001515	95.57	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.93	gold quality
descending thoracic aorta	UBERON:0002345	94.92	gold quality
right coronary artery	UBERON:0001625	94.84	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.69	gold quality
medial globus pallidus	UBERON:0002477	94.62	gold quality
globus pallidus	UBERON:0001875	94.59	gold quality
anterior cingulate cortex	UBERON:0009835	94.51	gold quality
subthalamic nucleus	UBERON:0001906	94.49	gold quality
ventral tegmental area	UBERON:0002691	94.23	gold quality
parietal lobe	UBERON:0001872	94.14	gold quality
saphenous vein	UBERON:0007318	94.08	gold quality
prefrontal cortex	UBERON:0000451	93.95	gold quality
postcentral gyrus	UBERON:0002581	93.85	gold quality
lateral globus pallidus	UBERON:0002476	93.67	gold quality
amygdala	UBERON:0001876	93.65	gold quality
Ammon’s horn	UBERON:0001954	93.36	gold quality
superior vestibular nucleus	UBERON:0007227	93.29	gold quality
frontal cortex	UBERON:0001870	93.20	gold quality
temporal lobe	UBERON:0001871	93.20	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.10	gold quality
midbrain	UBERON:0001891	93.07	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.99	gold quality
substantia nigra	UBERON:0002038	92.96	gold quality
medulla oblongata	UBERON:0001896	92.89	gold quality
spinal cord	UBERON:0002240	92.83	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.82	gold quality
entorhinal cortex	UBERON:0002728	92.80	gold quality
neocortex	UBERON:0001950	92.78	gold quality
superior frontal gyrus	UBERON:0002661	92.78	gold quality
endothelial cell	CL:0000115	92.74	silver quality
right frontal lobe	UBERON:0002810	92.64	gold quality
cerebral cortex	UBERON:0000956	92.61	gold quality
coronary artery	UBERON:0001621	92.17	gold quality
left coronary artery	UBERON:0001626	92.16	gold quality
mucosa of stomach	UBERON:0001199	92.10	gold quality
hypothalamus	UBERON:0001898	91.83	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.62	gold quality
body of uterus	UBERON:0009853	91.34	gold quality
left uterine tube	UBERON:0001303	91.13	gold quality
substantia nigra pars compacta	UBERON:0001965	91.11	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.11	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.09	gold quality
lower esophagus	UBERON:0013473	91.02	gold quality
smooth muscle tissue	UBERON:0001135	90.80	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.45	gold quality
substantia nigra pars reticulata	UBERON:0001966	90.44	gold quality
vena cava	UBERON:0004087	90.21	gold quality
left ventricle myocardium	UBERON:0006566	90.15	silver quality
myometrium	UBERON:0001296	90.01	gold quality
putamen	UBERON:0001874	89.94	gold quality
pons	UBERON:0000988	89.89	gold quality
cauda epididymis	UBERON:0004360	89.69	gold quality
forebrain	UBERON:0001890	89.62	gold quality
nucleus accumbens	UBERON:0001882	89.61	gold quality
cardiac atrium	UBERON:0002081	89.16	gold quality
right atrium auricular region	UBERON:0006631	88.88	gold quality
urethra	UBERON:0000057	88.79	gold quality
occipital lobe	UBERON:0002021	88.77	gold quality
caudate nucleus	UBERON:0001873	88.39	gold quality
brain	UBERON:0000955	88.23	gold quality
apex of heart	UBERON:0002098	87.30	gold quality
middle temporal gyrus	UBERON:0002771	86.86	silver quality
primary visual cortex	UBERON:0002436	86.77	gold quality
sperm	CL:0000019	86.68	silver quality
cortical plate	UBERON:0005343	85.79	gold quality
tibialis anterior	UBERON:0001385	85.58	silver quality
endocervix	UBERON:0000458	85.57	gold quality
cerebellar vermis	UBERON:0004720	85.06	gold quality
fundus of stomach	UBERON:0001160	84.87	gold quality
urinary bladder	UBERON:0001255	84.51	gold quality
heart	UBERON:0000948	84.31	gold quality
cardia of stomach	UBERON:0001162	83.03	gold quality
pericardium	UBERON:0002407	82.98	gold quality
myocardium	UBERON:0002349	82.50	silver quality
epididymis	UBERON:0001301	82.38	gold quality
right ovary	UBERON:0002118	82.36	gold quality
seminal vesicle	UBERON:0000998	82.07	gold quality
uterine cervix	UBERON:0000002	81.94	gold quality
nipple	UBERON:0002030	81.55	gold quality
Brodmann (1909) area 23	UBERON:0013554	81.43	gold quality
heart left ventricle	UBERON:0002084	81.33	gold quality
cardiac ventricle	UBERON:0002082	81.29	gold quality
prostate gland	UBERON:0002367	81.18	gold quality
ileal mucosa	UBERON:0000331	81.12	gold quality
ectocervix	UBERON:0012249	80.85	gold quality
pylorus	UBERON:0001166	80.84	gold quality
adult organism	UBERON:0007023	80.69	gold quality
right testis	UBERON:0004534	80.60	gold quality
heart right ventricle	UBERON:0002080	80.43	silver quality
left testis	UBERON:0004533	80.38	gold quality
colon	UBERON:0001155	80.04	gold quality
left ovary	UBERON:0002119	79.83	gold quality
large intestine	UBERON:0000059	79.66	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.96
E-ENAD-17	no	44.55
E-GEOD-70580	no	17.87
E-ENAD-27	no	3.79

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Hippocampus	tissue	104.7	low
Postcentral gyrus	tissue	96.0
Locus coeruleus	tissue	78.9
Frontal cortex	tissue	74.6
Prefrontal cortex	tissue	70.7
Cerebral cortex	tissue	70.7	low
Motor cortex	tissue	70.0
Insular cortex	tissue	62.3
Hippocampal formation	tissue	60.7
Entorhinal cortex	tissue	60.7
Somatosensory cortex	tissue	60.0
Temporal cortex	tissue	59.8
Nucleus accumbens	tissue	59.0
Retrosplenial and cingulate cortex	tissue	56.9
Retrosplenial cortex	tissue	56.4
Occipital cortex	tissue	55.8
Corpus callosum	tissue	53.9
Thalamus	tissue	48.1
Amygdala	tissue	46.2
Midbrain	tissue	44.5
Pons	tissue	39.5
Superior colliculi	tissue	39.0
Medulla oblongata	tissue	38.3
Caudate putamen	tissue	38.2
Spinal cord	tissue	36.9
Ventral forebrain	tissue	36.2
Substantia nigra	tissue	35.3
Olfactory bulb	tissue	33.2
Hypothalamus	tissue	31.6
Putamen	tissue	31.0
Septum	tissue	30.3
Smooth muscle	tissue	29.5	not detected
Basal ganglia	tissue	26.4	low
Periaqueductal gray	tissue	25.4
Seminal vesicle	tissue	23.1	medium
Endometrium 1	tissue	20.3	not detected
Choroid plexus	tissue	16.7
Vagina	tissue	14.8	low
Epididymis	tissue	13.5	medium
Ovary	tissue	10.8	not detected
Prostate	tissue	10.6	not detected
Heart muscle	tissue	10.5	not detected
Cervix	tissue	9.4	low
Cerebellum	tissue	9.3	not detected
Urinary bladder	tissue	9.2	not detected
Fallopian tube	tissue	7.9	not detected
Colon	tissue	7.4	low
Esophagus	tissue	6.9	low
Gallbladder	tissue	6.8	low
Rectum	tissue	6.3	medium
Appendix	tissue	5.6	low
Retina	tissue	5.4
Testis	tissue	5.2	not detected
Lung	tissue	5.0	low
Adipose tissue	tissue	4.6	not detected
Spleen	tissue	4.5	not detected
Small intestine	tissue	4.2	low
Pituitary gland	tissue	3.8
Duodenum	tissue	3.6	low
Kidney	tissue	3.2	high

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Parieto-temporal junction (white matter) (126.7), Posterior cingulate cortex (122.6), Occipital cortex (white matter) (119.5), Blood vessel (119.2), Temporal white matter (114.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EZH2, NKX2-5

miRNA regulators (miRDB)

Targeting DACT3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 55 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4685-5P	99.25	65.99	1563

Functional genomics

gnomAD constraint: pLI 0.651, LOEUF 0.703, missense Z -3.19 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000391916 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
19:46,648,485–46,649,686	656 / 601.8	1.09	no
19:46,649,687–46,661,064	252 / 325.6	0.77	no

Literature-anchored findings (GeneRIF, showing 3)

• Epigenetic repression of DACT3 leads to aberrant Wnt-beta-catenin signaling in colorectal cancer cells. (PMID:18538736)
• Butyrate mediates anti-inflammatory effects of Faecalibacterium prausnitzii in intestinal epithelial cells through Dact3. (PMID:33054518)
• DACT3 has a tumor-inhibiting role in acute myeloid leukemia via the suppression of Wnt/beta-catenin signaling by DVL2. (PMID:35187752)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dact3a	ENSDARG00000087910
mus_musculus	Dact3	ENSMUSG00000078794
rattus_norvegicus	Dact3	ENSRNOG00000052256

Paralogs (2): DACT2 (ENSG00000164488), DACT1 (ENSG00000165617)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:3654828) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 9 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased body weight	1
postnatal growth retardation	1
abnormal kidney morphology	1
renal interstitial fibrosis	1
increased lean body mass	1
increased susceptibility to injury	1
improved glucose tolerance	1
decreased circulating serum albumin level	1
abnormal renal tubule epithelium morphology	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Xenopus tropicalis	Q66KC9	93.2%	Diamond
Xenopus laevis	Q8QG92	93.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
DACT3-AS1	ncRNA	100506068
PRKD2	protein-coding	25865
STRN4	protein-coding	29888
FKRP	protein-coding	79147
MIR320E	ncRNA	100422913
PTGIR	protein-coding	5739
CALM3	protein-coding	808
GNG8	protein-coding	94235
SLC1A5	protein-coding	6510
PNMA8B	protein-coding	57469

Protein

Protein identifiers

Dapper homolog 3 — Q96B18 (reviewed: Q96B18)

Alternative names: Antagonist of beta-catenin Dapper homolog 3, Arginine-rich region 1 protein, Dapper antagonist of catenin 3

All UniProt accessions (3): A0A0C4DFP1, G5E9H6, Q96B18

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in regulation of intracellular signaling pathways during development. Specifically thought to play a role in canonical and/or non-canonical Wnt signaling pathways through interaction with DSH (Dishevelled) family proteins.

Subunit / interactions. Can form homodimers and heterodimers with DACT1 or DACT3. Interacts with CSNK1D, PKA catalytic subunit, PKC-type kinase, DVL1, DVL3, VANGL1, VANGL2 and CTNND1. Interacts with DVL2.

Domain organisation. The C-terminal PDZ-binding motif may mediate interaction with the PDZ domains of DSH (Dishevelled) family proteins.

Similarity. Belongs to the dapper family.

RefSeq proteins (2): NP_001287975, NP_659493* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024843	Dapper	Family

Pfam: PF15268

UniProt features (19 total): compositionally biased region 8, modified residue 6, region of interest 2, chain 1, coiled-coil region 1, short sequence motif 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96B18-F1	53.51	0.07

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles; nucleoplasm

Antibody reliability (HPA): IH approved · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6)

Type	Positions
Phosphoserine	6, 165, 239, 426, 478
Omega-n-methylarginine	258

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 89 (showing top): BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_GROWTH, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_TO_MESENCHYMAL_TRANSITION, CHANDRAN_METASTASIS_DN, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, SRF_C, GOBP_MESENCHYMAL_CELL_DIFFERENTIATION, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, VDR_Q3, GOBP_MESENCHYME_DEVELOPMENT, CDPCR3HD_01

