CENPX
protein-codingcentromere protein X, the group of Constitutive centromere associated network
Gene summary
Enables DNA binding activity. Contributes to double-stranded DNA binding activity. Involved in interstrand cross-link repair; replication fork processing; and resolution of meiotic recombination intermediates. Located in chromatin. Part of FANCM-MHF complex and Fanconi anaemia nuclear complex. [provided by Alliance of Genome Resources, Jun 2026]
- STRA13
- MHF2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.4 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 CENPX variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001271006.2. 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 | 2 | 2 | ||||
| missense | 2 | 2 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 7 | 0 | 0 | 7 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001257935.1 | 5 | MANE Select | |
| Ensembl | ENSP00000376168.3 | 5 | MANE Select | |
| RefSeq | NP_001257936.1 | 4 | Standard | |
| RefSeq | NP_001317465.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Fanconi anemia pathway - Homo sapiens (human)
- Fanconi Anemia Pathway
- DNA Repair
- Nucleosome assembly
- Chromosome Maintenance
Biological Process
- resolution of meiotic recombination intermediates
- replication fork processing
- positive regulation of protein ubiquitination
- CENP-A containing nucleosome assembly
- interstrand cross-link repair
Molecular Function
- DNA binding
- double-stranded DNA binding
- protein binding
Cellular Component
- condensed chromosome kinetochore
- nucleoplasm
- Fanconi anaemia nuclear complex
- FANCM-MHF complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000392359
- Coding exons
- 5
- Length
- 5406
- Individuals with no LoFs
- 107623
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 107627
- p
- 0.0000186
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0853 | 47 | 48.7 | 0.966 | 0.00000320 | 502 |
| Missense (PolyPhen) | 9 | 16.013 | 0.56204 | 210 | ||
| Synonymous | -2.16 | 36 | 22.9 | 1.57 | 0.00000176 | 158 |
| Loss of Function | 1.28 | 2 | 5.13 | 0.390 | 2.19e-7 | 65 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000082 | 0.000076 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000064 | 0.000060 | rare |
| European (Non-Finnish) | 0.000022 | 0.000021 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: DNA-binding component of the Fanconi anemia (FA) core complex. Required for the normal activation of the FA pathway, leading to monoubiquitination of the FANCI-FANCD2 complex in response to DNA damage, cellular resistance to DNA cross-linking drugs, and prevention of chromosomal breakage (PubMed:20347428, PubMed:20347429). In complex with CENPS (MHF heterodimer), crucial cofactor for FANCM in both binding and ATP-dependent remodeling of DNA. Stabilizes FANCM. In complex with CENPS and FANCM (but not other FANC proteins), rapidly recruited to blocked forks and promotes gene conversion at blocked replication forks (PubMed:20347428, PubMed:20347429). In complex with CENPS, CENPT and CENPW (CENP-T-W-S-X heterotetramer), involved in the formation of a functional kinetochore outer plate, which is essential for kinetochore-microtubule attachment and faithful mitotic progression (PubMed:19620631). As a component of MHF and CENP-T-W- S-X complexes, binds DNA and bends it to form a nucleosome-like structure (PubMed:20347428, PubMed:20347429). DNA-binding function is fulfilled in the presence of CENPS, with the following preference for DNA substates: Holliday junction > double-stranded > splay arm > single-stranded. Does not bind DNA on its own (PubMed:20347429). {ECO:0000269|PubMed:19620631, ECO:0000269|PubMed:20347428, ECO:0000269|PubMed:20347429}.;
Recessive Scores
- pRec
- 0.0858
Intolerance Scores
- RVIS EVS
- 0.5
- RVIS percentile EVS
- 79.79
Essentials
- Essential (gene trap)
- N