CENPM
protein-codingcentromere protein M, the group of Constitutive centromere associated network|Minor histocompatibility antigens
Gene summary
The protein encoded by this gene is an inner protein of the kinetochore, the multi-protein complex that binds spindle microtubules to regulate chromosome segregation during cell division. It belongs to the constitutive centromere-associated network protein group, whose members interact with outer kinetochore proteins and help to maintain centromere identity at each cell division cycle. The protein is structurally related to GTPases but cannot bind guanosine triphosphate. A point mutation that affects interaction with another constitutive centromere-associated network protein, CENP-I, impairs kinetochore assembly and chromosome alignment, suggesting that it is required for kinetochore formation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]
- C22orf18
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.6 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 CENPM variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024053.5. 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 | 27 | 27 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 28 | 0 | 0 | 28 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_076958.1 | 6 | MANE Select | |
| Ensembl | ENSP00000215980.5 | 6 | MANE Select | |
| RefSeq | NP_001002876.1 | 5 | Standard | |
| RefSeq | NP_001103685.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
- Amplification of signal from the kinetochores
- Mitotic Spindle Checkpoint
- Cell Cycle Checkpoints
Biological Process
- CENP-A containing nucleosome assembly
Cellular Component
- condensed chromosome kinetochore
- nucleoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000215980
- Coding exons
- 6
- Length
- 8444
- Individuals with no LoFs
- 125702
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 15
- Defined
- 125717
- p
- 0.0000597
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.543 | 91 | 107 | 0.852 | 0.00000614 | 1145 |
| Missense (PolyPhen) | 26 | 38.122 | 0.68202 | 415 | ||
| Synonymous | -0.333 | 51 | 48.1 | 1.06 | 0.00000262 | 384 |
| Loss of Function | 1.38 | 4 | 8.28 | 0.483 | 4.02e-7 | 96 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000088 | 0.000087 | rare |
| Ashkenazi Jewish | 0.00040 | 0.00040 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. {ECO:0000269|PubMed:16716197}.;
Recessive Scores
- pRec
- 0.115
Intolerance Scores
- LoFtool
- 0.419
- RVIS EVS
- -0.1
- RVIS percentile EVS
- 46.49
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.923
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |