MLEC

gene
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Summary

MLEC (malectin, HGNC:28973) is a protein-coding gene on chromosome 12q24.31, encoding Malectin (Q14165). Carbohydrate-binding protein with a strong ligand preference for Glc2-N-glycan.

This gene encodes the carbohydrate-binding protein malectin which is a Type I membrane-anchored endoplasmic reticulum protein. This protein has an affinity for Glc2Man9GlcNAc2 (G2M9) N-glycans and is involved in regulating glycosylation in the endoplasmic reticulum. This protein has also been shown to interact with ribophorin I and may be involved in the directing the degradation of misfolded proteins. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 9761 — RefSeq curated summary.

At a glance

  • GWAS associations: 4
  • Clinical variants (ClinVar): 30 total
  • Druggable target: yes
  • MANE Select transcript: NM_014730

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:28973
Approved symbolMLEC
Namemalectin
Location12q24.31
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000110917
Ensembl biotypeprotein_coding
OMIM613802
Entrez9761

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000228506, ENST00000412616, ENST00000535413, ENST00000535656, ENST00000545525, ENST00000873883, ENST00000873884, ENST00000873885, ENST00000915485

RefSeq mRNA: 3 — MANE Select: NM_014730 NM_001303627, NM_001303628, NM_014730

CCDS: CCDS76609, CCDS9206

Canonical transcript exons

ENST00000228506 — 5 exons

ExonStartEnd
ENSE00000756534120696316120701859
ENSE00001249670120695095120695152
ENSE00001249678120694824120695000
ENSE00001249688120694091120694269
ENSE00002306378120687149120687531

Expression profiles

Bgee: expression breadth ubiquitous, 303 present calls, max score 98.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 71.5404 / max 1451.4290, expressed in 1822 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
12837671.49611822
1283780.04438

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
mucosa of sigmoid colonUBERON:000499398.61gold quality
corpus epididymisUBERON:000435998.53gold quality
pancreatic ductal cellCL:000207998.34gold quality
pylorusUBERON:000116698.24gold quality
colonic mucosaUBERON:000031798.04gold quality
rectumUBERON:000105297.99gold quality
adrenal tissueUBERON:001830397.97gold quality
ileal mucosaUBERON:000033197.80gold quality
right adrenal gland cortexUBERON:003582797.77gold quality
cauda epididymisUBERON:000436097.69gold quality
adrenal cortexUBERON:000123597.68gold quality
left adrenal glandUBERON:000123497.67gold quality
right adrenal glandUBERON:000123397.62gold quality
adrenal glandUBERON:000236997.61gold quality
left adrenal gland cortexUBERON:003582597.59gold quality
mucosa of transverse colonUBERON:000499197.53gold quality
stromal cell of endometriumCL:000225597.39gold quality
caput epididymisUBERON:000435897.31gold quality
cardia of stomachUBERON:000116297.14gold quality
medial globus pallidusUBERON:000247796.98gold quality
duodenumUBERON:000211496.96gold quality
body of pancreasUBERON:000115096.87gold quality
deciduaUBERON:000245096.76gold quality
colonic epitheliumUBERON:000039796.66gold quality
islet of LangerhansUBERON:000000696.41gold quality
seminal vesicleUBERON:000099896.31gold quality
pancreasUBERON:000126496.28gold quality
right testisUBERON:000453496.21gold quality
left testisUBERON:000453396.20gold quality
renal medullaUBERON:000036296.12gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

ExperimentMarker?Max mean expression
E-GEOD-125970yes470.13
E-MTAB-9467yes48.77
E-HCAD-1yes43.33
E-HCAD-6yes23.72
E-CURD-122yes22.22
E-MTAB-9067yes14.22
E-CURD-112yes5.80
E-GEOD-81608yes4.43
E-MTAB-4850no236.29
E-HCAD-13no2.99
E-ANND-3no0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

227 targeting MLEC, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4533100.0069.482758
HSA-MIR-6758-5P100.0066.211470
HSA-MIR-6856-5P100.0065.471298
HSA-MIR-5193100.0067.261744
HSA-MIR-4262100.0073.263931
HSA-MIR-1252-5P100.0069.802774
HSA-MIR-4673100.0066.641490
HSA-MIR-8485100.0077.574731
HSA-MIR-3925-3P100.0069.951237
HSA-MIR-6867-5P100.0082.213464
HSA-MIR-3667-3P99.9967.171636
HSA-MIR-371B-5P99.9975.344759
HSA-MIR-520G-5P99.9966.76658
HSA-MIR-366299.9973.825684
HSA-MIR-150-5P99.9966.691976
HSA-MIR-181A-5P99.9972.962995
HSA-MIR-181B-5P99.9972.972996
HSA-MIR-181C-5P99.9972.952996
HSA-MIR-181D-5P99.9973.042997
HSA-MIR-373-5P99.9875.364753
HSA-MIR-616-5P99.9875.584775
HSA-MIR-4645-5P99.9865.811284
HSA-MIR-60799.9773.625593
HSA-MIR-568899.9673.234504
HSA-MIR-495-3P99.9672.814197
HSA-MIR-548AA99.9670.643753
HSA-MIR-548AP-3P99.9670.643753
HSA-MIR-548T-3P99.9670.643753
HSA-MIR-551B-5P99.9671.283493
HSA-MIR-3605-5P99.9667.12932

Literature-anchored findings (GeneRIF, showing 5)

  • Malectin is a novel carbohydrate-binding protein of the endoplasmic reticulum and a candidate player in the early steps of protein N-glycosylation (PMID:18524852)
  • These observations suggest a possible role of malectin in regulating newly synthesized glycoproteins via G2M9 recognition. (PMID:21813736)
  • Data indicate that malectin functions by forming a complex with ribophorin I. (PMID:22988243)
  • These results clearly demonstrate that the association of malectin with ribophorin I is required to capture misfolded alpha1-antitrypsin and direct them to the degradation pathway. (PMID:25451265)
  • The results of in vitro studies suggest that C alleles of rs10431386 and rs7964786 on MLEC promotes cerebral palsy (CP) by inhibiting M1 to M2 macrophage polarization. Generally, this work suggested the contribution of MLEC gene polymorphisms to the pathogenesis of CP (PMID:28972276)

Cross-species orthologs

5 orthologs

OrganismSymbolGene ID
danio_reriomlecENSDARG00000059630
mus_musculusMlecENSMUSG00000048578
rattus_norvegicusMlecENSRNOG00000064601
drosophila_melanogasterCG9257FBGN0032916
caenorhabditis_elegansWBGENE00018423

Protein

Protein identifiers

MalectinQ14165 (reviewed: Q14165)

All UniProt accessions (4): Q14165, F5GX14, F5H1S8, H0YG07

UniProt curated annotations — full annotation on UniProt →

Function. Carbohydrate-binding protein with a strong ligand preference for Glc2-N-glycan. May play a role in the early steps of protein N-glycosylation.

Subunit / interactions. Interacts with the oligosaccharyltransferase (OST) complex.

Subcellular location. Endoplasmic reticulum membrane.

Similarity. Belongs to the malectin family.

RefSeq proteins (3): NP_001290556, NP_001290557, NP_055545* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR021720Malectin_domDomain
IPR039155MLECFamily

Pfam: PF11721

UniProt features (17 total): binding site 5, turn 2, topological domain 2, compositionally biased region 2, signal peptide 1, chain 1, glycosylation site 1, helix 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

5 structures.

PDBMethodResolution (Å)
9IL3X-RAY DIFFRACTION1.45
9ILAX-RAY DIFFRACTION1.56
9ILFX-RAY DIFFRACTION1.56
9IKPX-RAY DIFFRACTION1.68
6S7TELECTRON MICROSCOPY3.5

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q14165-F181.030.63

Functional residue map

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

Ligand- & substrate-binding residues (5): 131; 132; 201; 82; 104

Glycosylation sites (1): 268

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

IDPathway
R-HSA-532668N-glycan trimming in the ER and Calnexin/Calreticulin cycle
R-HSA-6798695Neutrophil degranulation
R-HSA-168249Innate Immune System
R-HSA-168256Immune System
R-HSA-392499Metabolism of proteins
R-HSA-446203Asparagine N-linked glycosylation
R-HSA-597592Post-translational protein modification

MSigDB gene sets: 361 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, KAAB_FAILED_HEART_ATRIUM_DN, GOCC_SECRETORY_GRANULE, GTTAAAG_MIR302B, MORF_HDAC2, PRAMOONJAGO_SOX4_TARGETS_DN, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, COUP_01, CTCTAGA_MIR526C_MIR518F_MIR526A, GTGCCTT_MIR506, WEI_MYCN_TARGETS_WITH_E_BOX, GATA3_01, HNF4_DR1_Q3, MORF_RFC4, MORF_PRKDC

GO Biological Process (0):

GO Molecular Function (4): enzyme binding (GO:0019899), carbohydrate binding (GO:0030246), protein-folding chaperone binding (GO:0051087), protein binding (GO:0005515)

GO Cellular Component (6): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), oligosaccharyltransferase complex (GO:0008250), membrane (GO:0016020), specific granule membrane (GO:0035579)

Reactome top-level categories

Rollup of top-5 pathways:

CategoryPathways
Asparagine N-linked glycosylation1
Innate Immune System1
Immune System1
Post-translational protein modification1
Metabolism of proteins1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
protein binding2
binding2
cytoplasm1
endomembrane system1
intracellular membrane-bounded organelle1
organelle membrane1
nuclear outer membrane-endoplasmic reticulum membrane network1
endoplasmic reticulum subcompartment1
membrane1
cell periphery1
endoplasmic reticulum membrane1
membrane protein complex1
endoplasmic reticulum protein-containing complex1
transferase complex1
cellular anatomical structure1
secretory granule membrane1
specific granule1

Protein interactions and networks

STRING

672 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
MLECRPN1P04843801
MLECERLEC1Q96DZ1727
MLECLMAN2Q12907628
MLECUGGT1Q9NYU2618
MLECEDEM2Q9BV94570
MLECCANXP27824547
MLECMOGSQ13724543
MLECCALRP27797522
MLECEDEM1Q92611519
MLECSTT3AP46977513
MLECEDEM3Q9BZQ6503
MLECRPN2P04844492
MLECSTT3BQ8TCJ2477
MLECOS9Q13438475
MLECUGGT2Q9NYU1474

IntAct

109 interactions, top by confidence:

ABTypeScore
CFTRESYT2psi-mi:“MI:2364”(proximity)0.710
CFTRESYT2psi-mi:“MI:0914”(association)0.710
RPN1MLECpsi-mi:“MI:0915”(physical association)0.690
MLECRPN1psi-mi:“MI:0915”(physical association)0.690
STT3ARPN1psi-mi:“MI:0914”(association)0.560
RPN2SMPD2psi-mi:“MI:0914”(association)0.530
DAD1RPN1psi-mi:“MI:0915”(physical association)0.530
CEP78CEP43psi-mi:“MI:0914”(association)0.530
RPN1APBB1psi-mi:“MI:0914”(association)0.530
MLECUMODpsi-mi:“MI:0407”(direct interaction)0.440
FER1L5psi-mi:“MI:0915”(physical association)0.400
Dctn3psi-mi:“MI:0914”(association)0.350
Nedd1psi-mi:“MI:0914”(association)0.350
TSNAXpsi-mi:“MI:0914”(association)0.350
RAB7Apsi-mi:“MI:0914”(association)0.350
Tmed2psi-mi:“MI:0914”(association)0.350
Trip11PPLpsi-mi:“MI:0914”(association)0.350
GOLT1Bpsi-mi:“MI:0914”(association)0.350
ESYT2psi-mi:“MI:0914”(association)0.350
E5ESYT2psi-mi:“MI:0914”(association)0.350
HSCBRBP5psi-mi:“MI:0914”(association)0.350
DLSTpsi-mi:“MI:0914”(association)0.350

BioGRID (159): CTSD (Co-fractionation), RBM8A (Co-fractionation), MLEC (Affinity Capture-MS), MLEC (Proximity Label-MS), MLEC (Proximity Label-MS), MLEC (Proximity Label-MS), MLEC (Proximity Label-MS), MLEC (Proximity Label-MS), MLEC (Affinity Capture-MS), MLEC (Affinity Capture-MS), MLEC (Affinity Capture-MS), MLEC (Affinity Capture-MS), MLEC (Affinity Capture-MS), MLEC (Affinity Capture-MS), MLEC (Affinity Capture-MS)

ESM2 similar proteins: A0A7C9FSB8, A2TLM1, A6H7H7, B8BKI7, B9N1F9, B9SQI7, D2XV59, E0CSI1, F1N9S8, O00178, O08582, O35586, O35760, O48964, O48965, O76031, O81770, P11029, P11497, P58044, P69341, Q0J035, Q13085, Q13907, Q14165, Q1LZ95, Q1LZ96, Q28559, Q2R483, Q38929, Q39471, Q39472, Q39664, Q3UMR5, Q42553, Q4R4W5, Q5NVE1, Q5R8R6, Q5SWU9, Q5U2U0

Diamond homologs: A9C3P0, Q14165, Q5FVQ4, Q6INX3, Q6ZQI3, Q8AVF4

SIGNOR signaling

1 interactions.

AEffectBMechanism
MLEC“form complex”“OST-B complex”binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 115 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:

PathwayPartnersFoldFDR
PD-L1(CD274) glycosylation and translocation to plasma membrane1068.3×3e-14
Maturation of spike protein1138.4×4e-13
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane835.4×5e-09
Maturation of DENV proteins1233.4×2e-13
Translation of Structural Proteins526.8×8e-05
Late SARS-CoV-2 Infection Events519.3×3e-04
Degradation of CDH1512.9×2e-03
Anchoring of the basal body to the plasma membrane710.4×3e-04

GO biological processes:

GO termPartnersFoldFDR
obsolete protein N-linked glycosylation via asparagine1069.5×6e-14
protein N-linked glycosylation1129.9×3e-11
ERAD pathway713.1×3e-04
transmembrane transport610.4×5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance17
Likely benign0
Benign2

Top pathogenic / likely-pathogenic (0)

SpliceAI

739 predictions. Top by Δscore:

VariantEffectΔscore
12:120694082:T:Aacceptor_gain1.0000
12:120694089:A:AGacceptor_gain1.0000
12:120694090:G:GTacceptor_gain1.0000
12:120694090:GC:Gacceptor_gain1.0000
12:120694090:GCC:Gacceptor_gain1.0000
12:120694090:GCCT:Gacceptor_gain1.0000
12:120694090:GCCTC:Gacceptor_gain1.0000
12:120694207:G:GTdonor_gain1.0000
12:120694211:GGGAC:Gdonor_gain1.0000
12:120694268:AGG:Adonor_loss1.0000
12:120694270:G:GAdonor_loss1.0000
12:120694814:A:AGacceptor_gain1.0000
12:120694814:ATCCT:Aacceptor_gain1.0000
12:120694815:T:Gacceptor_gain1.0000
12:120694818:T:Aacceptor_gain1.0000
12:120694819:G:Aacceptor_gain1.0000
12:120694822:A:AGacceptor_gain1.0000
12:120694822:AG:Aacceptor_gain1.0000
12:120694823:G:Aacceptor_gain1.0000
12:120694823:G:GGacceptor_gain1.0000
12:120694823:GGT:Gacceptor_gain1.0000
12:120694823:GGTA:Gacceptor_gain1.0000
12:120694823:GGTAT:Gacceptor_gain1.0000
12:120694999:AGG:Adonor_loss1.0000
12:120695000:GGTA:Gdonor_loss1.0000
12:120695002:T:Gdonor_loss1.0000
12:120695089:TCCTA:Tacceptor_loss1.0000
12:120695090:CCTAG:Cacceptor_loss1.0000
12:120695091:CTA:Cacceptor_loss1.0000
12:120695092:TA:Tacceptor_loss1.0000

AlphaMissense

1891 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
12:120687460:G:AG55D1.000
12:120687525:G:CG77R1.000
12:120694093:T:CS80P1.000
12:120694102:G:CG83R1.000
12:120694103:G:AG83D1.000
12:120694103:G:TG83V1.000
12:120694163:G:CR103P1.000
12:120694237:G:CA128P1.000
12:120694240:G:AE129K1.000
12:120694241:A:TE129V1.000
12:120694242:G:CE129D1.000
12:120694242:G:TE129D1.000
12:120694246:T:GY131D1.000
12:120694249:T:AF132I1.000
12:120694249:T:CF132L1.000
12:120694249:T:GF132V1.000
12:120694250:T:CF132S1.000
12:120694250:T:GF132C1.000
12:120694251:T:AF132L1.000
12:120694251:T:GF132L1.000
12:120694267:A:GK138E1.000
12:120694269:G:CK138N1.000
12:120694269:G:TK138N1.000
12:120694827:T:CF140L1.000
12:120694828:T:CF140S1.000
12:120694829:T:AF140L1.000
12:120694829:T:GF140L1.000
12:120694869:G:CD154H1.000
12:120694870:A:TD154V1.000
12:120694875:T:CF156L1.000

dbSNP variants (sampled 300 via entrez): RS1000066995 (12:120691916 T>C), RS1000293643 (12:120691532 T>C,G), RS1000317612 (12:120699049 G>C), RS1000586845 (12:120696798 C>T), RS1000663938 (12:120691287 C>T), RS1000737325 (12:120688862 C>T), RS1001089126 (12:120686774 T>C,G), RS1001120538 (12:120686923 C>T), RS1001193095 (12:120692765 G>A,T), RS1001422854 (12:120687764 CTCA>C), RS1002226760 (12:120694749 G>A,T), RS1002602082 (12:120685542 G>A), RS1002941647 (12:120691474 A>G,T), RS1003073200 (12:120698615 G>C,T), RS1003096789 (12:120689269 T>C,G)

Disease associations

OMIM: gene MIM:613802 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

StudyTraitp-value
GCST005666_4Fractional excretion of metabolites in chronic kidney disease3.000000e-14
GCST006249_30Serum metabolite levels4.000000e-177
GCST012020_371Serum metabolite levels3.000000e-161
GCST012020_372Serum metabolite levels1.000000e-31

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0005116urinary metabolite measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067153 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
5.15Kd7055nMCHEMBL5653589
5.15ED507055nMCHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2148754: Binding affinity to human MLEC incubated for 45 mins by Kinobead based pull down assaykd7.0548uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects expression, increases expression3
bisphenol Aincreases expression2
Acetaminophendecreases expression, increases expression2
Tunicamycinincreases expression2
bisphenol Faffects cotreatment, increases expression1
testosterone enanthateaffects expression1
triphenyl phosphateaffects expression1
sodium arsenatedecreases expression1
tris(1,3-dichloro-2-propyl)phosphatedecreases expression1
di-n-butylphosphoric acidaffects expression1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideincreases expression1
nutlin 3affects cotreatment, increases secretion1
abrinedecreases expression1
bisphenol AFincreases expression1
Leflunomidedecreases expression1
Air Pollutantsdecreases expression1
Arsenicaffects methylation1
Cisplatinincreases expression1
Dactinomycinaffects cotreatment, increases secretion1
Dexamethasoneaffects cotreatment, increases expression1
Diazinonincreases methylation1
Diurondecreases expression1
Indomethacinaffects cotreatment, increases expression1
Ivermectindecreases expression1
Methyl Methanesulfonatedecreases expression1
Ribonucleotidesaffects binding1
Rotenoneincreases expression1
Seleniumaffects cotreatment, decreases expression, increases expression1
Dihydrotestosteroneincreases expression1
Dronabinolincreases expression1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL5651796BindingBinding affinity to human MLEC incubated for 45 mins by Kinobead based pull down assayNVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

CellosaurusNameCategorySex
CVCL_B1X7Abcam HeLa MLEC KOCancer cell lineFemale

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.