USP16
protein-codingubiquitin specific peptidase 16, the group of Ubiquitin specific peptidases
Gene summary
This gene encodes a deubiquitinating enzyme that is phosphorylated at the onset of mitosis and then dephosphorylated at the metaphase/anaphase transition. It can deubiquitinate H2A, one of two major ubiquitinated proteins of chromatin, in vitro and a mutant form of the protein was shown to block cell division. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~29.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to USP16 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006447.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 104 | 1 | 105 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 108 | 1 | 1 | 110 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006438.1 | 17 | MANE Select | |
| Ensembl | ENSP00000382858.2 | 17 | MANE Select | |
| RefSeq | NP_001001992.1 | 17 | Standard | |
| RefSeq | NP_001027582.1 | 17 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein modification
- Metabolism of proteins
- Ub-specific processing proteases
- Deubiquitination
Biological Process
- mitotic cell cycle
- regulation of transcription by RNA polymerase II
- ubiquitin-dependent protein catabolic process
- cellular response to DNA damage stimulus
- histone deubiquitination
Molecular Function
- transcription coactivator activity
- cysteine-type endopeptidase activity
- thiol-dependent ubiquitin-specific protease activity
- zinc ion binding
- thiol-dependent ubiquitinyl hydrolase activity
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000334352
- Coding exons
- 17
- Length
- 29860
- Individuals with no LoFs
- 125653
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 95
- Defined
- 125748
- p
- 0.000378
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.350 | 399 | 419 | 0.952 | 0.0000205 | 5505 |
| Missense (PolyPhen) | 137 | 177.44 | 0.77208 | 2405 | ||
| Synonymous | 1.29 | 126 | 146 | 0.865 | 0.00000747 | 1430 |
| Loss of Function | 2.83 | 21 | 40.4 | 0.520 | 0.00000186 | 559 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00084 | 0.00081 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00012 | 0.00011 | rare |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00032 | 0.00032 | rare |
| South Asian | 0.00082 | 0.00075 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Specifically deubiquitinates 'Lys-120' of histone H2A (H2AK119Ub), a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. Deubiquitination of histone H2A is a prerequisite for subsequent phosphorylation at 'Ser-11' of histone H3 (H3S10ph), and is required for chromosome segregation when cells enter into mitosis. In resting B- and T- lymphocytes, phosphorylation by AURKB leads to enhance its activity, thereby maintaining transcription in resting lymphocytes. Regulates Hox gene expression via histone H2A deubiquitination. Prefers nucleosomal substrates. Does not deubiquitinate histone H2B. {ECO:0000255|HAMAP-Rule:MF_03062, ECO:0000269|PubMed:10077596, ECO:0000269|PubMed:17914355}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving USP16 is a cause of Chronic myelomonocytic leukemia. Inversion inv(21) (q21;q22) with RUNX1/AML1.;
Recessive Scores
- pRec
- 0.108
Intolerance Scores
- LoFtool
- 0.981
- RVIS EVS
- -0.09
- RVIS percentile EVS
- 47.06
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.621
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |