TMED10

Summary

TMED10 (transmembrane p24 trafficking protein 10, HGNC:16998) is a protein-coding gene on chromosome 14q24.3, encoding Transmembrane emp24 domain-containing protein 10 (P49755). Cargo receptor involved in protein vesicular trafficking and quality control in the endoplasmic reticulum (ER) and Golgi. It is a selective cancer dependency (DepMap: 53.6% of cell lines).

This gene is a member of the EMP24/GP25L/p24 family and encodes a protein with a GOLD domain. This type I membrane protein is localized to the plasma membrane and golgi cisternae and is involved in vesicular protein trafficking. The protein is also a member of a heteromeric secretase complex and regulates the complex’s gamma-secretase activity without affecting its epsilon-secretase activity. Mutations in this gene have been associated with early-onset familial Alzheimer’s disease. This gene has a pseudogene on chromosome 8.

Source: NCBI Gene 10972 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 30 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 53.6% of screened cell lines
• MANE Select transcript: NM_006827

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16998
Approved symbol	TMED10
Name	transmembrane p24 trafficking protein 10
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Aliases	TMP21, P24(DELTA), p24d1, p24delta1, p23
Ensembl gene	ENSG00000170348
Ensembl biotype	protein_coding
OMIM	605406
Entrez	10972

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 9 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000303575, ENST00000555036, ENST00000555085, ENST00000555873, ENST00000556969, ENST00000557670, ENST00000622441, ENST00000874503, ENST00000874504, ENST00000874505, ENST00000874506, ENST00000874507, ENST00000918034, ENST00000918035, ENST00000943488

RefSeq mRNA: 1 — MANE Select: NM_006827 NM_006827

CCDS: CCDS9840

Canonical transcript exons

ENST00000303575 — 5 exons

Exon	Start	End
ENSE00001129888	75176355	75176612
ENSE00001272771	75131469	75135006
ENSE00003473463	75152032	75152143
ENSE00003532470	75147664	75147737
ENSE00003665689	75135760	75135886

Expression profiles

Bgee: expression breadth ubiquitous, 305 present calls, max score 99.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 165.9531 / max 940.2895, expressed in 1826 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144108	165.2692	1826
144106	0.6489	330
144107	0.0350	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.57	gold quality
islet of Langerhans	UBERON:0000006	99.45	gold quality
stromal cell of endometrium	CL:0002255	99.43	gold quality
germinal epithelium of ovary	UBERON:0001304	99.26	gold quality
type B pancreatic cell	CL:0000169	99.20	gold quality
corpus epididymis	UBERON:0004359	99.20	gold quality
caput epididymis	UBERON:0004358	99.08	gold quality
endometrium epithelium	UBERON:0004811	99.02	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.99	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.99	gold quality
upper leg skin	UBERON:0004262	98.95	gold quality
seminal vesicle	UBERON:0000998	98.94	gold quality
body of pancreas	UBERON:0001150	98.94	gold quality
skin of hip	UBERON:0001554	98.94	gold quality
pancreas	UBERON:0001264	98.90	gold quality
colonic mucosa	UBERON:0000317	98.89	gold quality
epididymis	UBERON:0001301	98.88	gold quality
endometrium	UBERON:0001295	98.83	gold quality
gall bladder	UBERON:0002110	98.81	gold quality
parietal pleura	UBERON:0002400	98.78	gold quality
rectum	UBERON:0001052	98.77	gold quality
nasal cavity mucosa	UBERON:0001826	98.71	gold quality
choroid plexus epithelium	UBERON:0003911	98.67	gold quality
bronchial epithelial cell	CL:0002328	98.64	gold quality
saliva-secreting gland	UBERON:0001044	98.64	gold quality
pleura	UBERON:0000977	98.63	gold quality
smooth muscle tissue	UBERON:0001135	98.60	gold quality
esophagus squamous epithelium	UBERON:0006920	98.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.50	gold quality
tibia	UBERON:0000979	98.50	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	80.74
E-MTAB-9467	yes	49.16
E-HCAD-4	yes	44.33
E-HCAD-6	yes	35.26
E-CURD-46	yes	13.48
E-HCAD-13	yes	12.94
E-MTAB-9067	yes	12.84
E-CURD-112	yes	12.68
E-MTAB-10042	yes	11.67
E-MTAB-9801	yes	5.85
E-GEOD-110499	no	2224.69
E-MTAB-7606	no	513.60
E-CURD-114	no	21.82
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

146 targeting TMED10, 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-432-3P	100.00	67.86	705
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-153-5P	99.89	73.86	6317

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 53.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 20)

• TMP21, a member of the p24 cargo protein family, is a component of presenilin complexes and differentially regulates gamma-secretase cleavage without affecting epsilon-secretase activity (PMID:16641999)
• TMP21 behaves as a regulator of gamma- but not epsilon-cleavages of beta-amyloid precursor protein generated by presenilin-dependent gamma-secretase complex. (PMID:18405662)
• p23 is widely distributed throughout the frontal cortex, hippocampus and cerebellum of control and Alzheimer disease (AD)brains; steady-state p23 levels are reduced in the brains of individuals with AD. (PMID:18652896)
• Taken together, these results indicate that the degradation of TMP21, as with the other presenilin-associated gamma-secretase complex members, is mediated by the ubiquitin-proteasome pathway. (PMID:19046380)
• the TMP21 transmembrane domain promotes its association with the presenilin complex that results in decreased gamma-cleavage activity (PMID:19710022)
• These results demonstrate that p23/Tmp21 acts as an anchor that distinctively modulates compartmentalization of C1 domain-containing proteins, and it plays an essential role in beta2-chimaerin relocalization. (PMID:20164256)
• Transmembrane protein 23 and p24A differentially control G-protein coupled receptor trafficking and signaling in astrocytes. (PMID:21219331)
• p23 acts as an anchoring protein that retains PKCdelta at the perinuclear region, thus limiting the availability of this kinase for activation in response to stimuli. (PMID:21454541)
• Results suggest that Tmp21 is a novel protein that preferentially binds to Beta(2)-microglobulin-free MHC-I heavy chains. (PMID:21699748)
• Data show that the level of p23 expression is critical for neuronal function, and p23 overexpression initiates a cascade in brainstem that leads to severe motor deficits and other neurological problems, culminating in premature death. (PMID:22204304)
• This study suggested that The role ofTMP21 in the modulation of gamma-secretase activity and protein trafficking and related to alzheimer disease. (PMID:22299712)
• Study demonstrates that NleF binds to the human Tmp21 protein and subsequently disrupts intracellular protein trafficking. (PMID:23434013)
• TMP21 modulates cell growth in papillary thyroid cancer cells by inducing autophagy, which may be associated with activation of AMPK/mTOR pathway. (PMID:26617795)
• Surface plasmon resonance and solution NMR analyses revealed that p24beta1 and p24delta1 GOLD domains interact weakly (Kd= ~10(-4)M). (PMID:27569046)
• Low TMED10 expression is associated with breast cancer. (PMID:28115518)
• TMP21 is genetically associated with Alzheimer’s disease, with the novel Tmp21 SNP as a risk factor for Alzheimer’s pathogenesis. (PMID:28233271)
• The AD-associated protein TMED10 negatively regulates autophagy by inhibiting ATG4B activity. (PMID:30821607)
• Study validated EXT1, TM9SF2, and TMED10 as important host factors for vaccinia virus infection. In addition, TMED10 was found to be crucial for virus-induced plasma membrane blebbing and phosphatidylserine-induced micropinocytosis. (PMID:30996093)
• Results indicate that transmembrane trafficking protein Tmp21(TMP21) could regulate autophagy by modulating reactive oxygen species (ROS) production and TOR serine-threonine kinases (mTOR) activation. (PMID:31472964)
• The circular RNA CDR1as regulate cell proliferation via TMED2 and TMED10. (PMID:32293333)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmed10	ENSDARG00000041391
mus_musculus	Tmed10	ENSMUSG00000021248
rattus_norvegicus	Tmed10	ENSRNOG00000007901
drosophila_melanogaster	bai	FBGN0045866
caenorhabditis_elegans		WBGENE00009829

Paralogs (8): TMED2 (ENSG00000086598), TMED1 (ENSG00000099203), TMED5 (ENSG00000117500), TMED7 (ENSG00000134970), TMED6 (ENSG00000157315), TMED4 (ENSG00000158604), TMED3 (ENSG00000166557), TMED9 (ENSG00000184840)

Protein

Protein identifiers

Transmembrane emp24 domain-containing protein 10 — P49755 (reviewed: P49755)

Alternative names: 21 kDa transmembrane-trafficking protein, S31I125, S31III125, Tmp-21-I, Transmembrane protein Tmp21, p23, p24 family protein delta-1, p24delta

All UniProt accessions (3): P49755, A0A024R6I3, G3V2K7

UniProt curated annotations — full annotation on UniProt →

Function. Cargo receptor involved in protein vesicular trafficking and quality control in the endoplasmic reticulum (ER) and Golgi. The p24 protein family is a group of transmembrane proteins that bind coat protein complex I/COPI and coat protein complex II/COPII involved in vesicular trafficking between the membranes. Acts at the lumenal side for incorporation of secretory cargo molecules into transport vesicles and involved in vesicle coat formation at the cytoplasmic side. Mainly functions in the early secretory pathway and cycles between the ER, ER-Golgi intermediate compartment (ERGIC) and Golgi, mediating cargo transport through COPI and COPII-coated vesicles. In COPII vesicle-mediated anterograde transport, involved in the transport of GPI-anchored proteins by acting together with TMED2 as their cargo receptor; the function specifically implies SEC24C and SEC24D of the COPII vesicle coat and lipid raft-like microdomains of the ER. Recognizes GPI anchors structural remodeled in the ER by the GPI inositol-deacylase/PGAP1 and the metallophosphoesterase MPPE1/PGAP5. In COPI vesicle-mediated retrograde transport, involved in the biogenesis of COPI vesicles and vesicle coat recruitment. Involved in trafficking of amyloid beta A4 protein and soluble APP-beta release (independent from the modulation of gamma-secretase activity). Involved in the KDELR2-mediated retrograde transport of the toxin A subunit (CTX-A-K63)together with COPI and the COOH terminus of KDELR2. On Golgi membranes, acts as a primary receptor for ARF1-GDP, a GTP-binding protein involved in COPI-vesicle formation. Increases coatomer-dependent GTPase-activating activity of ARFGAP2 which mediates the hydrolysis of ARF1-bound GTP and therefore modulates protein trafficking from the Golgi apparatus. Involved in the exocytic trafficking of G protein-coupled receptors F2LR1/PAR2 (trypsin and tryspin-like enzyme receptor), OPRM1 (opioid receptor) and P2RY4 (UTD and UDP receptor) from the Golgi to the plasma membrane, thus contributing to receptor resensitization. In addition to its cargo receptor activity, may also act as a protein channel after oligomerization, facilitating the post-translational entry of leaderless cytoplasmic cargo into the ERGIC. Involved in the translocation into ERGIC, the vesicle entry and the secretion of leaderless cargos (lacking the secretion signal sequence), including the mature form of interleukin 1/IL-1 family members, the alpha-crystallin B chain HSPB5, the carbohydrate-binding proteins galectin-1/LGALS1 and galectin-3/LGALS3, the microtubule-associated protein Tau/MAPT, and the annexin A1/ANXA1; the translocation process is dependent on cargo protein unfolding and enhanced by chaperones HSP90AB1 and HSP90B1/GRP9. Could also associates with the presenilin-dependent gamma-secretase complex in order to regulate gamma-cleavages of the amyloid beta A4 protein to yield amyloid-beta 40/Abeta40.

Subunit / interactions. Predominantly dimeric and to a lesser extent monomeric in the ER. Monomer and dimer in ERGIC and cis-Golgi network. Forms homooligomer (via GOLD domain); the assembly is promoted by direct binding with leaderless cargos and may form a protein channel that facilitates cargo entry into the ERGIC. Forms heterooligomeric complexes with other members of the p24 family such as TMED2, TMED7 and TMED9. Interacts (via GOLD domain) with TMED2 (via GOLD domain); the complex is required for export of TMED10 from the ER to the cis-Golgi network; the complex is proposed to be involved in cis-Golgi network dynamics and / or biogenesis. Associates with the COPI vesicle coat subunits (coatomer). Tetramerization of the cytoplasmic domain at the Golgi membrane in vitro; the complex is proposed to interact with COPI coatomer and induce budding of the vesicles. Interacts with COPG1; the interaction involves TMED10 homodimer. Interacts with ARF1 (GDP-bound); the interaction probably involves a TMED10 oligomer. Interacts with SEC23A, SEC24B, SEC24C and SEC24D components of the coat protein complex II/COPII, indicative of an association of TMED10 with the COPII vesicle coat. Interacts with CD59. Interacts with MPPE1/PGAP5; the complex might recruit and sort GPI-anchored proteins to the ER-exit site, or the interaction might lead to recycling of PGAP5 between the ER and the Golgi. Interacts with F2LR1/PAR2. Interacts with KDELR2/ERD2; the interaction is disrupted by KDELR2 ligand. Found in a complex composed at least of SURF4, TMED2 and TMED10. Associates with the presenilin-dependent gamma-secretase complex. Interacts with STX17; the interaction is direct. Interacts with IL-1; the interaction is direct. Interacts with RAB21 (active GTP-bound form); the interaction is indirect and regulates TMED10 abundance and localization at the Golgi.

Subcellular location. Endoplasmic reticulum membrane. Endoplasmic reticulum-Golgi intermediate compartment membrane. Golgi apparatus membrane. Golgi apparatus. cis-Golgi network membrane. trans-Golgi network membrane. Cytoplasmic vesicle. Secretory vesicle membrane. Cell membrane. Melanosome.

Domain organisation. The GOLD domain is required for proper p24 heterooligomeric complex formation and efficient transport of GPI-anchored proteins. The lumenal domain mediates localization to the plasma membrane by partially overriding the ER retention by the cytoplasmic domain.

Miscellaneous. Ectopic expression of TMED10 alone does not result in its proper cis-Golgi network localization. Interaction of TMED10 with TMED2 is both necessary and sufficient for transport of the couple to the cis-Golgi network, and TMED3 and/or TMED9 contribute to facilitating the process.

Similarity. Belongs to the EMP24/GP25L family.

Isoforms (3)

UniProt ID	Names	Canonical?
P49755-1	1	yes
P49755-2	2
P49755-3	3

RefSeq proteins (1): NP_006818* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009038	GOLD_dom	Domain
IPR015720	Emp24-like	Family

Pfam: PF01105

UniProt features (24 total): region of interest 4, splice variant 3, short sequence motif 2, modified residue 2, sequence variant 2, topological domain 2, mutagenesis site 2, sequence conflict 2, signal peptide 1, chain 1, glycosylation site 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49755-F1	87.88	0.60

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): 171, 176

Glycosylation sites (1): 179

Mutagenesis-validated functional residues (2):

Position	Phenotype
211–212	no decrease in binding to copg1. disrupts interaction with sec23a. disrupts interaction with copg1 and association with
215–216	significant reduction in binding to copg1. disrupts interaction with copg1 and association with coatomer; when associate

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-5694530	Cargo concentration in the ER
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-6811434	COPI-dependent Golgi-to-ER retrograde traffic

MSigDB gene sets: 322 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN, GRUETZMANN_PANCREATIC_CANCER_DN, CCAWYNNGAAR_UNKNOWN, MORF_RAB5A, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, KAAB_FAILED_HEART_ATRIUM_DN, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_VESICLE_TARGETING, HSIAO_HOUSEKEEPING_GENES, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION

GO Biological Process (18): intracellular protein transport (GO:0006886), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), Golgi organization (GO:0007030), positive regulation of interleukin-1 production (GO:0032732), vesicle cargo loading (GO:0035459), COPI-coated vesicle budding (GO:0035964), regulated exocytosis (GO:0045055), obsolete vesicle targeting, to, from or within Golgi (GO:0048199), COPI coating of Golgi vesicle (GO:0048205), COPII vesicle coat assembly (GO:0048208), positive regulation of protein secretion (GO:0050714), protein localization to ERGIC (GO:0106272), cytosol to ERGIC protein transport (GO:0106273), regulation of amyloid-beta formation (GO:1902003), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192), protein transmembrane transport (GO:0071806)

GO Molecular Function (3): transmembrane protein transporter activity (GO:0008320), syntaxin binding (GO:0019905), protein binding (GO:0005515)

GO Cellular Component (20): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), Golgi apparatus (GO:0005794), cis-Golgi network (GO:0005801), plasma membrane (GO:0005886), ER to Golgi transport vesicle membrane (GO:0012507), membrane (GO:0016020), transport vesicle (GO:0030133), COPII-coated ER to Golgi transport vesicle (GO:0030134), COPI-coated vesicle (GO:0030137), trans-Golgi network transport vesicle (GO:0030140), secretory granule membrane (GO:0030667), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), melanosome (GO:0042470), zymogen granule membrane (GO:0042589), gamma-secretase complex (GO:0070765), transport vesicle membrane (GO:0030658), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	3
Golgi-to-ER retrograde transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	5
bounding membrane of organelle	4
intracellular membrane-bounded organelle	4
protein transport	3
Golgi vesicle transport	3
transport	3
endomembrane system	3
intracellular protein localization	2
intracellular transport	2
Golgi apparatus	2
coated vesicle	2
Golgi-associated vesicle	2
transport vesicle	2
cytoplasmic vesicle membrane	2
intercellular transport	1
organelle organization	1
endomembrane system organization	1
positive regulation of cytokine production	1
interleukin-1 production	1
regulation of interleukin-1 production	1
vesicle-mediated transport	1
vesicle budding from membrane	1
exocytosis	1
COPI-coated vesicle budding	1
Golgi transport vesicle coating	1
vesicle coat assembly	1
protein-containing complex assembly	1
COPII-coated vesicle budding	1
protein secretion	1
regulation of protein secretion	1
positive regulation of protein transport	1
positive regulation of secretion by cell	1
protein localization to Golgi apparatus	1
amyloid-beta formation	1
regulation of amyloid precursor protein catabolic process	1
establishment of protein localization	1
cellular process	1
transmembrane transport	1
macromolecule transmembrane transporter activity	1
protein transmembrane transport	1

Protein interactions and networks

STRING

1776 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMED10	NCSTN	Q92542	966
TMED10	APH1A	Q96BI3	964
TMED10	PSENEN	Q9NZ42	899
TMED10	TMED5	Q9Y3A6	876
TMED10	TMED2	Q15363	825
TMED10	TMED9	Q9BVK6	795
TMED10	PSEN1	P49768	712
TMED10	TMED4	Q7Z7H5	657
TMED10	TMED1	Q13445	631
TMED10	GSAP	A4D1B5	630
TMED10	EIF2B2	P49770	621
TMED10	TMED3	Q9Y3Q3	603
TMED10	BSG	P35613	603
TMED10	ICAM5	Q9UMF0	586
TMED10	COPB2	P35606	578

IntAct

174 interactions, top by confidence:

A	B	Type	Score
TMED2	TMED10	psi-mi:“MI:0914”(association)	0.910
TMED10	TMED2	psi-mi:“MI:0914”(association)	0.910
TMED10	TMED2	psi-mi:“MI:0915”(physical association)	0.910
TMED2	TMED10	psi-mi:“MI:0915”(physical association)	0.910
CDK5RAP3	UFL1	psi-mi:“MI:0914”(association)	0.870
EMC7	EMC8	psi-mi:“MI:0914”(association)	0.790
TMED10	TMED1	psi-mi:“MI:0914”(association)	0.730
TMED7	TMED10	psi-mi:“MI:0914”(association)	0.730
TMED9	TMED10	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SCYL1	SEC31A	psi-mi:“MI:0914”(association)	0.710
SURF4	TMED10	psi-mi:“MI:0915”(physical association)	0.660
TMED10	SURF4	psi-mi:“MI:0914”(association)	0.660
TMED2	SURF4	psi-mi:“MI:0914”(association)	0.660
SURF4	TMED10	psi-mi:“MI:0914”(association)	0.660
TMED10	nleF	psi-mi:“MI:0915”(physical association)	0.630
TMED10	nleF	psi-mi:“MI:0407”(direct interaction)	0.630
TMED10	nleF	psi-mi:“MI:0403”(colocalization)	0.630
nleF	TMED10	psi-mi:“MI:0915”(physical association)	0.630
TMED10	PSEN1	psi-mi:“MI:0914”(association)	0.620
TMED10	PSEN1	psi-mi:“MI:0915”(physical association)	0.620
NCSTN	TMED10	psi-mi:“MI:0915”(physical association)	0.620

BioGRID (393): TMED10 (Affinity Capture-MS), TMED1 (Affinity Capture-MS), GOLGB1 (Affinity Capture-MS), TMED4 (Affinity Capture-MS), TMED2 (Affinity Capture-MS), TMED7 (Affinity Capture-MS), TMED3 (Affinity Capture-MS), TMED5 (Affinity Capture-MS), EMC7 (Affinity Capture-MS), TMED10 (Co-fractionation), TMED10 (Co-fractionation), TMED10 (Co-fractionation), TMED10 (Co-fractionation), TMED10 (Co-fractionation), TMED10 (Co-fractionation)

ESM2 similar proteins: A0AQ71, B3LVB0, B3P6T8, B4GE47, B4HJV5, B4JYU5, B4K4G5, B4KB41, B4LYB8, B4MGF8, B4NIY1, B4NKL0, B4PUZ3, B4PVC6, B4QWH9, F4J4Y0, O13770, O13946, O14324, O35587, O81045, P27869, P32803, P38819, P49755, P53198, Q05359, Q12403, Q12450, Q28735, Q3T133, Q4P958, Q54BN0, Q5E971, Q5I0E7, Q5RE32, Q63584, Q6C503, Q759T8, Q8GYG1

Diamond homologs: A0AQ71, B3LVB0, B3P6T8, B4GE47, B4JYU5, B4K4G5, B4MGF8, B4NIY1, B4PUZ3, O35587, P0CN72, P0CN73, P49755, P54837, Q28735, Q4WQL0, Q5A302, Q5B5L5, Q5E971, Q5RE32, Q63584, Q6BTC2, Q6C503, Q6CWW7, Q6IDL4, Q759T8, Q8RWM6, Q8SXY6, Q90515, Q9D1D4, Q9FVU0, O14324, Q4P958, Q9HEK4, B3MTS8, B3NZM5, B4GMC3, B4HJV5, B4JG34, B4KB41

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TMED10	up-regulates	PSEN1	binding
TMED5	“up-regulates activity”	TMED10	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 160 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:

Pathway	Partners	Fold	FDR
COPI-dependent Golgi-to-ER retrograde traffic	8	8.2×	1e-03
COPI-mediated anterograde transport	8	8.1×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
endoplasmic reticulum to Golgi vesicle-mediated transport	12	12.3×	3e-07
Golgi organization	8	8.1×	3e-03
intracellular protein transport	11	5.4×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

738 predictions. Top by Δscore:

Variant	Effect	Δscore
14:75135751:C:A	donor_gain	1.0000
14:75135758:A:AC	donor_gain	1.0000
14:75135759:C:CC	donor_gain	1.0000
14:75135883:CAAT:C	acceptor_gain	1.0000
14:75135884:AAT:A	acceptor_gain	1.0000
14:75135885:AT:A	acceptor_gain	1.0000
14:75135886:TC:T	acceptor_loss	1.0000
14:75135887:C:CA	acceptor_loss	1.0000
14:75135887:C:CC	acceptor_gain	1.0000
14:75147659:CATA:C	donor_loss	1.0000
14:75147662:A:C	donor_loss	1.0000
14:75147663:CCT:C	donor_gain	1.0000
14:75147733:TGTTC:T	acceptor_gain	1.0000
14:75147735:TTC:T	acceptor_gain	1.0000
14:75147736:TC:T	acceptor_gain	1.0000
14:75147737:CC:C	acceptor_gain	1.0000
14:75147738:C:CA	acceptor_loss	1.0000
14:75147738:C:CC	acceptor_gain	1.0000
14:75152026:ACT:A	donor_loss	1.0000
14:75152028:TCACC:T	donor_loss	1.0000
14:75152029:CA:C	donor_loss	1.0000
14:75152030:A:AC	donor_gain	1.0000
14:75152030:A:T	donor_loss	1.0000
14:75152030:AC:A	donor_gain	1.0000
14:75152030:ACC:A	donor_gain	1.0000
14:75152031:C:CG	donor_gain	1.0000
14:75152031:CC:C	donor_gain	1.0000
14:75152031:CCC:C	donor_gain	1.0000
14:75152031:CCCTT:C	donor_gain	1.0000
14:75152052:TCAA:T	donor_gain	1.0000

AlphaMissense

1426 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:75134912:G:C	F211L	0.999
14:75134912:G:T	F211L	0.999
14:75134914:A:G	F211L	0.999
14:75134959:A:G	C196R	0.999
14:75134975:G:C	S190R	0.999
14:75134975:G:T	S190R	0.999
14:75134977:T:G	S190R	0.999
14:75135826:A:G	S158P	0.999
14:75135828:A:G	L157P	0.999
14:75135837:A:G	L154P	0.999
14:75135846:A:G	L151P	0.999
14:75134895:A:G	L217S	0.998
14:75134909:G:C	F212L	0.998
14:75134909:G:T	F212L	0.998
14:75134911:A:G	F212L	0.998
14:75134922:A:G	L208P	0.998
14:75134991:C:G	R185P	0.998
14:75135004:A:G	S181P	0.998
14:75135771:C:G	R176P	0.998
14:75135867:A:G	L144P	0.998
14:75152046:C:G	C108S	0.998
14:75152047:A:G	C108R	0.998
14:75152047:A:T	C108S	0.998
14:75134910:A:G	F212S	0.997
14:75134911:A:T	F212I	0.997
14:75134950:C:G	G199R	0.997
14:75134950:C:T	G199R	0.997
14:75135820:A:G	S160P	0.997
14:75135840:C:G	R153P	0.997
14:75135843:C:G	R152P	0.997

dbSNP variants (sampled 300 via entrez): RS1000014550 (14:75176877 C>T), RS1000089904 (14:75163842 T>A), RS1000095531 (14:75173145 G>A), RS1000147606 (14:75173409 G>T), RS1000168389 (14:75136926 C>A,G,T), RS1000200212 (14:75160286 C>T), RS1000285770 (14:75170324 G>T), RS1000360445 (14:75148414 C>A), RS1000389810 (14:75148719 T>C), RS1000392552 (14:75167011 G>A,C), RS1000424536 (14:75166500 C>T), RS1000451907 (14:75173351 TGGAG>T,TGGAGGGAG,TGGAGGGAGGGAG), RS1000664696 (14:75145873 T>G), RS1000754547 (14:75166722 T>C), RS1000773461 (14:75139138 T>C)

Disease associations

OMIM: gene MIM:605406 | 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):

Study	Trait	p-value
GCST000372_5	Height	1.000000e-07
GCST006979_1008	Heel bone mineral density	2.000000e-20
GCST010002_156	Refractive error	7.000000e-25
GCST010479_34	Coronary artery disease	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295772 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, increases expression	4
bisphenol A	decreases expression, increases expression, affects cotreatment	3
sodium arsenite	decreases expression, increases expression	3
bisphenol F	increases expression, affects cotreatment	2
bisphenol S	affects cotreatment, increases expression	2
Tunicamycin	increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cannabidiol	increases expression	1
Clozapine	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diuron	decreases expression	1
Formaldehyde	decreases expression	1
Furaldehyde	affects cotreatment, affects localization, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	decreases expression	1
Ribonucleotides	affects binding	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118679	Binding	Binding affinity to TMED10 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3JD	Abcam HEK293T TMED10 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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