MIER2

Summary

MIER2 (MIER family member 2, HGNC:29210) is a protein-coding gene on chromosome 19p13.3, encoding Mesoderm induction early response protein 2 (Q8N344). Transcriptional repressor.

Enables histone deacetylase binding activity. Contributes to histone deacetylase activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Located in cytoplasm and nucleus. Part of protein-containing complex.

Source: NCBI Gene 54531 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 116 total — 1 likely-pathogenic
• MANE Select transcript: NM_017550

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29210
Approved symbol	MIER2
Name	MIER family member 2
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000105556
Ensembl biotype	protein_coding
OMIM	620092
Entrez	54531

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000264819, ENST00000586994, ENST00000587966, ENST00000592722, ENST00000619835, ENST00000621180, ENST00000635755, ENST00000871287, ENST00000871288, ENST00000931431, ENST00000931432

RefSeq mRNA: 8 — MANE Select: NM_017550 NM_001346105, NM_001387152, NM_001387153, NM_001387154, NM_001387155, NM_001387156, NM_001387157, NM_017550

CCDS: CCDS32855

Canonical transcript exons

ENST00000264819 — 14 exons

Exon	Start	End
ENSE00000680848	327133	327256
ENSE00000680884	326507	326598
ENSE00000680979	308801	308925
ENSE00000681037	308577	308665
ENSE00000854366	325635	325704
ENSE00000854367	313492	313643
ENSE00000854368	312191	312272
ENSE00000854369	311845	311939
ENSE00000854370	307119	307536
ENSE00001775612	344774	344796
ENSE00003474824	334400	334542
ENSE00003476474	336083	336173
ENSE00003620772	327864	327989
ENSE00003752603	305573	306711

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 92.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.4138 / max 50.1962, expressed in 1720 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177878	5.4138	1720

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	92.00	gold quality
right testis	UBERON:0004534	91.63	gold quality
left testis	UBERON:0004533	91.35	gold quality
lower esophagus mucosa	UBERON:0035834	91.22	gold quality
oocyte	CL:0000023	91.11	gold quality
stromal cell of endometrium	CL:0002255	90.24	gold quality
secondary oocyte	CL:0000655	90.17	gold quality
skin of abdomen	UBERON:0001416	89.53	gold quality
upper lobe of left lung	UBERON:0008952	89.35	gold quality
skin of leg	UBERON:0001511	89.19	gold quality
pancreatic ductal cell	CL:0002079	88.86	silver quality
body of uterus	UBERON:0009853	88.84	gold quality
ectocervix	UBERON:0012249	88.80	gold quality
omental fat pad	UBERON:0010414	88.78	gold quality
peritoneum	UBERON:0002358	88.70	gold quality
right lung	UBERON:0002167	88.62	gold quality
upper lobe of lung	UBERON:0008948	88.37	gold quality
heart left ventricle	UBERON:0002084	88.24	gold quality
testis	UBERON:0000473	88.20	gold quality
spleen	UBERON:0002106	88.13	gold quality
lower esophagus	UBERON:0013473	88.03	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.03	gold quality
ventricular zone	UBERON:0003053	87.90	gold quality
cardiac ventricle	UBERON:0002082	87.64	gold quality
adipose tissue of abdominal region	UBERON:0007808	87.57	gold quality
endocervix	UBERON:0000458	87.41	gold quality
gastrocnemius	UBERON:0001388	87.36	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.14	gold quality
left uterine tube	UBERON:0001303	87.07	gold quality
granulocyte	CL:0000094	87.05	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.84
E-MTAB-6142	no	60.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

87 targeting MIER2, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712

Literature-anchored findings (GeneRIF, showing 1)

• Histone deacetylase assays confirmed that MIER2, but not MIER3 complexes, have associated deacetylase activity. (PMID:28046085)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mier2	ENSDARG00000071413
mus_musculus	Mier2	ENSMUSG00000042570
rattus_norvegicus	Mier2	ENSRNOG00000000175
drosophila_melanogaster	CG1620	FBGN0033183
caenorhabditis_elegans		WBGENE00017352
caenorhabditis_elegans		WBGENE00020320

Paralogs (5): MTA3 (ENSG00000057935), MTA2 (ENSG00000149480), MIER3 (ENSG00000155545), MTA1 (ENSG00000182979), MIER1 (ENSG00000198160)

Protein

Protein identifiers

Mesoderm induction early response protein 2 — Q8N344 (reviewed: Q8N344)

All UniProt accessions (3): Q8N344, A0A087WZA4, A0A1B0GUC1

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor.

Subunit / interactions. Part of a complex containing at least CDYL, MIER1, MIER2, HDAC1 and HDAC2.

Subcellular location. Nucleus.

RefSeq proteins (8): NP_001333034, NP_001374081, NP_001374082, NP_001374083, NP_001374084, NP_001374085, NP_001374086, NP_060020* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000949	ELM2_dom	Domain
IPR001005	SANT/Myb	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017884	SANT_dom	Domain
IPR040138	MIER/MTA	Family

Pfam: PF00249, PF01448

UniProt features (12 total): sequence variant 5, domain 2, region of interest 2, chain 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N344-F1	58.63	0.18

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 (1): 11

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 82 (showing top): ATACCTC_MIR202, CACCAGC_MIR138, RICKMAN_METASTASIS_DN, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, GOBP_CHROMATIN_REMODELING, CAGCCTC_MIR4855P, SHEN_SMARCA2_TARGETS_DN, chr19p13, GOCC_HISTONE_DEACETYLASE_COMPLEX, GOMF_PROTEIN_LYSINE_DEACETYLASE_ACTIVITY, GOMF_HISTONE_DEACETYLASE_BINDING, GCACTTT_MIR175P_MIR20A_MIR106A_MIR106B_MIR20B_MIR519D, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_DN, GOMF_DEACETYLASE_ACTIVITY, GOMF_TRANSCRIPTION_COREPRESSOR_ACTIVITY

GO Biological Process (2): negative regulation of transcription by RNA polymerase II (GO:0000122), chromatin remodeling (GO:0006338)

GO Molecular Function (4): transcription corepressor activity (GO:0003714), histone deacetylase binding (GO:0042826), histone deacetylase activity (GO:0004407), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), protein-containing complex (GO:0032991)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of DNA-templated transcription	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
chromatin organization	1
transcription coregulator activity	1
enzyme binding	1
protein lysine deacetylase activity	1
histone modifying activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cellular_component	1

Protein interactions and networks

STRING

440 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MIER2	MBD3L4	A6NDZ8	507
MIER2	RSRC2	Q7L4I2	497
MIER2	OR5T1	Q8NG75	449
MIER2	OR4F17	Q8NGA8	447
MIER2	R3HDM4	Q96D70	446
MIER2	ZC2HC1C	Q53FD0	431
MIER2	MBD3L3	A6NE82	398
MIER2	WIZ	O95785	382
MIER2	MBD3L5	A6NJ08	370
MIER2	CIMAP1D	Q3SX64	370
MIER2	FAM174C	Q9BVV8	370
MIER2	OR2W1	Q9Y3N9	370
MIER2	VWA3A	A6NCI4	368
MIER2	MSLNL	Q96KJ4	368
MIER2	ZNF557	Q8N988	366

IntAct

39 interactions, top by confidence:

A	B	Type	Score
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
HDAC1	TNRC18	psi-mi:“MI:0914”(association)	0.790
HDAC1	ZNF609	psi-mi:“MI:0914”(association)	0.730
C16orf87	CDC27	psi-mi:“MI:0914”(association)	0.640
	MIER2	psi-mi:“MI:0915”(physical association)	0.560
MIER2	MCRS1	psi-mi:“MI:0915”(physical association)	0.560
IL16	MIER2	psi-mi:“MI:0915”(physical association)	0.560
CYBRD1	MIER1	psi-mi:“MI:0914”(association)	0.530
MIER2	WIZ	psi-mi:“MI:0914”(association)	0.530
NDN	MIER2	psi-mi:“MI:0915”(physical association)	0.370
MIER2	DBF4B	psi-mi:“MI:0915”(physical association)	0.370
MIER2	CFTR	psi-mi:“MI:0915”(physical association)	0.370
CFTR	MIER2	psi-mi:“MI:0915”(physical association)	0.370
Wiz	CLNS1A	psi-mi:“MI:0914”(association)	0.350
MIER2	AGAP1	psi-mi:“MI:0914”(association)	0.350
CDYL	LAMP2	psi-mi:“MI:0914”(association)	0.350
CYBRD1	HDAC1	psi-mi:“MI:0914”(association)	0.350
CDYL	RBBP4	psi-mi:“MI:0914”(association)	0.350
MAD2L1	MED19	psi-mi:“MI:0914”(association)	0.350
MIER2	PEX14	psi-mi:“MI:0914”(association)	0.350
HDAC1	KPNA3	psi-mi:“MI:0914”(association)	0.350
BUD13	RPSA2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (86): HDAC1 (Affinity Capture-MS), HDAC2 (Affinity Capture-MS), ACAD11 (Affinity Capture-MS), SIN3A (Affinity Capture-MS), USP11 (Affinity Capture-MS), EHMT1 (Affinity Capture-MS), PLK1 (Affinity Capture-MS), EHMT2 (Affinity Capture-MS), PHLDB3 (Affinity Capture-MS), L3MBTL2 (Affinity Capture-MS), PEX14 (Affinity Capture-MS), BRCA2 (Affinity Capture-MS), PLD1 (Affinity Capture-MS), MGA (Affinity Capture-MS), CDYL (Affinity Capture-MS)

ESM2 similar proteins: A2AKB4, A2RRU4, A4Q9F3, A4Q9F4, A5PJX4, A6NNM8, A8CVX7, D4A6L0, E1BBQ2, F1M5F3, O02695, O35141, P49796, P49797, P51509, P52734, P56182, P59644, P80560, P97260, P98174, Q12770, Q14679, Q15735, Q2KHI9, Q4R7H0, Q5EBH1, Q5MNU5, Q5SYB0, Q5T848, Q5XI57, Q6GQT6, Q6ZVT0, Q70EL4, Q80TE3, Q80UG8, Q8BUM9, Q8C419, Q8C4S8, Q8CDF7

Diamond homologs: A5PJX4, O75376, Q3U3N0, Q3UHF3, Q4KKX4, Q4R3R9, Q5REE1, Q5UAK0, Q5ZKT9, Q60974, Q7T105, Q7Z3K6, Q8N108, Q8N344, Q9WU42, Q9Y618, Q0GGX2, Q4R2Z8, Q59E36, Q5ZJ40, Q6PGA0, Q6PJG2, Q8BXJ2, Q8QG78, Q96PN7, Q9H0D2, Q9P2K3, Q62599, Q8K4B0, Q90WN5, Q13330, Q62901, Q80TZ9, Q9P2R6, Q18919

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 28 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.

GO biological processes:

GO term	Partners	Fold	FDR
chromatin remodeling	5	14.0×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	89
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
523266	GRCh37/hg19 19p13.3(chr19:259395-3152419)	Likely pathogenic

SpliceAI

3175 predictions. Top by Δscore:

Variant	Effect	Δscore
19:307117:A:AC	donor_gain	1.0000
19:307118:C:CC	donor_gain	1.0000
19:307188:T:TA	donor_gain	1.0000
19:307189:C:A	donor_gain	1.0000
19:308572:CTCA:C	donor_loss	1.0000
19:308573:TCACC:T	donor_loss	1.0000
19:308661:CGTCC:C	acceptor_gain	1.0000
19:308662:GTCC:G	acceptor_gain	1.0000
19:308663:TCC:T	acceptor_gain	1.0000
19:308664:CC:C	acceptor_gain	1.0000
19:308664:CCC:C	acceptor_gain	1.0000
19:308665:CC:C	acceptor_gain	1.0000
19:308666:C:CA	acceptor_loss	1.0000
19:308666:C:CC	acceptor_gain	1.0000
19:308777:A:AC	donor_gain	1.0000
19:308778:C:CC	donor_gain	1.0000
19:308778:CTG:C	donor_gain	1.0000
19:308799:A:AC	donor_gain	1.0000
19:308800:C:CC	donor_gain	1.0000
19:308820:A:AC	donor_gain	1.0000
19:308820:ACTT:A	donor_gain	1.0000
19:308821:C:CC	donor_gain	1.0000
19:308821:CTT:C	donor_gain	1.0000
19:308821:CTTC:C	donor_gain	1.0000
19:308823:T:TA	donor_gain	1.0000
19:308921:CGCAC:C	acceptor_gain	1.0000
19:308922:GCAC:G	acceptor_gain	1.0000
19:308923:CAC:C	acceptor_gain	1.0000
19:308923:CACC:C	acceptor_gain	1.0000
19:308924:AC:A	acceptor_gain	1.0000

AlphaMissense

3558 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:308880:A:G	W344R	1.000
19:308880:A:T	W344R	1.000
19:308897:A:T	V338D	1.000
19:311866:A:C	F321L	1.000
19:311866:A:T	F321L	1.000
19:311867:A:G	F321S	1.000
19:311868:A:G	F321L	1.000
19:311900:A:G	F310S	1.000
19:311925:A:G	W302R	1.000
19:311925:A:T	W302R	1.000
19:308875:C:A	K345N	0.999
19:308875:C:G	K345N	0.999
19:308878:C:A	W344C	0.999
19:308878:C:G	W344C	0.999
19:308889:A:C	Y341D	0.999
19:308899:A:C	C337W	0.999
19:308901:A:G	C337R	0.999
19:311858:A:T	I324N	0.999
19:311867:A:C	F321C	0.999
19:311872:C:A	K319N	0.999
19:311872:C:G	K319N	0.999
19:311891:C:T	G313D	0.999
19:311892:C:G	G313R	0.999
19:311899:A:C	F310L	0.999
19:311899:A:T	F310L	0.999
19:311901:A:G	F310L	0.999
19:311923:C:A	W302C	0.999
19:311923:C:G	W302C	0.999
19:313617:A:G	W228R	0.999
19:313617:A:T	W228R	0.999

dbSNP variants (sampled 300 via entrez): RS1000023456 (19:324190 C>G,T), RS1000025856 (19:326238 A>G), RS1000054651 (19:324340 G>A), RS1000128993 (19:336063 G>A,T), RS1000194970 (19:332593 C>A,T), RS1000264405 (19:327894 G>C), RS1000293143 (19:345189 C>T), RS1000330566 (19:309425 A>G), RS1000349480 (19:337700 C>T), RS1000457088 (19:311154 G>A), RS1000480121 (19:305815 C>A,T), RS1000530461 (19:331660 C>T), RS1000596246 (19:346121 T>C), RS1000696608 (19:328046 T>C), RS1000719565 (19:336945 T>A,G)

Disease associations

OMIM: gene MIM:620092 | 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
GCST001734_5	Non-small cell lung cancer	3.000000e-06
GCST008159_23	Waist-to-hip ratio adjusted for BMI	6.000000e-06
GCST008161_89	Waist circumference adjusted for body mass index	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
abrine	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation, increases methylation	1
Caffeine	decreases phosphorylation	1
Methapyrilene	increases methylation	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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