TMED2
protein-codingtransmembrane p24 trafficking protein 2, the group of Transmembrane p24 trafficking proteins
Gene summary
Predicted to enable frizzled binding activity and smoothened binding activity. Involved in several processes, including negative regulation of GTPase activity; protein localization to plasma membrane; and regulation of cargo loading into COPII-coated vesicle. Located in Golgi apparatus; endoplasmic reticulum; and endoplasmic reticulum-Golgi intermediate compartment. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TMED2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006815.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 16 | 16 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 17 | 0 | 0 | 17 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006806.1 | 4 | MANE Select | |
| Ensembl | ENSP00000262225.3 | 4 | MANE Select | |
| RefSeq | NP_001308374.1 | 5 | Standard | |
| Ensembl | ENSP00000405845.2 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miR-targeted genes in epithelium - TarBase
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
- miR-targeted genes in squamous cell - TarBase
- Vesicle-mediated transport
Biological Process
- neural tube closure
- maternal placenta development
- heart looping
- intracellular protein transport
- endoplasmic reticulum to Golgi vesicle-mediated transport
Molecular Function
- protein binding
Cellular Component
- Golgi membrane
- endoplasmic reticulum
- endoplasmic reticulum membrane
- endoplasmic reticulum-Golgi intermediate compartment
- Golgi apparatus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000262225
- Coding exons
- 4
- Length
- 14039
- Individuals with no LoFs
- 124849
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 124851
- p
- 0.00000801
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.91 | 56 | 113 | 0.495 | 0.00000550 | 1328 |
| Missense (PolyPhen) | 0 | 20.38 | 0 | 286 | ||
| Synonymous | -1.43 | 53 | 41.3 | 1.28 | 0.00000210 | 380 |
| Loss of Function | 2.49 | 0 | 7.23 | 0.00 | 3.03e-7 | 99 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000055 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0.000034 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- 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. {ECO:0000269|PubMed:10761932, ECO:0000269|PubMed:17693410, ECO:0000269|PubMed:20361938, ECO:0000269|PubMed:20427317, ECO:0000269|PubMed:21219331}.;
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- LoFtool
- 0.268
- RVIS EVS
- -0.12
- RVIS percentile EVS
- 44.54
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.881
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |