THAP11

Chr 16ARAD

THAP domain containing 11

Also known as: CTG-B43a, CTG-B45d, HRIHFB2206, MAHCL, RONIN, SCA51

This transcription factor regulates gene expression and chromatin accessibility, with particular importance for mitochondrial development, cobalamin metabolism, and neural development. Mutations cause methylmalonic aciduria with homocystinuria (cblL type) and spinocerebellar ataxia 51, with both autosomal recessive and autosomal dominant inheritance patterns reported. The gene is highly constrained against loss-of-function variants, reflecting its essential role in cellular metabolism and neurological function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAR/ADLOEUF 0.472 OMIM phenotypes
Clinical SummaryTHAP11
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Gene-Disease Validity (ClinGen)
methylmalonic aciduria and homocystinuria · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.83) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.47LOEUF
pLI 0.826
Z-score 2.66
OE 0.10 (0.030.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.15Z-score
OE missense 0.55 (0.460.65)
98 obs / 179.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.10 (0.030.47)
00.351.4
Missense OE0.55 (0.460.65)
00.61.4
Synonymous OE1.45
01.21.6
LoF obs/exp: 1 / 10.1Missense obs/exp: 98 / 179.0Syn Z: -3.08
DN
0.3196th %ile
GOF
0.3193th %ile
LOF
0.70top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.47

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

THAP11 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

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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