BLCAP

Summary

BLCAP (BLCAP apoptosis inducing factor, HGNC:1055) is a protein-coding gene on chromosome 20q11.23, encoding Apoptosis inducing factor BLCAP (P62952). Acts as a tumor suppressor; induces growth arrest at G(1)/S checkpoint and apoptosis via RB1-dependent and p53/TP53- and NF-kappa-B-independent mechanisms.

This gene encodes a protein that reduces cell growth by stimulating apoptosis. Alternative splicing and the use of alternative promoters result in multiple transcript variants encoding the same protein. This gene is imprinted in brain where different transcript variants are expressed from each parental allele. Transcript variants initiating from the upstream promoter are expressed preferentially from the maternal allele, while transcript variants initiating downstream of the interspersed NNAT gene (GeneID:4826) are expressed from the paternal allele. Transcripts at this locus may also undergo A to I editing, resulting in amino acid changes at three positions in the N-terminus of the protein.

Source: NCBI Gene 10904 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_006698

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1055
Approved symbol	BLCAP
Name	BLCAP apoptosis inducing factor
Location	20q11.23
Locus type	gene with protein product
Status	Approved
Aliases	BC10
Ensembl gene	ENSG00000166619
Ensembl biotype	protein_coding
OMIM	613110
Entrez	10904

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 26 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000373537, ENST00000397131, ENST00000397134, ENST00000397135, ENST00000397137, ENST00000411780, ENST00000414080, ENST00000414542, ENST00000432507, ENST00000445723, ENST00000447625, ENST00000456058, ENST00000467603, ENST00000613961, ENST00000894262, ENST00000894263, ENST00000894264, ENST00000894265, ENST00000894266, ENST00000894267, ENST00000917217, ENST00000917218, ENST00000917219, ENST00000917220, ENST00000963567, ENST00000963568, ENST00000963569, ENST00000963570, ENST00000963571, ENST00000963572

RefSeq mRNA: 7 — MANE Select: NM_006698 NM_001167820, NM_001167821, NM_001167822, NM_001167823, NM_001317074, NM_001317075, NM_006698

CCDS: CCDS13295

Canonical transcript exons

ENST00000373537 — 2 exons

Exon	Start	End
ENSE00001527437	37517417	37519350
ENSE00003842570	37527793	37527876

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 65.0875 / max 665.6993, expressed in 1822 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187200	52.7137	1821
187199	9.0444	1690
187201	2.9019	1530
187196	0.2951	45
187198	0.0531	12
187197	0.0529	21
187195	0.0264	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.74	gold quality
oocyte	CL:0000023	99.34	gold quality
nucleus accumbens	UBERON:0001882	99.10	gold quality
middle frontal gyrus	UBERON:0002702	99.05	gold quality
tibialis anterior	UBERON:0001385	99.02	gold quality
gluteal muscle	UBERON:0002000	99.00	gold quality
gastrocnemius	UBERON:0001388	98.98	gold quality
right uterine tube	UBERON:0001302	98.93	gold quality
deltoid	UBERON:0001476	98.81	gold quality
adenohypophysis	UBERON:0002196	98.69	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.68	gold quality
pituitary gland	UBERON:0000007	98.66	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.63	gold quality
frontal pole	UBERON:0002795	98.55	gold quality
caudate nucleus	UBERON:0001873	98.53	gold quality
muscle of leg	UBERON:0001383	98.52	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.50	gold quality
triceps brachii	UBERON:0001509	98.48	gold quality
superior vestibular nucleus	UBERON:0007227	98.45	gold quality
muscle organ	UBERON:0001630	98.43	gold quality
middle temporal gyrus	UBERON:0002771	98.42	gold quality
vastus lateralis	UBERON:0001379	98.41	gold quality
hypothalamus	UBERON:0001898	98.39	gold quality
putamen	UBERON:0001874	98.35	gold quality
quadriceps femoris	UBERON:0001377	98.22	gold quality
skeletal muscle tissue	UBERON:0001134	98.20	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.10	gold quality
superior frontal gyrus	UBERON:0002661	98.08	gold quality
pons	UBERON:0000988	98.00	gold quality
forebrain	UBERON:0001890	97.96	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	1521.68
E-HCAD-5	yes	641.19
E-ANND-3	yes	16.72

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3

miRNA regulators (miRDB)

147 targeting BLCAP, 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-8485	100.00	77.57	4731
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-539-5P	99.93	70.30	2855
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

Literature-anchored findings (GeneRIF, showing 12)

• might be a potential tumor suppressor gene in cervical carcinoma. (PMID:16675915)
• BLCAP may play a role not only in regulating cell proliferation but also in coordinating apoptosis and cell cycle via a novel way independent of p53 and NF-kappaB. (PMID:17031575)
• Blcap is imprinted in mouse and human brain, but not in other mouse tissues. (PMID:18836209)
• Data show that loss of BLCAP expression is associated with tumor progression. (PMID:19783793)
• observed a general decrease in BLCAP-editing level in astrocytomas, bladder cancer and colorectal cancer when compared with the related normal tissues (PMID:19908260)
• Immunoexpression analysis and prognostic value of BLCAP in breast cancer (PMID:23049907)
• Data show that the RNA-edited bladder cancer associated protein (BLCAP) gene may stably promote cell proliferation. (PMID:25499081)
• the functional association of BLCAP and Rb1 might play important roles in proliferation and apoptosis of HeLa cells. (PMID:26986503)
• Upregulated miR-9-3p has a positive role in human MTC progression by regulating the growth and apoptosis of cancer cells via targeting BLCAP. (PMID:27938505)
• Our findings reveal that A-to-I RNA editing events alter the genetically coded amino acid in BLCAP YXXQ motif, which drive the progression of cervical carcinogenesis through regulating STAT3 signaling pathway. (PMID:28455960)
• data indicates that Blcap is a novel Stat3 interaction partner and suggests a role for Blcap in the Stat3-mediated progression of precancerous lesions to invasive tumors of the bladder (PMID:29190807)
• MALAT1 regulates BLCAP mRNA expression through binding to miR-339-5p. (PMID:30683807)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	blcap	ENSDARG00000052073
mus_musculus	Blcap	ENSMUSG00000067787
rattus_norvegicus	Blcap	ENSRNOG00000024437
drosophila_melanogaster	bc10	FBGN0040239
caenorhabditis_elegans	Y73E7A.6	WBGENE00022273

Protein

Protein identifiers

Apoptosis inducing factor BLCAP — P62952 (reviewed: P62952)

Alternative names: Bladder cancer 10 kDa protein, Bladder cancer-associated protein

All UniProt accessions (4): A0A1Y8ELN7, A2A2K8, A2A2K9, P62952

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a tumor suppressor; induces growth arrest at G(1)/S checkpoint and apoptosis via RB1-dependent and p53/TP53- and NF-kappa-B-independent mechanisms. Modulates expression of genes involved in the regulation of proliferation, cell cycle and apoptosis.

Subunit / interactions. Interacts with RB1 (phosphorylated and unphosphorylated). Interacts with STAT3; the interaction is promoted by cell stimulation with IL6 and phosphorylation of STAT3.

Subcellular location. Cytoplasm. Nucleus. Membrane.

Tissue specificity. Cervical tissues (at protein level). Urothelium (at protein level). Endothelial cells of urinary bladder vessels (at protein level). Urinary bladder stromal cells (at protein level). Cervical tissues. Kidney. Ubiquitous.

Miscellaneous. Down-regulated in cervical carcinoma tissues. Expression in stage III-IV cervical carcinomas is significantly lower compared to stage I-II. Down-regulated in bladder carcinoma. Down-regulated in renal cell carcinoma. Down-regulated in colorectal cancerous tissues.

Similarity. Belongs to the BLCAP family.

RefSeq proteins (7): NP_001161292, NP_001161293, NP_001161294, NP_001161295, NP_001304003, NP_001304004, NP_006689* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009598	BCALP	Family

Pfam: PF06726

UniProt features (9 total): sequence variant 3, mutagenesis site 3, transmembrane region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62952-F1	63.24	0.00

Functional residue map

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

Mutagenesis-validated functional residues (3):

Position	Phenotype
16–19	no significant effect on activity.
74	reduces activity.
78	no significant effect on activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 266 (showing top): CREL_01, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GGTGTGT_MIR329, TGCACTT_MIR519C_MIR519B_MIR519A, ENK_UV_RESPONSE_KERATINOCYTE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GENTILE_RESPONSE_CLUSTER_D3, TGACCTY_ERR1_Q2, GGAMTNNNNNTCCY_UNKNOWN, CAIRO_HEPATOBLASTOMA_CLASSES_DN, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, CCTGTGA_MIR513, GATA1_01, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, ACATTCC_MIR1_MIR206

GO Biological Process (2): apoptotic nuclear changes (GO:0030262), apoptotic process (GO:0006915)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cellular component disassembly involved in execution phase of apoptosis	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

