TMED6

Summary

TMED6 (transmembrane p24 trafficking protein 6, HGNC:28331) is a protein-coding gene on chromosome 16q22.1, encoding Transmembrane emp24 domain-containing protein 6 (Q8WW62).

Predicted to be involved in Golgi organization; endoplasmic reticulum to Golgi vesicle-mediated transport; and intracellular protein transport. Predicted to be located in endoplasmic reticulum membrane. Predicted to be active in several cellular components, including COPII-coated ER to Golgi transport vesicle; Golgi apparatus; and endoplasmic reticulum-Golgi intermediate compartment.

Source: NCBI Gene 146456 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_144676

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28331
Approved symbol	TMED6
Name	transmembrane p24 trafficking protein 6
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC23911, p24gamma5, p24g5
Ensembl gene	ENSG00000157315
Ensembl biotype	protein_coding
Entrez	146456

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000288025, ENST00000568748, ENST00000905348

RefSeq mRNA: 1 — MANE Select: NM_144676 NM_144676

CCDS: CCDS10878

Canonical transcript exons

ENST00000288025 — 4 exons

Exon	Start	End
ENSE00001141377	69343250	69343640
ENSE00001141383	69351541	69351786
ENSE00003589572	69347788	69347936
ENSE00003619228	69349525	69349651

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 97.22.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3744 / max 379.0775, expressed in 34 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157902	0.3744	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	97.22	gold quality
right uterine tube	UBERON:0001302	95.09	gold quality
pancreas	UBERON:0001264	94.10	gold quality
islet of Langerhans	UBERON:0000006	92.49	gold quality
body of stomach	UBERON:0001161	86.74	gold quality
stomach	UBERON:0000945	83.84	gold quality
duodenum	UBERON:0002114	82.31	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.17	gold quality
fundus of stomach	UBERON:0001160	80.33	gold quality
epithelial cell of pancreas	CL:0000083	80.11	gold quality
kidney epithelium	UBERON:0004819	79.62	silver quality
rectum	UBERON:0001052	79.35	gold quality
oviduct epithelium	UBERON:0004804	79.04	gold quality
cardia of stomach	UBERON:0001162	77.65	gold quality
fallopian tube	UBERON:0003889	77.11	gold quality
mucosa of transverse colon	UBERON:0004991	75.34	gold quality
ileal mucosa	UBERON:0000331	74.01	silver quality
right lobe of liver	UBERON:0001114	73.39	gold quality
small intestine Peyer’s patch	UBERON:0003454	71.62	gold quality
adult mammalian kidney	UBERON:0000082	70.95	gold quality
small intestine	UBERON:0002108	70.85	gold quality
cortex of kidney	UBERON:0001225	70.37	gold quality
transverse colon	UBERON:0001157	70.30	gold quality
granulocyte	CL:0000094	69.97	gold quality
kidney	UBERON:0002113	69.66	gold quality
colonic mucosa	UBERON:0000317	69.46	gold quality
mucosa of sigmoid colon	UBERON:0004993	68.83	gold quality
leukocyte	CL:0000738	68.47	gold quality
monocyte	CL:0000576	68.37	gold quality
liver	UBERON:0002107	68.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	18.96
E-GEOD-81608	yes	4.42
E-GEOD-83139	yes	4.01

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting TMED6, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-4646-3P	98.65	66.98	693
HSA-MIR-3944-5P	98.50	67.55	997
HSA-MIR-4771	97.43	67.69	596
HSA-MIR-4433B-5P	95.91	66.56	727
HSA-MIR-4323	93.93	63.89	656

Literature-anchored findings (GeneRIF, showing 1)

• TMED6-COG8 chimera might act as a novel diagnostic marker in TFE3 translocation renal cell carcinoma. (PMID:26045774)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmed6	ENSDARG00000088079
mus_musculus	Tmed6	ENSMUSG00000031919
rattus_norvegicus	Tmed6	ENSRNOG00000020406
drosophila_melanogaster	loj	FBGN0061492
caenorhabditis_elegans		WBGENE00011606

Paralogs (8): TMED2 (ENSG00000086598), TMED1 (ENSG00000099203), TMED5 (ENSG00000117500), TMED7 (ENSG00000134970), TMED4 (ENSG00000158604), TMED3 (ENSG00000166557), TMED10 (ENSG00000170348), TMED9 (ENSG00000184840)

Protein

Protein identifiers

Transmembrane emp24 domain-containing protein 6 — Q8WW62 (reviewed: Q8WW62)

Alternative names: p24 family protein gamma-5

All UniProt accessions (1): Q8WW62

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Endoplasmic reticulum membrane.

Similarity. Belongs to the EMP24/GP25L family.

RefSeq proteins (1): NP_653277* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009038	GOLD_dom	Domain
IPR015720	Emp24-like	Family

Pfam: PF01105

UniProt features (9 total): topological domain 2, glycosylation site 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WW62-F1	82.13	0.56

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 (2): 107, 156

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 50 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, chr16q22, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, HNF1_Q6, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, GOCC_COATED_VESICLE, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, HNF1_C, HNF1_01, VECCHI_GASTRIC_CANCER_EARLY_DN, GOBP_GOLGI_ORGANIZATION, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ENDOPLASMIC_RETICULUM_GOLGI_INTERMEDIATE_COMPARTMENT

GO Biological Process (3): intracellular protein transport (GO:0006886), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), Golgi organization (GO:0007030)

GO Molecular Function (0):

GO Cellular Component (6): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), Golgi apparatus (GO:0005794), COPII-coated ER to Golgi transport vesicle (GO:0030134), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
intracellular membrane-bounded organelle	3
intracellular transport	2
endomembrane system	2
intracellular protein localization	1
protein transport	1
intercellular transport	1
Golgi vesicle transport	1
organelle organization	1
endomembrane system organization	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
coated vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

548 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMED6	COG8	Q96MW5	651
TMED6	A0A3B3ITX9	A0A3B3ITX9	593
TMED6	F8VZ95	F8VZ95	578
TMED6	TMED7	Q9Y3B3	551
TMED6	TMED9	Q9BVK6	542
TMED6	LARGE2	Q8N3Y3	500
TMED6	TMED10	P49755	499
TMED6	TMED2	Q15363	493
TMED6	TTC7B	Q86TV6	493
TMED6	CEP76	Q8TAP6	492
TMED6	COPZ2	Q9P299	491
TMED6	IQCF6	A8MYZ5	481
TMED6	TMEM132A	Q24JP5	478
TMED6	TMED3	Q9Y3Q3	478
TMED6	NIP7	Q9Y221	467

IntAct

4 interactions, top by confidence:

A	B	Type	Score
TMED6	SMPD2	psi-mi:“MI:0914”(association)	0.530
TMED6	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
SLC35A2	PRSS2	psi-mi:“MI:0914”(association)	0.350

BioGRID (59): ALG9 (Affinity Capture-MS), SMPD2 (Affinity Capture-MS), VEZT (Affinity Capture-MS), LRP12 (Affinity Capture-MS), ATP2A3 (Affinity Capture-MS), ITGA2 (Affinity Capture-MS), C1QL1 (Affinity Capture-MS), BTN2A2 (Affinity Capture-MS), CNTNAP3B (Affinity Capture-MS), CNNM1 (Affinity Capture-MS), B4GALNT1 (Affinity Capture-MS), CGRRF1 (Affinity Capture-MS), KCNJ8 (Affinity Capture-MS), FUT10 (Affinity Capture-MS), NETO2 (Affinity Capture-MS)

ESM2 similar proteins: B3MTS8, B3NZM5, B4GMC3, B4HJV5, B4JG34, B4KB41, B4LYB8, B4NKL0, B4PVC6, B4QWH9, F4J4Y0, O35587, O43909, P0CN72, P24387, P24388, P49755, Q0VCA9, Q14849, Q28557, Q28735, Q295B2, Q3T133, Q4WQL0, Q5B5L5, Q5E971, Q5I0E7, Q5RE32, Q5ZLK8, Q60571, Q63584, Q6AY64, Q6IDL4, Q6NZZ3, Q7Z7H5, Q8GYG1, Q8R1V4, Q8RWM6, Q8WW62, Q91653

Diamond homologs: Q0VCA9, Q8WW62, Q9CQG0

SIGNOR signaling

0 interactions.

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	0
Uncertain significance	37
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

772 predictions. Top by Δscore:

Variant	Effect	Δscore
16:69347884:T:C	acceptor_gain	1.0000
16:69351538:TA:T	donor_loss	1.0000
16:69351539:A:AG	donor_loss	1.0000
16:69351539:A:C	donor_loss	1.0000
16:69351540:C:CT	donor_loss	1.0000
16:69351540:CCT:C	donor_gain	1.0000
16:69351547:A:C	donor_gain	1.0000
16:69351539:A:AC	donor_gain	0.9900
16:69351540:C:CC	donor_gain	0.9900
16:69351601:T:TA	donor_gain	0.9900
16:69343405:G:C	donor_gain	0.9800
16:69343636:CCGTC:C	acceptor_gain	0.9600
16:69343637:CGTCC:C	acceptor_gain	0.9600
16:69343638:GTCC:G	acceptor_loss	0.9600
16:69343640:CCTA:C	acceptor_loss	0.9600
16:69343641:C:CC	acceptor_gain	0.9600
16:69343641:CT:C	acceptor_loss	0.9600
16:69347884:T:TC	acceptor_gain	0.9600
16:69351598:G:A	donor_gain	0.9600
16:69343637:CGTC:C	acceptor_gain	0.9400
16:69347883:CT:C	acceptor_gain	0.9400
16:69347884:TT:T	acceptor_gain	0.9400
16:69349691:CA:C	donor_gain	0.9300
16:69351540:CCTCG:C	donor_gain	0.9000
16:69349727:T:TA	donor_gain	0.8900
16:69351536:CATA:C	donor_gain	0.8900
16:69351542:TCGTA:T	donor_gain	0.8800
16:69351735:C:CT	acceptor_gain	0.8800
16:69351735:C:T	acceptor_gain	0.8800
16:69343603:A:C	acceptor_gain	0.8500

AlphaMissense

1592 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:69343503:G:C	S209R	0.994
16:69343503:G:T	S209R	0.994
16:69343505:T:G	S209R	0.994
16:69347921:C:G	C119S	0.979
16:69347922:A:T	C119S	0.979
16:69351590:C:G	C55S	0.979
16:69351591:A:T	C55S	0.979
16:69347876:A:G	L134P	0.974
16:69351591:A:G	C55R	0.973
16:69347924:A:G	L118P	0.970
16:69343579:C:G	R184P	0.969
16:69343517:A:G	S205P	0.965
16:69343484:C:G	G216R	0.963
16:69343484:C:T	G216R	0.963
16:69347931:A:C	Y116D	0.958
16:69343520:A:G	W204R	0.957
16:69343520:A:T	W204R	0.957
16:69351546:A:C	Y70D	0.956
16:69347932:A:C	F115L	0.955
16:69347932:A:T	F115L	0.955
16:69347934:A:G	F115L	0.955
16:69343483:C:T	G216E	0.953
16:69351622:A:C	F44L	0.953
16:69351622:A:T	F44L	0.953
16:69351624:A:G	F44L	0.953
16:69347918:A:G	L120P	0.952
16:69343597:C:G	R178P	0.951
16:69351589:G:C	C55W	0.950
16:69347922:A:G	C119R	0.949
16:69347882:A:T	V132E	0.947

dbSNP variants (sampled 300 via entrez): RS1000113971 (16:69344995 A>G), RS1000464612 (16:69344676 G>A,C), RS1000571616 (16:69349164 T>C), RS1000799614 (16:69348530 G>T), RS1000952872 (16:69343156 T>C), RS1001305903 (16:69349760 G>C,T), RS1002064463 (16:69349624 C>A,G), RS1002114621 (16:69343243 T>C,G), RS1002308382 (16:69348508 G>T), RS1002359429 (16:69348673 T>TG), RS1002583776 (16:69342922 C>T), RS1002732951 (16:69352628 C>G,T), RS1002784655 (16:69345661 C>A,G,T), RS1002916815 (16:69353239 G>A), RS1003315029 (16:69347260 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005951_13	Body mass index	5.000000e-11
GCST007006_16	Logical memory (delayed recall) in normal cognition	7.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004874	memory performance

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.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects expression, decreases expression	4
Cyclosporine	decreases expression, increases expression	3
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Leflunomide	decreases expression	1
Cisplatin	decreases expression	1
Formaldehyde	increases expression	1
Hydrogen Peroxide	affects expression	1
Lead	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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