THAP7

Chr 22

THAP domain containing 7

NCBI Gene: 80764 ENSG00000184436 UniProt: Q9BT49

THAP7 encodes a chromatin-associated protein that represses transcription by binding histone tails and recruiting HDAC3 and nuclear hormone receptor corepressors. Mutations cause autosomal dominant epileptic encephalopathy with onset in infancy or early childhood. The gene shows low constraint to loss-of-function variation in the general population.

ResearchSummary from RefSeq, UniProt

Enables several functions, including C2H2 zinc finger domain binding activity; histone deacetylase binding activity; and transcription corepressor binding activity. Involved in chromatin organization and negative regulation of transcription by RNA polymerase II. Located in chromatin; nuclear membrane; and nuclear speck. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.86

Clinical Summary— THAP7

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 50 VUS of 56 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.86LOEUF

pLI 0.013

Z-score 1.90

OE 0.41 (0.21–0.86)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.38Z-score

OE missense 0.92 (0.81–1.04)

171 obs / 185.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.41 (0.21–0.86)

0≤0.351.4

Missense OE?0.92 (0.81–1.04)

0≤0.61.4

Synonymous OE?1.32

0≤1.21.6

LoF obs/exp: 5 / 12.2Missense obs/exp: 171 / 185.8Syn Z: -2.20

This gene — mechanism propensity

0.6258th %ile

GOF

0.3986th %ile

LOF

0.3842th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

56 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS50

Likely Pathogenic

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	1	0	1
VUS	0	50	50
Likely Benign	0	0	0
Benign	0	0	0
Total	1	50	51

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

View in ClinVar →

360 pathogenic / likely-pathogenic (of 422) ClinVar copy-number / structural variants overlap THAP7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →