TMEM33
protein-codingtransmembrane protein 33
Gene summary
Involved in positive regulation of endoplasmic reticulum unfolded protein response; regulation of endoplasmic reticulum tubular network organization; and response to endoplasmic reticulum stress. Located in endoplasmic reticulum membrane; melanosome; and nuclear envelope. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~25.7 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 TMEM33 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018126.3. 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 | 3 | 3 | ||||
| missense | 33 | 33 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 38 | 0 | 0 | 38 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060596.2 | 7 | MANE Select | |
| Ensembl | ENSP00000422473.1 | 7 | MANE Select | |
| Ensembl | ENSP00000264452.5 | 3 | Standard | |
| Ensembl | ENSP00000422517.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- response to endoplasmic reticulum stress
- regulation of endoplasmic reticulum tubular network organization
- positive regulation of IRE1-mediated unfolded protein response
- positive regulation of PERK-mediated unfolded protein response
Molecular Function
- protein binding
Cellular Component
- nuclear envelope
- nuclear pore
- endoplasmic reticulum
- endoplasmic reticulum membrane
- integral component of endoplasmic reticulum membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000504986
- Coding exons
- 7
- Length
- 25453
- Individuals with no LoFs
- 125730
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 16
- Defined
- 125746
- p
- 0.0000636
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.788 | 107 | 133 | 0.807 | 0.00000654 | 1601 |
| Missense (PolyPhen) | 38 | 53.701 | 0.70762 | 630 | ||
| Synonymous | 0.0357 | 50 | 50.3 | 0.994 | 0.00000250 | 487 |
| Loss of Function | 1.99 | 6 | 14.1 | 0.427 | 8.24e-7 | 159 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.00040 | 0.00040 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.000026 | 0.000026 | rare |
| South Asian | 0.000068 | 0.000065 | rare |
| Other | 0.00018 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a regulator of the tubular endoplasmic reticulum (ER) network. Suppresses the RTN3/4-induced formation of the ER tubules (PubMed:25612671). Positively regulates PERK-mediated and IRE1-mediated unfolded protein response signaling (PubMed:26268696). {ECO:0000269|PubMed:25612671, ECO:0000269|PubMed:26268696}.;
Recessive Scores
- pRec
- 0.142
Intolerance Scores
- LoFtool
- 0.307
- RVIS EVS
- -0.32
- RVIS percentile EVS
- 31.46
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.801
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |