BCLAF1

Summary

BCLAF1 (BCL2 associated transcription factor 1, HGNC:16863) is a protein-coding gene on chromosome 6q23.3, encoding Bcl-2-associated transcription factor 1 (Q9NYF8). Death-promoting transcriptional repressor. It is a selective cancer dependency (DepMap: 82.9% of cell lines).

This gene encodes a transcriptional repressor that interacts with several members of the BCL2 family of proteins. Overexpression of this protein induces apoptosis, which can be suppressed by co-expression of BCL2 proteins. The protein localizes to dot-like structures throughout the nucleus, and redistributes to a zone near the nuclear envelope in cells undergoing apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 9774 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 182 total — 2 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 5 cancer types
• Cancer dependency (DepMap): dependent in 82.9% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• Transcription factor: yes — 10 downstream targets (CollecTRI)
• MANE Select transcript: NM_014739

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16863
Approved symbol	BCLAF1
Name	BCL2 associated transcription factor 1
Location	6q23.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0164, BTF
Ensembl gene	ENSG00000029363
Ensembl biotype	protein_coding
OMIM	612588
Entrez	9774

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 20 protein_coding, 7 retained_intron, 7 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000353331, ENST00000392348, ENST00000476194, ENST00000526228, ENST00000527536, ENST00000527613, ENST00000527759, ENST00000528229, ENST00000529522, ENST00000529826, ENST00000529917, ENST00000530429, ENST00000530767, ENST00000531224, ENST00000532076, ENST00000532384, ENST00000533422, ENST00000533621, ENST00000534269, ENST00000534321, ENST00000534762, ENST00000534792, ENST00000628517, ENST00000640069, ENST00000885860, ENST00000885861, ENST00000885862, ENST00000885863, ENST00000885864, ENST00000912032, ENST00000912034, ENST00000912035, ENST00000945210, ENST00000945211, ENST00000945212

RefSeq mRNA: 17 — MANE Select: NM_014739 NM_001077440, NM_001077441, NM_001301038, NM_001363659, NM_001386693, NM_001386694, NM_001386695, NM_001386696, NM_001386697, NM_001386698, NM_001386699, NM_001386700, NM_001386701, NM_001386702, NM_001386703, NM_001386704, NM_014739

CCDS: CCDS47485, CCDS47486, CCDS5177, CCDS75525, CCDS87444

Canonical transcript exons

ENST00000531224 — 13 exons

Exon	Start	End
ENSE00000458095	136275843	136276508
ENSE00000458096	136275532	136275701
ENSE00000764312	136277865	136278776
ENSE00001429785	136282584	136282687
ENSE00001432201	136279763	136279876
ENSE00003547832	136269437	136269612
ENSE00003587899	136271995	136272079
ENSE00003592316	136273082	136273187
ENSE00003592638	136267029	136267175
ENSE00003627950	136268162	136268339
ENSE00003669907	136261265	136261477
ENSE00003889872	136289713	136289846
ENSE00003891347	136256627	136261115

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 77.9801 / max 1909.0307, expressed in 1816 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75754	77.8715	1816
204216	0.1086	41

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.52	gold quality
tibia	UBERON:0000979	98.64	gold quality
embryo	UBERON:0000922	98.52	gold quality
caput epididymis	UBERON:0004358	98.50	gold quality
ventricular zone	UBERON:0003053	98.44	gold quality
upper leg skin	UBERON:0004262	98.43	gold quality
parietal pleura	UBERON:0002400	98.42	gold quality
corpus epididymis	UBERON:0004359	98.41	gold quality
esophagus squamous epithelium	UBERON:0006920	98.41	gold quality
epithelium of nasopharynx	UBERON:0001951	98.40	gold quality
skin of hip	UBERON:0001554	98.39	gold quality
palpebral conjunctiva	UBERON:0001812	98.38	gold quality
bronchial epithelial cell	CL:0002328	98.37	gold quality
ganglionic eminence	UBERON:0004023	98.36	gold quality
sural nerve	UBERON:0015488	98.35	gold quality
pigmented layer of retina	UBERON:0001782	98.34	gold quality
colonic epithelium	UBERON:0000397	98.32	gold quality
pleura	UBERON:0000977	98.30	gold quality
bone marrow cell	CL:0002092	98.28	gold quality
cauda epididymis	UBERON:0004360	98.12	gold quality
visceral pleura	UBERON:0002401	98.11	gold quality
germinal epithelium of ovary	UBERON:0001304	98.09	gold quality
mammary duct	UBERON:0001765	98.03	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.01	gold quality
adrenal tissue	UBERON:0018303	98.00	gold quality
tonsil	UBERON:0002372	97.99	gold quality
endometrium	UBERON:0001295	97.92	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.91	gold quality
cortical plate	UBERON:0005343	97.90	gold quality
corpus callosum	UBERON:0002336	97.89	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

10 targets.

Target	Regulation
BCLAF1
EPHB2
ERCC3
HPSE2
IRAG1
MADCAM1
NFKB
RRAS2
SIRT1
TP53	Unknown

Upstream regulators (CollecTRI, top): BCLAF1, KAT7, NFKB, RELA

miRNA regulators (miRDB)

202 targeting BCLAF1, 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-4262	100.00	73.26	3931
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-LET-7F-2-3P	99.98	70.98	2588

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 82.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 31)

• These results suggest that Btf localization is regulated by apoptotic signals, and that loss of emerin binding to Btf may be relevant to muscle wasting in Emery-Dreifuss muscular dystrophy. (PMID:15009215)
• These findings provide evidence that activation of TP53 gene transcription by PKCdelta triggers TP53-dependent apoptosis in response to DNA damage. (PMID:17938203)
• Two-dimensional differential in-gel electrophoresis (2D-DIGE) revealed the differential expression of 51 proteins in response to C16-ceramide. Cell death-promoting factor Btf was found to be implicated in the apoptotic signal triggered by ceramide. (PMID:19705920)
• Findings indicate a role for BCLAF1 in post-transcriptional processes that impact mRNA metabolism. (PMID:20661537)
• We replicated the association of BCL2L11 and CASP9 with non-Hodgkin’s lymphoma risk at the gene and SNP level, and identified novel associations with BCLAF1 and BAG5. (PMID:20855536)
• Sirt1 negatively regulates T cell activation via H3K56 deacetylation at the promoter region to inhibit transcription of Bclaf1 (PMID:21454709)
• In the absence of BclAF1 neutralization, viral gene expression and replication are inhibited. These data identify two temporally and mechanistically distinct functions used by human cytomegalovirus to down-regulate a cellular antiviral protein (PMID:22645331)
• BCLAF1 co-localized with gammaH2AX foci in nuclei and stabilized the Ku70/DNA-PKcs complex therein, facilitating non-homologous end joining (NHEJ)-based DSB repair in surviving cells. (PMID:22833098)
• BTF has functions distinct from TRAP150 in regulating the subcellular distribution of mRNAs in human cells. (PMID:23778535)
• findings showed that FXR1P interacts with BTF in vivo and proved that FXR1P and BTF can co-localize mainly in the cytoplasm around the nucleus (PMID:24389646)
• SRSF10 is a key regulator of BCLAF1 pre-mRNA splicing and the maintenance of oncogenic features in human colon cancer cells (PMID:25091051)
• both cytoplasmic BCLAF1 expression and nuclear BCLAF1 expression are increased in post-neoadjuvant therapy rectal cancer, and that negative and weak nuclear BCLAF1 expression are independently associated with a poor prognosis (PMID:26183150)
• SMYD3 physically interacts with the promoter of BCLAF1 and upregulates its expression by accumulating di- and trimethylation of H3K4 at the BCLAF1 locus. BCLAF1 depletion inhibits SMYD3-induced autophagy. (PMID:26676636)
• The Bclaf1 can interact with the leucine zipper region of C/EBPbeta and cooperate with C/EBPbeta to upregulate IL-8. (PMID:26794446)
• findings link treatment responsiveness to re-instatement of miR-194-5p/BCLAF1 balance (PMID:28216661)
• LTBR and BCLAF1 showed higher DNA methylation percentages in the marsupialized OKCs, but this difference did not affect gene expression (P > .05). (PMID:28864293)
• Results indicate a role for the RNA processing factors THRAP3 and BCLAF1 in the regulation of the cellular DNA damage response (DDR) pathway. (PMID:29112714)
• frequently up-regulated in hepatocellular carcinoma and associated with lower survival rates (PMID:30015413)
• Bclaf1 levels increase in hypoxia in a HIF-1alpha dependent manner. Therefore, Bclaf1 is a novel positive regulator of HIF-1alpha in the hypoxic microenvironment, providing new incentives for promoting Bcalf1 as a potential therapeutic target for an anti-hepatocellular carcinoma strategy. (PMID:30367150)
• Study identified Bcl2-associated factor 1 (BCLAF1) as a phosphorylation-dependent SDS22 ligand. (PMID:30661852)
• promotes cell proliferation, invasion and drug-resistance though targeting lncRNA NEAT1 in hepatocellular carcinoma (PMID:31870774)
• Bclaf1 is a direct target of HIF-1 and critically regulates the stability of HIF-1alpha under hypoxia. (PMID:32029898)
• Role of BCLAF-1 in PD-L1 stabilization in response to ionizing irradiation. (PMID:34251713)
• New insights from Whole Genome Sequencing: BCLAF1 deletion as a structural variant that predisposes cells towards cellular transformation. (PMID:34490482)
• TET2-BCLAF1 transcription repression complex epigenetically regulates the expression of colorectal cancer gene Ascl2 via methylation of its promoter. (PMID:35660018)
• BCLAF1-induced HIF-1alpha accumulation under normoxia enhances PD-L1 treatment resistances via BCLAF1-CUL3 complex. (PMID:37906282)
• BCLAF1 is Expressed as a Potential Anti-oncogene in Bile Duct Cancer. (PMID:38198022)
• BCLAF1 binds SPOP to stabilize PD-L1 and promotes the development and immune escape of hepatocellular carcinoma. (PMID:38340178)
• BCLAF1 drives esophageal squamous cell carcinoma progression through regulation of YTHDF2-dependent SIX1 mRNA degradation. (PMID:38636894)
• CircZFR promotes colorectal cancer progression via stabilizing BCLAF1 and regulating the miR-3127-5p/RTKN2 axis. (PMID:38805063)
• MED23 depletion induces premature senescence in NSCLC cells by interacting with BCLAF1 and then suppressing NUPR1 expression. (PMID:39366174)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bclaf1	ENSMUSG00000037608
rattus_norvegicus	Mtfr2	ENSRNOG00000058050

Paralogs (2): THRAP3 (ENSG00000054118), BCLAF3 (ENSG00000173681)

Protein

Protein identifiers

Bcl-2-associated transcription factor 1 — Q9NYF8 (reviewed: Q9NYF8)

Alternative names: BCLAF1 and THRAP3 family member 1

All UniProt accessions (10): A0A1W2PQ43, E9PJA7, E9PK09, E9PK91, E9PKI6, E9PQN2, Q9NYF8, H0YF00, H0YF14, H0YF63

UniProt curated annotations — full annotation on UniProt →

Function. Death-promoting transcriptional repressor. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3’end of the CCND1 gene and its mRNA.

Subunit / interactions. Interacts with Bcl-2 related proteins, EMD, with the adenovirus E1B 19 kDa protein and with DNA. Component of the SNARP complex which consists at least of SNIP1, SNW1, THRAP3, BCLAF1 and PNN. Component of a MACOM-like complex, named WTAP complex, composed of WTAP, ZC3H13, CBLL1, KIAA1429, RBM15, BCLAF1 and THRAP3.

Subcellular location. Cytoplasm. Nucleus. Nucleus speckle. Nucleoplasm.

Tissue specificity. Ubiquitous.

Post-translational modifications. Citrullinated by PADI4.

Similarity. Belongs to the BCLAF1/THRAP3 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9NYF8-1	1	yes
Q9NYF8-2	2, Btf-l
Q9NYF8-3	3, Btf-s, BP-1
Q9NYF8-4	4

RefSeq proteins (17): NP_001070908, NP_001070909, NP_001287967, NP_001350588, NP_001373622, NP_001373623, NP_001373624, NP_001373625, NP_001373626, NP_001373627, NP_001373628, NP_001373629, NP_001373630, NP_001373631, NP_001373632, NP_001373633, NP_055554* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029199	THRAP3_BCLAF1	Family

Pfam: PF15440

UniProt features (111 total): modified residue 54, cross-link 25, compositionally biased region 16, sequence variant 6, region of interest 5, splice variant 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7RJR	X-RAY DIFFRACTION	1.45
7RJN	X-RAY DIFFRACTION	1.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NYF8-F1	47.04	0.01

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 (79): 339, 102, 104, 152, 177, 181, 196, 198, 219, 222, 259, 262, 264, 268, 284, 285, 290, 297, 300, 315 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 254 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, HSIAO_HOUSEKEEPING_GENES, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_APOPTOTIC_SIGNALING_PATHWAY, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_REGULATION_OF_CATABOLIC_PROCESS, MODULE_206, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, DER_IFN_BETA_RESPONSE_UP

GO Biological Process (13): apoptotic process (GO:0006915), DNA damage response (GO:0006974), positive regulation of apoptotic process (GO:0043065), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), cellular response to leukemia inhibitory factor (GO:1990830), positive regulation of DNA-templated transcription initiation (GO:2000144), positive regulation of intrinsic apoptotic signaling pathway (GO:2001244), nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:0000184), mRNA processing (GO:0006397), regulation of translation (GO:0006417), RNA splicing (GO:0008380), mRNA transport (GO:0051028)

GO Molecular Function (5): DNA binding (GO:0003677), transcription coregulator activity (GO:0003712), RNA binding (GO:0003723), mRNA binding (GO:0003729), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mediator complex (GO:0016592), nuclear speck (GO:0016607), exon-exon junction complex (GO:0035145)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of DNA-templated transcription	2
RNA processing	2
nucleic acid binding	2
cellular anatomical structure	2
nuclear protein-containing complex	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular response to stress	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
DNA-templated transcription initiation	1
regulation of DNA-templated transcription initiation	1
intrinsic apoptotic signaling pathway	1
positive regulation of intracellular signal transduction	1
positive regulation of apoptotic signaling pathway	1
regulation of intrinsic apoptotic signaling pathway	1
nuclear-transcribed mRNA catabolic process	1
mRNA metabolic process	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
RNA transport	1
transcription regulator activity	1
RNA binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
core mediator complex	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

3462 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCLAF1	EMD	P50402	961
BCLAF1	BCL2	P10415	926
BCLAF1	H2AX	P16104	923
BCLAF1	CCNB1	P14635	912
BCLAF1	THRAP3	Q9Y2W1	877
BCLAF1	BRCA1	P38398	790
BCLAF1	CBLL1	Q75N03	727
BCLAF1	L3MBTL3	Q96JM7	724
BCLAF1	VIRMA	Q69YN4	715
BCLAF1	ZC3H13	Q5T200	709
BCLAF1	RBM15	Q96T37	709
BCLAF1	SNW1	Q13573	695
BCLAF1	LEMD3	Q9Y2U8	617
BCLAF1	CEBPB	P17676	592
BCLAF1	SNIP1	Q8TAD8	589

IntAct

294 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
CSNK2A1	EIF3J	psi-mi:“MI:0914”(association)	0.810
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
PNN	CASC3	psi-mi:“MI:0914”(association)	0.640
FGF12	TCOF1	psi-mi:“MI:0914”(association)	0.610
BCLAF1	EMD	psi-mi:“MI:0915”(physical association)	0.590
EMD	BCLAF1	psi-mi:“MI:0407”(direct interaction)	0.590
EMD	BCLAF1	psi-mi:“MI:0915”(physical association)	0.590
Mad2l1	BUB1B	psi-mi:“MI:0915”(physical association)	0.560
MTA3	KDM1A	psi-mi:“MI:0914”(association)	0.530
DLD	PDHB	psi-mi:“MI:0914”(association)	0.530
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530
SUPT5H	POLR2D	psi-mi:“MI:0914”(association)	0.530
SNRNP70	GTPBP1	psi-mi:“MI:0914”(association)	0.530
LUC7L2	CASC3	psi-mi:“MI:0914”(association)	0.530
SNIP1	CASC3	psi-mi:“MI:0914”(association)	0.530
PAIP2B	CASC3	psi-mi:“MI:0914”(association)	0.530
SRPK2	RRP9	psi-mi:“MI:0914”(association)	0.530
WSB2	UBB	psi-mi:“MI:0914”(association)	0.530
SNRPC	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
GSPT2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
BCLAF1	CORO2A	psi-mi:“MI:0915”(physical association)	0.500
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480

BioGRID (474): BCLAF1 (Affinity Capture-RNA), BCLAF1 (Affinity Capture-RNA), BCLAF1 (Affinity Capture-MS), BCLAF1 (Affinity Capture-MS), BCLAF1 (Affinity Capture-MS), BCLAF1 (Affinity Capture-MS), BCLAF1 (Affinity Capture-MS), BCLAF1 (Affinity Capture-MS), BCLAF1 (Affinity Capture-MS), BCLAF1 (Affinity Capture-MS), BCLAF1 (Affinity Capture-MS), BCLAF1 (Affinity Capture-MS), BCLAF1 (Affinity Capture-MS), BCLAF1 (Affinity Capture-MS), BCLAF1 (Affinity Capture-MS)

ESM2 similar proteins: A0JNI5, A2AJT4, D3ZTQ1, O35691, O75376, P79149, Q05519, Q12872, Q14241, Q149C2, Q3USH5, Q4KKX4, Q4R6F6, Q53F19, Q568R1, Q569Z6, Q5BJ39, Q5BL56, Q5HZB6, Q5M7V8, Q5R5X0, Q5SFM8, Q5T8P6, Q5ZM19, Q60974, Q63187, Q6DFQ2, Q6NZN0, Q6PJT7, Q6WKW9, Q6ZPZ3, Q8BZR9, Q8BZX4, Q8CB77, Q8CFC7, Q8K019, Q8K3W3, Q8K3X0, Q8N2M8, Q8QG78

Diamond homologs: A2AG58, A2AJT9, Q569Z6, Q5BJ39, Q5M7V8, Q8K019, Q9NYF8, Q9Y2W1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
BCLAF1	“up-regulates quantity by expression”	TP53	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 217 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
Transport of Mature Transcript to Cytoplasm	7	18.8×	5e-06
RNA Polymerase II Transcription Termination	11	17.0×	4e-09
mRNA Polyadenylation	25	15.5×	1e-20
mRNA 3’-end processing	11	15.2×	1e-08
mRNA Splicing	19	14.7×	5e-15
HIV Transcription Elongation	6	14.2×	2e-04
mRNA Capping	5	13.4×	1e-03
Processing of Capped Intron-Containing Pre-mRNA	22	12.7×	4e-16

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	6	24.8×	3e-05
U2-type prespliceosome assembly	6	20.2×	8e-05
spliceosomal complex assembly	6	19.5×	9e-05
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	5	12.7×	3e-03
mRNA splicing, via spliceosome	24	11.9×	4e-16
regulation of alternative mRNA splicing, via spliceosome	9	11.9×	2e-05
mRNA export from nucleus	7	11.2×	4e-04
negative regulation of protein ubiquitination	7	10.8×	4e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 5 cancer types — AML, MEL, PRAD, STAD, UCS.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	114
Likely benign	16
Benign	5

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1696847	NM_014739.3(BCLAF1):c.493C>A (p.Gln165Lys)	Pathogenic
1696857	NM_014739.3(BCLAF1):c.813G>T (p.Arg271Ser)	Pathogenic

SpliceAI

2576 predictions. Top by Δscore:

Variant	Effect	Δscore
6:136261029:CATT:C	donor_gain	1.0000
6:136261260:TATA:T	donor_loss	1.0000
6:136261262:TACC:T	donor_loss	1.0000
6:136261272:T:TA	donor_gain	1.0000
6:136261473:TCATG:T	acceptor_gain	1.0000
6:136261474:CATG:C	acceptor_gain	1.0000
6:136261474:CATGC:C	acceptor_gain	1.0000
6:136261475:ATG:A	acceptor_gain	1.0000
6:136261476:TG:T	acceptor_gain	1.0000
6:136261476:TGC:T	acceptor_loss	1.0000
6:136261477:GCT:G	acceptor_loss	1.0000
6:136261478:C:CC	acceptor_gain	1.0000
6:136261478:CTA:C	acceptor_loss	1.0000
6:136261479:T:C	acceptor_loss	1.0000
6:136261481:C:CT	acceptor_gain	1.0000
6:136261482:A:T	acceptor_gain	1.0000
6:136267040:T:TA	donor_gain	1.0000
6:136268156:A:AC	donor_gain	1.0000
6:136268157:C:CC	donor_gain	1.0000
6:136268159:TAC:T	donor_loss	1.0000
6:136268160:A:AC	donor_gain	1.0000
6:136268160:A:AG	donor_loss	1.0000
6:136268161:C:CA	donor_gain	1.0000
6:136268161:CA:C	donor_gain	1.0000
6:136268161:CAA:C	donor_gain	1.0000
6:136268161:CAAA:C	donor_gain	1.0000
6:136268161:CAAAG:C	donor_gain	1.0000
6:136268164:AGGTT:A	donor_gain	1.0000
6:136268335:GTTTA:G	acceptor_gain	1.0000
6:136268336:TTTA:T	acceptor_gain	1.0000

AlphaMissense

6018 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:136261361:C:A	W887C	1.000
6:136261361:C:G	W887C	1.000
6:136261362:C:G	W887S	1.000
6:136261363:A:G	W887R	1.000
6:136261363:A:T	W887R	1.000
6:136261466:T:A	R852S	1.000
6:136261466:T:G	R852S	1.000
6:136261467:C:A	R852I	1.000
6:136261473:T:A	D850V	1.000
6:136261473:T:G	D850A	1.000
6:136261474:C:G	D850H	1.000
6:136261477:G:C	H849D	1.000
6:136267032:G:C	F847L	1.000
6:136267032:G:T	F847L	1.000
6:136267033:A:G	F847S	1.000
6:136267034:A:G	F847L	1.000
6:136267036:T:C	Y846C	1.000
6:136267037:A:C	Y846D	1.000
6:136267037:A:G	Y846H	1.000
6:136267041:C:A	K844N	1.000
6:136267041:C:G	K844N	1.000
6:136267044:G:C	S843R	1.000
6:136267044:G:T	S843R	1.000
6:136267046:T:G	S843R	1.000
6:136267047:C:A	K842N	1.000
6:136267047:C:G	K842N	1.000
6:136267051:G:T	P841Q	1.000
6:136267052:G:A	P841S	1.000
6:136267058:A:G	Y839H	1.000
6:136267068:C:A	W835C	1.000

dbSNP variants (sampled 300 via entrez): RS1000005090 (6:136272408 T>C), RS1000028179 (6:136287049 A>G), RS1000116163 (6:136265579 T>G), RS1000231232 (6:136265321 G>A), RS1000284641 (6:136274038 C>G), RS1000450027 (6:136266948 G>A,C,T), RS1000486987 (6:136267724 T>G), RS1000563797 (6:136266762 A>T), RS1000642318 (6:136262361 T>C), RS1000646419 (6:136273977 C>A), RS1000670945 (6:136258778 C>A,T), RS1000711183 (6:136272667 T>C), RS1000722639 (6:136256903 T>C,G), RS1000805407 (6:136257263 A>C), RS1000881666 (6:136289939 C>T)

Disease associations

OMIM: gene MIM:612588 | disease phenotypes: MIM:616487, MIM:617667

GenCC curated gene-disease

Mondo (2): epidermolysis bullosa simplex with nail dystrophy (MONDO:0014661), Fraser syndrome 3 (MONDO:0054739)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724748 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.27	Kd	5.406	nM	CHEMBL5653589
8.27	ED50	5.406	nM	CHEMBL5653589
7.52	IC50	30	nM	MOLIBRESIB
7.50	Kd	32	nM	MOLIBRESIB

PubChem BioAssay actives

3 with measured affinity, of 9 total; 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147945: Binding affinity to human BCLAF1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0054	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178465: Inhibition of BCLAF1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.0300	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, affects cotreatment	7
bisphenol A	decreases expression, affects cotreatment	2
trichostatin A	decreases expression	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
bisphenol S	decreases expression, affects cotreatment	2
Vorinostat	decreases expression	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Benzo(a)pyrene	affects methylation, increases expression	2
Hydrogen Peroxide	affects expression	2
Ozone	increases oxidation, increases abundance, affects cotreatment	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
deoxynivalenol	increases expression	1
geraniol	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cypermethrin	increases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
coumarin	affects phosphorylation	1
beta-methylcholine	affects expression	1
tamibarotene	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650987	Binding	Binding affinity to human BCLAF1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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