TMBIM4
protein-codingtransmembrane BAX inhibitor motif containing 4, the group of Transmembrane BAX inhibitor motif containing
Gene summary
Predicted to enable calcium channel activity. Involved in negative regulation of apoptotic process and regulation of calcium-mediated signaling. Located in Golgi stack and endoplasmic reticulum membrane. [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 ~34.2 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 TMBIM4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016056.4. 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 | 1 | 1 | ||||
| missense | 32 | 2 | 34 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 36 | 3 | 0 | 39 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057140.2 | 7 | MANE Select | |
| Ensembl | ENSP00000350965.3 | 7 | MANE Select | |
| RefSeq | NP_001269535.1 | 8 | Standard | |
| RefSeq | NP_001269538.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- apoptotic process
- negative regulation of apoptotic process
- regulation of calcium-mediated signaling
Molecular Function
- protein binding
Cellular Component
- Golgi membrane
- Golgi stack
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000358230
- Coding exons
- 7
- Length
- 46144
- Individuals with no LoFs
- 124623
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 165
- Defined
- 124788
- p
- 0.000661
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.511 | 98 | 113 | 0.865 | 0.00000565 | 1504 |
| Missense (PolyPhen) | 33 | 37.271 | 0.88542 | 505 | ||
| Synonymous | 0.959 | 39 | 47.4 | 0.823 | 0.00000242 | 483 |
| Loss of Function | 0.426 | 9 | 10.5 | 0.858 | 4.41e-7 | 157 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00020 | 0.00019 | rare |
| Latino/Admixed American | 0.00016 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00032 | 0.00028 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.0012 | 0.0012 | notable |
| South Asian | 0.00055 | 0.00049 | rare |
| Other | 0.00051 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Anti-apoptotic protein which can inhibit apoptosis induced by intrinsic and extrinsic apoptotic stimuli. Can modulate both capacitative Ca2+ entry and inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ release. {ECO:0000269|PubMed:17319741, ECO:0000269|PubMed:19553469}.;
Recessive Scores
- pRec
- 0.123
Intolerance Scores
- LoFtool
- 0.763
- RVIS EVS
- 0.24
- RVIS percentile EVS
- 68.98
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.868
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |