OTUD7A

Chr 15AR

OTU deubiquitinase 7A

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

NCBI Gene: 161725ENSG00000169918UniProt: Q8TE49OMIM: 612024

OTUD7A encodes a deubiquitinase that cleaves lysine-11-linked polyubiquitin chains and regulates nuclear factor kappa B signaling through its action on TRAF6. Mutations cause autosomal recessive neurodevelopmental disorder with hypotonia and seizures. The gene is highly constrained against loss-of-function mutations (pLI 0.95, LOEUF 0.33), indicating that functional copies are essential for normal development.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.331 OMIM phenotype
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
99 unique Pathogenic / Likely Pathogenic· 44 VUS of 161 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — OTUD7A
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
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
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
LoF OE0.16 (0.08–0.33)
0≤0.351.4
Missense OE0.62 (0.56–0.69)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 5 / 31.6Missense obs/exp: 284 / 456.2Syn Z: -0.57
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedOTUD7A-related 15q13.3 deletions phenocopyLOFAD
DN
0.3495th %ile
GOF
0.4973th %ile
LOF
0.76top 10%

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

LOFprediction above median · LOEUF 0.33

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

161 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic93
Likely Pathogenic6
VUS44
Likely Benign3
Benign10
Conflicting5
93
Pathogenic
6
Likely Pathogenic
44
VUS
3
Likely Benign
10
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
92
0
93
Likely Pathogenic
0
0
6
0
6
VUS
1
17
26
0
44
Likely Benign
0
0
3
0
3
Benign
0
2
7
1
10
Conflicting
—5
Total1201341161

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
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
Biallelic loss of OTUD7A causes severe muscular hypotonia, intellectual disability, and seizures.
Suzuki H et al.·Am J Med Genet A
2021Case 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
Prenatal diagnosis of 15q13.3 deletion and duplication syndrome: what do we tell the prospective parents?
Luo X et al.·Arch Gynecol Obstet
2025
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients