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6 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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THAP4
THAP domain containing 4
Chromosome 2 · 2q37.3
NCBI Gene: 51078Ensembl: ENSG00000176946.14HGNC: HGNC:23187UniProt: Q8WY91
38PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingheme bindingidentical protein bindingperoxynitrite isomerase activityneurodegenerative diseasehypothyroidismthyroid diseasenephrotic syndrome
✦AI Summary

THAP4 is a nuclear protein containing a C-terminal nitrobindin (Nb) domain that functions as a heme-binding peroxynitrite detoxification enzyme 1. The ferric heme-Fe(III) center catalyzes the conversion of peroxynitrite to nitrate while protecting free L-tyrosine from peroxynitrite-mediated nitration, operating through peroxynitrite isomerase activity 2. THAP4 localizes to both the cytoplasm and nucleus via a nuclear localization sequence, where the N-terminal region possesses transcriptional activity that may be modulated by the C-terminal Nb domain acting as a nitric oxide and peroxynitrite sensor 2. The protein represents an evolutionarily conserved component of cellular antioxidant defenses against reactive nitrogen and oxygen species 2. Clinically, THAP4 is relevant to peripheral T-cell lymphomas (PTCLs), where recurrent gene fusions (VAV1-THAP4) have been identified that drive oncogenic VAV1 activation 34. Additionally, THAP4 loss through 2q37 microdeletion contributes to neurodevelopmental phenotypes including developmental delay, microcephaly, and epilepsy, suggesting a role in cortical and corpus callosum development 5.

Sources cited
1
THAP4 contains a C-terminal nitrobindin domain that catalyzes peroxynitrite detoxification via ferric heme-Fe(III) conversion to nitrate
PMID: 30524950
2
THAP4 localizes to cytoplasm and nucleus; acts as a peroxynitrite sensor coupling heme reactivity to transcriptional activity
PMID: 32295384
3
VAV1-THAP4 fusion gene identified in peripheral T-cell lymphomas drives oncogenic signaling
PMID: 28062691
4
VAV1-THAP4 fusion transcripts detected in PTCL samples; confirms THAP4 involvement in lymphoma pathogenesis
PMID: 34147695
5
THAP4 deletion in 2q37 microdeletion syndrome associates with developmental delay, microcephaly, and epilepsy
PMID: 26238961
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.34Weak
hypothyroidismOpen Targets
0.33Weak
thyroid diseaseOpen Targets
0.21Weak
nephrotic syndromeOpen Targets
0.14Weak
Tietze syndromeOpen Targets
0.08Suggestive
Testicular regression syndromeOpen Targets
0.04Suggestive
spermatogenic failure, X-linked, 2Open Targets
0.04Suggestive
Isolated follicle stimulating hormone deficiencyOpen Targets
0.03Suggestive
Abnormality of the skeletal systemOpen Targets
0.03Suggestive
sialolithiasisOpen Targets
0.02Suggestive
systemic inflammatory response syndromeOpen Targets
0.02Suggestive
cancerOpen Targets
0.01Suggestive
acute lymphoblastic leukemiaOpen Targets
0.01Suggestive
mature T-cell and NK-cell non-Hodgkin lymphomaOpen Targets
0.00Suggestive
posterior cortical atrophyOpen Targets
0.00Suggestive
Sjogren syndromeOpen Targets
0.00Suggestive
glioma susceptibility 1Open Targets
0.00Suggestive
lung cancerOpen Targets
0.00Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.00Suggestive
papillary renal cell carcinomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
THAP12Protein interaction91%THAP11Protein interaction91%
Tissue Expression6 tissues
Heart
100%
Liver
52%
Ovary
49%
Lung
46%
Brain
43%
Bone Marrow
41%
Gene Interaction Network
Click a node to explore
THAP4THAP12THAP11
PROTEIN STRUCTURE
Preparing viewer…
PDB3IA8 · 1.79 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.58Moderately Constrained
pLIⓘ
0.50Intermediate
Observed/Expected LoF0.39 [0.27–0.58]
RankingsWhere THAP4 stands among ~20K protein-coding genes
  • #10,554of 20,598
    Most Researched38
  • #3,938of 17,882
    Most Constrained (LOEUF)0.58 · top quartile
Genes detectedTHAP4
Sources retrieved6 papers
Response time—
📄 Sources
6▼
1
Mycobacterial and Human Nitrobindins: Structure and Function.
PMID: 32295384
Antioxid Redox Signal · 2020
1.00
2
Nitrobindin: An Ubiquitous Family of All β-Barrel Heme-proteins.
PMID: 27080126
IUBMB Life · 2016
0.83
3
Human nitrobindin: the first example of an all-β-barrel ferric heme-protein that catalyzes peroxynitrite detoxification.
PMID: 30524950
FEBS Open Bio · 2018
0.67
4
Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas.
PMID: 28062691
Proc Natl Acad Sci U S A · 2017
0.50
5
Detection of Gene Fusion Transcripts in Peripheral T-Cell Lymphoma Using a Multiplexed Targeted Sequencing Assay.
PMID: 34147695
J Mol Diagn · 2021
0.33