MTA2

Summary

MTA2 (metastasis associated 1 family member 2, HGNC:7411) is a protein-coding gene on chromosome 11q12.3, encoding Metastasis-associated protein MTA2 (O94776). May function as a transcriptional coregulator.

This gene encodes a protein that has been identified as a component of NuRD, a nucleosome remodeling deacetylase complex identified in the nucleus of human cells. It shows a very broad expression pattern and is strongly expressed in many tissues. It may represent one member of a small gene family that encode different but related proteins involved either directly or indirectly in transcriptional regulation. Their indirect effects on transcriptional regulation may include chromatin remodeling. It is closely related to another member of this family, a protein that has been correlated with the metastatic potential of certain carcinomas. These two proteins are so closely related that they share the same types of domains. These domains include two DNA binding domains, a dimerization domain, and a domain commonly found in proteins that methylate DNA. One of the proteins known to be a target protein for this gene product is p53. Deacetylation of p53 is correlated with a loss of growth inhibition in transformed cells supporting a connection between these gene family members and metastasis.

Source: NCBI Gene 9219 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 78 total
• Druggable target: yes
• MANE Select transcript: NM_004739

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7411
Approved symbol	MTA2
Name	metastasis associated 1 family member 2
Location	11q12.3
Locus type	gene with protein product
Status	Approved
Aliases	MTA1-L1
Ensembl gene	ENSG00000149480
Ensembl biotype	protein_coding
OMIM	603947
Entrez	9219

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 retained_intron, 3 protein_coding

ENST00000278823, ENST00000524902, ENST00000526844, ENST00000527204, ENST00000531179, ENST00000531261, ENST00000532239

RefSeq mRNA: 2 — MANE Select: NM_004739 NM_001330292, NM_004739

CCDS: CCDS8022, CCDS81576

Canonical transcript exons

ENST00000278823 — 18 exons

Exon	Start	End
ENSE00000990806	62597316	62597415
ENSE00000990808	62596458	62596532
ENSE00000990809	62596279	62596337
ENSE00000990811	62595752	62595891
ENSE00000990812	62595264	62595492
ENSE00000990813	62594981	62595070
ENSE00000990815	62594259	62594407
ENSE00001063186	62601423	62601865
ENSE00001143014	62594516	62594634
ENSE00001770460	62596637	62596825
ENSE00002145826	62593214	62594040
ENSE00003496820	62598024	62598141
ENSE00003511773	62600622	62600689
ENSE00003551968	62597610	62597712
ENSE00003553996	62598327	62598390
ENSE00003578863	62600166	62600259
ENSE00003591092	62598522	62598639
ENSE00003608868	62596010	62596107

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 97.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 52.6008 / max 379.3068, expressed in 1822 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120149	17.0081	1784
120152	16.9692	1807
120151	13.6153	1788
120147	4.6263	1648
120148	0.3432	158
120146	0.0304	8
120145	0.0083	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.87	gold quality
lower esophagus mucosa	UBERON:0035834	97.50	gold quality
ganglionic eminence	UBERON:0004023	97.38	gold quality
skin of abdomen	UBERON:0001416	96.22	gold quality
cortical plate	UBERON:0005343	96.06	gold quality
skin of leg	UBERON:0001511	95.93	gold quality
left uterine tube	UBERON:0001303	95.77	gold quality
rectum	UBERON:0001052	95.69	gold quality
smooth muscle tissue	UBERON:0001135	95.60	gold quality
ventricular zone	UBERON:0003053	95.52	gold quality
right ovary	UBERON:0002118	95.18	gold quality
tibial nerve	UBERON:0001323	95.15	gold quality
leukocyte	CL:0000738	95.04	gold quality
gall bladder	UBERON:0002110	95.02	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.99	gold quality
esophagus mucosa	UBERON:0002469	94.92	gold quality
monocyte	CL:0000576	94.85	gold quality
upper lobe of left lung	UBERON:0008952	94.85	gold quality
mucosa of transverse colon	UBERON:0004991	94.78	gold quality
left ovary	UBERON:0002119	94.74	gold quality
body of uterus	UBERON:0009853	94.73	gold quality
adenohypophysis	UBERON:0002196	94.64	gold quality
ectocervix	UBERON:0012249	94.62	gold quality
transverse colon	UBERON:0001157	94.58	gold quality
minor salivary gland	UBERON:0001830	94.39	gold quality
islet of Langerhans	UBERON:0000006	94.38	gold quality
omental fat pad	UBERON:0010414	94.37	gold quality
esophagus	UBERON:0001043	94.35	gold quality
spleen	UBERON:0002106	94.29	gold quality
peritoneum	UBERON:0002358	94.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.31

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
CDH1	Repression
FSHR	Repression
IFNA1
IFNG
IL4	Unknown
MTA2
SELENOP

Upstream regulators (CollecTRI, top): ESR1, FOXN1, MTA2, SP1, TBX5

miRNA regulators (miRDB)

38 targeting MTA2, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312
HSA-MIR-655-5P	98.74	65.93	888
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-3145-5P	98.57	67.83	900
HSA-MIR-5088-3P	98.29	66.63	1310
HSA-MIR-4443	98.02	66.25	1928

Literature-anchored findings (GeneRIF, showing 40)

• Deacetylation and functional interactions by the PID/MTA2-associated NuRD complex may represent an important pathway to regulate p53 function. (PMID:11099047)
• interaction with mCpG-binding domain of MBD2 (PMID:12124384)
• MTA1 and MTA2 repress transcription specifically, are located in the nucleus, and contain associated histone deacetylase activity; MTA1 associates with a different set of transcription factors from MTA2 (PMID:12920132)
• MTA2 is a repressor of estrogen receptor (ER)alpha activity and that it could represent a new therapeutic target of ERalpha action in human breast tumors (PMID:16645043)
• Findings indicate a tight correlation between the MTA2 expression level and hepatocellular carcinoma size and differentiation. (PMID:19702911)
• The expression of MTA2 had positive correlation with clinical stage and lymph node metastasis. (PMID:20704817)
• Our data suggested that MTA2 might play roles in both the nucleus and cytoplasm in the progression of NSCLC. (PMID:22585429)
• High nuclear MTA2 expression is associated with thymoma. (PMID:22833212)
• Sertoli cell-specific expression of MTA2 is required for transcriptional regulation of FSHR gene during spermatogenesis. (PMID:23086931)
• MTA2 is highly expressed in the primary lesions of gastric cancer than that in adjacent non-cancerous tissues, and is closely related with tumor invasion. MTA2 expression is elevated in Sp1 positive gastric cancer. (PMID:23158992)
• High expression levels of MTA2 is associated with pancreatic ductal adenocarcinoma. (PMID:23400716)
• MTA2 knockdown impairs invasion and metastasis of gastric cancer cells. (PMID:24010737)
• results reveal a novel post-translational regulation of MTA2 by the way of p300-dependent acetylation, which is important for tumor cells growth and migration and provides a potential target for clinical cancer research (PMID:24468085)
• Mta2 and Tipin cooperate to maintain replication fork integrity, especially on regions that are intrinsically difficult to duplicate. (PMID:24830473)
• Study demonstrates that hBD-3 inhibits the progression of colon cancer in a paracrine fashion through downregulation of MTA2 expression. (PMID:24969834)
• High MTA2 protein and mRNA expression is associated with glioma. (PMID:25048531)
• MTA2 depletion could significantly inhibit human breast cancer cell growth and metastasis, implying that MTA2 might be involved in the progression of breast cancer. (PMID:25081667)
• MTA2 acts as a central hub for cytoskeletal organization and transcription and provides a link between nuclear and cytoskeletal organization. (PMID:25394532)
• MTA2 overexpression enhances colony formation and tumor growth of gastric cancer cells, but not plays important role in cancer cell migration and metastasis. IL-11 is one of the downstream effectors of MTA2 in regulating gastric cancer cells growth (PMID:25929737)
• MTA-2 protein may facilitate the invasive potential of non-small-cell lung cancer cells through the inhibition of the cell adhesion molecule Ep-CAM and E-cadherin, suggesting that it might be a potential therapeutic target in NSCLC. (PMID:25969565)