GO Biological Process (4): Wnt signaling pathway (GO:0016055), negative regulation of Wnt signaling pathway (GO:0030178), negative regulation of cell growth (GO:0030308), negative regulation of canonical Wnt signaling pathway (GO:0090090)

GO Molecular Function (5): protein kinase C binding (GO:0005080), identical protein binding (GO:0042802), protein kinase A binding (GO:0051018), delta-catenin binding (GO:0070097), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

16 GO namespaces:

Category	Terms
protein binding	3
cell surface receptor signaling pathway	1
negative regulation of signal transduction	1
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
protein kinase binding	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of Wnt signaling pathway	BP	direct assay
negative regulation of canonical Wnt signaling pathway	BP	direct assay
negative regulation of cell growth	BP	direct assay

Protein interactions and networks

STRING

showing 15 of 346 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DACT3	DACT2	Q5SW24	924
DACT3	CTNNB1	P35222	581
DACT3	CDK13	Q14004	416
DACT3	DACT1	Q9NYF0	409
DACT3	SNX8	Q9Y5X2	370
DACT3	DUSP11	O75319	370
DACT3	WDFY3	Q8IZQ1	368
DACT3	MEX3B	Q6ZN04	360
DACT3	DVL1	O14640	356
DACT3	C1QL1	O75973	345
DACT3	GFOD1	Q9NXC2	336
DACT3	BLCAP	P62952	334
DACT3	DVL2	O14641	323
DACT3	PALM3	A6NDB9	311
DACT3	AIRE	O43918	291

IntAct

Human interaction partners of DACT3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

Partner	Interaction type	MIscore	Records
GALE	association	0.350	1
PKD2	association	0.350	1
CBY1	physical association	0.000	1
GIGYF1	physical association	0.000	1
KCTD3	physical association	0.000	1
KIF13B	physical association	0.000	1
KSR1	physical association	0.000	1
ZBTB21	physical association	0.000	1

BioGRID (22 interactions; top human partners by supporting records): SESTD1 (Two-hybrid; 2 records), CBY1 (Affinity Capture-MS), DAK (Affinity Capture-MS), DDX39A (Affinity Capture-RNA), DDX58 (Affinity Capture-RNA), DUSP3 (Affinity Capture-MS), GALE (Affinity Capture-MS), GIGYF1 (Affinity Capture-MS), IFT22 (Affinity Capture-MS), KCTD3 (Affinity Capture-MS), KIF13B (Affinity Capture-MS), KSR1 (Affinity Capture-MS), PKD2 (Affinity Capture-MS), POLI (Reconstituted Complex), RELA (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
EZH2	“down-regulates quantity by repression”	DACT3	“transcriptional regulation”

Disease & clinical

Genetic variants

Variant evidence for DACT3: 119 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	117
Likely benign	1
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 247):

Position(s)	Effect	Δscore	Sites
19:46652813–46652814	acceptor_loss	1.0000	6
19:46652996	donor_gain	1.0000
19:46653084	acceptor_gain	1.0000
19:46660814–46660815	donor_loss	1.0000	5
19:46649889	acceptor_gain	0.9900
19:46652658–46652659	donor_loss	0.9900	6
19:46652822–46652823	acceptor_gain	0.9900	2
19:46652977–46652978	donor_loss	0.9900	5
19:46653076–46653077	acceptor_loss	0.9900	6
19:46653084	acceptor_gain	0.9900

AlphaMissense

1,293 missense substitutions predicted likely pathogenic (of 3,905 scored), across 324 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M626	9	0.996	1.000
F618	8	0.997	1.000
H609	8	0.992	0.999
F602	8	0.978	0.997
D521	8	0.967	0.991
D566	8	0.963	0.991
F7	8	0.960	0.996
F5	8	0.957	0.995
S551	8	0.895	0.997
S553	8	0.875	0.994
S520	8	0.868	0.989
H31	8	0.857	0.991
H222	8	0.761	0.909
I615	7	0.997	1.000
I605	7	0.996	1.000
W575	7	0.988	0.999
K612	7	0.986	1.000
K614	7	0.986	0.999
K606	7	0.984	1.000
W476	7	0.982	0.997

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Glioblastoma Multiforme)

Disease associations

OMIM: gene MIM:611112 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	increases expression	3
Tobacco Smoke Pollution	increases expression	2
Tretinoin	increases expression	2
Valproic Acid	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
OTX015	increases expression	1
FR900359	decreases phosphorylation	1
mivebresib	increases expression	1
propionaldehyde	increases expression	1
trichostatin A	affects acetylation, affects cotreatment, affects expression, affects methylation	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
beta-methylcholine	affects expression	1
pentanal	increases expression	1
3-deazaneplanocin	affects acetylation, affects cotreatment, affects methylation, affects expression	1
abrine	increases expression	1
licochalcone B	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Aldehydes	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Calcitriol	decreases expression	1
Cisplatin	increases expression	1
Dexamethasone	decreases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects cotreatment, decreases expression	1
Lead	affects expression	1
Lipopolysaccharides	increases expression, affects response to substance	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 204 trials:

NCT	Phase	Status	Title
NCT05657860	Phase 4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	Phase 4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	Phase 4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	Phase 4	RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	Phase 3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	Phase 2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	Phase 2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	Phase 2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	Phase 2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	Phase 1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	Phase 1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	Phase 1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	Phase 1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	Phase 1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	Phase 2/3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	Phase 1/2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	Early Phase 1	TERMINATED	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders
NCT02862808	Not specified	COMPLETED	Molecular Diagnosis of Syndromic or Isolated Severe Intellectual Disability Using Whole Exome Sequencing : a Pilot Study
NCT02881333	Not specified	UNKNOWN	Various Type of Genetic Events in Patients With Intellectual Disability
NCT02889068	Not specified	COMPLETED	Targeted Next Generation Sequencing and Intellectual Disability
NCT02914951	Not specified	ENROLLING_BY_INVITATION	Cognitive-Behavioral Therapy for Irritability in Children With Autism Spectrum Disorder and Intellectual Disability
NCT02919826	Not specified	COMPLETED	Dialectical Behaviour Group Therapy for Adults With Intellectual Disabilities
NCT02934854	Not specified	WITHDRAWN	Biomarker for Creatine Deficiency Syndromes (BioCDS)
NCT03033797	Not specified	UNKNOWN	Augmentative and Alternative Communication in Games With Virtual Reality in Intellectual Disabilities
NCT03135236	Not specified	COMPLETED	Parents as the Primary Sexuality Educators for Their Young Adults With Down Syndrome
NCT03139760	Not specified	COMPLETED	POWERSforID: A Telehealth Weight Management System for Adults With Intellectual Disability
NCT03203226	Not specified	COMPLETED	The Feldenkrais Method for People With Intellectual Disability
NCT03212092	Not specified	COMPLETED	Reducing Aggression Among People With an Intellectual Disability
NCT03218462	Not specified	COMPLETED	Effect of Sensory Adapted Dental Environment on Dental Anxiety of Children With Intellectual and Developmental Disabilities
NCT03234231	Not specified	UNKNOWN	Supervised Brushing Programme for Intellectual Disabled Students
NCT03348124	Not specified	UNKNOWN	Prevention Among Young People With Intellectual Disability
NCT03424772	Not specified	UNKNOWN	Whole Genome Sequencing in the Detection of Rare Undiagnosed Genetic Diseases in Children in China
NCT03426059	Not specified	COMPLETED	Mapping the Phenotype in Adults With Phelan-McDermid Syndrome
NCT03492060	Not specified	RECRUITING	Longitudinal Study of Neurogenetic Disorders
NCT03501914	Not specified	COMPLETED	A Pilot Trial of Mindfulness Based Intervention Program for People With Intellectual Disabilities in a Low Income Setting
NCT03522337	Not specified	COMPLETED	Oral Health Promotion Among Preschool Children With Special Needs
NCT03525431	Not specified	COMPLETED	Clinical Utility of Pediatric Whole Exome Sequencing