TBPL1
protein-codingTATA-box binding protein like 1
Gene summary
This gene encodes a member of the TATA box-binding protein family. TATA box-binding proteins play a critical role in transcription by RNA polymerase II as components of the transcription factor IID (TFIID) complex. The encoded protein does not bind to the TATA box and initiates transcription from TATA-less promoters. This gene plays a critical role in spermatogenesis, and single nucleotide polymorphisms in this gene may be associated with male infertility. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 3. [provided by RefSeq, Nov 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~38.3 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 TBPL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004865.4. 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 | 0 | |||||
| missense | 7 | 7 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 9 | 0 | 0 | 9 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004856.1 | 6 | MANE Select | |
| Ensembl | ENSP00000237264.3 | 6 | MANE Select | |
| RefSeq | NP_001240605.1 | 6 | Standard | |
| Ensembl | ENSP00000356843.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Huntington,s disease - Homo sapiens (human)
- HTLV-I infection - Homo sapiens (human)
- Basal transcription factors - Homo sapiens (human)
- Viral carcinogenesis - Homo sapiens (human)
- Epstein-Barr virus infection - Homo sapiens (human)
Biological Process
- acrosome assembly
- dTTP biosynthetic process
- transcription by RNA polymerase II
- spermatid nucleus differentiation
- positive regulation of transcription by RNA polymerase II
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- RNA polymerase II core promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- RNA polymerase III regulatory region DNA binding
- DNA-binding transcription activator activity, RNA polymerase II-specific
Cellular Component
- transcription factor TFIIIB complex
- transcription factor complex
- transcription factor TFIID complex
- transcription factor TFIIA complex
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000237264
- Coding exons
- 6
- Length
- 38263
- Individuals with no LoFs
- 125470
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125472
- p
- 0.00000797
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.50 | 30 | 101 | 0.298 | 0.00000533 | 1209 |
| Missense (PolyPhen) | 8 | 34.599 | 0.23122 | 397 | ||
| Synonymous | 1.74 | 19 | 31.4 | 0.606 | 0.00000154 | 354 |
| Loss of Function | 2.18 | 2 | 9.09 | 0.220 | 3.81e-7 | 127 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Part of a specialized transcription system that mediates the transcription of most ribosomal proteins through the 5'-TCT-3' motif which is a core promoter element at these genes. Seems to also mediate the transcription of NF1. Does not bind the TATA box. {ECO:0000269|PubMed:10082669, ECO:0000269|PubMed:10220372, ECO:0000269|PubMed:15767669, ECO:0000269|PubMed:24958592}.;
Recessive Scores
- pRec
- 0.240
Intolerance Scores
- RVIS EVS
- 0.32
- RVIS percentile EVS
- 72.94
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.991
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |