MTA3

Summary

MTA3 (metastasis associated 1 family member 3, HGNC:23784) is a protein-coding gene on chromosome 2p21, encoding Metastasis-associated protein MTA3 (Q9BTC8). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin.

Predicted to enable histone deacetylase binding activity; transcription coactivator activity; and transcription corepressor activity. Involved in chromatin remodeling and negative regulation of DNA-templated transcription. Located in nucleoplasm. Part of NuRD complex.

Source: NCBI Gene 57504 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 73 total — 1 likely-pathogenic
• Transcription factor: yes — 14 downstream targets (CollecTRI)
• MANE Select transcript: NM_001330442

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23784
Approved symbol	MTA3
Name	metastasis associated 1 family member 3
Location	2p21
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1266
Ensembl gene	ENSG00000057935
Ensembl biotype	protein_coding
OMIM	609050
Entrez	57504

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 10 protein_coding, 6 protein_coding_CDS_not_defined, 4 retained_intron, 3 nonsense_mediated_decay

ENST00000405094, ENST00000405592, ENST00000406652, ENST00000406911, ENST00000407270, ENST00000409019, ENST00000430763, ENST00000433553, ENST00000454356, ENST00000461256, ENST00000467925, ENST00000472767, ENST00000475383, ENST00000478602, ENST00000482875, ENST00000484780, ENST00000490611, ENST00000491314, ENST00000493983, ENST00000860174, ENST00000925935, ENST00000956431, ENST00000956432

RefSeq mRNA: 6 — MANE Select: NM_001330442 NM_001282755, NM_001282756, NM_001330442, NM_001330443, NM_001330444, NM_020744

CCDS: CCDS46267, CCDS62900, CCDS82441

Canonical transcript exons

ENST00000405094 — 17 exons

Exon	Start	End
ENSE00001069441	42704194	42704318
ENSE00001200613	42708874	42709096
ENSE00001215871	42682401	42682589
ENSE00001215876	42659763	42659862
ENSE00001556190	42753374	42756946
ENSE00001559523	42568632	42568773
ENSE00003472441	42640173	42640236
ENSE00003495039	42707903	42708054
ENSE00003561487	42579107	42579200
ENSE00003579950	42656200	42656302
ENSE00003586324	42644127	42644244
ENSE00003591855	42695765	42695839
ENSE00003607527	42697776	42697834
ENSE00003621238	42609458	42609584
ENSE00003653493	42722889	42723035
ENSE00003656354	42570437	42570504
ENSE00003683072	42718988	42719074

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 96.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.8309 / max 375.5111, expressed in 1771 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19945	12.2222	1701
19946	6.9491	1655
19944	1.8910	1158
19938	0.1936	68
19942	0.1866	96
19943	0.1778	43
19940	0.0865	52
19941	0.0730	37
19939	0.0511	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	96.10	gold quality
right adrenal gland	UBERON:0001233	95.94	gold quality
left adrenal gland	UBERON:0001234	95.24	gold quality
left adrenal gland cortex	UBERON:0035825	95.08	gold quality
lower esophagus mucosa	UBERON:0035834	95.08	gold quality
adrenal tissue	UBERON:0018303	94.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.86	gold quality
adrenal gland	UBERON:0002369	94.52	gold quality
colonic epithelium	UBERON:0000397	94.07	gold quality
adrenal cortex	UBERON:0001235	93.94	gold quality
oocyte	CL:0000023	93.69	gold quality
left ovary	UBERON:0002119	93.43	gold quality
right ovary	UBERON:0002118	92.57	gold quality
ventricular zone	UBERON:0003053	92.36	gold quality
secondary oocyte	CL:0000655	92.11	gold quality
thymus	UBERON:0002370	91.76	gold quality
left testis	UBERON:0004533	91.54	gold quality
right testis	UBERON:0004534	91.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.33	gold quality
esophagus mucosa	UBERON:0002469	91.10	gold quality
ovary	UBERON:0000992	91.05	gold quality
mucosa of transverse colon	UBERON:0004991	90.99	gold quality
islet of Langerhans	UBERON:0000006	90.84	gold quality
ileal mucosa	UBERON:0000331	90.78	silver quality
testis	UBERON:0000473	90.54	gold quality
ectocervix	UBERON:0012249	90.49	gold quality
stromal cell of endometrium	CL:0002255	90.36	gold quality
upper arm skin	UBERON:0004263	90.29	silver quality
ganglionic eminence	UBERON:0004023	90.14	gold quality
calcaneal tendon	UBERON:0003701	89.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.75

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

14 targets.

Target	Regulation
ACTR6
AURKAIP1
BCAS3
CDH1
CDH2
CGB5	Repression
CTSG
KMT2E
MTA3
NCOA3
POLR1F
SNAI1	Repression
WNT4	Repression
ZNF217

Upstream regulators (CollecTRI, top): ESR1, HDAC1, MTA1, MTA3, SNAI1, ZEB2

miRNA regulators (miRDB)

50 targeting MTA3, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-2052	99.79	69.37	2031

Literature-anchored findings (GeneRIF, showing 26)

• The absence of MTA3 leads to aberrant expression of Snail, a master regulator of epithelial to mesenchymal transitions. This results in loss of expression of E-cadherin, causing changes in epithelial architecture and invasive growth. (PMID:12705869)
• MTA3 does not repress transcription to a significant level and appears to have a diffused pattern of subcellular localization, suggesting a biological role distinct from that of the other two MTA proteins. (PMID:12920132)
• estrogen receptor-alpha regulates metastatic tumor antigen 3 pathway (PMID:15169784)
• Molecular dissection of the MTA3 promoter using transient transfection assays identified a composite element required for high-level transcription consisting of an SP1 site in close proximity to a consensus estrogen response element half-site. (PMID:15358836)
• a cell type-specific subunit of the corepressor complex Mi-2/NuRD,a cofactor for BCL-6-dependent B cell fate determination. (PMID:15454082)
• These findings identify MTA3 as an upstream physiologic repressor of Wnt4 in mammary epithelial cells. (PMID:17050676)
• the high expression level of MTA proteins in human chorionic cells might facilitate trophoblast cell migration and neoangiogenesis (PMID:19363681)
• MTA3 is not a useful marker to assess and identify high-risk patients with endometrial adenocarcinomas (PMID:20865667)
• Down-regulation of MTA3 and up-regulation of CGB5 and Snail are associated with preeclampsia. (PMID:23510993)
• MTA3 expression is an independent prognostic factor in patients with gastroesophageal junction adenocarcinoma. (PMID:23671646)
• MTA3 depletion induced cell cycle arrest at the G1/S boundary. Western blotting analysis revealed that the knockdown of MTA3 decreased the protein levels of cyclin A, cyclin D1 and p-Rb. These results indicate that MTA3 plays an important role in NSCLC progression (PMID:23840517)
• MAT3 over-expression in non-small cell lung carcinoma and MAT3 mRNA level is a risk factor for lymph node metastasis and survival. (PMID:24107548)
• Using western blotting and luciferase assays, MTA3 was identified as a target of miR-495 (PMID:24293376)
• This review focuses on the current knowledge about the function and regulation of MTA1 and MTA3 proteins in gynecological cancer, including ovarian, endometrial, and cervical tumors. (PMID:25319202)
• role in terminal trophoblast differentiation (PMID:26198267)
• MTA3 suppress apoptosis of A549 an H157 cells by inhibiting BAX, PARP expression. (PMID:26483332)
• Studies indicate that metastasis associated family, member 3 protein (MTA3) is expressed in various tissues and is associated with different physiological functions, and appears to play more complicated roles in cancers. (PMID:27033852)
• MTA3 is an oncogene of HCC, predicts poor prognosis of HCC, and may be a future marker of HCC treatment. (PMID:27992674)
• As a master regulator, MTA3 governs the target selection for nucleosome remodeling and histone deacetylation and functions as a transcriptional repressor. MTA3 dysregulation is associated with tumor progression, invasion, and metastasis in various cancers. MTA is also a key regulator of E-cadherin expression and epithelial-to-mesenchymal transition. (PMID:28279208)
• Our results demonstrated that MTA3 overexpression contributes to colorectal cancer carcinogenesis, progression, and chemoresistance. MTA3 could serve as a potential therapeutic target in colorectal cancer (PMID:28351306)
• Results show that metastasis associated 1 family member 3 (MTA3) level was decreased in colorectal cancer and significantly correlated with tumor cell invasion and metastasis, and that MTA3 might serve as a potential marker of tumor recurrence and prognosis of colorectal cancer. (PMID:28418887)
• The authors demonstrate that the SIX3/LSD1/NuRD(MTA3) complex inhibits carcinogenesis in breast cancer cells and suppresses metastasis in breast cancer. (PMID:29463994)
• associated with Infantile hypertrophic pyloric stenosis risk (PMID:30281099)
• LncRNA HCG11 suppresses the growth of glioma by cooperating with the miR-4425/MTA3 axis. (PMID:30706982)
• The circ_0021093/miR-766-3p/MTA3 regulatory axis may be an effective therapeutic target for HCC. (PMID:31330234)
• Inhibition of MTA2 and MTA3 induces mesendoderm specification of human embryonic stem cells. (PMID:33744762)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mta3	ENSDARG00000054903
mus_musculus	Mta3	ENSMUSG00000055817
rattus_norvegicus	Mta3	ENSRNOG00000004685
drosophila_melanogaster	MTA1-like	FBGN0027951

Paralogs (5): MIER2 (ENSG00000105556), MTA2 (ENSG00000149480), MIER3 (ENSG00000155545), MTA1 (ENSG00000182979), MIER1 (ENSG00000198160)

Protein

Protein identifiers

Metastasis-associated protein MTA3 — Q9BTC8 (reviewed: Q9BTC8)

All UniProt accessions (7): Q9BTC8, C9JR73, E7EQY4, E7EV10, E9PCS8, E9PF88, F6RRE2

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin. Plays a role in maintenance of the normal epithelial architecture through the repression of SNAI1 transcription in a histone deacetylase-dependent manner, and thus the regulation of E-cadherin levels. Contributes to transcriptional repression by BCL6.

Subunit / interactions. Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5. The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes. Interacts with BCL6. Interacts with NACC2. Interacts with PWWP2B.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in germinal centers of lymphoid tissues. No expression in nonepithelial cells.

Induction. By estrogen.

Similarity. Belongs to the metastasis-associated protein family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BTC8-1	1	yes
Q9BTC8-2	2

RefSeq proteins (6): NP_001269684, NP_001269685, NP_001317371, NP_001317372, NP_001317373, NP_065795 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000679	Znf_GATA	Domain
IPR000949	ELM2_dom	Domain
IPR001005	SANT/Myb	Domain
IPR001025	BAH_dom	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017884	SANT_dom	Domain
IPR035170	MTA1_R1	Domain
IPR040138	MIER/MTA	Family
IPR043151	BAH_sf	Homologous_superfamily

Pfam: PF00249, PF00320, PF01426, PF01448, PF17226

UniProt features (13 total): modified residue 4, domain 3, splice variant 2, sequence conflict 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BTC8-F1	79.25	0.51

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 (4): 428, 430, 455, 519

Function

Pathways and Gene Ontology

Reactome pathways

30 pathways

ID	Pathway
R-HSA-3214815	HDACs deacetylate histones
R-HSA-427389	ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression
R-HSA-73762	RNA Polymerase I Transcription Initiation
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-9843940	Regulation of endogenous retroelements by KRAB-ZFP proteins
R-HSA-9844594	Transcriptional regulation of brown and beige adipocyte differentiation by EBF2
R-HSA-9845323	Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)
R-HSA-9937850	NuRD complex assembly
R-HSA-9940951	Interaction of NuRD complexes with transcription factors
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-5250913	Positive epigenetic regulation of rRNA expression
R-HSA-5663205	Infectious disease
R-HSA-6807070	PTEN Regulation
R-HSA-73854	RNA Polymerase I Promoter Clearance
R-HSA-73864	RNA Polymerase I Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9006925	Intracellular signaling by second messengers
R-HSA-9679506	SARS-CoV Infections
R-HSA-9824446	Viral Infection Pathways
R-HSA-9842860	Regulation of endogenous retroelements
R-HSA-9843743	Transcriptional regulation of brown and beige adipocyte differentiation
R-HSA-9843745	Adipogenesis

MSigDB gene sets: 0 (showing top):

GO Biological Process (12): G2/M transition of mitotic cell cycle (GO:0000086), negative regulation of transcription by RNA polymerase II (GO:0000122), chromatin remodeling (GO:0006338), positive regulation of G2/M transition of mitotic cell cycle (GO:0010971), regulation of cell fate specification (GO:0042659), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of granulosa cell proliferation (GO:1904197), granulosa cell proliferation (GO:1990739), regulation of stem cell differentiation (GO:2000736), regulation of DNA-templated transcription (GO:0006355), cell population proliferation (GO:0008283)

GO Molecular Function (10): chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), histone deacetylase binding (GO:0042826), sequence-specific DNA binding (GO:0043565), protein-containing complex binding (GO:0044877), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), NuRD complex (GO:0016581)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Regulation of endogenous retroelements	2
Chromatin modifying enzymes	1
Positive epigenetic regulation of rRNA expression	1
RNA Polymerase I Promoter Clearance	1
PTEN Regulation	1
SARS-CoV Infections	1
Transcriptional regulation of brown and beige adipocyte differentiation	1
CHD3, CHD4, CHD5 subfamily	1
NuRD complex assembly	1
Differentiation of T cells	1
Intracellular signaling by second messengers	1
Gene expression (Transcription)	1
Chromatin organization	1
Epigenetic regulation of gene expression	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	3
binding	3
negative regulation of DNA-templated transcription	2
regulation of DNA-templated transcription	2
transcription coregulator activity	2
cellular anatomical structure	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G2/M phase transition	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
chromatin organization	1
G2/M transition of mitotic cell cycle	1
regulation of G2/M transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G2/M phase transition	1
cell fate specification	1
regulation of cell fate commitment	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
positive regulation of epithelial cell proliferation	1
regulation of granulosa cell proliferation	1
granulosa cell proliferation	1
epithelial cell proliferation	1
regulation of cell differentiation	1
stem cell differentiation	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular process	1
positive regulation of DNA-templated transcription	1
transition metal ion binding	1
enzyme binding	1
DNA binding	1
nucleic acid binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
histone deacetylase complex	1
transcription regulator complex	1

Protein interactions and networks

STRING

940 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTA3	HDAC1	Q13547	978
MTA3	RBBP7	Q16576	973
MTA3	CHD3	Q12873	970
MTA3	CHD4	Q14839	968
MTA3	HDAC2	Q92769	964
MTA3	RBBP4	P31149	962
MTA3	GATAD2A	Q86YP4	913
MTA3	MTA1	Q13330	896
MTA3	GATAD2B	Q8WXI9	881
MTA3	BCL6	P41182	835
MTA3	ASPH	Q12797	807
MTA3	CDH1	P12830	745
MTA3	SNAI1	O95863	718
MTA3	GATA3	P23771	675
MTA3	KDM1A	O60341	660

IntAct

162 interactions, top by confidence:

A	B	Type	Score
HDAC1	KDM1A	psi-mi:“MI:0914”(association)	0.910
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
MTA3	HDAC1	psi-mi:“MI:0914”(association)	0.880
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
CHD3	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
HDAC1	TNRC18	psi-mi:“MI:0914”(association)	0.790
GATAD2B	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
CHD4	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
GATAD2A	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
CDK2AP1	MTA2	psi-mi:“MI:0914”(association)	0.730
HDAC1	ZNF609	psi-mi:“MI:0914”(association)	0.730
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730
MBD3	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
MTA3	MBD3	psi-mi:“MI:0914”(association)	0.690
ZNF219	CDK2AP1	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
GATAD2B	MTA2	psi-mi:“MI:0914”(association)	0.640
CHD4	MTA2	psi-mi:“MI:0914”(association)	0.630

BioGRID (291): MTA3 (Affinity Capture-MS), MTA3 (Affinity Capture-MS), MTA3 (Affinity Capture-MS), MTA3 (Affinity Capture-MS), MTA3 (Affinity Capture-MS), MTA3 (Affinity Capture-MS), MTA3 (Affinity Capture-MS), GATAD2A (Co-fractionation), GATAD2B (Co-fractionation), MBD2 (Co-fractionation), MBD3 (Co-fractionation), MTA1 (Co-fractionation), MTA2 (Co-fractionation), MTA3 (Co-fractionation), MTA3 (Co-fractionation)

ESM2 similar proteins: A6QL72, A7E300, B1WAV2, B9VTT2, E9Q5G3, F1MF74, O00763, O42611, O43815, O55106, O60447, O94776, O94851, P10687, P10894, P48380, P48381, P51400, P54283, P70483, P97366, Q02641, Q0V9K5, Q32NR3, Q4R3I8, Q5EAP5, Q5JSJ4, Q62769, Q63744, Q6DCD0, Q6GL57, Q6PCM2, Q7SYD9, Q811S7, Q8BPM2, Q8CC27, Q8R3Z5, Q8VGC3, Q90828, Q90ZY6

Diamond homologs: A6QL72, O94776, Q13330, Q62599, Q8K4B0, Q924K8, Q9BTC8, Q9R190, Q59E36, Q62901, Q6NRZ0, Q80TZ9, Q9P2R6, Q5REE1, Q5UAK0, Q5ZKT9, Q8N108

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
MTA1	“down-regulates quantity by repression”	MTA3	“transcriptional regulation”
MTA3	“form complex”	“MBD2/NuRD complex”	binding
MTA3	“form complex”	“MBD3/NuRD complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 123 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of TP53 Activity through Acetylation	11	51.8×	1e-14
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	10	39.2×	3e-12
RNA Polymerase I Transcription Initiation	12	27.7×	1e-12
Regulation of PTEN gene transcription	14	25.8×	2e-14
NuRD complex assembly	15	21.8×	2e-14
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	14	21.1×	3e-13
Interaction of NuRD complexes with transcription factors	16	20.9×	1e-14
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	12	18.8×	9e-11

GO biological processes:

GO term	Partners	Fold	FDR
regulation of stem cell differentiation	10	63.8×	7e-14
NLS-bearing protein import into nucleus	5	33.4×	4e-05
DNA methylation-dependent constitutive heterochromatin formation	7	31.7×	3e-07
positive regulation of stem cell population maintenance	6	17.2×	2e-04
epigenetic regulation of gene expression	5	16.0×	2e-03
chromatin remodeling	20	12.2×	7e-14
cellular response to transforming growth factor beta stimulus	5	11.5×	5e-03
protein autophosphorylation	7	8.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	55
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
599574	NM_001330442.2(MTA3):c.635G>A (p.Cys212Tyr)	Likely pathogenic

SpliceAI

3100 predictions. Top by Δscore:

Variant	Effect	Δscore
2:42570430:A:G	acceptor_gain	1.0000
2:42570431:TTACA:T	acceptor_loss	1.0000
2:42570432:TACA:T	acceptor_loss	1.0000
2:42570433:ACAGA:A	acceptor_loss	1.0000
2:42570434:CAGAT:C	acceptor_loss	1.0000
2:42570435:A:AG	acceptor_gain	1.0000
2:42570435:AGATT:A	acceptor_loss	1.0000
2:42570436:G:GA	acceptor_gain	1.0000
2:42570436:GA:G	acceptor_gain	1.0000
2:42570436:GATT:G	acceptor_gain	1.0000
2:42570436:GATTA:G	acceptor_gain	1.0000
2:42570501:CAAG:C	donor_loss	1.0000
2:42570502:AAG:A	donor_loss	1.0000
2:42570503:AGGTA:A	donor_loss	1.0000
2:42570504:GGT:G	donor_loss	1.0000
2:42570505:GT:G	donor_loss	1.0000
2:42570506:T:A	donor_loss	1.0000
2:42579104:TAG:T	acceptor_loss	1.0000
2:42579105:A:AG	acceptor_gain	1.0000
2:42579106:G:GC	acceptor_loss	1.0000
2:42579106:G:GG	acceptor_gain	1.0000
2:42579106:GA:G	acceptor_gain	1.0000
2:42579106:GACT:G	acceptor_gain	1.0000
2:42579189:A:G	donor_gain	1.0000
2:42579196:TGCTA:T	donor_gain	1.0000
2:42579197:GCTA:G	donor_gain	1.0000
2:42579197:GCTAG:G	donor_gain	1.0000
2:42579198:CTA:C	donor_gain	1.0000
2:42579199:TA:T	donor_gain	1.0000
2:42579200:AG:A	donor_loss	1.0000

AlphaMissense

3891 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:42568761:T:C	Y6H	1.000
2:42568761:T:G	Y6D	1.000
2:42568770:G:A	G9R	1.000
2:42568770:G:C	G9R	1.000
2:42570443:T:A	V12D	1.000
2:42570448:T:C	F14L	1.000
2:42570450:T:A	F14L	1.000
2:42570450:T:G	F14L	1.000
2:42570470:C:A	P21Q	1.000
2:42570479:T:A	I24K	1.000
2:42570479:T:G	I24R	1.000
2:42570482:G:C	R25T	1.000
2:42570482:G:T	R25I	1.000
2:42570486:G:C	R26S	1.000
2:42570486:G:T	R26S	1.000
2:42570488:T:A	I27K	1.000
2:42570488:T:G	I27R	1.000
2:42570497:T:A	L30H	1.000
2:42570497:T:C	L30P	1.000
2:42579128:G:C	A40P	1.000
2:42579149:A:G	R47G	1.000
2:42579150:G:C	R47T	1.000
2:42579150:G:T	R47I	1.000
2:42579151:A:C	R47S	1.000
2:42579151:A:T	R47S	1.000
2:42609533:G:C	R89T	1.000
2:42609533:G:T	R89M	1.000
2:42609534:G:C	R89S	1.000
2:42609534:G:T	R89S	1.000
2:42609539:T:A	L91H	1.000

dbSNP variants (sampled 300 via entrez): RS1000013938 (2:42624444 C>A,T), RS1000015181 (2:42641953 C>G), RS1000023056 (2:42586050 G>A,T), RS1000039143 (2:42659147 T>G), RS1000042496 (2:42701841 G>A,C), RS1000064851 (2:42548041 C>G,T), RS1000079848 (2:42636274 C>A,T), RS1000080749 (2:42496642 A>C,T), RS1000081244 (2:42532368 G>C), RS1000081769 (2:42592120 C>T), RS1000084665 (2:42588630 T>TAAA), RS1000116698 (2:42548365 C>G), RS1000117455 (2:42702824 A>G), RS1000121895 (2:42741933 T>C,G), RS1000133229 (2:42663321 C>T)

Disease associations

OMIM: gene MIM:609050 | 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
GCST002715_2	Breastfeeding duration	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006864	breastfeeding duration

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, affects expression	7
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	4
trichostatin A	affects expression, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	affects methylation	1
coumarin	increases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
dorsomorphin	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1
Caffeine	increases phosphorylation	1
Carbamazepine	affects expression	1
Estradiol	increases expression	1
Formaldehyde	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Melphalan	decreases expression	1
Methapyrilene	increases methylation	1
Rotenone	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B7YD	Abcam Raji MTA3 KO	Cancer cell line	Male
CVCL_B9Z2	Abcam THP-1 MTA3 KO	Cancer cell line	Male
CVCL_C7AS	Abcam PC-3 MTA3 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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