VPS72
protein-codingvacuolar protein sorting 72 homolog, the group of SRCAP complex|Tip60/Nua4 histone acetyltransferase complex subunits
Gene summary
The protein encoded by this gene is a shared subunit of two multi-component complexes, the histone acetyltransferase complex TRRAP/TIP60 as well as the chromatin remodeling SRCAP-containing complex. The TRRAP/TIP60 complex acetylates nucleosomal histones important for transcriptional regulation, double strand DNA break repair and apoptosis. The SRCAP-containing complex catalyzes the exchange of histone H2A with the histone variant Htz1 (H2AFZ) into nucleosomes. This protein may be responsible for binding H2AFZ, which has a role in chromosome segregation. This protein may also have a role in regulating long-term hematopoietic stem cell activity. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Aug 2012]
- TCFL1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.0 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 VPS72 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005997.3. 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 | ||||
| missense | 5 | 5 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 10 | 0 | 0 | 10 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005988.1 | 6 | MANE Select | |
| Ensembl | ENSP00000357887.5 | 6 | MANE Select | |
| RefSeq | NP_001258016.1 | 6 | Standard | |
| RefSeq | NP_001258017.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Chromatin modifying enzymes
- HATs acetylate histones
- Chromatin organization
Biological Process
- negative regulation of transcription by RNA polymerase II
- somatic stem cell population maintenance
- histone exchange
Molecular Function
- DNA binding
- protein binding
- histone binding
Cellular Component
- nucleus
- nucleoplasm
- nuclear speck
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000354473
- Coding exons
- 6
- Length
- 25335
- Individuals with no LoFs
- 125713
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 34
- Defined
- 125747
- p
- 0.000135
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.57 | 169 | 237 | 0.712 | 0.0000150 | 2384 |
| Missense (PolyPhen) | 37 | 71.849 | 0.51497 | 740 | ||
| Synonymous | 0.820 | 81 | 90.9 | 0.891 | 0.00000516 | 811 |
| Loss of Function | 2.05 | 9 | 18.5 | 0.485 | 0.00000128 | 195 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00017 | 0.00017 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Deposition-and-exchange histone chaperone specific for H2AFZ, specifically chaperones H2AFZ and deposits it into nucleosomes. As component of the SRCAP complex, mediates the ATP- dependent exchange of histone H2AFZ/H2B dimers for nucleosomal H2A/H2B, leading to transcriptional regulation of selected genes by chromatin remodeling. {ECO:0000269|PubMed:26974126}.;
Recessive Scores
- pRec
- 0.145
Intolerance Scores
- LoFtool
- 0.242
- RVIS EVS
- 0.22
- RVIS percentile EVS
- 68.13
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.834
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |