TMBIM1
protein-codingtransmembrane BAX inhibitor motif containing 1, the group of Transmembrane BAX inhibitor motif containing
Gene summary
Enables death receptor binding activity. Involved in negative regulation of Fas signaling pathway; negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; and negative regulation of protein localization to plasma membrane. Located in Golgi membrane; endosome membrane; and lysosomal 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 ~18.4 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 TMBIM1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022152.6. 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 | 5 | 5 | ||||
| missense | 1 | 47 | 2 | 50 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 11 | 11 | ||||
| Total | 0 | 1 | 63 | 2 | 0 | 66 |
Highest pathogenic variant AF is 0.000022309063
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_071435.2 | 11 | MANE Select | |
| Ensembl | ENSP00000258412.3 | 11 | MANE Select | |
| RefSeq | NP_001308356.1 | 11 | Standard | |
| RefSeq | NP_001308357.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neutrophil degranulation
- Innate Immune System
- Immune System
Biological Process
- negative regulation of catalytic activity
- neutrophil degranulation
- negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
- negative regulation of Fas signaling pathway
- negative regulation of protein localization to plasma membrane
Molecular Function
- death receptor binding
Cellular Component
- lysosomal membrane
- Golgi apparatus
- plasma membrane
- endosome membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000444881
- Coding exons
- 11
- Length
- 18395
- Individuals with no LoFs
- 125696
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 52
- Defined
- 125748
- p
- 0.000207
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.683 | 153 | 179 | 0.856 | 0.00000990 | 1985 |
| Missense (PolyPhen) | 50 | 64.294 | 0.77767 | 757 | ||
| Synonymous | -0.289 | 73 | 69.9 | 1.04 | 0.00000417 | 623 |
| Loss of Function | 1.16 | 15 | 20.7 | 0.726 | 0.00000115 | 210 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00032 | 0.00031 | rare |
| Latino/Admixed American | 0.00044 | 0.00043 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00025 | 0.00023 | rare |
| European (Non-Finnish) | 0.00016 | 0.00016 | rare |
| South Asian | 0.00025 | 0.00023 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Negatively regulates aortic matrix metalloproteinase-9 (MMP9) production and may play a protective role in vascular remodeling.;
Recessive Scores
- pRec
- 0.114
Intolerance Scores
- LoFtool
- 0.838
- RVIS EVS
- 0.04
- RVIS percentile EVS
- 57.15
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.689
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |