CABIN1
protein-codingcalcineurin binding protein 1, the group of HIRA histone chaperone complex subunits
Gene summary
Calcineurin plays an important role in the T-cell receptor-mediated signal transduction pathway. The protein encoded by this gene binds specifically to the activated form of calcineurin and inhibits calcineurin-mediated signal transduction. The encoded protein is found in the nucleus and contains a leucine zipper domain as well as several PEST motifs, sequences which confer targeted degradation to those proteins which contain them. Alternative splicing results in multiple transcript variants encoding two different isoforms. [provided by RefSeq, Jan 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~167.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0021061
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CABIN1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012295.4. 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 | 5 | 24 | 6 | 35 | ||
| missense | 307 | 16 | 10 | 333 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 15 | 15 | ||||
| Total | 0 | 0 | 330 | 40 | 16 | 386 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036427.1 | 36 | MANE Select | |
| Ensembl | ENSP00000263119.5 | 36 | MANE Select | |
| RefSeq | NP_001186210.1 | 36 | Standard | |
| RefSeq | NP_001188358.1 | 35 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- role of mef2d in t-cell apoptosis
- Formation of Senescence-Associated Heterochromatin Foci (SAHF)
- DNA Damage/Telomere Stress Induced Senescence
- Cellular Senescence
- Cellular responses to stress
Biological Process
- DNA replication-independent nucleosome assembly
- cell surface receptor signaling pathway
- negative regulation of phosphoprotein phosphatase activity
Molecular Function
- protein phosphatase inhibitor activity
- nucleosome binding
Cellular Component
- nucleus
- nucleoplasm
- cytosol
- aggresome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000398319
- Coding exons
- 36
- Length
- 166955
- Individuals with no LoFs
- 125625
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 123
- Defined
- 125748
- p
- 0.000489
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.92 | 1059 | 1.25e+3 | 0.847 | 0.0000801 | 14388 |
| Missense (PolyPhen) | 420 | 556.26 | 0.75504 | 6700 | ||
| Synonymous | -0.207 | 533 | 527 | 1.01 | 0.0000344 | 4537 |
| Loss of Function | 4.99 | 45 | 98.5 | 0.457 | 0.00000525 | 1178 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00055 | 0.00055 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.00061 | 0.00058 | rare |
| South Asian | 0.00059 | 0.00059 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May be required for replication-independent chromatin assembly. May serve as a negative regulator of T-cell receptor (TCR) signaling via inhibition of calcineurin. Inhibition of activated calcineurin is dependent on both PKC and calcium signals. Acts as a negative regulator of p53/TP53 by keeping p53 in an inactive state on chromatin at promoters of a subset of it's target genes. {ECO:0000269|PubMed:14718166, ECO:0000269|PubMed:9655484}.;
Intolerance Scores
- LoFtool
- 0.723
- RVIS EVS
- -0.66
- RVIS percentile EVS
- 15.95
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.800
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |