THAP4

Chr 2

THAP domain containing 4

Also known as: CGI-36, Nb(III), PP238

The THAP4 protein is a heme-binding protein that acts as a peroxynitrite isomerase, converting peroxynitrite to nitrate and protecting against reactive nitrogen and oxygen species toxicity. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset typically in infancy or early childhood. The gene shows moderate constraint to loss-of-function variants (LOEUF 0.5), suggesting some intolerance to complete protein loss.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
106
P/LP submissions
0%
P/LP missense
0.50
LOEUF
Mechanism
Clinical SummaryTHAP4
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
104 unique Pathogenic / Likely Pathogenic· 101 VUS of 231 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.50LOEUF
pLI 0.276
Z-score 3.24
OE 0.24 (0.120.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.90Z-score
OE missense 0.72 (0.650.80)
261 obs / 362.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.24 (0.120.50)
00.351.4
Missense OE0.72 (0.650.80)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 5 / 21.0Missense obs/exp: 261 / 362.9Syn Z: -0.10

ClinVar Variant Classifications

231 submitted variants in ClinVar

Classification Summary

Pathogenic92
Likely Pathogenic12
VUS101
Likely Benign7
92
Pathogenic
12
Likely Pathogenic
101
VUS
7
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
92
0
92
Likely Pathogenic
0
0
12
0
12
VUS
0
80
21
0
101
Likely Benign
0
6
0
1
7
Benign
0
0
0
0
0
Total0861251212

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

THAP4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC