THAP11

Chr 16ARAD

THAP domain containing 11

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

NCBI Gene: 57215 ENSG00000168286 UniProt: Q96EK4 OMIM: 609119

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene contains a THAP domain, which is a conserved DNA-binding domain that has striking similarity to the site-specific DNA-binding domain (DBD) of Drosophila P element transposases. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismAR/ADLOEUF 0.472 OMIM phenotypes

Clinical Summary— THAP11

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Gene-Disease Validity (ClinGen)

methylmalonic aciduria and homocystinuria · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

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

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 74 VUS of 159 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — THAP11

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.47LOEUF

pLI 0.826

Z-score 2.66

OE 0.10 (0.03–0.47)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.15Z-score

OE missense 0.55 (0.46–0.65)

98 obs / 179.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.10 (0.03–0.47)

0≤0.351.4

Missense OE?0.55 (0.46–0.65)

0≤0.61.4

Synonymous OE?1.45

0≤1.21.6

LoF obs/exp: 1 / 10.1Missense obs/exp: 98 / 179.0Syn Z: -3.08

This gene — mechanism propensity

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

159 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic1

VUS74

Likely Benign70

Benign11

Conflicting2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	1	0	1
Likely Pathogenic	0	1	0	0	1
VUS	0	64	1	9	74
Likely Benign	0	49	2	19	70
Benign	0	5	2	4	11
Conflicting	—				2
Total	0	119	6	32	159

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

View in ClinVar →

25 pathogenic / likely-pathogenic (of 36) ClinVar copy-number / structural variants overlap THAP11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →