MEST

Summary

MEST (mesoderm specific transcript, HGNC:7028) is a protein-coding gene on chromosome 7q32.2, encoding Mesoderm-specific transcript homolog protein (Q5EB52). Plays an important role in enabling neurons to transition from bipolar to multipolar shapes, a process essential for their correct migration toward the cortical plate during brain development.

This gene encodes a member of the alpha/beta hydrolase superfamily. It is imprinted, exhibiting preferential expression from the paternal allele in fetal tissues, and isoform-specific imprinting in lymphocytes. The loss of imprinting of this gene has been linked to certain types of cancer and may be due to promotor switching. The encoded protein may play a role in development. Alternatively spliced transcript variants encoding multiple isoforms have been identified for this gene. Pseudogenes of this gene are located on the short arm of chromosomes 3 and 4, and the long arm of chromosomes 6 and 15.

Source: NCBI Gene 4232 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 47 total — 1 likely-pathogenic
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_002402

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7028
Approved symbol	MEST
Name	mesoderm specific transcript
Location	7q32.2
Locus type	gene with protein product
Status	Approved
Aliases	PEG1
Ensembl gene	ENSG00000106484
Ensembl biotype	protein_coding
OMIM	601029
Entrez	4232

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 14 protein_coding, 3 retained_intron

ENST00000223215, ENST00000341441, ENST00000378576, ENST00000393187, ENST00000399874, ENST00000416162, ENST00000421001, ENST00000427521, ENST00000433159, ENST00000437637, ENST00000437945, ENST00000458161, ENST00000462132, ENST00000463263, ENST00000475188, ENST00000488093, ENST00000494868

RefSeq mRNA: 6 — MANE Select: NM_002402 NM_001253900, NM_001253901, NM_001253902, NM_002402, NM_177524, NM_177525

CCDS: CCDS5822, CCDS5823, CCDS59081

Canonical transcript exons

ENST00000223215 — 12 exons

Exon	Start	End
ENSE00000723327	130497156	130497235
ENSE00001039842	130492085	130492339
ENSE00003337101	130503933	130503996
ENSE00003489324	130498139	130498275
ENSE00003563880	130495368	130495522
ENSE00003584174	130500462	130500532
ENSE00003589724	130499875	130499915
ENSE00003604980	130500789	130500890
ENSE00003646573	130497936	130498013
ENSE00003790962	130502644	130502720
ENSE00003791546	130498419	130498477
ENSE00003827825	130504939	130506465

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 76.8634 / max 2982.4105, expressed in 1367 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81126	51.3912	1024
81125	18.0265	842
81127	5.1571	765
81123	1.0575	381
81124	0.5901	235
81128	0.4376	175
81122	0.1898	102
81129	0.0136	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	99.07	gold quality
placenta	UBERON:0001987	98.92	gold quality
secondary oocyte	CL:0000655	98.87	gold quality
oocyte	CL:0000023	98.52	gold quality
adrenal tissue	UBERON:0018303	98.14	gold quality
pericardium	UBERON:0002407	97.95	gold quality
parietal pleura	UBERON:0002400	97.68	gold quality
ventricular zone	UBERON:0003053	97.31	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.44	gold quality
omental fat pad	UBERON:0010414	96.32	gold quality
peritoneum	UBERON:0002358	96.31	gold quality
embryo	UBERON:0000922	96.17	gold quality
adipose tissue	UBERON:0001013	96.13	gold quality
mammary duct	UBERON:0001765	95.70	gold quality
adrenal gland	UBERON:0002369	95.59	gold quality
right adrenal gland	UBERON:0001233	95.57	gold quality
left adrenal gland	UBERON:0001234	95.54	gold quality
pleura	UBERON:0000977	95.38	gold quality
left adrenal gland cortex	UBERON:0035825	95.38	gold quality
adrenal cortex	UBERON:0001235	95.33	gold quality
connective tissue	UBERON:0002384	95.19	gold quality
right adrenal gland cortex	UBERON:0035827	95.06	gold quality
pigmented layer of retina	UBERON:0001782	94.76	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.65	gold quality
thoracic mammary gland	UBERON:0005200	94.64	gold quality
mammary gland	UBERON:0001911	94.59	gold quality
ganglionic eminence	UBERON:0004023	94.20	gold quality
epithelium of mammary gland	UBERON:0003244	94.10	gold quality
dorsal root ganglion	UBERON:0000044	93.37	gold quality
superior vestibular nucleus	UBERON:0007227	93.25	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	7736.95
E-HCAD-24	yes	5171.56
E-ENAD-20	yes	4887.83
E-MTAB-8221	yes	3364.94
E-MTAB-10042	yes	2502.99
E-MTAB-10018	yes	2320.49
E-MTAB-9906	yes	1832.55
E-MTAB-7407	yes	1369.08
E-GEOD-124472	yes	1184.19
E-MTAB-8894	yes	1154.40
E-MTAB-6701	yes	122.63
E-HCAD-5	yes	47.95
E-HCAD-10	yes	43.92
E-GEOD-84465	yes	26.71
E-HCAD-6	yes	19.85

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
CTNNB1	Repression

Upstream regulators (CollecTRI, top): JDP2, RARA, SOX6

miRNA regulators (miRDB)

88 targeting MEST, 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-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• MEST gene is imprinted in an isoform-specific manner in adult lymphocytes. (PMID:10631159)
• Findings suggest that PEG1/MEST can be excluded as a major determinant of Silver-Russell syndrome. (PMID:11754049)
• An imprinted PEG1/MEST antisense expressed predominantly in human testis and in mature spermatozoa. (PMID:11821432)
• Mutation screening and imprinting analysis of candidate genes for autism in the 7q32 region (PMID:11920156)
• a novel mechanism /promoter switch/ leading to biallelic expression in invasive breast cancer (PMID:12023987)
• An intron contains a sequence, MESTIT1, which is transcribed only from the paternal allele, may be involved in MEST regulation (PMID:12095916)
• Lof imprinting of PEG1/MESTOI may be related to tumorigenesis and malignant transformation, especially in NSCLC (PMID:15547750)
• PEG1 isoform 2 is in fact imprinted in a large subset of human placentae. (PMID:16338457)
• Hypermethylation of paternally expressed genes including PEG1/MEST, which have growth-promoting effects, may be relevant to low birth weight in subjects conceived by assisted reproduction techniques. (PMID:17450433)
• Type of epimutation at the PEG1/MEST locus does not play a relevant role in Silver-Russell syndrome. (PMID:18585117)
• MEST is localized to the endoplasmic reticulum/Golgi apparatus where its putative enzymatic properties as a lipase or acyltransferase, predicted from sequence homology with members of the alpha/beta fold hydrolase superfamily. (PMID:18644838)
• data demonstrated that tumorigenesis of leiomyoma is associated with overexpression of isoform 1 of PEG1/MEST gene, but not with loss of imprinting of the gene (PMID:20339302)
• Regardless of conception method, the PEG1 methylation percentage in chorionic villus from spontaneous abortions is significantly higher than in villus from induced abortions and multifetal reduction. (PMID:21575949)
• Data indicate that ARMCX2, COL1A1, MDK, MEST and MLH1 genes acquired methylation in drug-resistant ovarian cancer-sustaining (side population) cells. (PMID:22249249)
• In cortices, the MEST promoter was hemimethylated, as expected for a differentially methylated imprinting control region, whereas the COPG2 and TSGA14 promoters were completely demethylated, typical for transcriptionally active non-imprinted genes. (PMID:22456293)
• MEST showed tissue-specific imprinting, being paternally expressed in skeletal muscle, fat, pituitary gland, heart, kidney, lung, stomach and uterus, and maternally expressed in spleen and liver. (PMID:22531794)
• These results support the idea that intrauterine exposure to gestational diabetes mellitus has long-lasting effects on the epigenome of the offspring. (PMID:23209187)
• The expression levels of miR-335 significantly correlated with those of MEST, supporting the notion that the intronic miR-335 is co-expressed with its host gene (PMID:23229728)
• DNA methylation level at the H19 and MEST differentially methylated regions (DMRs)is reduced in placentas from pregnancies conceived by IVF/ICSI when compared with placentas from spontaneous conception. (PMID:23343754)
• Paternal methylation aberrations at imprinting control regions of DLK1-GTL2, MEST (PEG1), and ZAC (PLAGL1) and global methylation levels are not associated with idiopathic recurrent spontaneous miscarriages. (PMID:23415968)
• altered DNA methylation at imprinted domains including IGF2/H19 and PEG1/MEST may mediate the association between human papillomavirus infection and invasive cervical cancer (PMID:23775149)
• strongly expressed in invasive extravillous trophoblasts during the first trimester (PMID:27697227)
• G4 formation at motifs not previously identified through bioinformatic analysis of the MEST promoter, is reported. (PMID:28052120)
• Some growth-regulating imprinted genes such as MEST and MEG3, are susceptible to non-imprinted allele during development and differentiation, whereas the intergenic differentially methylated region of others (i.e. PEG3) are strictly maintained. (PMID:28854270)
• We conclude methylation changes at some CpG sites of MEST and DLK differentially methylated regions in preeclamptic group (PMID:29157033)
• Study provides evidence that MEST mediates the impact of prenatal bisphenol A exposure on long-term body weight development in offspring by triggering adipocyte differentiation. (PMID:29721103)
• Imprinting methylation in SNRPN and MEST1 in adult blood predicts cognitive ability. (PMID:30707743)
• MEST induces Twist-1-mediated EMT through STAT3 activation in breast cancers. (PMID:30903102)
• Long intergenic noncoding RNA (LINC00) 284 (LINC00284) is involved in angiogenesis during ovarian cancer (OC) development by recruiting nuclear factor kappa B (NF-kappaB1) and down-regulating mesoderm-specific transcript (MEST). (PMID:31574234)
• The effect of folic acid deficiency on Mest/Peg1 in neural tube defects. (PMID:32241207)
• The sperm epigenome does not display recurrent epimutations in patients with severely impaired spermatogenesis. (PMID:32375885)
• MEST promotes lung cancer invasion and metastasis by interacting with VCP to activate NF-kappaB signaling. (PMID:34560900)
• Hypermethylation of Mest promoter causes aberrant Wnt signaling in patients with Alzheimer’s disease. (PMID:34625606)
• miR-145-5p Modulates Gefitinib Resistance by Targeting NRAS and MEST in Non-Small Cell Lung Cancer. (PMID:34686504)
• Human umbilical cord blood mesenchymal stem cells-derived exosomal microRNA-503-3p inhibits progression of human endometrial cancer cells through downregulating MEST. (PMID:34997218)
• Increased co-expression of MEST and BRCA1 is associated with worse prognosis and immune infiltration in ovarian cancer. (PMID:35042621)
• MiR-29c-3p represses gastric cancer development via modulating MEST. (PMID:36269039)
• Genome-wide CRISPR/Cas9 screening identifies a targetable MEST-PURA interaction in cancer metastasis. (PMID:37149929)
• alpha1,3-fucosylation of MEST promotes invasion potential of cytotrophoblast cells by activating translation initiation. (PMID:37798282)
• MEST promotes immune escape in gastric cancer by downregulating MHCI expression via SHP2. (PMID:39181599)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	mest	ENSDARG00000032319
mus_musculus	Mest	ENSMUSG00000051855
rattus_norvegicus	Mest	ENSRNOG00000048088
drosophila_melanogaster	CG5704	FBGN0026570
drosophila_melanogaster	CG5707	FBGN0026593
drosophila_melanogaster	CG15879	FBGN0035309
drosophila_melanogaster	CG15820	FBGN0035312
drosophila_melanogaster	CG11309	FBGN0037070
drosophila_melanogaster	CG7632	FBGN0037071
caenorhabditis_elegans	C31H5.1	WBGENE00007854
caenorhabditis_elegans		WBGENE00017335
caenorhabditis_elegans		WBGENE00018077
caenorhabditis_elegans		WBGENE00019525
caenorhabditis_elegans		WBGENE00022258
caenorhabditis_elegans		WBGENE00022259
caenorhabditis_elegans		WBGENE00022260

Paralogs (12): ABHD5 (ENSG00000011198), ABHD4 (ENSG00000100439), EPHX3 (ENSG00000105131), ABHD11 (ENSG00000106077), ABHD14B (ENSG00000114779), EPHX2 (ENSG00000120915), ABHD8 (ENSG00000127220), BPHL (ENSG00000137274), ABHD6 (ENSG00000163686), EPHX4 (ENSG00000172031), SERHL2 (ENSG00000183569), ABHD14A (ENSG00000248487)

Protein

Protein identifiers

Mesoderm-specific transcript homolog protein — Q5EB52 (reviewed: Q5EB52)

Alternative names: Paternally-expressed gene 1 protein

All UniProt accessions (9): Q5EB52, A4D1L9, C9JCM6, C9JG66, C9JRA9, C9JUD2, C9JW74, C9JWU9, R4GN52

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in enabling neurons to transition from bipolar to multipolar shapes, a process essential for their correct migration toward the cortical plate during brain development. This function is likely achieved through the regulation of N-cadherin-dependent cell adhesion and the modulation of Akt and canonical Wnt signaling pathways. Essential for the development and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development. Negatively regulates the canonical Wnt signaling pathway during adipogenic differentiation by reducing the glycosylation, maturation, and cell membrane localization of the Wnt coreceptor LRP6.

Subunit / interactions. Interacts with LRP6; this interaction inhibits LRP6 maturation by reducing its glycosylation, preventing proper processing and localization to the cell membrane.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Highly expressed in hydatidiform moles, but barely expressed in dermoid cysts. Biallelic expression is detected in blood lymphocytes. Seems to imprinted in an isoform-specific manner rather than in a tissue-specific manner in lymphocytes. Isoform 1 is expressed only from the paternal allele. Isoform 2 is expressed from both the paternal allele and the maternal allele.

Similarity. Belongs to the AB hydrolase superfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5EB52-1	1	yes
Q5EB52-2	2, Isoform b
Q5EB52-3	3

RefSeq proteins (6): NP_001240829, NP_001240830, NP_001240831, NP_002393, NP_803490, NP_803491 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000073	AB_hydrolase_1	Domain
IPR000639	Epox_hydrolase-like	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR050266	AB_hydrolase_sf	Family

Pfam: PF00561

UniProt features (12 total): transmembrane region 3, sequence conflict 3, splice variant 2, chain 1, domain 1, short sequence motif 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5EB52-F1	91.88	0.75

Functional residue map

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

Glycosylation sites (1): 163

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 266 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, LI_CISPLATIN_RESISTANCE_DN, MODULE_52, GOBP_REGULATION_OF_LIPID_STORAGE, GRUETZMANN_PANCREATIC_CANCER_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS

GO Biological Process (10): mesoderm development (GO:0007498), negative regulation of glycoprotein biosynthetic process (GO:0010561), regulation of lipid storage (GO:0010883), response to retinoic acid (GO:0032526), fat cell differentiation (GO:0045444), neuron development (GO:0048666), regulation of neurogenesis (GO:0050767), negative regulation of canonical Wnt signaling pathway (GO:0090090), radial glia-guided pyramidal neuron migration (GO:0140650), negative regulation of protein localization to plasma membrane (GO:1903077)

GO Molecular Function (3): hydrolase activity (GO:0016787), catalytic activity (GO:0003824), protein binding (GO:0005515)

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), extracellular exosome (GO:0070062), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tissue development	1
glycoprotein biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
regulation of glycoprotein biosynthetic process	1
negative regulation of glycoprotein metabolic process	1
lipid storage	1
regulation of cellular process	1
response to lipid	1
response to oxygen-containing compound	1
cell differentiation	1
neuron differentiation	1
cell development	1
neurogenesis	1
regulation of nervous system development	1
regulation of cell development	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
neuron migration	1
protein localization to plasma membrane	1
regulation of protein localization to plasma membrane	1
negative regulation of protein localization to cell periphery	1
negative regulation of protein localization to membrane	1
catalytic activity	1
molecular_function	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1770 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MEST	PEG3	P78418	910
MEST	COPG2	Q9UBF2	908
MEST	GRB10	Q13322	905
MEST	CEP41	Q9BYV8	874
MEST	PLAGL1	Q9UM63	867
MEST	PEG10	Q86TG7	862
MEST	ZIM2	Q9NZV7	814
MEST	SNRPN	P14648	804
MEST	DLK1	P15803	768
MEST	ZFP57	Q9NU63	760
MEST	CPA4	Q9UI42	721
MEST	NNAT	Q16517	717
MEST	IGF2	P01344	714
MEST	CDKN1C	P49918	676
MEST	SGCE	O43556	674

IntAct

48 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
MEST	CIDEB	psi-mi:“MI:0915”(physical association)	0.560
MEST	LIME1	psi-mi:“MI:0915”(physical association)	0.560
MEST	RNF19B	psi-mi:“MI:0915”(physical association)	0.560
GAD2	MEST	psi-mi:“MI:0915”(physical association)	0.560
C6orf47	MEST	psi-mi:“MI:0915”(physical association)	0.560
MEST	CIAO2A	psi-mi:“MI:0915”(physical association)	0.560
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
MEST	MPZL2	psi-mi:“MI:0915”(physical association)	0.370
CD300C	MEST	psi-mi:“MI:0915”(physical association)	0.370
MEST	SNX7	psi-mi:“MI:0915”(physical association)	0.370
CRELD2	MEST	psi-mi:“MI:0915”(physical association)	0.370
MEST	BLOC1S2	psi-mi:“MI:0915”(physical association)	0.370
MEST	CEP70	psi-mi:“MI:0915”(physical association)	0.370
CMTM3	MEST	psi-mi:“MI:0915”(physical association)	0.370
DBN1	MEST	psi-mi:“MI:0915”(physical association)	0.370
MEST	FEZ1	psi-mi:“MI:0915”(physical association)	0.370
FST	MEST	psi-mi:“MI:0915”(physical association)	0.370
ING5	MEST	psi-mi:“MI:0915”(physical association)	0.370
KIFAP3	MEST	psi-mi:“MI:0915”(physical association)	0.370
MEST	ZNF205	psi-mi:“MI:0915”(physical association)	0.370
ZNF579	MEST	psi-mi:“MI:0915”(physical association)	0.370
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (44): ABCD3 (Affinity Capture-MS), MEST (Affinity Capture-MS), MEST (Biochemical Activity), MEST (Co-fractionation), VDAC3 (Co-fractionation), MEST (Co-fractionation), MEST (Co-fractionation), MEST (Affinity Capture-MS), RNF19B (Two-hybrid), CIDEB (Two-hybrid), GAD2 (Two-hybrid), FAM96A (Two-hybrid), LIME1 (Two-hybrid), C6orf47 (Two-hybrid), MEST (Affinity Capture-MS)

ESM2 similar proteins: B9S2H4, C5FTV7, F4J3R7, O22141, O23614, O24509, O48917, O64749, O80333, O81000, O81312, P29001, Q07646, Q0WUG6, Q14703, Q18801, Q2HJM9, Q39041, Q43857, Q4VY51, Q5EB52, Q5H8A5, Q5H8A6, Q6P5P5, Q6YRM6, Q6ZDJ7, Q84KI6, Q84W56, Q8H0B2, Q8H0B6, Q8H0V1, Q8H930, Q8NBZ7, Q8S4F6, Q8S8T4, Q8VZ10, Q8VZC0, Q8W471, Q9FI17, Q9LES4

Diamond homologs: A5I3F5, A8YWL3, C0ZKI1, C3K630, C7TMK0, D5H0J3, H2KZ86, O52866, P46541, P46542, P46544, P52278, P52279, P96084, Q03NE0, Q07646, Q184M8, Q1G8L9, Q2HJM9, Q5EB52, Q5FMT1, Q6P5P5, Q76KX0, Q87DF8, Q890D8, Q97A76, Q97UA2, Q9PD69, A0A126P745, A0A1L5BTC1, A0A242M8J4, A7MFY0, A8IAD8, B0SY51, B2HJU9, B4RF90, B8H3S9, C5CN82, D4Z2G1, G5EDL5

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SOX6	“up-regulates quantity by expression”	MEST	“transcriptional regulation”
MEST	“down-regulates activity”	LRP6
MEST	down-regulates	CTNNB1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	22
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
208394	NM_002402.4(MEST):c.559C>T (p.Pro187Ser)	Likely pathogenic

SpliceAI

1767 predictions. Top by Δscore:

Variant	Effect	Δscore
7:130492336:GCAG:G	donor_gain	1.0000
7:130492340:G:GG	donor_gain	1.0000
7:130492340:GTG:G	donor_loss	1.0000
7:130497153:TA:T	acceptor_loss	1.0000
7:130497154:A:AG	acceptor_gain	1.0000
7:130497154:A:AT	acceptor_loss	1.0000
7:130497155:G:GT	acceptor_gain	1.0000
7:130497155:GACT:G	acceptor_gain	1.0000
7:130497231:ACAAG:A	donor_loss	1.0000
7:130497233:AAGG:A	donor_loss	1.0000
7:130497236:G:T	donor_loss	1.0000
7:130497237:T:G	donor_loss	1.0000
7:130497931:TGTA:T	acceptor_loss	1.0000
7:130497932:GTAG:G	acceptor_loss	1.0000
7:130497933:TA:T	acceptor_loss	1.0000
7:130497934:A:AG	acceptor_gain	1.0000
7:130497934:A:G	acceptor_loss	1.0000
7:130497935:G:GG	acceptor_gain	1.0000
7:130497935:G:GT	acceptor_loss	1.0000
7:130497935:GATTT:G	acceptor_gain	1.0000
7:130498011:CCGGT:C	donor_loss	1.0000
7:130498012:CGGT:C	donor_loss	1.0000
7:130498013:GGTA:G	donor_loss	1.0000
7:130498014:G:C	donor_loss	1.0000
7:130498015:T:A	donor_loss	1.0000
7:130498135:TCA:T	acceptor_loss	1.0000
7:130498136:CAGA:C	acceptor_loss	1.0000
7:130498137:A:AG	acceptor_gain	1.0000
7:130498137:A:C	acceptor_loss	1.0000
7:130498138:G:A	acceptor_loss	1.0000

AlphaMissense

2178 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:130498239:A:T	D147V	1.000
7:130503947:G:T	G281W	1.000
7:130503948:G:A	G281E	1.000
7:130497206:T:C	F78L	0.999
7:130497208:T:A	F78L	0.999
7:130497208:T:G	F78L	0.999
7:130497218:A:C	S82R	0.999
7:130497220:C:A	S82R	0.999
7:130497220:C:G	S82R	0.999
7:130497227:T:A	W85R	0.999
7:130497227:T:C	W85R	0.999
7:130497981:G:C	D103H	0.999
7:130497982:A:C	D103A	0.999
7:130497982:A:T	D103V	0.999
7:130497990:G:C	G106R	0.999
7:130498002:A:C	S110R	0.999
7:130498004:T:A	S110R	0.999
7:130498004:T:G	S110R	0.999
7:130498235:C:G	H146D	0.999
7:130498238:G:C	D147H	0.999
7:130498238:G:T	D147Y	0.999
7:130498239:A:C	D147A	0.999
7:130498239:A:G	D147G	0.999
7:130498245:G:A	G149E	0.999
7:130498245:G:T	G149V	0.999
7:130498254:T:A	V152D	0.999
7:130498266:T:C	L156P	0.999
7:130498473:T:A	N177K	0.999
7:130498473:T:G	N177K	0.999
7:130498474:G:A	G178R	0.999

dbSNP variants (sampled 300 via entrez): RS1000112642 (7:130499205 G>A), RS1000379468 (7:130488957 G>A), RS1000811781 (7:130493595 G>A), RS1001391380 (7:130504520 T>C), RS1002321381 (7:130490522 G>A), RS1002431172 (7:130484272 C>A), RS1002675403 (7:130490305 A>T), RS1002989238 (7:130493279 G>T), RS1003092254 (7:130486891 C>G,T), RS1003212771 (7:130498772 C>G,T), RS1003264657 (7:130491470 T>C), RS1003383637 (7:130485398 G>A), RS1003434674 (7:130485672 A>C), RS1003777628 (7:130498178 G>A,C), RS1003947132 (7:130491121 A>G)

Disease associations

OMIM: gene MIM:601029 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): childhood-onset schizophrenia (MONDO:0957430)

Orphanet (1): Childhood-onset schizophrenia (Orphanet:641496)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005958_14	Waist-to-hip ratio adjusted for BMI (age >50)	1.000000e-07
GCST005962_34	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	6.000000e-07

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): CHEMBL4523324 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3807348	MEST, MIR335		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
bisphenol A	affects cotreatment, decreases methylation, decreases expression	3
Air Pollutants	increases abundance, increases oxidation, decreases expression, affects cotreatment	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
entinostat	decreases expression, affects cotreatment	2
Cisplatin	affects response to substance, increases expression	2
Doxorubicin	decreases expression, affects response to substance	2
Tretinoin	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
sotorasib	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
cobaltiprotoporphyrin	affects expression	1
lead acetate	increases expression, decreases methylation	1
beta-lapachone	decreases expression	1
arsenite	increases methylation	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
didecyldimethylammonium	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
diallyl trisulfide	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
seocalcitol	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1

ChEMBL screening assays

20 unique, capped per target: 20 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4482362	Binding	Inhibition of human recombinant MEST T579B (2 to 335 amino acids) expressed in Sf9 cell membranes assessed as reduction in glycerol 3-phosphate acyltransferase activity at 200 uM using [3H]-glycerol 3-phosphate and palmitoyl CoA incubated f	Test system for measuring mest activity as well as methods and uses involving the same

Clinical trials (associated diseases)

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