THAP3

Chr 1

THAP domain containing 3

NCBI Gene: 90326 ENSG00000041988 UniProt: Q8WTV1 OMIM: 612532

THAP3 encodes a transcription factor that binds DNA and regulates RNA polymerase II transcription as part of a complex with THAP1, HCFC1, and OGT. Currently, no established Mendelian diseases have been linked to mutations in this gene, though it appears relatively tolerant to loss-of-function variation based on population genetic data.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable DNA binding activity and zinc ion binding activity. Involved in positive regulation of transcription by RNA polymerase II. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.36

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.36LOEUF

pLI 0.007

Z-score 0.96

OE 0.60 (0.29–1.36)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.20Z-score

OE missense 0.95 (0.83–1.10)

135 obs / 141.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.60 (0.29–1.36)

0≤0.351.4

Missense OE?0.95 (0.83–1.10)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 4 / 6.7Missense obs/exp: 135 / 141.8Syn Z: -0.33

Background carrier burden — how many people carry a rare variant somewhere in THAP3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

443 rare PASS variants

Rare truncating (LoF)

1 in 860

95 rare PASS variants

Rare synonymous (reference)

1 in 230

183 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for THAP3. 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 130	1 in 1,000
South Asian	~43k	1 in 110	1 in 330
Remaining (unassigned)	~30k	1 in 120	1 in 1,200
European (Finnish)	~27k	1 in 230	1 in 2,700
Admixed American	~22k	1 in 85	1 in 460
African / African American	~21k	1 in 86	1 in 1,100
East Asian	~20k	1 in 120	1 in 2,500
Ashkenazi Jewish	~13k	1 in 270	1 in 930
Middle Eastern	~2,884	1 in 83	≈ 1 in 950

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 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