TMED2

Summary

TMED2 (transmembrane p24 trafficking protein 2, HGNC:16996) is a protein-coding gene on chromosome 12q24.31, encoding Transmembrane emp24 domain-containing protein 2 (Q15363). Involved in vesicular protein trafficking. It is a selective cancer dependency (DepMap: 66.3% of cell lines).

Predicted to enable frizzled binding activity and smoothened binding activity. Involved in several processes, including Golgi organization; negative regulation of GTPase activity; and protein localization to plasma membrane. Located in Golgi apparatus; endoplasmic reticulum; and endoplasmic reticulum-Golgi intermediate compartment.

Source: NCBI Gene 10959 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 21 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 66.3% of screened cell lines
• MANE Select transcript: NM_006815

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16996
Approved symbol	TMED2
Name	transmembrane p24 trafficking protein 2
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	RNP24, P24A, p24beta1, p24b1
Ensembl gene	ENSG00000086598
Ensembl biotype	protein_coding
OMIM	619642
Entrez	10959

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 2 retained_intron

ENST00000262225, ENST00000438031, ENST00000509052, ENST00000543425, ENST00000544188, ENST00000884026, ENST00000939543, ENST00000939544, ENST00000948623

RefSeq mRNA: 2 — MANE Select: NM_006815 NM_001321445, NM_006815

CCDS: CCDS9250

Canonical transcript exons

ENST00000262225 — 4 exons

Exon	Start	End
ENSE00000551381	123590342	123590449
ENSE00001281765	123596605	123598582
ENSE00002315357	123584552	123584816
ENSE00003559654	123586747	123586939

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 99.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 115.1442 / max 788.4564, expressed in 1825 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128581	113.5134	1825
128583	1.3427	858
128582	0.2882	124

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.76	gold quality
corpus epididymis	UBERON:0004359	99.65	gold quality
pylorus	UBERON:0001166	99.64	gold quality
pericardium	UBERON:0002407	99.56	gold quality
trachea	UBERON:0003126	99.55	gold quality
caput epididymis	UBERON:0004358	99.51	gold quality
cardia of stomach	UBERON:0001162	99.49	gold quality
penis	UBERON:0000989	99.47	gold quality
superior surface of tongue	UBERON:0007371	99.44	gold quality
mammary duct	UBERON:0001765	99.39	gold quality
choroid plexus epithelium	UBERON:0003911	99.39	gold quality
pharyngeal mucosa	UBERON:0000355	99.38	gold quality
nipple	UBERON:0002030	99.37	gold quality
synovial joint	UBERON:0002217	99.37	gold quality
upper arm skin	UBERON:0004263	99.37	gold quality
urethra	UBERON:0000057	99.35	gold quality
seminal vesicle	UBERON:0000998	99.35	gold quality
endometrium	UBERON:0001295	99.28	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.28	gold quality
oral cavity	UBERON:0000167	99.26	gold quality
cauda epididymis	UBERON:0004360	99.25	gold quality
bronchial epithelial cell	CL:0002328	99.19	gold quality
epithelium of mammary gland	UBERON:0003244	99.19	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.18	gold quality
tongue	UBERON:0001723	99.14	gold quality
colonic mucosa	UBERON:0000317	99.13	gold quality
renal medulla	UBERON:0000362	99.13	gold quality
saphenous vein	UBERON:0007318	99.13	gold quality
ileal mucosa	UBERON:0000331	99.10	gold quality
calcaneal tendon	UBERON:0003701	99.10	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	83.18
E-MTAB-10042	yes	11.53
E-CURD-97	no	780.46
E-CURD-112	no	2.32
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

96 targeting TMED2, 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-4481	100.00	66.42	1669
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4495	99.82	72.08	3080

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 66.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• p24A is a regulator of signal-dependent trafficking that controls ARF1-dependent resensitization of PAR-2 (PMID:17693410)
• These results suggest that p24A is the limiting factor in CaSR trafficking in the early secretory pathway, and that cycling between the ER and ERGIC protects CaSR from degradation. (PMID:20361938)
• Both p24A transmembrane protein and p23 are specific cargo receptors of G protein-coupled receptors (GPCR) and differentially regulate GPCR signaling in astrocytes. (PMID:21219331)
• TMED2/p24beta1 is expressed in all gestational stages of human placentas and in choriocarcinoma cell lines. (PMID:22212250)
• Surface plasmon resonance and solution NMR analyses revealed that p24beta1 and p24delta1 GOLD domains interact weakly (Kd= ~10(-4)M). (PMID:27569046)
• TMED2 associates with MITA only upon viral stimulation, and this process potentiates MITA activation by reinforcing its dimerization and facilitating its trafficking. (PMID:30540941)
• The circular RNA CDR1as regulate cell proliferation via TMED2 and TMED10. (PMID:32293333)
• Transmembrane p24 trafficking protein 2 regulates inflammation through the TLR4/NF-kappaB signaling pathway in lung adenocarcinoma. (PMID:35135563)
• VIRMA facilitates intrahepatic cholangiocarcinoma progression through epigenetic augmentation of TMED2 and PARD3B mRNA stabilization. (PMID:37391589)
• TMED2 Induces Cisplatin Resistance in Breast Cancer via Targeting the KEAP1-Nrf2 Pathway. (PMID:37615927)
• TMED2 promotes glioma tumorigenesis by being involved in EGFR recycling transport. (PMID:38354922)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmed2	ENSDARG00000026908
mus_musculus	Tmed2	ENSMUSG00000029390
rattus_norvegicus	Tmed2	ENSRNOG00000001053
drosophila_melanogaster	p24-1	FBGN0030341
caenorhabditis_elegans		WBGENE00011606

Paralogs (8): TMED1 (ENSG00000099203), TMED5 (ENSG00000117500), TMED7 (ENSG00000134970), TMED6 (ENSG00000157315), TMED4 (ENSG00000158604), TMED3 (ENSG00000166557), TMED10 (ENSG00000170348), TMED9 (ENSG00000184840)

Protein

Protein identifiers

Transmembrane emp24 domain-containing protein 2 — Q15363 (reviewed: Q15363)

Alternative names: Membrane protein p24A, p24, p24 family protein beta-1

All UniProt accessions (4): Q15363, E7EQ72, F5GX39, Q6FHT8

UniProt curated annotations — full annotation on UniProt →

Function. Involved in vesicular protein trafficking. Mainly functions in the early secretory pathway but also in post-Golgi membranes. Thought to act as cargo receptor at the lumenal side for incorporation of secretory cargo molecules into transport vesicles and to be involved in vesicle coat formation at the cytoplasmic side. In COPII vesicle-mediated anterograde transport involved in the transport of GPI-anchored proteins and proposed to act together with TMED10 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 PGAP1 and MPPE1. In COPI vesicle-mediated retrograde transport inhibits the GTPase-activating activity of ARFGAP1 towards ARF1 thus preventing immature uncoating and allowing cargo selection to take place. Involved in trafficking of G protein-coupled receptors (GPCRs). Regulates F2RL1, OPRM1 and P2RY4 exocytic trafficking from the Golgi to the plasma membrane thus contributing to receptor resensitization. Facilitates CASR maturation and stabilization in the early secretory pathway and increases CASR plasma membrane targeting. Proposed to be involved in organization of intracellular membranes such as the maintenance of the Golgi apparatus. May also play a role in the biosynthesis of secreted cargo such as eventual processing.

Subunit / interactions. Monomer and homodimer in the endoplasmic reticulum, endoplasmic reticulum-Golgi intermediate compartment and Golgi. Probably oligomerizes with other members of the EMP24/GP25L family such as TMED7, TMED9 and TMED10. Interacts (via GOLD domain) with TMED10 (via GOLD domain). Associates with the COPI vesicle coat (coatomer); TMED10:TMED2 heterotetramers are proposed to be involved in coatomer association. Interacts (via C-terminus) with COPG1; the interaction involves dimeric TMED2. Interacts with SEC23A; indicative for an association of TMED2 with the COPII vesicle coat. Interacts with ARF1 and ARFGAP1. Interacts with CD59, SEC24A, SEC24B, SEC24C, SEC24D and ATL1. Interacts with KDELR1; the interaction is decreased by KDEL ligand. Interacts with F2RL1; the interaction occurs at the Golgi apparatus. Interacts with CASR (immaturely glycosylated form); the interaction occurs in the endoplasmic reticulum-Golgi intermediate compartment or cis-Golgi. Interacts with F2RL1; the interaction occurs at the Golgi apparatus. Interacts with GORASP1 and GORASP2. Found in a complex composed at least of SURF4, TMED2 and TMED10.

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

Miscellaneous. Ectopic expression of TMED2 alone does not result in its proper cis-Golgi network localization. Coexpression of TMED10 is necessary, and coexpression of TMED3 and/or TMED9 is facilitating localization. Down-regulation of TMED10 expression reduces TMED2 protein level.

Similarity. Belongs to the EMP24/GP25L family.

RefSeq proteins (2): NP_001308374, NP_006806* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009038	GOLD_dom	Domain
IPR015720	Emp24-like	Family
IPR036598	GOLD_dom_sf	Homologous_superfamily

Pfam: PF01105

UniProt features (23 total): strand 8, mutagenesis site 4, short sequence motif 2, topological domain 2, region of interest 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5AZW	X-RAY DIFFRACTION	1.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15363-F1	87.16	0.55

Functional residue map

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

Mutagenesis-validated functional residues (4):

Position	Phenotype
194–195	disrupts association with coatomer; when associated with s-198-199-s.
194–195	reduced surface and total expression of casr.
198–199	disrupts association with coatomer; when associated with a-194-195-a.
198–199	no inhibition of coatomer-dependent gtp hydrolysis.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1912420	Pre-NOTCH Processing in Golgi
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: 364 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, REACTOME_SIGNALING_BY_NOTCH, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, TAATAAT_MIR126, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, GOBP_AXIS_SPECIFICATION, MORF_MBD4, PAX4_01, MORF_RAB5A, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_INFLAMMATORY_RESPONSE, GOBP_EMBRYONIC_AXIS_SPECIFICATION

GO Biological Process (36): neural tube closure (GO:0001843), maternal placenta development (GO:0001893), heart looping (GO:0001947), intracellular protein transport (GO:0006886), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), inflammatory response (GO:0006954), Golgi organization (GO:0007030), protein secretion (GO:0009306), positive regulation of gene expression (GO:0010628), dorsal/ventral neural tube patterning (GO:0021904), somite rostral/caudal axis specification (GO:0032525), negative regulation of GTPase activity (GO:0034260), multicellular organism growth (GO:0035264), vesicle cargo loading (GO:0035459), post-anal tail morphogenesis (GO:0036342), PERK-mediated unfolded protein response (GO:0036499), negative regulation of smoothened signaling pathway (GO:0045879), COPI coating of Golgi vesicle (GO:0048205), COPII vesicle coat assembly (GO:0048208), branching involved in labyrinthine layer morphogenesis (GO:0060670), labyrinthine layer blood vessel development (GO:0060716), chorion development (GO:0060717), maintenance of protein localization in organelle (GO:0072595), protein localization to plasma membrane (GO:0072659), endoplasmic reticulum membrane organization (GO:0090158), negative regulation of protein localization to plasma membrane (GO:1903077), allantois development (GO:1905069), regulation of SREBP signaling pathway (GO:2000638), in utero embryonic development (GO:0001701), somitogenesis (GO:0001756), embryonic placenta development (GO:0001892), endoplasmic reticulum organization (GO:0007029), intracellular protein localization (GO:0008104), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192), embryonic morphogenesis (GO:0048598)

GO Molecular Function (3): frizzled binding (GO:0005109), smoothened binding (GO:0005119), protein binding (GO:0005515)

GO Cellular Component (16): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), Golgi apparatus (GO:0005794), 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), COPI-coated vesicle membrane (GO:0030663), Golgi cisterna membrane (GO:0032580), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), zymogen granule membrane (GO:0042589), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	3
Pre-NOTCH Expression and Processing	1
Golgi-to-ER retrograde transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	5
endomembrane system	3
intracellular membrane-bounded organelle	3
protein transport	2
intracellular transport	2
G protein-coupled receptor binding	2
bounding membrane of organelle	2
organelle membrane	2
coated vesicle membrane	2
cytoplasmic vesicle	2
coated vesicle	2
primary neural tube formation	1
tube closure	1
placenta development	1
developmental process involved in reproduction	1
anatomical structure development	1
maternal process involved in female pregnancy	1
embryonic heart tube morphogenesis	1
determination of heart left/right asymmetry	1
intracellular protein localization	1
intercellular transport	1
Golgi vesicle transport	1
defense response	1
organelle organization	1
endomembrane system organization	1
secretion by cell	1
establishment of protein localization to extracellular region	1
protein localization to extracellular region	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
dorsal/ventral pattern formation	1
neural tube patterning	1
embryonic axis specification	1
somitogenesis	1
anterior/posterior axis specification	1
GTPase activity	1
regulation of GTPase activity	1
negative regulation of biological process	1
negative regulation of hydrolase activity	1

Protein interactions and networks

STRING

1798 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMED2	TMED10	P49755	825
TMED2	TMED5	Q9Y3A6	738
TMED2	TMED9	Q9BVK6	668
TMED2	STX5	Q13190	650
TMED2	ARF1	P10947	616
TMED2	TRAPPC3	O43617	526
TMED2	VAMP8	Q9BV40	525
TMED2	TMED6	Q8WW62	493
TMED2	GOLM2	Q6P4E1	483
TMED2	SERP1	Q9Y6X1	474
TMED2	LMAN1	P49257	466
TMED2	MAN1B1	Q9UKM7	441
TMED2	SPCS2	Q15005	433
TMED2	SURF4	O15260	432
TMED2	SEC23A	Q15436	430

IntAct

126 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
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
TMED7	TMED10	psi-mi:“MI:0914”(association)	0.730
TMED10	TMED1	psi-mi:“MI:0914”(association)	0.730
TMED9	TMED10	psi-mi:“MI:0914”(association)	0.730
F2RL1	TMED2	psi-mi:“MI:0915”(physical association)	0.700
TMED2	F2RL1	psi-mi:“MI:0403”(colocalization)	0.700
TMED2	F2RL1	psi-mi:“MI:0915”(physical association)	0.700
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
TMED2	ATP9A	psi-mi:“MI:0914”(association)	0.640
CHST8	CANX	psi-mi:“MI:0914”(association)	0.640
TMED10	PSEN1	psi-mi:“MI:0914”(association)	0.620
NCSTN	TMED10	psi-mi:“MI:0915”(physical association)	0.620
TMED2	CD59	psi-mi:“MI:0915”(physical association)	0.580
CD59	TMED10	psi-mi:“MI:0403”(colocalization)	0.580
TMED2		psi-mi:“MI:0915”(physical association)	0.550

BioGRID (226): TMED2 (Affinity Capture-MS), TMED2 (Affinity Capture-MS), TMED2 (Affinity Capture-MS), ERGIC1 (Co-fractionation), HNRNPUL1 (Co-fractionation), HSD17B12 (Co-fractionation), RPS10 (Co-fractionation), TM9SF4 (Co-fractionation), TMED10 (Co-fractionation), TMED2 (Co-fractionation), TMED2 (Co-fractionation), TMED2 (Co-fractionation), TMED2 (Co-fractionation), TMED2 (Co-fractionation), TMED2 (Co-fractionation)

ESM2 similar proteins: A0A365, A0QHM5, A0QX51, A1E9V4, A1EA38, A1KIW9, A2AKQ0, A2VE55, A4FIS6, B8ZR76, F1QGW6, P06247, P0C315, P0C316, P20461, P41091, P49020, P53033, P60161, P60162, P65263, P81795, P9WK98, P9WK99, Q15363, Q15B89, Q1KXS9, Q2KHU8, Q2MI71, Q2MIF8, Q2VEF0, Q33C02, Q3C1M5, Q49KW8, Q4VZI6, Q5HZM6, Q5R797, Q5RIC0, Q5ZHS1, Q5ZMS3

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, Q9S7M9, O13946, P54837, Q4HY20, Q4WQL0, Q5A302

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 113 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
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	8	39.4×	8e-09
Cargo concentration in the ER	8	33.6×	2e-08
Regulation of cholesterol biosynthesis by SREBP (SREBF)	6	23.8×	1e-05
COPII-mediated vesicle transport	9	18.4×	2e-07
ER to Golgi Anterograde Transport	8	13.3×	1e-05
SARS-CoV-2-host interactions	8	11.9×	2e-05
Metabolism of steroids	6	10.3×	7e-04
Transport to the Golgi and subsequent modification	8	10.3×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
COPII-coated vesicle cargo loading	7	73.0×	1e-09
endoplasmic reticulum to Golgi vesicle-mediated transport	13	18.6×	2e-10
Golgi organization	7	9.8×	2e-03
intracellular protein transport	13	8.9×	7e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

535 predictions. Top by Δscore:

Variant	Effect	Δscore
12:123584838:C:G	donor_gain	1.0000
12:123586738:T:A	acceptor_gain	1.0000
12:123586745:A:AG	acceptor_gain	1.0000
12:123586746:G:GA	acceptor_gain	1.0000
12:123586746:GA:G	acceptor_gain	1.0000
12:123586746:GAT:G	acceptor_gain	1.0000
12:123586746:GATT:G	acceptor_gain	1.0000
12:123586746:GATTA:G	acceptor_gain	1.0000
12:123586935:AGAAG:A	donor_loss	1.0000
12:123586936:GAAG:G	donor_gain	1.0000
12:123586937:AAGGT:A	donor_loss	1.0000
12:123586938:AGG:A	donor_loss	1.0000
12:123586939:GGT:G	donor_loss	1.0000
12:123586941:T:A	donor_loss	1.0000
12:123586981:C:G	donor_gain	1.0000
12:123590328:A:AG	acceptor_gain	1.0000
12:123590329:A:G	acceptor_gain	1.0000
12:123590331:T:G	acceptor_gain	1.0000
12:123590339:T:G	acceptor_gain	1.0000
12:123590340:A:AC	acceptor_loss	1.0000
12:123590340:A:AG	acceptor_gain	1.0000
12:123590341:G:GT	acceptor_gain	1.0000
12:123590341:GC:G	acceptor_gain	1.0000
12:123590341:GCT:G	acceptor_gain	1.0000
12:123590341:GCTC:G	acceptor_gain	1.0000
12:123590422:G:GT	donor_gain	1.0000
12:123590445:AGCCA:A	donor_gain	1.0000
12:123590446:GCCA:G	donor_gain	1.0000
12:123590446:GCCAG:G	donor_gain	1.0000
12:123590447:CCA:C	donor_gain	1.0000

AlphaMissense

1334 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:123584775:T:C	F47L	1.000
12:123584777:C:A	F47L	1.000
12:123584777:C:G	F47L	1.000
12:123584790:G:C	G52R	1.000
12:123584790:G:T	G52C	1.000
12:123586847:T:C	F94S	1.000
12:123586854:C:A	N96K	1.000
12:123586854:C:G	N96K	1.000
12:123586878:A:C	K104N	1.000
12:123586878:A:T	K104N	1.000
12:123590378:T:C	L137P	1.000
12:123590411:A:C	Q148P	1.000
12:123584730:T:A	C32S	0.999
12:123584730:T:C	C32R	0.999
12:123584731:G:C	C32S	0.999
12:123584770:T:C	L45P	0.999
12:123584791:G:T	G52V	0.999
12:123584793:G:T	G53C	0.999
12:123584796:T:C	F54L	0.999
12:123584798:C:A	F54L	0.999
12:123584798:C:G	F54L	0.999
12:123584802:G:C	D56H	0.999
12:123584803:A:T	D56V	0.999
12:123586817:C:A	A84D	0.999
12:123586829:G:A	G88E	0.999
12:123586829:G:T	G88V	0.999
12:123586843:T:A	C93S	0.999
12:123586843:T:C	C93R	0.999
12:123586844:G:A	C93Y	0.999
12:123586844:G:C	C93S	0.999

dbSNP variants (sampled 300 via entrez): RS1000106686 (12:123584457 A>G,T), RS1000112090 (12:123598890 G>A), RS1000372981 (12:123597854 T>TTG), RS1000423998 (12:123598158 A>G), RS1000756977 (12:123596218 C>T), RS1001020749 (12:123585456 G>A), RS1001472156 (12:123584579 C>T), RS1001623767 (12:123590881 G>A), RS1001876836 (12:123584410 G>A), RS1002123434 (12:123595318 T>C), RS1002187860 (12:123596970 G>A), RS1002241193 (12:123592417 G>A,T), RS1002302274 (12:123595665 C>T), RS1002399278 (12:123585363 C>G,T), RS1002451591 (12:123585574 C>G)

Disease associations

OMIM: gene MIM:619642 | 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
GCST002598_15	Educational attainment	7.000000e-08
GCST005956_10	Waist-to-hip ratio adjusted for BMI	6.000000e-08
GCST005958_11	Waist-to-hip ratio adjusted for BMI (age >50)	4.000000e-07
GCST005962_22	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004784	self reported educational attainment
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): CHEMBL6066301 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, increases expression	3
methylmercuric chloride	increases expression, affects cotreatment	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
Tunicamycin	increases expression	2
Cyclosporine	increases expression	2
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
arsenite	affects binding, increases reaction	1
methylparaben	increases expression	1
sodium arsenite	increases expression, affects cotreatment	1
cupric chloride	decreases expression	1
pinosylvin	increases expression	1
2,3-dimethoxy-1,4-naphthoquinone	decreases expression	1
chloropicrin	decreases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dimethylarsinous acid	increases expression	1
pyrimidifen	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Erlotinib Hydrochloride	decreases response to substance	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Benzo(a)pyrene	decreases methylation	1
Dimethylnitrosamine	decreases expression	1
Diuron	decreases expression	1
Estradiol	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652644	Binding	Binding affinity to human TMED2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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