BANF1
protein-codingBAF nuclear assembly factor 1
Gene summary
The protein encoded by this gene was first identified by its ability to protect retroviruses from intramolecular integration and therefore promote intermolecular integration into the host cell genome. The protein forms a homodimer which localizes to both the nucleus and cytoplasm and is specifically associated with chromosomes during mitosis. This protein binds to double stranded DNA in a non-specific manner and also binds to LEM-domain containing proteins of the nuclear envelope. This protein is thought to facilitate nuclear reassembly by binding with both DNA and inner nuclear membrane proteins and thereby recruit chromatin to the nuclear periphery. Alternative splicing results in multiple transcript variants encoding the same protein.[provided by RefSeq, Jan 2009]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0013523
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0013523
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0013523
Submitter: ClinGen
The BANF1 gene is located on chromosome 11 at 11q13.1 and encodes the barrier to autointegration nuclear assembly factor 1 protein, a non-specific DNA-binding protein that plays key roles in mitotic nuclear reassembly, chromatin organization, DNA damage response, gene expression and intrinsic immunity against foreign DNA. BANF1 was first reported in relation to autosomal recessive Néstor-Guillermo Progeria Syndrome (NGPS) in 2011 (Puente et al., PMID: 21549337;). NGPS is a unique progeria with a relatively long lifespan with features such as signs of aging, growth delay, reduced subcutaneous fat, decreased diameter of limbs, and stiffening of the joints. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found clear differences in inheritance pattern and phenotypic variability between the following disease entities which have therefore been split: autosomal recessive NGPS and BANF1-related neurodevelopmental disorder. The split curation for autosomal dominant BANF1-related neurodevelopmental disorder has been curated separately. One missense variant (possible founder variant in Spanish families) that has been reported in 3 probands in 2 publications (PMIDs: 21549337, 32783369) is included in this curation. The mechanism of pathogenicity appears to be loss-of-function. This gene-disease relationship is also supported by experimental evidence, including protein interaction and biochemical functional evidence, specifically interaction evidence with lamin, and function in DNA stability/repair activity (PMIDs: 36039758, 33660778). In summary, there is limited evidence supporting the relationship between BANF1 and autosomal recessive NGPS. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Syndromic Disorders GCEP on the meeting date April 3rd, 2024 (SOP Version 10).
Inheritance Pattern: AD
Disease ID:MONDO:0700092
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0020127
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0013523
Submitter: PanelApp Australia
Inheritance Pattern: Unknown
Disease ID:MONDO:0013523
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0013523
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to BANF1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003860.4. 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 | 1 | 1 | 2 | |||
| missense | 1 | 1 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 4 | 0 | 1 | 5 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003851.1 | 2 | MANE Select | |
| Ensembl | ENSP00000310275.2 | 2 | MANE Select | |
| RefSeq | NP_001137457.1 | 2 | Standard | |
| RefSeq | NP_001427547.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Disease
- HIV Life Cycle
- Host Interactions of HIV factors
- HIV Infection
- Vpr-mediated nuclear import of PICs
Biological Process
- mitotic nuclear envelope reassembly
- response to virus
- DNA integration
- negative regulation of viral genome replication
- nuclear transport
Molecular Function
- DNA binding
- protein binding
- protein C-terminus binding
- enzyme binding
- identical protein binding
Cellular Component
- condensed chromosome
- nucleus
- nuclear envelope
- nucleoplasm
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000312175
- Coding exons
- 2
- Length
- 2071
- Individuals with no LoFs
- 125744
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 4
- Defined
- 125748
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.43 | 23 | 52.0 | 0.442 | 0.00000324 | 578 |
| Missense (PolyPhen) | 3 | 16.314 | 0.1839 | 222 | ||
| Synonymous | -0.713 | 26 | 21.8 | 1.19 | 0.00000145 | 175 |
| Loss of Function | 1.71 | 0 | 3.41 | 0.00 | 1.97e-7 | 37 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000026 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays fundamental roles in nuclear assembly, chromatin organization, gene expression and gonad development. May potently compress chromatin structure and be involved in membrane recruitment and chromatin decondensation during nuclear assembly. Contains 2 non-specific dsDNA-binding sites which may promote DNA cross-bridging. {ECO:0000269|PubMed:12163470}.; FUNCTION: (Microbial infection) In case of poxvirus infection, has an antiviral activity by blocking viral DNA replication. {ECO:0000269|PubMed:18005698}.;
- Disease
- DISEASE: Nestor-Guillermo progeria syndrome (NGPS) [MIM:614008]: An atypical progeroid syndrome characterized by normal development in the first years of life, later followed by the emergence of generalized lipoatrophy, severe osteoporosis, and marked osteolysis. The atrophic facial subcutaneous fat pad and the marked osteolysis of the maxilla and mandible result in a typical pseudosenile facial appearance with micrognathia, prominent subcutaneous venous patterning, a convex nasal ridge, and proptosis. Cognitive development is completely normal. Patients do not have cardiovascular dysfunction, atherosclerosis, or metabolic anomalies. {ECO:0000269|PubMed:21549337}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.375
Intolerance Scores
- LoFtool
- 0.488
- RVIS EVS
- -0.01
- RVIS percentile EVS
- 52.85
Essentials
- Essential (CRISPR)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.781
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Low | Low | Low |
| Cancer | Low | Low | Low |