THAP12

Chr 11

THAP domain containing 12

Also known as: DAP4, P52rIPK, PRKRIR, THAP0

NCBI Gene: 5612 ENSG00000137492 UniProt: O43422 OMIM: 607374

THAP12 encodes a nuclear protein that regulates interferon-induced protein kinase R (PKR) and suppresses cell growth through negative regulation of cell proliferation. The gene is highly constrained against loss-of-function variants (pLI 0.97, LOEUF 0.32), suggesting that mutations would likely cause severe developmental phenotypes, though specific disease associations have not yet been established. Any pathogenic variants would be expected to follow an autosomal dominant or autosomal recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable several functions, including DNA binding activity; protein dimerization activity; and zinc ion binding activity. Predicted to be involved in negative regulation of cell population proliferation and signal transduction. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.32

LOEUF· LoF intol.

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.32LOEUF

pLI 0.968

Z-score 4.24

OE 0.14 (0.07–0.32)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.34Z-score

OE missense 0.66 (0.60–0.73)

251 obs / 379.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.14 (0.07–0.32)

0≤0.351.4

Missense OE?0.66 (0.60–0.73)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 4 / 28.3Missense obs/exp: 251 / 379.2Syn Z: 0.37

Background carrier burden — how many people carry a rare variant somewhere in THAP12?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

623 rare PASS variants

Rare truncating (LoF)

1 in 2,800

49 rare PASS variants

Rare synonymous (reference)

1 in 130

298 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for THAP12. 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 3,100
South Asian	~43k	1 in 150	1 in 4,600
Remaining (unassigned)	~30k	1 in 120	1 in 4,100
European (Finnish)	~27k	1 in 470	1 in 3,700
Admixed American	~22k	1 in 150	1 in 2,300
African / African American	~21k	1 in 120	1 in 2,300
East Asian	~20k	1 in 150	none seen
Ashkenazi Jewish	~13k	1 in 280	none seen
Middle Eastern	~2,884	1 in 110	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): 3 of 5 coding exons well covered in gnomAD exomes; exons 1, 4 marginal. Genomes: all 5.? see exons ↓