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TMED3

gene
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Also known as p24Bp24gamma4p24g4

Summary

TMED3 (transmembrane p24 trafficking protein 3, HGNC:28889) is a protein-coding gene on chromosome 15q25.1, encoding Transmembrane emp24 domain-containing protein 3 (Q9Y3Q3). Potential role in vesicular protein trafficking, mainly in the early secretory pathway.

Predicted to be involved in Golgi organization; endoplasmic reticulum to Golgi vesicle-mediated transport; and intracellular protein transport. Located in Golgi apparatus; endoplasmic reticulum; and endoplasmic reticulum-Golgi intermediate compartment.

Source: NCBI Gene 23423 — RefSeq curated summary.

At a glance

  • GWAS associations: 1
  • Clinical variants (ClinVar): 38 total
  • MANE Select transcript: NM_007364

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:28889
Approved symbolTMED3
Nametransmembrane p24 trafficking protein 3
Location15q25.1
Locus typegene with protein product
StatusApproved
Aliasesp24B, p24gamma4, p24g4
Ensembl geneENSG00000166557
Ensembl biotypeprotein_coding
OMIM620437
Entrez23423

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000299705, ENST00000424155, ENST00000536821, ENST00000543455, ENST00000558562, ENST00000896882, ENST00000964020

RefSeq mRNA: 4 — MANE Select: NM_007364 NM_001301203, NM_001330376, NM_001363735, NM_007364

CCDS: CCDS10310, CCDS73768, CCDS81914, CCDS86480

Canonical transcript exons

ENST00000299705 — 3 exons

ExonStartEnd
ENSE000011041617931375779314005
ENSE000011041667932197879322840
ENSE000018952697931111279311417

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 99.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 86.3459 / max 970.0310, expressed in 1820 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter IDTPM avgSamples expressed
14794447.45421810
14794332.44361811
1479455.84441605
2076070.6037345

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
parotid glandUBERON:000183199.38gold quality
body of pancreasUBERON:000115098.64gold quality
lower esophagus mucosaUBERON:003583498.39gold quality
saliva-secreting glandUBERON:000104498.36gold quality
minor salivary glandUBERON:000183098.11gold quality
endometrium epitheliumUBERON:000481198.01gold quality
stromal cell of endometriumCL:000225597.97gold quality
olfactory segment of nasal mucosaUBERON:000538697.97gold quality
mouth mucosaUBERON:000372997.78gold quality
esophagus mucosaUBERON:000246997.61gold quality
palpebral conjunctivaUBERON:000181297.59gold quality
skin of legUBERON:000151197.42gold quality
skin of abdomenUBERON:000141697.28gold quality
adenohypophysisUBERON:000219697.26gold quality
islet of LangerhansUBERON:000000697.13gold quality
pancreasUBERON:000126497.05gold quality
pituitary glandUBERON:000000796.98gold quality
esophagus squamous epitheliumUBERON:000692096.93gold quality
zone of skinUBERON:000001496.71gold quality
right lobe of thyroid glandUBERON:000111996.60gold quality
gingival epitheliumUBERON:000194996.60gold quality
gingivaUBERON:000182896.58gold quality
epithelium of esophagusUBERON:000197696.58gold quality
left lobe of thyroid glandUBERON:000112096.57gold quality
tongue squamous epitheliumUBERON:000691996.32gold quality
nasal cavity mucosaUBERON:000182696.31gold quality
type B pancreatic cellCL:000016996.12gold quality
thyroid glandUBERON:000204696.07gold quality
oral cavityUBERON:000016795.79gold quality
mucosa of transverse colonUBERON:000499195.79gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

ExperimentMarker?Max mean expression
E-MTAB-5061yes27.32
E-HCAD-31yes21.95
E-CURD-112yes7.10
E-ANND-3no0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting TMED3, 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-188-3P100.0068.761240
HSA-MIR-1212499.6869.172700
HSA-MIR-186-3P99.5166.241685
HSA-MIR-6727-3P99.4965.921333
HSA-MIR-806499.4566.92875
HSA-MIR-449B-3P99.2067.241047
HSA-MIR-6852-5P99.1766.692073
HSA-MIR-670-3P99.0368.882404
HSA-MIR-5001-3P98.9167.281394
HSA-MIR-1178-3P98.5767.09890
HSA-MIR-216B-3P98.5567.191223
HSA-MIR-392097.7569.021168
HSA-MIR-425397.4865.11692
HSA-MIR-6862-5P97.4864.84713

Literature-anchored findings (GeneRIF, showing 9)

  • AIM1, ERGIC1, and TPX2 were shown to be highly expressed especially in prostate cancer tissues, and high mRNA expression of ERGIC1 and TMED3 associated with AR and ERG oncogene expression (PMID:22761906)
  • This genome-wide screen has identified two novel metastatic suppressors: TMED3 and SOX12, the knockdown of which increases metastatic growth after direct seeding. (PMID:24920608)
  • Study demonstrates that transmembrane p24 trafficking protein 3 (TMED3) promotes hepatocellular carcinoma (HCC) metastasis and is a potential prognostic biomarker in hepatocellular carcinoma. Study propose that TMED3 promotes HCC metastasis through IL-11/STAT3 signaling. (PMID:27901021)
  • Knockdown of TMED3 inhibits cell viability and migration and increases apoptosis in human chordoma cells. (PMID:33760171)
  • TMED3 promotes the progression and development of lung squamous cell carcinoma by regulating EZR. (PMID:34429402)
  • TMED3 exerts a protumor function in non-small cell lung cancer by enhancing the Wnt/beta-catenin pathway via regulation of AKT. (PMID:34758370)
  • Trafficking protein TMED3 promotes esophageal squamous cell carcinoma. (PMID:35358714)
  • Analysis and Validation of TMED3 correlates with poor prognosis and tumor immune infiltration of glioma. (PMID:35951089)
  • TMED3 stabilizes SMAD2 by counteracting NEDD4-mediated ubiquitination to promote ovarian cancer. (PMID:38411267)

Cross-species orthologs

5 orthologs

OrganismSymbolGene ID
danio_reriotmed3ENSDARG00000028816
mus_musculusTmed3ENSMUSG00000032353
rattus_norvegicusTmed3ENSRNOG00000013889
drosophila_melanogasterp24-1FBGN0030341
caenorhabditis_elegansWBGENE00011606

Paralogs (8): TMED2 (ENSG00000086598), TMED1 (ENSG00000099203), TMED5 (ENSG00000117500), TMED7 (ENSG00000134970), TMED6 (ENSG00000157315), TMED4 (ENSG00000158604), TMED10 (ENSG00000170348), TMED9 (ENSG00000184840)

Protein

Protein identifiers

Transmembrane emp24 domain-containing protein 3 — Q9Y3Q3 (reviewed: Q9Y3Q3)

Alternative names: Membrane protein p24B, p24 family protein gamma-4, p26

All UniProt accessions (4): A0A140VKD1, Q9Y3Q3, F5H4M7, G3V1J9

UniProt curated annotations — full annotation on UniProt →

Function. Potential role in vesicular protein trafficking, mainly in the early secretory pathway. Contributes to the coupled localization of TMED2 and TMED10 in the cis-Golgi network.

Subunit / interactions. Monomer in endoplasmic reticulum, endoplasmic reticulum-Golgi intermediate compartment and cis-Golgi network. Interacts (via C-terminus) with COPG1; the interaction involves dimeric TMED3; however, there are conflicting reports on the interaction. Interacts with GORASP1 and GORASP2.

Subcellular location. Endoplasmic reticulum-Golgi intermediate compartment membrane. Golgi apparatus. cis-Golgi network membrane. Golgi stack membrane. Endoplasmic reticulum membrane. Cytoplasmic vesicle. COPI-coated vesicle membrane.

Similarity. Belongs to the EMP24/GP25L family.

Isoforms (2)

UniProt IDNamesCanonical?
Q9Y3Q3-11yes
Q9Y3Q3-22

RefSeq proteins (4): NP_001288132, NP_001317305, NP_001350664, NP_031390* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR009038GOLD_domDomain
IPR015720Emp24-likeFamily
IPR036598GOLD_dom_sfHomologous_superfamily

Pfam: PF01105

UniProt features (10 total): topological domain 2, short sequence motif 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9Y3Q3-F188.510.69

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

IDPathway
R-HSA-6807878COPI-mediated anterograde transport
R-HSA-6811434COPI-dependent Golgi-to-ER retrograde traffic

MSigDB gene sets: 211 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, MODULE_52, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, MODULE_255, ENK_UV_RESPONSE_KERATINOCYTE_UP, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, MODULE_317, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, GOCC_COATED_VESICLE, GOCC_GOLGI_ASSOCIATED_VESICLE, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, GOCC_VESICLE_COAT

GO Biological Process (4): intracellular protein transport (GO:0006886), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), Golgi organization (GO:0007030), protein transport (GO:0015031)

GO Molecular Function (0):

GO Cellular Component (13): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), Golgi apparatus (GO:0005794), COPI vesicle coat (GO:0030126), transport vesicle (GO:0030133), COPII-coated ER to Golgi transport vesicle (GO:0030134), Golgi cisterna membrane (GO:0032580), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), membrane (GO:0016020), COPI-coated vesicle membrane (GO:0030663), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-2 pathways:

CategoryPathways
ER to Golgi Anterograde Transport1
Golgi-to-ER retrograde transport1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cytoplasm5
endomembrane system3
intracellular membrane-bounded organelle3
intracellular protein localization2
intracellular transport2
Golgi apparatus2
bounding membrane of organelle2
organelle membrane2
protein transport1
intercellular transport1
Golgi vesicle transport1
organelle organization1
endomembrane system organization1
transport1
establishment of protein localization1
nuclear outer membrane-endoplasmic reticulum membrane network1
endoplasmic reticulum subcompartment1
vesicle coat1
COPI-coated vesicle membrane1
cytoplasmic vesicle1
coated vesicle1
Golgi cisterna1
endoplasmic reticulum-Golgi intermediate compartment1
cellular anatomical structure1
COPI-coated vesicle1
Golgi-associated vesicle membrane1
coated vesicle membrane1
intracellular vesicle1

Protein interactions and networks

STRING

1308 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
TMED3TMED10P49755603
TMED3AKAP12Q02952486
TMED3TMED6Q8WW62478
TMED3CNIH4Q9P003463
TMED3CCT3P49368424
TMED3BABAM1Q9NWV8395
TMED3VAV3Q9UKW4391
TMED3GORASP1Q9BQQ3384
TMED3SMIM13P0DJ93374
TMED3TMED9Q9BVK6356
TMED3TMED8Q6PL24350
TMED3PHKBQ93100349
TMED3RBM26Q5T8P6345
TMED3SPRYD4Q8WW59343
TMED3GUCA2AQ02747341

IntAct

32 interactions, top by confidence:

ABTypeScore
TMED10TMED1psi-mi:“MI:0914”(association)0.730
TMED9TMED10psi-mi:“MI:0914”(association)0.730
TMED2ATP9Apsi-mi:“MI:0914”(association)0.640
TMED3HS1BP3psi-mi:“MI:0914”(association)0.530
SEC23ATMED3psi-mi:“MI:0915”(physical association)0.400
Tmed10TARS3psi-mi:“MI:0914”(association)0.350
Tmed2psi-mi:“MI:0914”(association)0.350
MYBBP1ATMED10psi-mi:“MI:0914”(association)0.350
PGRMC1NBASpsi-mi:“MI:0914”(association)0.350
PSMB10DDX46psi-mi:“MI:0914”(association)0.350
TMED10PGRMC1psi-mi:“MI:0914”(association)0.350
TCTN2TMEM131Lpsi-mi:“MI:0914”(association)0.350
SPPL2BGPR89Apsi-mi:“MI:0914”(association)0.350
CHST8NDUFS8psi-mi:“MI:0914”(association)0.350
SPPL2BHAS3psi-mi:“MI:0914”(association)0.350
TMED2SMPD2psi-mi:“MI:0914”(association)0.350
TMED10CYC1psi-mi:“MI:0914”(association)0.350
TMED2ATP12Apsi-mi:“MI:0914”(association)0.350
CLDND1PPLpsi-mi:“MI:0914”(association)0.350
SAAL1TMEM223psi-mi:“MI:0914”(association)0.350
SPPL2BPOC1B-GALNT4psi-mi:“MI:0914”(association)0.350
TMED10TMED7-TICAM2psi-mi:“MI:0914”(association)0.350
TMED2psi-mi:“MI:0914”(association)0.350
MFSD5ILVBLpsi-mi:“MI:0914”(association)0.350
SLC30A10GOLIM4psi-mi:“MI:0914”(association)0.350
SLC30A7ESYT2psi-mi:“MI:0914”(association)0.350

BioGRID (56): TMED3 (Affinity Capture-RNA), TMED3 (Affinity Capture-RNA), TMED3 (Affinity Capture-MS), CCPG1 (Affinity Capture-MS), TMED4 (Affinity Capture-MS), OSBPL8 (Affinity Capture-MS), TMED2 (Affinity Capture-MS), HS1BP3 (Affinity Capture-MS), BLZF1 (Affinity Capture-MS), TMEM30A (Affinity Capture-MS), KIAA1715 (Affinity Capture-MS), TMED10 (Co-fractionation), TMED3 (Co-fractionation), TMED3 (Affinity Capture-MS), TMED3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2KTI4, A0A7U2QYM2, A1CKN5, A5AAA1, A7SXK3, A8N0V8, B0CPJ0, B0WEV5, B2VVF0, F4JJJ3, O04015, O04226, O17528, P32296, P55014, P55015, P55016, P58421, P91926, Q0CNR4, Q13621, Q28BQ6, Q29N38, Q2KJ84, Q4HY20, Q5B5L5, Q5B971, Q5R809, Q69SA9, Q6AXN3, Q6AY25, Q78IS1, Q7QG73, Q870U4, Q948T9, Q949M9, Q94BV7, Q9CXE7, Q9DEB5, Q9HEK4

Diamond homologs: A7SXK3, D3ZTX0, O17528, P32803, P49020, Q15363, Q3T133, Q54BN0, Q5I0E7, Q63524, Q6AY25, Q6BTC2, Q769F9, Q78IS1, Q7Z7H5, Q8R1V4, Q99KF1, Q9P7I9, Q9R0Q3, Q9Y3B3, Q9Y3Q3, O13770, Q13445, Q28BQ6, Q2KJ84, Q2TBK5, Q3V009, Q5BK85, Q5R7E6, Q5R809, Q6AXN3, Q9BVK6, Q9CXE7, Q9Y3A6, P39704, Q12450, Q05359, Q4P958, B3MTS8, B3NZM5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 40 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 termPartnersFoldFDR
intracellular protein transport510.4×3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance29
Likely benign3
Benign1

Top pathogenic / likely-pathogenic (0)

SpliceAI

601 predictions. Top by Δscore:

VariantEffectΔscore
15:79311418:G:Adonor_loss1.0000
15:79313755:A:AGacceptor_gain1.0000
15:79313756:G:GGacceptor_gain1.0000
15:79313756:GGTC:Gacceptor_gain1.0000
15:79314002:CCAGG:Cdonor_loss1.0000
15:79314004:AGGTG:Adonor_loss1.0000
15:79314006:G:GAdonor_loss1.0000
15:79314007:T:Adonor_loss1.0000
15:79311379:G:GTdonor_gain0.9900
15:79311383:TG:Tdonor_gain0.9900
15:79311384:GG:Gdonor_gain0.9900
15:79311418:G:GGdonor_gain0.9900
15:79313747:T:TAacceptor_gain0.9900
15:79313748:G:Aacceptor_gain0.9900
15:79313755:AG:Aacceptor_gain0.9900
15:79313756:GG:Gacceptor_gain0.9900
15:79313756:GGT:Gacceptor_gain0.9900
15:79313756:GGTCA:Gacceptor_gain0.9900
15:79313874:G:GTdonor_gain0.9900
15:79314006:G:GGdonor_gain0.9900
15:79321971:T:TAacceptor_gain0.9900
15:79321972:GCCCA:Gacceptor_loss0.9900
15:79321973:CCCAG:Cacceptor_loss0.9900
15:79321974:CCAG:Cacceptor_loss0.9900
15:79321976:A:ACacceptor_loss0.9900
15:79321976:A:AGacceptor_gain0.9900
15:79321976:AGAT:Aacceptor_gain0.9900
15:79321976:AGATG:Aacceptor_gain0.9900
15:79321977:G:GGacceptor_gain0.9900
15:79321977:GAT:Gacceptor_gain0.9900

AlphaMissense

1421 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
15:79313924:G:CK112N0.999
15:79313924:G:TK112N0.999
15:79313929:T:AV114D0.999
15:79313893:T:CF102S0.998
15:79313899:A:TN104I0.998
15:79313900:T:AN104K0.998
15:79313900:T:GN104K0.998
15:79313782:T:AV65D0.997
15:79313904:T:CF106L0.997
15:79313906:T:AF106L0.997
15:79313906:T:GF106L0.997
15:79313922:A:GK112E0.997
15:79313923:A:TK112M0.997
15:79322012:T:CL151P0.997
15:79322140:A:CS194R0.997
15:79322142:C:AS194R0.997
15:79322142:C:GS194R0.997
15:79313767:G:AG60E0.995
15:79313898:A:TN104Y0.995
15:79322045:G:CR162P0.995
15:79322066:G:CR169P0.995
15:79313923:A:CK112T0.994
15:79322056:G:CA166P0.994
15:79311371:T:CF41S0.993
15:79313892:T:CF102L0.993
15:79313894:C:AF102L0.993
15:79313894:C:GF102L0.993
15:79313908:C:TS107F0.993
15:79313922:A:CK112Q0.993
15:79322074:G:CA172P0.993

dbSNP variants (sampled 300 via entrez): RS1000018760 (15:79396404 C>T), RS1000027917 (15:79354747 G>T), RS1000039156 (15:79354904 G>A), RS1000077196 (15:79383553 G>A), RS1000099393 (15:79386299 A>G), RS1000131508 (15:79377155 T>A), RS1000210279 (15:79379205 T>A), RS1000227754 (15:79337013 C>T), RS1000302577 (15:79367194 A>G,T), RS1000414632 (15:79354838 GC>G,GCC), RS1000531739 (15:79381799 C>G), RS1000544621 (15:79320085 A>G), RS1000566162 (15:79340123 G>A), RS1000622715 (15:79315899 G>A), RS1000644746 (15:79356425 A>G)

Disease associations

OMIM: gene MIM:620437 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

StudyTraitp-value
GCST004735_29Epstein-Barr virus copy number in lymphoblastoid cell lines3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

ChemicalActions (top 5)PubMed papers
Cisplatinaffects expression, affects response to substance2
triphenyl phosphateaffects expression1
sodium arsenitedecreases expression1
tebuconazoledecreases expression1
jinfukangincreases expression1
XAV939decreases reaction, increases expression1
MK 2206decreases reaction, increases expression, increases phosphorylation1
(+)-JQ1 compounddecreases expression1
Decitabineaffects expression1
Azacitidineincreases expression1
Benzo(a)pyreneincreases methylation1
Cadmiumincreases expression, increases abundance1
Doxorubicinincreases expression1
Hydralazineincreases expression, affects cotreatment1
Ivermectindecreases expression1
Leadaffects expression1
Smokedecreases expression1
Tobacco Smoke Pollutionincreases expression1
Valproic Acidincreases expression, affects cotreatment1
Cadmium Chlorideincreases expression, increases abundance1
Copper Sulfatedecreases expression1

Clinical trials (associated diseases)

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

  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): Epstein-Barr virus infection

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 75

This page pulls from 75 datasets indexed by BioBTree:

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