THAP1

THAP domain containing 1, the group of THAP domain containing

Basic information

Region (hg38): 8:42836674-42843325

Previous symbols: [ "DYT6" ]

Links

ENSG00000131931 ∙ NCBI:55145 ∙ OMIM:609520 ∙ HGNC:20856 ∙ Uniprot:Q9NVV9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• torsion dystonia 6 (Strong), mode of inheritance: AD
• torsion dystonia 6 (Strong), mode of inheritance: AD
• torsion dystonia 6 (Strong), mode of inheritance: AD
• torsion dystonia 6 (Supportive), mode of inheritance: AD
• torsion dystonia 6 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dystonia 6, torsion	AD	General	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	Neurologic	9382482; 17702011; 19345147; 19345148; 19182804; 20211909; 20083799; 21520283; 21793105; 21839475; 21847143; 21949105; 22377579

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the THAP1 gene.

• Torsion_dystonia_6 (129 variants)
• not_provided (43 variants)
• Inborn_genetic_diseases (19 variants)
• not_specified (5 variants)
• THAP1-related_disorder (2 variants)
• Dystonic_disorder (1 variants)
• Young-onset_Parkinson_disease (1 variants)
• Multiple_mitochondrial_dysfunctions_syndrome_9b (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the THAP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018105.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	23	1	25
missense	6	14	59	4	1	84
nonsense	4	3				7
start loss	2	1				3
frameshift	13	7	1			21
splice donor/acceptor (+/-2bp)		2	1			3
Total	25	27	62	27	2

Highest pathogenic variant AF is 0.000021070688

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
THAP1	protein_coding	protein_coding	ENST00000254250	3	6652

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.801	0.198	125741	0	7	125748	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.37	74	115	0.641	0.00000584	1404
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000442	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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

Haploinsufficiency Scores

• pHI: 0.210
• hipred: Y
• hipred_score: 0.775
• ghis: 0.660

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Low	Medium
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Thap1
• Phenotype: cellular phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;endothelial cell proliferation;transcription, DNA-templated;regulation of transcription, DNA-templated;cell cycle;regulation of mitotic cell cycle
• Cellular component: fibrillar center;nucleus;PML body;intracellular membrane-bounded organelle
• 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;identical protein binding;protein homodimerization activity;sequence-specific DNA binding