TMED2

protein-coding

transmembrane 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

NM_006815.4

Inheritance

—

ClinVar variants

U:17

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr12:123,584,533-123,598,582

External References & Databases

Transcript & Mutation Effects

hg38 • Region Span ~14.0 kb
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GenCC 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

1 Conditions Cataloged
not specifiedTotal: 15

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.

EffectPLPVUSLBBSum
synonymous
0
missense
16
clinvar
16
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
1
clinvar
1
Total00170017
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_006815.4RefSeqNP_006806.14MANE Select
ENST00000262225.8EnsemblENSP00000262225.34MANE Select
NM_001321445.2RefSeqNP_001308374.15Standard
ENST00000438031.2EnsemblENSP00000405845.24Standard

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: gnomAD

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-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.91561130.4950.000005501328
Missense (PolyPhen)020.380286
Synonymous-1.435341.31.280.00000210380
Loss of Function2.4907.230.003.03e-799

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian0.0000550.000055rare
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian0.0000340.000033rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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