OTUD7A

Chr 15AR

OTU deubiquitinase 7A

Also known as: C15orf16, C16ORF15, CEZANNE2, NEDHS, OTUD7

NCBI Gene: 161725ENSG00000169918UniProt: Q8TE49

The protein encoded by this gene is a deubiquitinizing enzyme and possible tumor suppressor. The encoded protein acts on TNF receptor associated factor 6 (TRAF6) to control nuclear factor kappa B expression. However, this gene is downregulated by SNAIL1 in hepatocellular carcinoma cells, contributing to their progression and malignancy. [provided by RefSeq, Aug 2016]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with hypotonia and seizuresMIM #620790
AR
454
ClinVar variants
191
Pathogenic / LP
0.95
pLI score· haploinsufficient
0
Active trials
Clinical Summary— OTUD7A
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
191 Pathogenic / Likely Pathogenic· 217 VUS of 454 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.33LOEUF
pLI 0.952
Z-score 4.39
OE 0.16 (0.08–0.33)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
2.86Z-score
OE missense 0.62 (0.56–0.69)
284 obs / 456.2 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.0.16 (0.08–0.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.62 (0.56–0.69)
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.1.05
0≤1.21.6
LoF obs/exp: 5 / 31.6Missense obs/exp: 284 / 456.2Syn Z: -0.57

ClinVar Variant Classifications

454 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic180
Likely Pathogenic11
VUS217
Likely Benign18
Benign19
Conflicting9
180
Pathogenic
11
Likely Pathogenic
217
VUS
18
Likely Benign
19
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
178
0
180
Likely Pathogenic
1
0
10
0
11
VUS
4
148
65
0
217
Likely Benign
0
1
9
8
18
Benign
0
1
12
6
19
Conflicting
—9
Total615127414454

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

View in ClinVar →

Protein Context — Lollipop Plot

OTUD7A · protein map & ClinVar variants

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

Gene2Phenotype Curations

OTUD7A-related 15q13.3 deletions phenocopy

limited
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with hypotonia and seizures

MIM #620790

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — OTUD7A
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Impaired OTUD7A-dependent Ankyrin regulation mediates neuronal dysfunction in mouse and human models of the 15q13.3 microdeletion syndrome.
Unda BK et al.·Mol Psychiatry
2023Functional
Report of the first patient with a homozygous OTUD7A variant responsible for epileptic encephalopathy and related proteasome dysfunction.
Garret P et al.·Clin Genet
2020Case report
Genetic counseling of prenatally detected familial 15q13.2q13.3 microdeletion encompassing CHRNA7 and OTUD7A with asymptomatic carriers in the family.
Chen CP et al.·Taiwan J Obstet Gynecol
2025Case report
Biallelic loss of OTUD7A causes severe muscular hypotonia, intellectual disability, and seizures.
Suzuki H et al.·Am J Med Genet A
2021Case report
Loss of function of OTUD7A in the schizophrenia- associated 15q13.3 deletion impairs synapse development and function in human neurons.
Kozlova A et al.·Am J Hum Genet
2022
Sequencing individual genomes with recurrent genomic disorder deletions: an approach to characterize genes for autosomal recessive rare disease traits.
Yuan B et al.·Genome Med
2022Meta-analysis
Chromosome 15q Structural Variants Associated with Syndromic Autism Spectrum Disorder: Clinical and Genomic Insights from Three Case Reports in a Brazilian Reference Center.
Gigonzac TCV et al.·Int J Mol Sci
2025Case report
Phenotype prediction using biologically interpretable neural networks on multi-cohort multi-omics data.
van Hilten A et al.·NPJ Syst Biol Appl
2024Cohort
Prenatal diagnosis of 15q13.3 deletion and duplication syndrome: what do we tell the prospective parents?
Luo X et al.·Arch Gynecol Obstet
2025
Mice with mutations in Trpm1, a gene in the locus of 15q13.3 microdeletion syndrome, display pronounced hyperactivity and decreased anxiety-like behavior.
Hori T et al.·Mol Brain
2021
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