ACIN1
protein-codingapoptotic chromatin condensation inducer 1, the group of ASAP complex
Gene summary
Apoptosis is defined by several morphologic nuclear changes, including chromatin condensation and nuclear fragmentation. This gene encodes a nuclear protein that induces apoptotic chromatin condensation after activation by caspase-3, without inducing DNA fragmentation. This protein has also been shown to be a component of a splicing-dependent multiprotein exon junction complex (EJC) that is deposited at splice junctions on mRNAs, as a consequence of pre-mRNA splicing. It may thus be involved in mRNA metabolism associated with splicing. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]
- ACINUS
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~37.1 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 ACIN1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001386863.1. 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 | 4 | 1 | 5 | |||
| missense | 162 | 3 | 165 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 172 | 4 | 0 | 176 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001373792.1 | 19 | MANE Select | |
| Ensembl | ENSP00000474349.1 | 19 | MANE Select | |
| RefSeq | NP_001158286.2 | 19 | Standard | |
| RefSeq | NP_001158287.2 | 18 | 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)
- Spliceosome - Homo sapiens (human)
- Apoptotic cleavage of cellular proteins
- Apoptotic execution phase
Biological Process
- mRNA processing
- RNA splicing
- erythrocyte differentiation
- apoptotic chromosome condensation
- positive regulation of monocyte differentiation
Molecular Function
- nucleic acid binding
- RNA binding
- protein binding
- ATPase activity
- enzyme binding
Cellular Component
- nucleus
- nucleoplasm
- nucleolus
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000262710
- Coding exons
- 19
- Length
- 37051
- Individuals with no LoFs
- 125707
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 41
- Defined
- 125748
- p
- 0.000163
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.20 | 601 | 773 | 0.777 | 0.0000478 | 8583 |
| Missense (PolyPhen) | 180 | 272.83 | 0.65975 | 2948 | ||
| Synonymous | -1.31 | 306 | 278 | 1.10 | 0.0000141 | 2746 |
| Loss of Function | 6.99 | 8 | 72.0 | 0.111 | 0.00000466 | 801 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00021 | 0.00021 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: 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 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; ACIN1 confers RNA-binding to the complex. The ASAP complex can inhibit RNA 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 formation of proapoptotic isoforms such as Bcl-X(S); the activity is different from the established EJC assembly and function. Induces apoptotic chromatin condensation after activation by CASP3. Regulates cyclin A1, but not cyclin A2, expression in leukemia cells. {ECO:0000269|PubMed:10490026, ECO:0000269|PubMed:12665594, ECO:0000269|PubMed:18559500, ECO:0000269|PubMed:22203037, ECO:0000269|PubMed:22388736}.;
Recessive Scores
- pRec
- 0.423
Intolerance Scores
- LoFtool
- 0.464
- RVIS EVS
- -0.44
- RVIS percentile EVS
- 24.71
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.948
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |