SAP18
protein-codingSin3A associated protein 18, the group of ASAP complex|Spliceosomal C complex|Spliceosomal Bact complex|SIN3 histone deacetylase complex subunits
Gene summary
Histone acetylation plays a key role in the regulation of eukaryotic gene expression. Histone acetylation and deacetylation are catalyzed by multisubunit complexes. The protein encoded by this gene is a component of the histone deacetylase complex, which includes SIN3, SAP30, HDAC1, HDAC2, RbAp46, RbAp48, and other polypeptides. This protein directly interacts with SIN3 and enhances SIN3-mediated transcriptional repression when tethered to the promoter. A pseudogene has been identified on chromosome 2. [provided by RefSeq, Dec 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.0 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 SAP18 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005870.5. 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 | 0 | |||||
| missense | 14 | 14 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 17 | 0 | 0 | 17 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005861.2 | 4 | MANE Select | |
| Ensembl | ENSP00000371973.4 | 4 | MANE Select | |
| RefSeq | NP_001353572.1 | 4 | Standard | |
| Ensembl | ENSP00000391846.2 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- mRNA surveillance pathway - Homo sapiens (human)
- RNA transport - Homo sapiens (human)
- HH-Ncore
- Hedgehog Signaling Pathway
- NoRC negatively regulates rRNA expression
Biological Process
- regulation of alternative mRNA splicing, via spliceosome
- regulation of transcription by RNA polymerase II
- mRNA processing
- RNA splicing
- histone deacetylation
Molecular Function
- transcription corepressor activity
- RNA binding
- histone deacetylase activity
- protein binding
Cellular Component
- histone deacetylase complex
- nucleoplasm
- cytosol
- nuclear body
- nuclear speck
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000382533
- Coding exons
- 4
- Length
- 8569
- Individuals with no LoFs
- 125706
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 40
- Defined
- 125747
- p
- 0.000163
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.768 | 80 | 102 | 0.786 | 0.00000508 | 1107 |
| Missense (PolyPhen) | 7 | 20.638 | 0.33917 | 261 | ||
| Synonymous | -1.90 | 53 | 38.1 | 1.39 | 0.00000186 | 338 |
| Loss of Function | 1.74 | 3 | 8.48 | 0.354 | 4.29e-7 | 95 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000068 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00016 | 0.00015 | rare |
| South Asian | 0.00080 | 0.00072 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the SIN3-repressing complex. Enhances the ability of SIN3-HDAC1-mediated transcriptional repression. When tethered to the promoter, it can direct the formation of a repressive complex to core histone proteins. Auxiliary component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Component of the ASAP and PSAP complexes which bind RNA in a sequence-independent manner and are proposed to be recruited to the EJC prior to or during the splicing process and to regulate specific excision of introns in specific transcription subsets. The ASAP complex can inhibit mRNA processing during in vitro splicing reactions. The ASAP complex promotes apoptosis and is disassembled after induction of apoptosis. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits the formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function. {ECO:0000269|PubMed:12665594, ECO:0000269|PubMed:20966198, ECO:0000269|PubMed:22203037, ECO:0000269|PubMed:9150135}.;
Recessive Scores
- pRec
- 0.149
Intolerance Scores
- LoFtool
- 0.388
- RVIS EVS
- -0.12
- RVIS percentile EVS
- 44.54
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.998
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |