OTUD7B

Chr 1

OTU deubiquitinase 7B

Also known as: CEZANNE, ZA20D1

NCBI Gene: 56957 ENSG00000264522 UniProt: Q6GQQ9 OMIM: 611748

Enables K48-linked deubiquitinase activity and cysteine-type deubiquitinase activity. Involved in several processes, including negative regulation of protein localization to nucleus; protein deubiquitination; and regulation of intracellular signal transduction. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.48

Clinical Summary— OTUD7B

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

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ClinVar Variants

120 VUS of 144 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.48LOEUF

pLI 0.011

Z-score 4.07

OE 0.29 (0.18–0.48)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.79Z-score

OE missense 0.90 (0.83–0.97)

436 obs / 485.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.29 (0.18–0.48)

0≤0.351.4

Missense OE?0.90 (0.83–0.97)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 11 / 38.1Missense obs/exp: 436 / 485.2Syn Z: -0.05

This gene — mechanism propensity

0.6161th %ile

GOF

0.6735th %ile

LOF

0.3939th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

144 submitted variants in ClinVar

ClinVar

Classification Summary

VUS120

Likely Benign4

Benign8

120

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	120	0	0	120
Likely Benign	3	0	1	4
Benign	0	5	3	8
Total	123	5	4	132

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap OTUD7B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →