TMED9
protein-codingtransmembrane p24 trafficking protein 9, the group of Transmembrane p24 trafficking proteins
Gene summary
This gene is a member of a family of genes encoding transport proteins located in the endoplasmic reticulum and the Golgi. A similar gene in mouse is the target of microRNA miR-296, which is part of an imprinted cluster. [provided by RefSeq, Jul 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.0 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 TMED9 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017510.6. 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 | 2 | 2 | ||||
| missense | 22 | 1 | 23 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 29 | 1 | 0 | 30 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_059980.2 | 5 | MANE Select | |
| Ensembl | ENSP00000330945.6 | 5 | MANE Select | |
| Ensembl | ENSP00000554876.1 | 5 | Standard | |
| Ensembl | ENSP00000554876.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vesicle-mediated transport
- Membrane Trafficking
- Post-translational protein modification
- Metabolism of proteins
- Transport to the Golgi and subsequent modification
Biological Process
- intracellular protein transport
- endoplasmic reticulum to Golgi vesicle-mediated transport
- retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum
- Golgi organization
- positive regulation of organelle organization
Molecular Function
- protein binding
- syntaxin 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
- ENST00000332598
- Coding exons
- 5
- Length
- 3967
- Individuals with no LoFs
- 125733
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 125748
- p
- 0.0000596
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.929 | 104 | 134 | 0.774 | 0.00000696 | 1500 |
| Missense (PolyPhen) | 25 | 54.018 | 0.46281 | 646 | ||
| Synonymous | -0.264 | 58 | 55.5 | 1.05 | 0.00000271 | 470 |
| Loss of Function | 2.05 | 6 | 14.4 | 0.417 | 8.73e-7 | 131 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.000064 | 0.000062 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Appears to be involved in vesicular protein trafficking, mainly in the early secretory pathway. In COPI vesicle-mediated retrograde transport involved in the coatomer recruitment to membranes of the early secretory pathway. Increases coatomer- dependent activity of ARFGAP2. Thought to play a crucial role in the specific retention of p24 complexes in cis-Golgi membranes; specifically contributes to the coupled localization of TMED2 and TMED10 in the cis-Golgi network. May be involved in organization of intracellular membranes, such as of the ER-Golgi intermediate compartment and the Golgi apparatus. Involved in ER localization of PTPN2 isoform PTPB. {ECO:0000269|PubMed:10852829, ECO:0000269|PubMed:14600267, ECO:0000269|PubMed:16595549, ECO:0000269|PubMed:18287528, ECO:0000269|PubMed:19296914}.;
Recessive Scores
- pRec
- 0.108
Intolerance Scores
- LoFtool
- 0.480
- RVIS EVS
- -0.03
- RVIS percentile EVS
- 51.4
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.368
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |