THAP7

Chr 22

THAP domain containing 7

NCBI Gene: 80764 ENSG00000184436 UniProt: Q9BT49 OMIM: 609518

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.

OMIM 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 and nuclear speck. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.86

LOEUF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in THAP7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

479 rare PASS variants

Rare truncating (LoF)

1 in 3,800

68 rare PASS variants

Rare synonymous (reference)

1 in 140

217 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for THAP7. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 3,900
South Asian	~43k	1 in 180	1 in 1,700
Remaining (unassigned)	~30k	1 in 110	≈ 1 in 7,500
European (Finnish)	~27k	1 in 270	≈ 1 in 24,000
Admixed American	~22k	1 in 140	≈ 1 in 5,700
African / African American	~21k	1 in 160	1 in 2,800
East Asian	~20k	1 in 110	1 in 1,300
Ashkenazi Jewish	~13k	1 in 330	none seen
Middle Eastern	~2,884	1 in 120	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