• MTA2 is a crucial biomarker that is closely related with prognosis of colorectal carcinoma and also a potential molecular target for evaluating the prognosis and treatment of CRC. (PMID:26261611)
• These results indicated there might be a tight correlation among MTA2, Ki-67 and hepatocellular carcinoma prognosis (PMID:26722504)
• Authors identify non-canonical nuclear factor-kappaB (NF-kappaB) signaling up regulated and it was directly linked with the tumor necrosis with MT2A and pFADD genes. pFADD with MT2A can inhibit the apoptosis and promote proliferation, of colorectal cancer cells. (PMID:28061540)
• Taken together with previous findings this suggests, that MTA-RBBP is a stable complex, with a central role in the initial assembly of the human NuRD complex. (PMID:28179136)
• Reciprocal loop of hypoxia-inducible factor-1alpha and metastasis-associated protein 2 contributes to the progression of pancreatic adenocarcinoma by suppressing E-cadherin transcription and promoting epithelial mesenchymal transformation. (PMID:29708271)
• MTA1 and MTA2 play opposing roles in the metastasis of ZR-75-30 luminal B breast cancer cells in vitro. (PMID:30642362)
• Authors revealed that MTA2 promoted PDAC cell proliferation, migration, and invasion in vitro and PDAC tumor growth in vivo by downregulation of PTEN. (PMID:30814496)
• Results indicate that metastasis associated 1 family member 2 (MTA2) represses a cohort of genes including FERM domain containing 6 protein (FRMD6) that are critically involved in the growth and mobility of hepatocellular carcinoma (HCC). (PMID:31128910)
• MTA2 expression in oral cancer cells was markedly higher than that in normal oral cells. MTA2 knockdown can inhibit cell migration and invasion of human oral cancer cells. (PMID:31359510)
• The HOX antisense intergenic RNA (HOTAIR)-miR-326-metastasis-associated gene 2 (MTA2) axis may contribute to a better understanding of oral squamous cell carcinoma (OSCC) pathogenesis and be a potential therapeutic target for OSCC. (PMID:31995261)
• Metastasis-Associated Protein 2 Represses NF-kappaB to Reduce Lung Tumor Growth and Inflammation. (PMID:32816854)
• SNHG5 inhibits the progression of EMT through the ubiquitin-degradation of MTA2 in oesophageal cancer. (PMID:33095847)
• MTA2 promotes the metastasis of esophageal squamous cell carcinoma via EIF4E-Twist feedback loop. (PMID:33340431)
• Comparative analysis of the AIB1 interactome in breast cancer reveals MTA2 as a repressive partner which silences E-Cadherin to promote EMT and associates with a pro-metastatic phenotype. (PMID:33420368)
• Inhibition of MTA2 and MTA3 induces mesendoderm specification of human embryonic stem cells. (PMID:33744762)
• MTA2 triggered R-loop trans-regulates BDH1-mediated beta-hydroxybutyrylation and potentiates propagation of hepatocellular carcinoma stem cells. (PMID:33795651)
• MTA2 silencing attenuates the metastatic potential of cervical cancer cells by inhibiting AP1-mediated MMP12 expression via the ASK1/MEK3/p38/YB1 axis. (PMID:33958583)
• Prognostic, Immunological, and Mutational Analysis of MTA2 in Pan-Cancer and Drug Screening for Hepatocellular Carcinoma. (PMID:37371463)
• CircMTA2 Drives Gastric Cancer Progression through Suppressing MTA2 Degradation via Interacting with UCHL3. (PMID:38474064)
• lncRNA LINC00941 modulates MTA2/NuRD occupancy to suppress premature human epidermal differentiation. (PMID:38649186)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mta2	ENSDARG00000013031
mus_musculus	Mta2	ENSMUSG00000071646
rattus_norvegicus	Mta2	ENSRNOG00000019913
drosophila_melanogaster	MTA1-like	FBGN0027951

Paralogs (5): MTA3 (ENSG00000057935), MIER2 (ENSG00000105556), MIER3 (ENSG00000155545), MTA1 (ENSG00000182979), MIER1 (ENSG00000198160)

Protein

Protein identifiers

Metastasis-associated protein MTA2 — O94776 (reviewed: O94776)

Alternative names: Metastasis-associated 1-like 1, p53 target protein in deacetylase complex

All UniProt accessions (1): O94776

UniProt curated annotations — full annotation on UniProt →

Function. May function as a transcriptional coregulator. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin.

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 CHD3. Interacts with CHD4. Interacts with GATAD2A. Interacts with HDAC7. Interacts with MBD3. Interacts with p53/TP53. Interacts with MINT. Interacts with PIMREG. Interacts with NACC2. Interacts with ERCC6. Interacts with PWWP2B. Interacts with transcription factor BCL11A.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed.

Similarity. Belongs to the metastasis-associated protein family.

Isoforms (2)

UniProt ID	Names	Canonical?
O94776-1	1	yes
O94776-2	2

RefSeq proteins (2): NP_001317221, NP_004730* (*=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 (26 total): modified residue 10, cross-link 5, domain 3, region of interest 3, chain 1, splice variant 1, sequence conflict 1, zinc finger region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94776-F1	76.31	0.44

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 (15): 54, 152, 433, 435, 460, 522, 531, 534, 548, 492, 492, 508, 559, 595, 52

Function

Pathways and Gene Ontology

Reactome pathways

35 pathways

ID	Pathway
R-HSA-3214815	HDACs deacetylate histones
R-HSA-427389	ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression
R-HSA-6804758	Regulation of TP53 Activity through Acetylation
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-212436	Generic Transcription Pathway
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-4839726	Chromatin organization
R-HSA-5250913	Positive epigenetic regulation of rRNA expression
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-5663205	Infectious disease
R-HSA-6807070	PTEN Regulation
R-HSA-73854	RNA Polymerase I Promoter Clearance
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-73864	RNA Polymerase I Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9006925	Intracellular signaling by second messengers

MSigDB gene sets: 171 (showing top): PID_HDAC_CLASSI_PATHWAY, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, GOBP_REGULATION_OF_FIBROBLAST_MIGRATION, AAAYRNCTG_UNKNOWN, EFC_Q6, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, WATANABE_COLON_CANCER_MSI_VS_MSS_UP, MODULE_379, GGAANCGGAANY_UNKNOWN, DAVIES_MULTIPLE_MYELOMA_VS_MGUS_UP, AGGAGTG_MIR483, GOBP_GENOMIC_IMPRINTING, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, P300_01, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION

GO Biological Process (11): negative regulation of transcription by RNA polymerase II (GO:0000122), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), regulation of fibroblast migration (GO:0010762), 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 transcription by RNA polymerase II (GO:0045944), genomic imprinting (GO:0071514), regulation of stem cell differentiation (GO:2000736), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (14): chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), transcription corepressor activity (GO:0003714), histone deacetylase activity (GO:0004407), zinc ion binding (GO:0008270), histone deacetylase binding (GO:0042826), sequence-specific DNA binding (GO:0043565), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), DNA binding (GO:0003677), transcription coregulator activity (GO:0003712), protein binding (GO:0005515), nucleosomal DNA binding (GO:0031492), metal ion binding (GO:0046872), DNA-binding transcription factor binding (GO:0140297)

GO Cellular Component (9): histone deacetylase complex (GO:0000118), chromosome, telomeric region (GO:0000781), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), membrane (GO:0016020), NuRD complex (GO:0016581), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Regulation of endogenous retroelements	2
Chromatin modifying enzymes	1
Positive epigenetic regulation of rRNA expression	1
Regulation of TP53 Activity	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
RNA Polymerase II Transcription	1
Chromatin organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	3
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
regulation of DNA-templated transcription	2
positive regulation of DNA-templated transcription	2
binding	2
transcription coregulator activity	2
cellular component organization	1
chromatin organization	1
fibroblast migration	1
regulation of cell migration	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
germ cell development	1
epigenetic programming of gene expression	1
regulation of cell differentiation	1
stem cell differentiation	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
protein lysine deacetylase activity	1
histone modifying activity	1
transition metal ion binding	1
enzyme binding	1
DNA binding	1
DNA-binding transcription factor binding	1
nucleic acid binding	1
transcription regulator activity	1
chromatin DNA binding	1
nucleosome binding	1
cation binding	1
transcription factor binding	1
nucleoplasm	1
nuclear protein-containing complex	1
catalytic complex	1
chromosomal region	1
chromosome	1

Protein interactions and networks

STRING

1382 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTA2	CHD4	Q14839	997
MTA2	RBBP7	Q16576	997
MTA2	RBBP4	P31149	996
MTA2	HDAC1	Q13547	995
MTA2	HDAC2	Q92769	993
MTA2	GATAD2A	Q86YP4	983
MTA2	CHD3	Q12873	979
MTA2	GATAD2B	Q8WXI9	964
MTA2	MTA1	Q13330	960
MTA2	MBD3	O95983	791
MTA2	KDM1A	O60341	735
MTA2	BCL11B	Q9C0K0	679
MTA2	RCOR1	Q9UKL0	652
MTA2	MBD2	Q9UBB5	601
MTA2	H3C1	P02295	601

IntAct

272 interactions, top by confidence:

A	B	Type	Score
HDAC1	MTA2	psi-mi:“MI:0915”(physical association)	0.950
HDAC1	MTA2	psi-mi:“MI:0403”(colocalization)	0.950
MTA2	RBBP7	psi-mi:“MI:0915”(physical association)	0.920
HDAC1	KDM1A	psi-mi:“MI:0914”(association)	0.910
MTA2	RBBP4	psi-mi:“MI:0914”(association)	0.890
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
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
GATAD2B	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
HMG20A	KDM1A	psi-mi:“MI:0914”(association)	0.730
CHD4	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
MTA2	KPNA2	psi-mi:“MI:0914”(association)	0.690
KPNA2	MTA2	psi-mi:“MI:0914”(association)	0.690
MTA2	EHMT2	psi-mi:“MI:0407”(direct interaction)	0.680
GATAD2B	MTA2	psi-mi:“MI:0914”(association)	0.640
ZNF219	CDK2AP1	psi-mi:“MI:0914”(association)	0.640
SH3KBP1	USP27X	psi-mi:“MI:0914”(association)	0.640

BioGRID (814): MTA2 (Affinity Capture-MS), MTA2 (Affinity Capture-MS), MTA2 (Affinity Capture-MS), MTA2 (Reconstituted Complex), MTA2 (Affinity Capture-MS), MTA2 (Affinity Capture-MS), MTA2 (Affinity Capture-MS), MTA2 (Affinity Capture-MS), MTA2 (Affinity Capture-MS), MTA2 (Affinity Capture-MS), MTA2 (Affinity Capture-MS), MTA2 (Affinity Capture-MS), MTA2 (Affinity Capture-MS), MTA2 (Affinity Capture-Western), MTA2 (Affinity Capture-Western)

ESM2 similar proteins: A1L1C7, O08873, O42611, O60716, O94776, O94967, P83094, Q01826, Q0P5J8, Q15542, Q3UHE1, Q3UVG3, Q4R8N2, Q58A45, Q5EY87, Q5JSJ4, Q5M7R9, Q5R7S4, Q5RAR8, Q5TKA1, Q60611, Q640Q5, Q658Y4, Q68FH0, Q6ISB3, Q6NT76, Q6TEP1, Q80U28, Q8BIE6, Q8BJA3, Q8C092, Q8C0V0, Q8C735, Q8C8N2, Q8CGF6, Q8K5C0, Q8N9R8, Q8VI24, Q8WXG6, Q90ZY6

Diamond homologs: A6QL72, O94776, Q13330, Q62599, Q8K4B0, Q924K8, Q9BTC8, Q9R190, Q59E36, Q62901, Q6NRZ0, Q80TZ9, Q9P2R6, Q5REE1, Q5UAK0, Q5ZKT9, Q8N108, O75376, Q0GGX2, Q18919, Q4KKX4, Q4R2Z8, Q5FWT8, Q5ZJ40, Q60974, Q6P116, Q6PGA0, Q8BXJ2, Q8C796, Q8CFE3, Q8IZ40, Q90WN5, Q95Y41, Q9H0D2, Q9P2K3, Q9UKL0, O35126, P54258, P54259, Q09228

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MTA2	“down-regulates quantity by repression”	FSHR	“transcriptional regulation”
TBX5	“down-regulates quantity by repression”	MTA2	“transcriptional regulation”
MTA2	“form complex”	“MBD2/NuRD complex”	binding
MTA2	“form complex”	“MBD3/NuRD complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 173 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	8	30.4×	1e-08
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	9	28.6×	2e-09
Regulation of PTEN gene transcription	13	19.3×	2e-11
RNA Polymerase I Transcription Initiation	10	18.7×	1e-08
Interaction of NuRD complexes with transcription factors	17	18.0×	3e-14
NuRD complex assembly	15	17.6×	1e-12
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	13	15.9×	2e-10
Regulation of MECP2 expression and activity	5	15.3×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of stem cell differentiation	9	44.8×	6e-11
DNA methylation-dependent constitutive heterochromatin formation	8	28.2×	5e-08
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	5	13.0×	3e-03
positive regulation of stem cell population maintenance	5	11.2×	5e-03
positive regulation of transcription elongation by RNA polymerase II	5	9.8×	8e-03
protein import into nucleus	9	8.4×	2e-04
chromatin remodeling	17	8.1×	9e-09
double-strand break repair	6	7.9×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2394 predictions. Top by Δscore:

Variant	Effect	Δscore
11:62594041:C:CC	acceptor_gain	1.0000
11:62594046:C:CT	acceptor_gain	1.0000
11:62594046:C:T	acceptor_gain	1.0000
11:62594047:A:T	acceptor_gain	1.0000
11:62594055:C:CT	acceptor_gain	1.0000
11:62594056:A:T	acceptor_gain	1.0000
11:62594254:CTTAC:C	donor_loss	1.0000
11:62594257:A:AC	donor_gain	1.0000
11:62594257:ACCT:A	donor_loss	1.0000
11:62594258:C:CC	donor_gain	1.0000
11:62594403:GCCAT:G	acceptor_gain	1.0000
11:62594404:CCAT:C	acceptor_gain	1.0000
11:62594404:CCATC:C	acceptor_gain	1.0000
11:62594405:CAT:C	acceptor_gain	1.0000
11:62594405:CATC:C	acceptor_gain	1.0000
11:62594407:TCTGG:T	acceptor_loss	1.0000
11:62594408:C:CA	acceptor_loss	1.0000
11:62594408:C:CC	acceptor_gain	1.0000
11:62594509:AACTC:A	donor_loss	1.0000
11:62594511:CTC:C	donor_loss	1.0000
11:62594512:TCAC:T	donor_loss	1.0000
11:62594513:CACAG:C	donor_loss	1.0000
11:62594514:A:AC	donor_gain	1.0000
11:62594515:C:CA	donor_gain	1.0000
11:62594515:CA:C	donor_gain	1.0000
11:62594515:CAG:C	donor_gain	1.0000
11:62594515:CAGT:C	donor_gain	1.0000
11:62594632:CCA:C	acceptor_gain	1.0000
11:62594633:CA:C	acceptor_gain	1.0000
11:62594633:CAC:C	acceptor_gain	1.0000

AlphaMissense

4325 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:62595311:G:T	A479D	1.000
11:62595801:C:A	G402V	1.000
11:62595801:C:T	G402E	1.000
11:62595802:C:A	G402W	1.000
11:62595802:C:G	G402R	1.000
11:62595802:C:T	G402R	1.000
11:62595809:C:A	K399N	1.000
11:62595809:C:G	K399N	1.000
11:62595810:T:G	K399T	1.000
11:62595811:T:C	K399E	1.000
11:62595812:C:A	W398C	1.000
11:62595812:C:G	W398C	1.000
11:62595813:C:G	W398S	1.000
11:62595814:A:G	W398R	1.000
11:62595814:A:T	W398R	1.000
11:62595821:C:A	W395C	1.000
11:62595821:C:G	W395C	1.000
11:62595823:A:G	W395R	1.000
11:62595823:A:T	W395R	1.000
11:62595824:A:C	C394W	1.000
11:62595825:C:A	C394F	1.000
11:62595825:C:G	C394S	1.000
11:62595825:C:T	C394Y	1.000
11:62595826:A:G	C394R	1.000
11:62595826:A:T	C394S	1.000
11:62595833:A:C	C391W	1.000
11:62595834:C:A	C391F	1.000
11:62595834:C:G	C391S	1.000
11:62595834:C:T	C391Y	1.000
11:62595835:A:G	C391R	1.000

dbSNP variants (sampled 300 via entrez): RS1000199823 (11:62594840 A>C), RS1000446112 (11:62598835 A>G), RS1000692205 (11:62601142 C>T), RS1001183217 (11:62598187 G>A), RS1001237165 (11:62598444 C>A,T), RS1002090549 (11:62601885 G>A), RS1002567276 (11:62601696 G>A), RS1002617759 (11:62597099 G>A,C), RS1002860322 (11:62596359 G>A,C), RS1002912552 (11:62596680 A>C,T), RS1003495984 (11:62603388 C>T), RS1003604937 (11:62598798 C>T), RS1004204769 (11:62600767 G>A,T), RS1004258597 (11:62600537 T>C), RS1004437794 (11:62593836 C>G,T)

Disease associations

OMIM: gene MIM:603947 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005956_12	Waist-to-hip ratio adjusted for BMI	2.000000e-06
GCST005956_2	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST005962_37	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	5.000000e-07
GCST005962_51	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-07
GCST90020025_945	Waist-to-hip ratio adjusted for BMI	3.000000e-16
GCST90020027_1464	Waist-hip index	3.000000e-16

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724628 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
deoxynivalenol	increases expression	1
trichostatin A	affects expression	1
zinc chloride	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
rofecoxib	decreases expression	1
systhane	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
jinfukang	increases expression, affects cotreatment	1
LDN 193189	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Vorinostat	decreases expression	1
Leflunomide	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	increases abundance, decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	affects cotreatment, increases expression	1
Clozapine	affects cotreatment, decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697217	Binding	Inhibition of MTA2 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8KY	Abcam HCT 116 MTA2 KO	Cancer cell line	Male
CVCL_B8Z5	Abcam MCF-7 MTA2 KO	Cancer cell line	Female
CVCL_B9N5	Abcam A-549 MTA2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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