NACC2
protein-codingNACC family member 2, the group of BTB domain containing|BEN domain containing
Gene summary
Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; histone deacetylase binding activity; and protein homodimerization activity. Involved in several processes, including negative regulation of transcription by RNA polymerase II; positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage; and protein homooligomerization. Located in chromatin and nucleus. [provided by Alliance of Genome Resources, Jun 2026]
- BTBD14A
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~88.8 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 NACC2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_144653.5. 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 | 2 | 3 | |||
| missense | 56 | 3 | 59 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 58 | 4 | 2 | 64 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_653254.1 | 5 | MANE Select | |
| Ensembl | ENSP00000277554.2 | 5 | MANE Select | |
| Ensembl | ENSP00000360818.1 | 5 | Standard | |
| Ensembl | ENSP00000600540.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of transcription by RNA polymerase II
- positive regulation of cell population proliferation
- negative regulation of cell population proliferation
- histone deacetylation
- cellular protein-containing complex localization
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- transcription corepressor activity
- histone deacetylase activity
- protein binding
- protein homodimerization activity
Cellular Component
- nuclear chromatin
- nucleus
- nucleolus
- mitochondrion
- nuclear body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000371753
- Coding exons
- 5
- Length
- 88749
- Individuals with no LoFs
- 124834
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 124837
- p
- 0.0000120
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.73 | 120 | 186 | 0.644 | 0.0000141 | 3762 |
| Missense (PolyPhen) | 40 | 82.673 | 0.48384 | 1366 | ||
| Synonymous | -1.42 | 99 | 82.6 | 1.20 | 0.00000661 | 1242 |
| Loss of Function | 2.04 | 2 | 8.35 | 0.239 | 3.55e-7 | 191 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000066 | 0.000062 | rare |
| Latino/Admixed American | 0.000060 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functions as a transcriptional repressor through its association with the NuRD complex. Recruits the NuRD complex to the promoter of MDM2, leading to the repression of MDM2 transcription and subsequent stability of p53/TP53. {ECO:0000269|PubMed:22926524}.;
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Indispensability pred.
- N
- Indispensability score
- 0.209
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |