THAP1
protein-codingTHAP domain containing 1, the group of THAP domain containing
Gene summary
The protein encoded by this gene contains a THAP domain, a conserved DNA-binding domain. This protein colocalizes with the apoptosis response protein PAWR/PAR-4 in promyelocytic leukemia (PML) nuclear bodies, and functions as a proapoptotic factor that links PAWR to PML nuclear bodies. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]
- DYT6
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0011264
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0011264
Submitter: Laboratory for Molecular Medicine
This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.
Inheritance Pattern: SD
Disease ID:MONDO:0011264
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0011264
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0011264
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0011264
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to THAP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018105.3. 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 | 1 | 25 | 1 | 27 | ||
| missense | 5 | 17 | 69 | 4 | 1 | 96 |
| nonsense | 4 | 5 | 9 | |||
| start loss | 3 | 1 | 4 | |||
| frameshift | 13 | 6 | 1 | 20 | ||
| splice donor/acceptor (+/-2bp) | 2 | 1 | 3 | |||
| Total | 25 | 31 | 72 | 29 | 2 | 159 |
Highest pathogenic variant AF is 0.000021070688
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060575.1 | 3 | MANE Select | |
| Ensembl | ENSP00000254250.3 | 3 | MANE Select | |
| RefSeq | NP_945354.1 | 2 | Standard | |
| Ensembl | ENSP00000344966.2 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of transcription by RNA polymerase II
- endothelial cell proliferation
- transcription, DNA-templated
- regulation of transcription, DNA-templated
- cell cycle
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- protein binding
- zinc ion binding
Cellular Component
- fibrillar center
- nucleus
- PML body
- intracellular membrane-bounded organelle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000254250
- Coding exons
- 3
- Length
- 6652
- Individuals with no LoFs
- 125741
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125748
- p
- 0.0000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.37 | 74 | 115 | 0.641 | 0.00000584 | 1404 |
| Missense (PolyPhen) | 10 | 27.917 | 0.3582 | 360 | ||
| Synonymous | 0.520 | 39 | 43.4 | 0.900 | 0.00000235 | 398 |
| Loss of Function | 2.59 | 1 | 9.70 | 0.103 | 5.60e-7 | 111 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: DNA-binding transcription regulator that regulates endothelial cell proliferation and G1/S cell-cycle progression. Specifically binds the 5'-[AT]NTNN[GT]GGCA[AGT]-3' core DNA sequence and acts by modulating expression of pRB-E2F cell-cycle target genes, including RRM1. Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. May also have pro-apoptopic activity by potentiating both serum-withdrawal and TNF-induced apoptosis. {ECO:0000269|PubMed:12717420, ECO:0000269|PubMed:17003378, ECO:0000269|PubMed:20200153}.;
Recessive Scores
- pRec
- 0.130
Intolerance Scores
- LoFtool
- 0.348
- RVIS EVS
- -0.1
- RVIS percentile EVS
- 46.2
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |