TFEB
protein-codingtranscription factor EB, the group of Basic helix-loop-helix proteins
Gene summary
Enables DNA-binding transcription factor activity; enzyme binding activity; and transcription cis-regulatory region binding activity. Involved in several processes, including antibacterial innate immune response; cellular response to amino acid starvation; and regulation of lysosome organization. Located in cytosol and lysosomal membrane. Is active in nucleus. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~52.3 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 TFEB variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001271944.2. 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 | 1 | 3 | |||
| missense | 23 | 1 | 24 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 32 | 1 | 1 | 34 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001258873.1 | 8 | MANE Select | |
| Ensembl | ENSP00000362124.1 | 8 | MANE Select | |
| RefSeq | NP_001161299.2 | 9 | Standard | |
| RefSeq | NP_001258872.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Mitophagy - animal - Homo sapiens (human)
- PI3K-AKT-mTOR signaling pathway and therapeutic opportunities
- Type 2 papillary renal cell carcinoma
Biological Process
- embryonic placenta development
- adaptive immune response
- regulation of transcription, DNA-templated
- autophagy
- humoral immune response
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- transcription regulatory region DNA binding
- protein dimerization activity
Cellular Component
- nucleus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000230323
- Coding exons
- 8
- Length
- 52282
- Individuals with no LoFs
- 125692
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 125702
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.77 | 192 | 274 | 0.699 | 0.0000164 | 3082 |
| Missense (PolyPhen) | 58 | 103.77 | 0.55895 | 1198 | ||
| Synonymous | 0.560 | 110 | 118 | 0.934 | 0.00000749 | 943 |
| Loss of Function | 3.60 | 3 | 20.6 | 0.145 | 0.00000115 | 210 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0.00034 | 0.00030 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000011 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcription factor that specifically recognizes and binds E-box sequences (5'-CANNTG-3'). Efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFE3 or MITF. In association with TFE3, activates the expression of CD40L in T-cells, thereby playing a role in T- cell-dependent antibody responses in activated CD4(+) T-cells and thymus-dependent humoral immunity. Specifically recognizes and binds the CLEAR-box sequence (5'-GTCACGTGAC-3') present in the regulatory region of many lysosomal genes, leading to activate their expression. It thereby plays a central role in expression of lysosomal genes. Acts as a positive regulator of autophagy by promoting expression of genes involved in autophagy. Specifically recognizes the gamma-E3 box, a subset of E-boxes, present in the heavy-chain immunoglobulin enhancer. Plays a role in the signal transduction processes required for normal vascularization of the placenta. {ECO:0000269|PubMed:19556463, ECO:0000269|PubMed:23434374}.;
Recessive Scores
- pRec
- 0.172
Intolerance Scores
- LoFtool
- 0.0717
- RVIS EVS
- -0.6
- RVIS percentile EVS
- 17.91
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.179
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |