THAP9

Chr 4

THAP domain containing 9

Also known as: hTh9

THAP9 encodes an active transposase that recognizes specific DNA sequences and mediates transposition, functioning in DNA integration processes within the nucleoplasm. The gene is extremely intolerant to loss-of-function variants (pLI ~1.0, LOEUF 0.98), suggesting mutations would likely cause severe developmental disorders, though specific disease associations have not yet been established. Given the high constraint scores, pathogenic variants would likely follow an autosomal dominant inheritance pattern with early onset developmental phenotypes.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
36
P/LP submissions
0%
P/LP missense
0.98
LOEUF
DN
Mechanism· predicted
Clinical SummaryTHAP9
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
36 unique Pathogenic / Likely Pathogenic· 107 VUS of 149 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.98LOEUF
pLI 0.000
Z-score 1.65
OE 0.70 (0.500.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.44Z-score
OE missense 0.81 (0.740.88)
370 obs / 456.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.70 (0.500.98)
00.351.4
Missense OE0.81 (0.740.88)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 24 / 34.5Missense obs/exp: 370 / 456.8Syn Z: 0.92
DN
0.6551th %ile
GOF
0.4085th %ile
LOF
0.3355th %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

149 submitted variants in ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic3
VUS107
Likely Benign5
33
Pathogenic
3
Likely Pathogenic
107
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
33
0
33
Likely Pathogenic
0
0
3
0
3
VUS
0
105
2
0
107
Likely Benign
0
4
0
1
5
Benign
0
0
0
0
0
Total0109381148

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

View in ClinVar →

Protein Context — Lollipop Plot

THAP9 · 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.

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Clinical Literature
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