MCL1
protein-codingMCL1 apoptosis regulator, BCL2 family member, the group of BCL2 family
Gene summary
This gene encodes an anti-apoptotic protein, which is a member of the Bcl-2 family. Alternative splicing results in multiple transcript variants. The longest gene product (isoform 1) enhances cell survival by inhibiting apoptosis while the alternatively spliced shorter gene products (isoform 2 and isoform 3) promote apoptosis and are death-inducing. [provided by RefSeq, Oct 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~18.8 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 MCL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021960.5. 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 | 1 | 4 | 1 | 6 | ||
| missense | 27 | 1 | 28 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 32 | 4 | 2 | 38 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_068779.1 | 3 | MANE Select | |
| Ensembl | ENSP00000358022.2 | 3 | MANE Select | |
| RefSeq | NP_001184249.1 | 4 | Standard | |
| RefSeq | NP_877495.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- Jak-STAT signaling pathway - Homo sapiens (human)
- MicroRNAs in cancer - Homo sapiens (human)
- Apoptosis - Homo sapiens (human)
- Apoptosis Modulation and Signaling
Biological Process
- cell fate determination
- multicellular organism development
- intrinsic apoptotic signaling pathway in response to DNA damage
- negative regulation of autophagy
- cytokine-mediated signaling pathway
Molecular Function
- protein binding
- protein transmembrane transporter activity
- protein homodimerization activity
- protein heterodimerization activity
- BH3 domain binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- mitochondrion
- mitochondrial outer membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000369026
- Coding exons
- 3
- Length
- 5035
- Individuals with no LoFs
- 118455
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 118457
- p
- 0.00000844
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.364 | 208 | 194 | 1.07 | 0.00000871 | 2211 |
| Missense (PolyPhen) | 38 | 54.381 | 0.69877 | 627 | ||
| Synonymous | -0.490 | 92 | 86.2 | 1.07 | 0.00000400 | 778 |
| Loss of Function | 2.97 | 0 | 10.3 | 0.00 | 4.49e-7 | 116 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis. {ECO:0000269|PubMed:10766760, ECO:0000269|PubMed:16543145}.;
Recessive Scores
- pRec
- 0.481
Intolerance Scores
- RVIS EVS
- -0.18
- RVIS percentile EVS
- 39.95
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.981
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |