BANF1

Summary

BANF1 (barrier to autointegration nuclear assembly factor 1, HGNC:17397) is a protein-coding gene on chromosome 11q13.1, encoding Barrier-to-autointegration factor (O75531). 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. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

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.

Source: NCBI Gene 8815 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Nestor-Guillermo progeria syndrome (Moderate, GenCC) — +2 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 34 total
• Phenotypes (HPO): 49
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_003860

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17397
Approved symbol	BANF1
Name	barrier to autointegration nuclear assembly factor 1
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	BAF
Ensembl gene	ENSG00000175334
Ensembl biotype	protein_coding
OMIM	603811
Entrez	8815

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 26 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000312175, ENST00000445560, ENST00000524628, ENST00000524663, ENST00000527348, ENST00000528648, ENST00000530204, ENST00000533166, ENST00000894314, ENST00000894315, ENST00000894316, ENST00000894317, ENST00000894318, ENST00000894319, ENST00000894320, ENST00000894321, ENST00000935797, ENST00000935798, ENST00000935799, ENST00000935800, ENST00000935801, ENST00000935802, ENST00000935803, ENST00000935804, ENST00000935805, ENST00000935806, ENST00000935807, ENST00000941425, ENST00000941426

RefSeq mRNA: 2 — MANE Select: NM_003860 NM_001143985, NM_003860

CCDS: CCDS8125

Canonical transcript exons

ENST00000312175 — 3 exons

Exon	Start	End
ENSE00001189976	66003235	66003373
ENSE00001189984	66002503	66002570
ENSE00002191965	66003626	66004149

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 99.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 174.7682 / max 1152.3094, expressed in 1826 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115261	140.1778	1825
115258	11.9896	1790
115260	11.4347	1732
115262	5.9397	1673
115259	5.1405	1661
115257	0.0503	17
115263	0.0356	15

Top tissues by expression

292 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.15	gold quality
ventricular zone	UBERON:0003053	99.13	gold quality
right uterine tube	UBERON:0001302	99.11	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.10	gold quality
gastrocnemius	UBERON:0001388	98.94	gold quality
apex of heart	UBERON:0002098	98.94	gold quality
ascending aorta	UBERON:0001496	98.91	gold quality
thoracic aorta	UBERON:0001515	98.91	gold quality
cortical plate	UBERON:0005343	98.88	gold quality
embryo	UBERON:0000922	98.83	gold quality
body of uterus	UBERON:0009853	98.80	gold quality
descending thoracic aorta	UBERON:0002345	98.78	gold quality
right coronary artery	UBERON:0001625	98.76	gold quality
right adrenal gland	UBERON:0001233	98.73	gold quality
aorta	UBERON:0000947	98.71	gold quality
left uterine tube	UBERON:0001303	98.71	gold quality
left ovary	UBERON:0002119	98.71	gold quality
endocervix	UBERON:0000458	98.70	gold quality
right testis	UBERON:0004534	98.70	gold quality
left coronary artery	UBERON:0001626	98.66	gold quality
left adrenal gland	UBERON:0001234	98.62	gold quality
left testis	UBERON:0004533	98.61	gold quality
mucosa of transverse colon	UBERON:0004991	98.61	gold quality
popliteal artery	UBERON:0002250	98.60	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.60	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.60	gold quality
right adrenal gland cortex	UBERON:0035827	98.60	gold quality
tibial artery	UBERON:0007610	98.59	gold quality
left adrenal gland cortex	UBERON:0035825	98.58	gold quality
lower esophagus	UBERON:0013473	98.57	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	21.93
E-MTAB-10042	yes	9.76
E-MTAB-6108	no	559.55
E-MTAB-7037	no	258.39
E-MTAB-6379	no	168.77
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, CRX, NONO, SUZ12

miRNA regulators (miRDB)

32 targeting BANF1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-128-2-5P	99.33	60.83	311
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-4769-3P	97.95	68.17	1002
HSA-MIR-6817-5P	97.95	67.86	1026
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-134-5P	97.11	66.52	976
HSA-MIR-3118	97.11	66.58	984

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• The barrier-to-autointegration factor (BAF)-binding domain of emerin is located at the emerin N-terminus (residues 70-178) and includes the LEM-domain. (PMID:11792821)
• BAF is required for the assembly of emerin and A-type lamins at the reforming nuclear envelope during telophase and may mediate their stability in the subsequent interphase. (PMID:11792822)
• BAF may have a role in regulating emerin-GCL repressor complexes (PMID:12493765)
• report that BAF protein is a component of preintegration complexes isolated from HIV-1-infected cells (PMID:12663813)
• HB and barrier-to-autointegration factor are the same protein (PMID:14523012)
• BAF protein was detected in activated but not resting CD4+ T-lymphocytes. BAF bound directly to both p55 Gag and its cleaved product, matrix. (PMID:14645565)
• Data describe the mobility of barrier-to-autointegration factor to its partners emerin, LAP2 beta, and MAN1 in the nuclear membrane of living HeLa cells. (PMID:15109603)
• LAP2alpha and BAF transiently localize to telomeres and specific regions on chromatin during nuclear assembly (PMID:15546916)
• BAF bridges DNA using two pairs of helix-hairpin-helix motifs located on opposite surfaces of the BAF dimer without changing its conformation. (PMID:16155580)
• phosphorylation at Ser175 regulates the dissociation of emerin from BAF (PMID:16204256)
• Ser-4 phosphorylation inhibits BAF binding to emerin and lamin A, and thereby weakens emerin-lamin interactions during both mitosis and interphase. (PMID:16371512)
• These results indicate that barrier-to-autointegration factor is required for the integrity of the nuclear lamina and normal progression of S phase in human cells. (PMID:17519288)
• We now show that BAF acts as a potent inhibitor of poxvirus replication unless its DNA-binding activity is blocked by B1-mediated phosphorylation. (PMID:18005698)
• analyses in human cells showed that barrier-to-autointegration factor (BAF), assembled first at the distinct ;core’ region of the telophase chromosome and formed an immobile complex by binding with NE proteins, such as lamin A and emerin. (PMID:18628300)
• BAF and emerin have dynamic roles in genome integrity and might help couple DNA damage responses to the nuclear lamina network (PMID:19759913)
• These findings are supported by coimmunoprecipitation of prelamin A or progerin with BAF in vivo and suggest that BAF could mediate prelamin A-induced chromatin effects. (PMID:20581439)
• Cooperation of ATP-dependent remodeling, histone methylation, and kinase activation, followed by H1 displacement, is a prerequisite for the subsequent displacement of histone H2A/H2B catalyzed by PCAF and BAF. (PMID:21447625)
• These nuclear abnormalities are rescued by ectopic expression of wild-type BANF1, providing evidence for the causal role of this mutation. (PMID:21549337)
• Data determined that the knockdown of Banf1 alters the cell cycle distribution of both human and mouse ESCs by causing an uncharacteristic increase in the proportion of cells in the G2-M phase of the cell cycle. (PMID:21750191)
• The authors demonstrate that the DNA binding and dimerization capabilities of BAF are essential for its function as an antipoxviral effector, while the presence of emerin is not required. (PMID:21880762)
• A single copy of normal BANF1 is sufficient to avoid the development of Nestor-Guillermo progeria syndrome. (PMID:21932319)
• The absence of direct binding of BAF to MAN1-C eliminates disruption of this interaction as the cause of the premature aging phenotype. (PMID:21966431)
• BAF associated in vivo with SET/I2PP2A (protein phosphatase 2A inhibitor; blocks H3 dephosphorylation) and G9a (H3-K9 methyltransferase), but showed no detectable association with HDAC1 or HATs. (PMID:22127260)
• The accumulation of wild-type prelamin A detected in restrictive dermopathy as well as the accumulation of mutated forms identified in familial partial lipodystrophy and mandibuloacral dysplasia affect the nuclear localization of BAF protein. (PMID:22935701)
• Activation of BANF1 possibly suppresses S100A9 expression and inactivates c-Jun, resulting in suppression of cutaneous inflammation (PMID:23664529)
• The decrease in vaccinia virus transcription caused by loss of B1 kinase can be rescued by depletion of BAF. (PMID:23891157)
• Emerin and BAF associated only in histone- and lamin-B-containing fractions. The S173D mutation specifically and selectively reduced GFP-emerin association with BAF by 58% (PMID:24014020)
• Data indicate that the major phosphatase responsible for dephosphorylation of of BAF Ser-4 to be protein phosphatase 4 catalytic subunit. (PMID:24265311)
• VRK1 deficiency disrupts nuclear envelope morphology and leads to BAF retention on mitotic chromosomes. (PMID:24430874)
• Altogether, these data demonstrate that phosphoregulation of BAF by viral and cellular enzymes modulates this protein at multiple molecular levels, thus determining its effectiveness as an antiviral factor and likely other functions as well. (PMID:24600006)
• Association of emerin with nuclear BAF in cells required the LEM domain (residues 1-47). (PMID:25052089)
• The BANF1, alanine 12 threonine (A12T) mutant is impaired in its ability to bind DNA while its interaction with nuclear envelope proteins is unperturbed. (PMID:25495845)
• These data suggest that VRK3-mediated phosphorylation of BAF may facilitate DNA replication or gene expression by facilitating the dissociation of nuclear envelope proteins and chromatin during interphase. (PMID:25899223)
• BAF is a cytosolic DNA sensor that leads to exogenous DNA avoiding autophagy. (PMID:25991860)
• results demonstrate a novel function of BAF as an epigenetic regulator of HSV lytic infection; hypothesize that BAF facilitates Herpes Simplex Virus IE and E gene expression by recruiting the SETD1A methyltransferase to viral IE and E gene promoters (PMID:26015494)
• The findings unveil a unique mechanism where the nuclear periphery proteins lamin-A/C, LAP2alpha and BAF1 are assembled into a protein complex during mitosis in order to regulate assembly and positioning of the mitotic spindle. (PMID:26092935)
• Vaccinia virus B1 kinase is needed for multiple critical junctures in the poxviral life cycle in a manner that is both dependent on and independent of BAF. (PMID:26223647)
• we demonstrate that BAF is necessary to modulate prelamin A effects on chromatin structure (PMID:26701887)
• antiviral capabilities of the barrier to autointegration factor (BAF/BANF1) and how its function and regulation places BAF at the junction of multiple pathways protecting a cell’s genetic integrity (PMID:26842478)
• It has been concluded that the LEM domain, responsible for binding to the chromatin protein BAF, undergoes a conformational change during self-assembly of emerin N-terminal region. (PMID:27960036)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	banf1	ENSDARG00000037009
mus_musculus	Banf1	ENSMUSG00000024844
rattus_norvegicus	Banf1	ENSRNOG00000020460
caenorhabditis_elegans		WBGENE00000235

Paralogs (1): BANF2 (ENSG00000125888)

Protein

Protein identifiers

Barrier-to-autointegration factor — O75531 (reviewed: O75531)

Alternative names: Breakpoint cluster region protein 1

All UniProt accessions (2): E9PJJ8, O75531

UniProt curated annotations — full annotation on UniProt →

Function. 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. Contains two non-specific double-stranded DNA (dsDNA)-binding sites which promote DNA cross-bridging. Plays a key role in nuclear membrane reformation at the end of mitosis by driving formation of a single nucleus in a spindle-independent manner. Transiently cross-bridges anaphase chromosomes via its ability to bridge distant DNA sites, leading to the formation of a dense chromatin network at the chromosome ensemble surface that limits membranes to the surface. Also acts as a negative regulator of innate immune activation by restricting CGAS activity toward self-DNA upon acute loss of nuclear membrane integrity. Outcompetes CGAS for DNA-binding, thereby preventing CGAS activation and subsequent damaging autoinflammatory responses. Also involved in DNA damage response: interacts with PARP1 in response to oxidative stress, thereby inhibiting the ADP-ribosyltransferase activity of PARP1. Involved in the recognition of exogenous dsDNA in the cytosol: associates with exogenous dsDNA immediately after its appearance in the cytosol at endosome breakdown and is required to avoid autophagy. In case of poxvirus infection, has an antiviral activity by blocking viral DNA replication. (Microbial infection) Exploited by retroviruses for inhibiting self-destructing autointegration of retroviral DNA, thereby promoting integration of viral DNA into the host chromosome. EMD and BAF are cooperative cofactors of HIV-1 infection. Association of EMD with the viral DNA requires the presence of BAF and viral integrase. The association of viral DNA with chromatin requires the presence of BAF and EMD.

Subunit / interactions. Homodimer. Heterodimerizes with BANF2. Interacts with ANKLE2/LEM4, leading to decreased phosphorylation by VRK1 and promoting dephosphorylation by protein phosphatase 2A (PP2A). Binds non-specifically to double-stranded DNA, and is found as a hexamer or dodecamer upon DNA binding. Binds to LEM domain-containing nuclear proteins such as LEMD3/MAN1, TMPO/LAP2 and EMD (emerin). Interacts with ANKLE1 (via LEM domain); the interaction may favor BANF1 dimerization. Interacts with CRX and LMNA (lamin-A). Binds linker histone H1.1 and core histones H3. Interacts with LEMD2 (via LEM domain). Interacts with PARP1; interaction takes place in response to oxidative DNA damage. (Microbial infection) Interacts with HIV-1 pre-integration complex in cytoplasm by binding to viral matrix protein and Gag polyprotein.

Subcellular location. Nucleus. Chromosome. Nucleus envelope. Cytoplasm.

Tissue specificity. Widely expressed. Expressed in colon, brain, heart, kidney, liver, lung, ovary, pancreas, placenta, prostate, skeletal muscle, small intestine, spleen and testis. Not detected in thymus and peripheral blood leukocytes.

Post-translational modifications. Ser-4 is the major site of phosphorylation as compared to Thr-2 and Thr-3. Phosphorylation on Thr-2; Thr-3 and Ser-4 disrupts its ability to bind DNA and reduces its ability to bind LEM domain-containing proteins. Non phosphorylated BAF seems to enhance binding between EMD and LMNA. Dephosphorylated by protein phosphatase 2A (PP2A) following interaction with ANKLE2/LEM4 during mitotic exit, leading to mitotic nuclear envelope reassembly. (Microbial infection) Phosphorylated by poxvirus B1 kinase (VPK1) on serine and threonine residues, leading to BANF1 relocalization to the cytoplasm, loss of dimerization and impaired DNA binding activity. (Microbial infection) Phosphorylated at the N-terminus by vaccinia virus (VacV) B1 kinase, leading to BANF1 relocalization to the cytoplasm, loss of dimerization and impaired DNA binding activity. Hyperphosphorylation is linked to the loss of ability to suppress vaccinia virus replication.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Has a helix-hairpin-helix (HhH) structural motif conserved among proteins that bind non-specifically to DNA. LEM domain proteins bind centrally on the BAF dimer.

Similarity. Belongs to the BAF family.

RefSeq proteins (2): NP_001137457, NP_003851* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004122	BAF_prot	Family
IPR036617	BAF_sf	Homologous_superfamily
IPR051387	BAF	Family

Pfam: PF02961

UniProt features (61 total): mutagenesis site 42, modified residue 7, helix 6, chain 2, initiator methionine 1, sequence variant 1, domain 1, turn 1

Structure

Experimental structures (PDB)

29 structures.

PDB	Method	Resolution (Å)
7NDY	X-RAY DIFFRACTION	1.44
7Z21	X-RAY DIFFRACTION	1.63
6URE	X-RAY DIFFRACTION	1.65
6URJ	X-RAY DIFFRACTION	1.65
6URZ	X-RAY DIFFRACTION	1.65
6US0	X-RAY DIFFRACTION	1.65
6US1	X-RAY DIFFRACTION	1.65
6US7	X-RAY DIFFRACTION	1.65
6USD	X-RAY DIFFRACTION	1.65
6USI	X-RAY DIFFRACTION	1.65
6URN	X-RAY DIFFRACTION	1.68
6USB	X-RAY DIFFRACTION	1.68
6URL	X-RAY DIFFRACTION	1.72
6UNT	X-RAY DIFFRACTION	1.75
6URR	X-RAY DIFFRACTION	1.8
6URK	X-RAY DIFFRACTION	1.86
1CI4	X-RAY DIFFRACTION	1.9
6GHD	X-RAY DIFFRACTION	2.1
6RPR	X-RAY DIFFRACTION	2.26
2BZF	X-RAY DIFFRACTION	2.87
7ABM	X-RAY DIFFRACTION	3
9J8M	ELECTRON MICROSCOPY	3.82
9J8O	ELECTRON MICROSCOPY	4.05
9J8N	ELECTRON MICROSCOPY	7.14
1QCK	SOLUTION NMR
2EZX	SOLUTION NMR
2EZY	SOLUTION NMR
2EZZ	SOLUTION NMR
2ODG	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75531-F1	96.87	0.97

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (7): 4, 1, 2, 2, 2, 3, 3

Mutagenesis-validated functional residues (42):

Position	Phenotype
2–4	95% nuclear localization. loss of baf phosphorylation and ability to suppress vaccinia virus dna replication.
2–4	85% cytoplasmic localization.
2–3	no effect on the initial rate of phosphorylation but a second slow phase of phosphorylation is absent.
4	delayed phosphorylation with a 10-fold decrease in the initial phosphorylation rate. 71% loss of binding to lamin a.
4	75% cytoplasmic localization.
4	complete loss of phosphorylation and mislocalization of emd in nucleus.
6	complete loss of lemd3/man1 and histone h1/h3 binding.
6	complete loss of dsdna and lemd3/man1 binding.
8	enhances histone h1/h3 binding.
8	complete loss of lemd3/man1 binding.
9	reduces binding to dsdna, lemd3/man1 and histone h1/h3. reduced interaction with parp1.
14	no effect on lemd3/man1 and enhances histone h1/h3 binding.
18	no effect on histone h1/h3 binding.
25	complete loss of dsdna, emd, histone h1/h3 and lemd3/man1 binding.
25	complete loss of emd binding and reduces dsdna binding.
26	reduces histone h1/h3 and lemd3/man1 binding. fails to promote hiv-1 genome integration.
26	fails to promote hiv-1 genome integration.
27	fails to bind dsdna.
27	reduces binding to dsdna.
29	no effect on histone h1/h3 binding.
32	no effect on histone h1/h3 binding.
33	no effect on histone h1/h3 binding.
37	no effect on histone h1/h3 binding.
37	reduces lemd3/man1 binding.
41	no effect on histone h1/h3 and lemd3/man1 binding.

Function

Pathways and Gene Ontology

Reactome pathways

23 pathways

ID	Pathway
R-HSA-162592	Integration of provirus
R-HSA-164843	2-LTR circle formation
R-HSA-175567	Integration of viral DNA into host genomic DNA
R-HSA-177539	Autointegration results in viral DNA circles
R-HSA-180689	APOBEC3G mediated resistance to HIV-1 infection
R-HSA-180910	Vpr-mediated nuclear import of PICs
R-HSA-2980766	Nuclear Envelope Breakdown
R-HSA-2995383	Initiation of Nuclear Envelope (NE) Reformation
R-HSA-162587	HIV Life Cycle
R-HSA-162594	Early Phase of HIV Life Cycle
R-HSA-162906	HIV Infection
R-HSA-162909	Host Interactions of HIV factors
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-176033	Interactions of Vpr with host cellular proteins
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-2995410	Nuclear Envelope (NE) Reassembly
R-HSA-5663205	Infectious disease
R-HSA-68875	Mitotic Prophase
R-HSA-68882	Mitotic Anaphase
R-HSA-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 454 (showing top): MORF_MTA1, GOBP_CHROMOSOME_ORGANIZATION, GOBP_NUCLEAR_MEMBRANE_REASSEMBLY, REACTOME_INTERACTIONS_OF_VPR_WITH_HOST_CELLULAR_PROTEINS, REACTOME_INTEGRATION_OF_PROVIRUS, GOBP_MEMBRANE_BIOGENESIS, ENK_UV_RESPONSE_KERATINOCYTE_UP, MORF_UBE2I, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, MORF_RAD21, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_DNA_INTEGRATION, MORF_PSMC2

GO Biological Process (14): chromatin organization (GO:0006325), response to oxidative stress (GO:0006979), mitotic nuclear membrane reassembly (GO:0007084), response to virus (GO:0009615), negative regulation of protein ADP-ribosylation (GO:0010836), DNA integration (GO:0015074), negative regulation of type I interferon production (GO:0032480), negative regulation of viral genome replication (GO:0045071), negative regulation of innate immune response (GO:0045824), chromosome organization (GO:0051276), negative regulation of cGAS/STING signaling pathway (GO:0160049), DNA repair (GO:0006281), positive regulation of type I interferon production (GO:0032481), cGAS/STING signaling pathway (GO:0140896)

GO Molecular Function (5): DNA binding (GO:0003677), double-stranded DNA binding (GO:0003690), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (8): chromatin (GO:0000785), condensed chromosome (GO:0000793), nucleus (GO:0005634), nuclear envelope (GO:0005635), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Integration of provirus	3
Host Interactions of HIV factors	2
HIV Infection	2
M Phase	2
Early Phase of HIV Life Cycle	1
Interactions of Vpr with host cellular proteins	1
Mitotic Prophase	1
Nuclear Envelope (NE) Reassembly	1
HIV Life Cycle	1
Viral Infection Pathways	1
Mitotic Anaphase	1
Disease	1
Mitotic Metaphase and Anaphase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
DNA metabolic process	2
regulation of type I interferon production	2
type I interferon production	2
chromosome	2
cellular component organization	1
response to stress	1
mitotic cell cycle	1
nuclear membrane reassembly	1
mitotic nuclear membrane organization	1
response to other organism	1
regulation of protein ADP-ribosylation	1
negative regulation of catalytic activity	1
NAD+-protein mono-ADP-ribosyltransferase activity	1
negative regulation of cytokine production	1
viral genome replication	1
regulation of viral genome replication	1
negative regulation of viral process	1
negative regulation of response to biotic stimulus	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
innate immune response	1
regulation of innate immune response	1
negative regulation of immune response	1
organelle organization	1
negative regulation of cytoplasmic pattern recognition receptor signaling pathway	1
cGAS/STING signaling pathway	1
DNA damage response	1
positive regulation of cytokine production	1
cytoplasmic pattern recognition receptor signaling pathway	1
nucleic acid binding	1
DNA binding	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
binding	1
intracellular membrane-bounded organelle	1
nucleus	1
endomembrane system	1
organelle envelope	1

Protein interactions and networks

STRING

2822 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BANF1	SMARCA4	P51532	998
BANF1	EMD	P50402	998
BANF1	LEMD3	Q9Y2U8	996
BANF1	H3-3A	P06351	953
BANF1	H3C14	Q71DI3	952
BANF1	H3-5	Q6NXT2	952
BANF1	H3C1	P02295	952
BANF1	H3-4	Q16695	952
BANF1	PAX6	P26367	952
BANF1	H3-7	Q5TEC6	952
BANF1	ACTL6B	O94805	934
BANF1	ACTL6A	O96019	931
BANF1	SMARCE1	Q969G3	919
BANF1	PHF10	Q8WUB8	909
BANF1	DPF1	Q92782	888

IntAct

266 interactions, top by confidence:

A	B	Type	Score
BANF1	EMD	psi-mi:“MI:0915”(physical association)	0.940
EMD	BANF1	psi-mi:“MI:0915”(physical association)	0.940
BANF1	TMIGD1	psi-mi:“MI:0915”(physical association)	0.640
BANF1	TMIGD1	psi-mi:“MI:0407”(direct interaction)	0.640
BANF1	TMIGD1	psi-mi:“MI:0403”(colocalization)	0.640
BANF1	BANF1	psi-mi:“MI:0407”(direct interaction)	0.620
BANF1	BANF2	psi-mi:“MI:0915”(physical association)	0.560
GATA2	BANF1	psi-mi:“MI:0914”(association)	0.530
STAT3	BANF1	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	SEC16A	psi-mi:“MI:0914”(association)	0.530
HDGFL2	CDC7	psi-mi:“MI:0914”(association)	0.530
BANF1	RELA	psi-mi:“MI:0915”(physical association)	0.460
BANF1	RELA	psi-mi:“MI:0403”(colocalization)	0.460
BANF1	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
BANF1	PARD3B	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (288): BANF1 (Affinity Capture-MS), BANF1 (Two-hybrid), SOX4 (Affinity Capture-Western), ASPSCR1 (Co-fractionation), DNAJC2 (Co-fractionation), BANF1 (Proximity Label-MS), BANF1 (Proximity Label-MS), BANF1 (Proximity Label-MS), BANF1 (Affinity Capture-MS), BANF1 (Affinity Capture-MS), BANF1 (Affinity Capture-MS), BANF1 (Affinity Capture-MS), BANF1 (Affinity Capture-MS), BANF1 (Affinity Capture-MS), BANF1 (Affinity Capture-MS)

ESM2 similar proteins: A5DCF5, A5E121, A7RS11, A8MVJ9, A8XAC6, B9EMY6, G5ECQ8, O13728, O14134, O24308, O54962, O75531, O93796, O94489, P11103, P18493, P30182, P31669, P45573, P53978, P56152, P61283, Q01879, Q03565, Q09464, Q0J0S6, Q11207, Q11208, Q3T0X7, Q4R6C5, Q5HZM3, Q5RBU9, Q5YLB4, Q66KV4, Q6BLF4, Q6DGT7, Q6NTS2, Q6P026, Q6PAF4, Q7EYV7

Diamond homologs: A8XAC6, O54962, O75531, P61283, Q03565, Q32PE7, Q5HZM3, Q5RBU9, Q66KV4, Q6NTS2, Q6P026, Q8BVR0, Q9H503, Q9R1T1, Q9VLU0

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
VRK1	down-regulates	BANF1	phosphorylation
VRK2	down-regulates	BANF1	phosphorylation
PPP4C	up-regulates	BANF1	dephosphorylation
VRK3	“down-regulates activity”	BANF1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 195 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
EPHA-mediated growth cone collapse	5	13.5×	7e-03
EPH-ephrin mediated repulsion of cells	6	9.3×	7e-03
Neurexins and neuroligins	6	8.4×	9e-03
Estrogen-dependent gene expression	11	5.9×	2e-03
Signaling by Interleukins	11	5.0×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	7	23.8×	1e-05
receptor clustering	5	18.2×	2e-03
positive regulation of miRNA transcription	8	13.6×	7e-05
peptidyl-tyrosine phosphorylation	5	12.3×	6e-03
response to ethanol	8	6.9×	4e-03
positive regulation of MAPK cascade	10	4.7×	6e-03
nervous system development	14	3.8×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

34 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	5
Benign	11

Top pathogenic / likely-pathogenic (0)

SpliceAI

502 predictions. Top by Δscore:

Variant	Effect	Δscore
11:66003233:A:AG	acceptor_gain	1.0000
11:66003234:G:GG	acceptor_gain	1.0000
11:66003343:C:T	donor_gain	1.0000
11:66003353:G:GT	donor_gain	1.0000
11:66003356:G:GT	donor_gain	1.0000
11:66003357:A:T	donor_gain	1.0000
11:66003616:T:A	acceptor_gain	1.0000
11:66003621:T:A	acceptor_gain	1.0000
11:66003623:CAGGC:C	acceptor_loss	1.0000
11:66003624:A:AG	acceptor_gain	1.0000
11:66003624:AG:A	acceptor_gain	1.0000
11:66003625:G:GA	acceptor_gain	1.0000
11:66003625:GG:G	acceptor_gain	1.0000
11:66003625:GGC:G	acceptor_gain	1.0000
11:66003625:GGCC:G	acceptor_gain	1.0000
11:66003625:GGCCT:G	acceptor_gain	1.0000
11:66002376:G:GT	donor_gain	0.9900
11:66003224:G:A	acceptor_gain	0.9900
11:66003234:GATT:G	acceptor_gain	0.9900
11:66003234:GATTA:G	acceptor_gain	0.9900
11:66003332:G:GT	donor_gain	0.9900
11:66003346:G:GT	donor_gain	0.9900
11:66003623:CAGG:C	acceptor_gain	0.9900
11:66002273:G:GT	donor_gain	0.9800
11:66002358:A:T	donor_gain	0.9800
11:66002568:CGGGT:C	donor_loss	0.9800
11:66002569:GG:G	donor_gain	0.9800
11:66002569:GGGT:G	donor_loss	0.9800
11:66002570:GG:G	donor_gain	0.9800
11:66002570:GGT:G	donor_loss	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000204984 (11:66004026 C>T), RS1000668160 (11:66002373 A>G), RS1001227845 (11:66001879 C>T), RS1001228704 (11:66002164 G>A), RS1001575937 (11:66001632 T>C), RS1002541002 (11:66000565 T>C), RS1002835470 (11:66002773 G>A,T), RS1004687209 (11:66004423 C>A,T), RS1004804099 (11:66003175 G>A,C,T), RS1004972174 (11:66002576 C>T), RS1005329725 (11:66004491 C>T), RS1006784913 (11:66000255 G>A,C), RS1007693394 (11:66000592 A>G), RS1008436945 (11:66001959 C>A), RS1009510537 (11:66004100 C>G)

Disease associations

OMIM: gene MIM:603811 | disease phenotypes: MIM:614008

GenCC curated gene-disease

Disease	Classification	Inheritance
Nestor-Guillermo progeria syndrome	Moderate	Autosomal recessive
hereditary peripheral neuropathy	Limited	Autosomal dominant
neurodevelopmental disorder	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Nestor-Guillermo progeria syndrome	Limited	AR

Mondo (3): Nestor-Guillermo progeria syndrome (MONDO:0013523), hereditary peripheral neuropathy (MONDO:0020127), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): Nestor-Guillermo progeria syndrome (Orphanet:280576)

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000233	Thin vermilion border
HP:0000308	Microretrognathia
HP:0000347	Micrognathia
HP:0000444	Convex nasal ridge
HP:0000520	Proptosis
HP:0000653	Sparse eyelashes
HP:0000678	Dental crowding
HP:0000689	Dental malocclusion
HP:0000822	Hypertension
HP:0000883	Thin ribs
HP:0000905	Progressive clavicular acroosteolysis
HP:0000939	Osteoporosis
HP:0000958	Dry skin
HP:0001015	Prominent superficial veins
HP:0001371	Flexion contracture
HP:0001387	Joint stiffness
HP:0001476	Delayed closure of the anterior fontanelle
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001596	Alopecia
HP:0001653	Mitral regurgitation
HP:0002092	Pulmonary arterial hypertension
HP:0002094	Dyspnea
HP:0002209	Sparse scalp hair
HP:0002280	Enlarged cisterna magna
HP:0002389	Cavum septum pellucidum
HP:0002621	Atherosclerosis
HP:0002650	Scoliosis
HP:0002756	Pathologic fracture

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002481_8	Acne (severe)	3.000000e-11
GCST007294_7	Body fat distribution (trunk fat ratio)	8.000000e-12
GCST007294_75	Body fat distribution (trunk fat ratio)	1.000000e-07
GCST007295_158	Body fat distribution (leg fat ratio)	8.000000e-06
GCST007295_48	Body fat distribution (leg fat ratio)	3.000000e-09
GCST008103_21	Bipolar disorder	2.000000e-08
GCST010512_19	Serum uric acid levels	2.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004341	body fat distribution
EFO:0004761	uric acid measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169063 (PROTEIN-PROTEIN INTERACTION)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S,4R)-N-[[2-[2-[4-[[4-[3-amino-6-(2-hydroxyphenyl)pyridazin-4-yl]piperazin-1-yl]methyl]phenoxy]ethoxy]-4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carboxamide	1849944: PROTAC activity at VHL/BAF in human MV4-11 cells assessed as induction of BAF degradation incubated for 18 hrs by Western blot analysis	ec50	0.0320	uM

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
bisphenol F	increases expression	1
bisphenol A	increases expression	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
coumarin	decreases phosphorylation	1
cupric oxide	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	increases expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
K 7174	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
pyrimidifen	increases expression	1
pyrachlostrobin	increases expression	1
bisphenol S	increases expression	1
picoxystrobin	increases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Antimycin A	increases expression	1
Atrazine	decreases expression	1
Caffeine	decreases phosphorylation	1
Coumestrol	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Diuron	decreases expression	1
Doxorubicin	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5104666	Binding	PROTAC activity at VHL/BAF in human MV4-11 cells assessed as induction of BAF degradation incubated for 18 hrs by Western blot analysis	Proteolysis targeting chimera (PROTAC) in drug discovery paradigm: Recent progress and future challenges. — Eur J Med Chem

Clinical trials (associated diseases)

203 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT03278093	Not specified	UNKNOWN	Effect of Orthoses and Underfoot Vibration on Balance in Neuropathy
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge