THAP11

Chr 16ARAD

THAP domain containing 11

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

NCBI Gene: 57215ENSG00000168286UniProt: Q96EK4

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]

Primary Disease Associations & Inheritance

?Methylmalonic aciduria and homocystinuria, cblL typeMIM #620940
AR
Spinocerebellar ataxia 51MIM #620947
AD
192
ClinVar variants
27
Pathogenic / LP
0.83
pLI score
0
Active trials
Clinical Summary— THAP11
🧬
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.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 82 VUS of 192 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.10 (0.03–0.47)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.55 (0.46–0.65)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.45
0≤1.21.6
LoF obs/exp: 1 / 10.1Missense obs/exp: 98 / 179.0Syn Z: -3.08

ClinVar Variant Classifications

192 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic3
VUS82
Likely Benign70
Benign11
Conflicting2
24
Pathogenic
3
Likely Pathogenic
82
VUS
70
Likely Benign
11
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
1
2
0
3
VUS
0
45
28
9
82
Likely Benign
0
0
51
19
70
Benign
0
0
7
4
11
Conflicting
—2
Total04611232192

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Methylmalonic aciduria and homocystinuria, cblL type

MIM #620940

Molecular basis of disorder known

Autosomal recessive

Spinocerebellar ataxia 51

MIM #620947

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — THAP11
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
An Update on the Adult-Onset Hereditary Cerebellar Ataxias: Novel Genetic Causes and New Diagnostic Approaches.
Rudaks LI et al.·Cerebellum
2024Review
Recent Advances in the Genetics of Ataxias: An Update on Novel Autosomal Dominant Repeat Expansions.
Pellerin D et al.·Curr Neurol Neurosci Rep
2025Review
Rapamycin alleviates neurodegeneration in a Drosophila model of spinocerebellar ataxia type 51.
Wei C et al.·J Genet Genomics
2025Functional
Inherited defects of cobalamin metabolism.
Watkins D et al.·Vitam Horm
2022
THAP11F80L cobalamin disorder-associated mutation reveals normal and pathogenic THAP11 functions in gene expression and cell proliferation.
Dehaene H et al.·PLoS One
2020
Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities.
Quintana AM et al.·Hum Mol Genet
2017Case report
THAP11 down-regulation may contribute to cardio-protective effects of sevoflurane anesthesia: Evidence from clinical and molecular evidence.
Duan Z et al.·Life Sci
2021
Prenatal diagnosis of combined methylmalonic acidemia and homocystinuria cobalamin C type using clinical exome sequencing and targeted gene analysis.
Hwang N et al.·Mol Genet Genomic Med
2021Case report
Loss at 16q22.1 identified as a risk factor for intrahepatic recurrence in hepatocellular carcinoma and screening of differentially expressed genes.
Chen L et al.·Neoplasma
2016
X-Linked Cobalamin Disorder (HCFC1) Mimicking Nonketotic Hyperglycinemia With Increased Both Cerebrospinal Fluid Glycine and Methylmalonic Acid.
Scalais E et al.·Pediatr Neurol
2017Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools