MEX3A

Summary

MEX3A (mex-3 RNA binding family member A, HGNC:33482) is a protein-coding gene on chromosome 1q22, encoding RNA-binding protein MEX3A (A1L020). RNA binding protein, may be involved in post-transcriptional regulatory mechanisms. It is a selective cancer dependency (DepMap: 15.2% of cell lines).

Enables RNA binding activity. Located in P-body and cytosol.

Source: NCBI Gene 92312 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 31 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 15.2% of screened cell lines
• MANE Select transcript: NM_001093725

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33482
Approved symbol	MEX3A
Name	mex-3 RNA binding family member A
Location	1q22
Locus type	gene with protein product
Status	Approved
Aliases	RNF162
Ensembl gene	ENSG00000254726
Ensembl biotype	protein_coding
OMIM	611007
Entrez	92312

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000442784, ENST00000532414

RefSeq mRNA: 1 — MANE Select: NM_001093725 NM_001093725

CCDS: CCDS53377

Canonical transcript exons

ENST00000532414 — 2 exons

Exon	Start	End
ENSE00002192814	156081545	156082465
ENSE00002229876	156072013	156077682

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 97.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.0233 / max 211.4608, expressed in 1115 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15069	2.3951	898
15066	1.2601	204
15067	1.1460	196
15068	0.8854	426
15063	0.1498	79
15064	0.1081	54
15065	0.0788	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	97.01	gold quality
cortical plate	UBERON:0005343	95.72	gold quality
ventricular zone	UBERON:0003053	95.35	gold quality
kidney epithelium	UBERON:0004819	90.26	gold quality
upper arm skin	UBERON:0004263	89.89	silver quality
buccal mucosa cell	CL:0002336	89.55	silver quality
left ventricle myocardium	UBERON:0006566	88.07	gold quality
vena cava	UBERON:0004087	87.24	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.76	silver quality
parotid gland	UBERON:0001831	86.37	silver quality
lateral globus pallidus	UBERON:0002476	86.22	silver quality
lateral nuclear group of thalamus	UBERON:0002736	85.75	gold quality
body of tongue	UBERON:0011876	83.90	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	83.33	silver quality
sperm	CL:0000019	83.21	silver quality
subthalamic nucleus	UBERON:0001906	83.09	silver quality
substantia nigra pars compacta	UBERON:0001965	82.51	silver quality
dorsal plus ventral thalamus	UBERON:0001897	82.41	silver quality
tendon of biceps brachii	UBERON:0008188	82.28	gold quality
substantia nigra pars reticulata	UBERON:0001966	82.00	silver quality
oocyte	CL:0000023	81.37	gold quality
inferior vagus X ganglion	UBERON:0005363	81.35	silver quality
cardia of stomach	UBERON:0001162	81.23	silver quality
tongue	UBERON:0001723	80.75	silver quality
ventral tegmental area	UBERON:0002691	80.70	silver quality
pons	UBERON:0000988	80.35	silver quality
pylorus	UBERON:0001166	80.13	silver quality
superior vestibular nucleus	UBERON:0007227	79.87	silver quality
trachea	UBERON:0003126	79.44	silver quality
medulla oblongata	UBERON:0001896	79.43	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	8.77
E-MTAB-6075	no	64.08
E-ANND-3	no	2.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

237 targeting MEX3A, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-12136	99.98	72.81	5713
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 15.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 20)

• MEX3A promotes triple negative breast cancer proliferation and migration via the PI3K/AKT signaling pathway. (PMID:32738346)
• Mex3a interacts with LAMA2 to promote lung adenocarcinoma metastasis via PI3K/AKT pathway. (PMID:32792503)
• The RNA-binding protein MEX3A is a prognostic factor and regulator of resistance to gemcitabine in pancreatic ductal adenocarcinoma. (PMID:33159833)
• MEX3A is upregulated in esophageal squamous cell carcinoma (ESCC) and promotes development and progression of ESCC through targeting CDK6. (PMID:33188661)
• MEX3A contributes to development and progression of glioma through regulating cell proliferation and cell migration and targeting CCL2. (PMID:33414423)
• Mex3a promotes oncogenesis through the RAP1/MAPK signaling pathway in colorectal cancer and is inhibited by hsa-miR-6887-3p. (PMID:33638620)
• Comprehensive Analysis of Prognostic Value of MEX3A and Its Relationship with Immune Infiltrates in Ovarian Cancer. (PMID:34189143)
• Mex-3 RNA binding MEX3A promotes the proliferation and migration of breast cancer cells via regulating RhoA/ROCK1/LIMK1 signaling pathway. (PMID:34486491)
• MEX3A promotes nasopharyngeal carcinoma progression via the miR-3163/SCIN axis by regulating NF-kappaB signaling pathway. (PMID:35490173)
• SMYD2 epigenetically activates MEX3A and suppresses CDX2 in colorectal cancer cells to augment cancer growth. (PMID:35637161)
• MEX3A promotes the malignant progression of ovarian cancer by regulating intron retention in TIMELESS. (PMID:35715407)
• MEX3A Impairs DNA Mismatch Repair Signaling and Mediates Acquired Temozolomide Resistance in Glioblastoma. (PMID:36112059)
• MEX3A Mediates p53 Degradation to Suppress Ferroptosis and Facilitate Ovarian Cancer Tumorigenesis. (PMID:36354374)
• RNA-Binding Protein MEX3A Interacting with DVL3 Stabilizes Wnt/beta-Catenin Signaling in Endometrial Carcinoma. (PMID:36614043)
• MEX3A promotes angiogenesis in colorectal cancer via glycolysis. (PMID:37155144)
• The RNA binding protein MEX3A promotes tumor progression of breast cancer by post-transcriptional regulation of IGFBP4. (PMID:37433992)
• MEX3A determines in vivo hepatocellular carcinoma progression and induces resistance to sorafenib in a Hippo-dependent way. (PMID:37460832)
• MEX3A induces the development of thyroid cancer via targeting CREB1. (PMID:37529875)
• Mex-3 RNA binding family member A (MEX3A)/circMPP6 complex promotes colorectal cancer progression by inhibiting autophagy. (PMID:38565536)
• MEX3A promotes colorectal cancer migration, invasion and EMT via regulating the Wnt/beta-catenin signaling pathway. (PMID:38914858)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000076638
mus_musculus	Mex3a	ENSMUSG00000074480
rattus_norvegicus	Mex3a	ENSRNOG00000058654
drosophila_melanogaster	CG11360	FBGN0039920
caenorhabditis_elegans	mex-3	WBGENE00003229

Paralogs (3): MEX3C (ENSG00000176624), MEX3D (ENSG00000181588), MEX3B (ENSG00000183496)

Protein

Protein identifiers

RNA-binding protein MEX3A — A1L020 (reviewed: A1L020)

Alternative names: RING finger and KH domain-containing protein 4

All UniProt accessions (1): A1L020

UniProt curated annotations — full annotation on UniProt →

Function. RNA binding protein, may be involved in post-transcriptional regulatory mechanisms.

Subcellular location. Cytoplasm. Nucleus. P-body.

Tissue specificity. Highest levels found in fetal brain and testis. Detected also in thymus, salivary gland and uterus.

Post-translational modifications. Phosphorylated.

Domain organisation. Binds RNA through its KH domains.

RefSeq proteins (1): NP_001087194* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR004087	KH_dom	Domain
IPR004088	KH_dom_type_1	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR036612	KH_dom_type_1_sf	Homologous_superfamily
IPR047226	KH-I_MEX3_rpt2	Domain
IPR047227	MEX3	Family
IPR047228	KH-I_MEX3_rpt1	Domain

Pfam: PF00013, PF13920

UniProt features (10 total): domain 2, region of interest 2, compositionally biased region 2, modified residue 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A1L020-F1	65.91	0.31

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 (2): 338, 462

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 106 (showing top): chr1q22, CUI_TCF21_TARGETS_2_UP, GOCC_RIBONUCLEOPROTEIN_GRANULE, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, LEE_BMP2_TARGETS_DN, GOCC_P_BODY, GOCC_SUPRAMOLECULAR_COMPLEX, PCGF1_TARGET_GENES, ZNF664_TARGET_GENES, GSE10240_CTRL_VS_IL17_AND_IL22_STIM_PRIMARY_BRONCHIAL_EPITHELIAL_CELLS_DN, MIR335_3P, MIR4795_3P, MIR548E_5P, MIR6809_3P, MIR3121_3P

GO Biological Process (0):

GO Molecular Function (4): RNA binding (GO:0003723), zinc ion binding (GO:0008270), nucleic acid binding (GO:0003676), metal ion binding (GO:0046872)

GO Cellular Component (4): P-body (GO:0000932), nucleus (GO:0005634), cytosol (GO:0005829), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
nucleic acid binding	1
transition metal ion binding	1
binding	1
cation binding	1
cytoplasmic ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

714 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MEX3A	DCP1A	Q9NPI6	830
MEX3A	AGO2	Q9UKV8	803
MEX3A	HNRNPK	P61978	702
MEX3A	AGO1	Q9UL18	667
MEX3A	LAMA2	P24043	604
MEX3A	LRIG1	Q96JA1	505
MEX3A	LGR5	O75473	494
MEX3A	RIGI	O95786	472
MEX3A	CDX2	Q99626	472
MEX3A	MSI1	O43347	454
MEX3A	MEX3B	Q6ZN04	435
MEX3A	HOPX	Q9BPY8	434
MEX3A	OLFM4	Q6UX06	420
MEX3A	UBAP2L	Q14157	410
MEX3A	SLC41A1	Q8IVJ1	400

IntAct

10 interactions, top by confidence:

A	B	Type	Score
ERP44	MEX3A	psi-mi:“MI:0914”(association)	0.530
MAPT	MEX3A	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
LIN28A	MEX3A	psi-mi:“MI:0914”(association)	0.350
LIN28B	MEX3A	psi-mi:“MI:2364”(proximity)	0.270
DDX6	RPSA2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (414): MEX3A (Affinity Capture-MS), MEX3A (Affinity Capture-MS), MEX3A (Affinity Capture-MS), MEX3A (Affinity Capture-MS), MEX3A (Reconstituted Complex), MEX3A (Reconstituted Complex), MEX3A (Protein-RNA), MEX3A (Affinity Capture-MS), DDX58 (Affinity Capture-Western), MEX3A (Affinity Capture-Western), MEX3A (Proximity Label-MS), MEX3A (Proximity Label-MS), MEX3A (Proximity Label-MS), MEX3A (Proximity Label-MS), MEX3A (Proximity Label-MS)

ESM2 similar proteins: A1L020, A1L3F4, A7X8B3, A7X8B5, A7X8B7, A7X8B9, A7X8C2, A7X8C4, A7X8C7, A7X8C9, A7X8D2, A7X8D4, A7XW25, O97775, O97776, O97952, O97960, P06401, P10275, P84550, P84551, P89463, Q01JD1, Q05A36, Q0VDT2, Q3UE17, Q5PQQ7, Q5U5Q3, Q69Z36, Q6QT55, Q6ZK57, Q6ZN04, Q71FD5, Q7RTV3, Q7TSJ6, Q7XQN1, Q7XT42, Q84SL2, Q86XN8, Q8BQ89

Diamond homologs: A1E2V0, A1L020, A1L3F4, A5D8Q0, A9JTP3, A9ULZ2, D3ZDI6, E3SCZ8, O08863, O10296, O10324, O14064, O15392, O62640, O70201, O88738, P40629, P41435, P41436, P41437, P41454, P47732, P98170, Q05AK5, Q0WPJ7, Q13489, Q13490, Q28ER3, Q28H51, Q50L39, Q557E7, Q5BKL8, Q5R881, Q5RAH9, Q60989, Q62210, Q69Z36, Q6I6F4, Q6J1J1, Q6NTT6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	MEX3A	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	25
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1460461	NC_000001.10:g.(?155581953)(156851434_?)del	Pathogenic

SpliceAI

297 predictions. Top by Δscore:

Variant	Effect	Δscore
1:156081540:CTTA:C	donor_loss	1.0000
1:156081542:TACCT:T	donor_loss	1.0000
1:156077694:C:CT	acceptor_gain	0.9900
1:156077695:G:T	acceptor_gain	0.9900
1:156081543:A:AC	donor_gain	0.9900
1:156081544:C:CC	donor_gain	0.9900
1:156081544:CCTTG:C	donor_gain	0.9900
1:156081548:G:A	donor_gain	0.9900
1:156077679:CAGC:C	acceptor_gain	0.9800
1:156077683:C:CC	acceptor_gain	0.9800
1:156077688:A:AC	acceptor_gain	0.9800
1:156077681:GC:G	acceptor_gain	0.9700
1:156077681:GCCTG:G	acceptor_loss	0.9700
1:156077682:CC:C	acceptor_gain	0.9700
1:156077684:T:C	acceptor_loss	0.9700
1:156077688:A:C	acceptor_gain	0.9700
1:156081544:CCTT:C	donor_gain	0.9700
1:156081544:C:CA	donor_gain	0.9600
1:156081544:CCT:C	donor_gain	0.9600
1:156076597:G:A	donor_gain	0.9400
1:156077678:GCAGC:G	acceptor_gain	0.9400
1:156077679:CAGCC:C	acceptor_gain	0.9400
1:156076489:A:AC	donor_gain	0.9300
1:156076499:T:A	donor_gain	0.9300
1:156077680:AGC:A	acceptor_gain	0.9300
1:156077680:AGCC:A	acceptor_gain	0.9300
1:156077681:GCCT:G	acceptor_gain	0.9300
1:156077683:C:T	acceptor_gain	0.9300
1:156081085:A:AC	donor_gain	0.9300
1:156081543:AC:A	donor_gain	0.9300

AlphaMissense

3327 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:156076584:A:C	I518R	1.000
1:156076584:A:G	I518T	1.000
1:156076584:A:T	I518K	1.000
1:156076590:A:C	I516S	1.000
1:156076590:A:G	I516T	1.000
1:156076590:A:T	I516N	1.000
1:156076593:G:T	A515D	1.000
1:156076613:G:C	C508W	1.000
1:156076614:C:A	C508F	1.000
1:156076614:C:G	C508S	1.000
1:156076614:C:T	C508Y	1.000
1:156076615:A:G	C508R	1.000
1:156076615:A:T	C508S	1.000
1:156076622:A:C	C505W	1.000
1:156076623:C:A	C505F	1.000
1:156076623:C:G	C505S	1.000
1:156076623:C:T	C505Y	1.000
1:156076624:A:C	C505G	1.000
1:156076624:A:G	C505R	1.000
1:156076624:A:T	C505S	1.000
1:156076643:G:C	C498W	1.000
1:156076644:C:T	C498Y	1.000
1:156076656:G:T	A494E	1.000
1:156076657:C:G	A494P	1.000
1:156076658:A:C	C493W	1.000
1:156076659:C:A	C493F	1.000
1:156076659:C:G	C493S	1.000
1:156076659:C:T	C493Y	1.000
1:156076660:A:G	C493R	1.000
1:156076660:A:T	C493S	1.000

dbSNP variants (sampled 300 via entrez): RS1000052361 (1:156073740 TA>T,TAA), RS1000109884 (1:156081652 C>T), RS1000134001 (1:156078422 C>G), RS1000222586 (1:156074026 G>A), RS1000296361 (1:156073772 C>A,T), RS1000428024 (1:156082177 C>T), RS1000777684 (1:156082493 T>A,C,G), RS1001027043 (1:156072053 C>T), RS1001150519 (1:156082838 G>A), RS1001812316 (1:156074101 A>T), RS1002138635 (1:156074632 G>A), RS1002166133 (1:156080691 G>C), RS1002569189 (1:156078230 G>T), RS1002710314 (1:156083036 G>A), RS1002820962 (1:156084236 T>C)

Disease associations

OMIM: gene MIM:611007 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): Charcot-Marie-Tooth disease type 2 (MONDO:0018993)

Orphanet (1): Autosomal dominant Charcot-Marie-Tooth disease type 2 (Orphanet:64746)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST009391_1446	Metabolite levels	6.000000e-06
GCST009391_1819	Metabolite levels	6.000000e-06
GCST010988_256	Adult body size	2.000000e-19

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010409	triacylglycerol 50:2 measurement
EFO:0010404	triacylglycerol 48:1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	10
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, decreases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
sodium arsenite	decreases expression	1
entinostat	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
licochalcone B	decreases expression	1
bisphenol S	decreases methylation	1
LDN 193189	increases expression, affects cotreatment	1
NSC 689534	decreases expression, affects binding	1
(+)-JQ1 compound	decreases expression	1
2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido(4,3-d)pyrimidin-5(6H)-one	increases activity, decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Allergens	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Calcitriol	decreases expression, affects cotreatment	1
Copper	affects binding, decreases expression	1
Estradiol	decreases expression, affects cotreatment	1
Lead	affects expression	1
Melphalan	increases expression	1
Progesterone	affects cotreatment, decreases expression	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Testosterone	affects cotreatment, decreases expression	1
Dronabinol	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05902351	Not specified	RECRUITING	Natural History Study for Charcot Marie Tooth Disease