570 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BLCAP	NNAT	Q16517	968
BLCAP	CYFIP2	Q96F07	684
BLCAP	COG3	Q96JB2	638
BLCAP	AZIN1	O14977	627
BLCAP	ADAR	P55265	580
BLCAP	GRB10	Q13322	578
BLCAP	CSNK2A1	P19138	547
BLCAP	RBBP9	O75884	529
BLCAP	HERC3	Q15034	521
BLCAP	H0Y8G9	H0Y8G9	521
BLCAP	CHMP2A	O43633	507
BLCAP	KCNK9	Q9NPC2	492
BLCAP	CSNK2A2	P19784	491
BLCAP	MAGEL2	Q9UJ55	491
BLCAP	ASB4	Q9Y574	476

IntAct

55 interactions, top by confidence:

A	B	Type	Score
NOTCH2NLA	BLCAP	psi-mi:“MI:0915”(physical association)	0.670
BLCAP	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.670
SKAP1	BLCAP	psi-mi:“MI:0915”(physical association)	0.560
BLCAP	SKAP1	psi-mi:“MI:0915”(physical association)	0.560
BLCAP	GJA5	psi-mi:“MI:0915”(physical association)	0.560
ASGR1	BLCAP	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	BLCAP	psi-mi:“MI:0915”(physical association)	0.560
BLCAP	TMEM237	psi-mi:“MI:0915”(physical association)	0.560
	BLCAP	psi-mi:“MI:0915”(physical association)	0.560
GOSR2	BLCAP	psi-mi:“MI:0915”(physical association)	0.560
BLCAP	FAM241B	psi-mi:“MI:0915”(physical association)	0.560
BLCAP	SSMEM1	psi-mi:“MI:0915”(physical association)	0.560
BLCAP	CLDND2	psi-mi:“MI:0915”(physical association)	0.560
GJA5	BLCAP	psi-mi:“MI:0915”(physical association)	0.560
BLCAP	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
LRAT	BLCAP	psi-mi:“MI:0915”(physical association)	0.560
BLCAP	MFSD5	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	BLCAP	psi-mi:“MI:0915”(physical association)	0.560
BLCAP	LEMD1	psi-mi:“MI:0915”(physical association)	0.560
BLCAP	GIMAP1	psi-mi:“MI:0915”(physical association)	0.560
BLCAP	ESR1	psi-mi:“MI:0407”(direct interaction)	0.530
ESR1	BLCAP	psi-mi:“MI:0915”(physical association)	0.530
BLCAP	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
BLCAP	HOXA1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): BLCAP (Two-hybrid), NOTCH2NL (Two-hybrid), BLCAP (Affinity Capture-RNA), BLCAP (Two-hybrid), BLCAP (Two-hybrid), BLCAP (Two-hybrid), BLCAP (Two-hybrid), BLCAP (Two-hybrid), BLCAP (Two-hybrid), BLCAP (Two-hybrid), BLCAP (Two-hybrid), C10orf35 (Two-hybrid), TMEM31 (Two-hybrid), MFSD5 (Two-hybrid), LEMD1 (Two-hybrid)

ESM2 similar proteins: A0A023PXM2, A6NCI5, G2TRM1, O13550, O13576, O14263, P0C5R5, P17575, P28626, P36073, P36710, P38161, P38322, P38730, P38864, P47034, P47174, P53876, P62950, P62951, P62952, P62953, P62954, P68478, P68479, P76163, P85052, P87263, P93277, Q04501, Q04502, Q04838, Q10493, Q12070, Q12307, Q1Q7V2, Q4G2S9, Q5R692, Q6UY13, Q6ZVL8

Diamond homologs: P62950, P62951, P62952, P62953, P62954, Q4G2S9, Q4R504, Q4V7Q2, Q5EAT6, Q5M8I8, Q5R692, Q90WT7, Q9IB61

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

866 predictions. Top by Δscore:

Variant	Effect	Δscore
20:37521403:GGTA:G	donor_loss	0.9900
20:37521404:G:GA	donor_loss	0.9900
20:37521405:T:G	donor_loss	0.9900
20:37526854:AAG:A	donor_gain	0.9900
20:37526855:A:C	donor_gain	0.9900
20:37527135:T:TA	donor_gain	0.9900
20:37521400:GCAG:G	donor_gain	0.9800
20:37521404:G:GG	donor_gain	0.9800
20:37526854:A:AC	donor_gain	0.9700
20:37522666:GGT:G	acceptor_gain	0.9600
20:37522663:GCA:G	acceptor_loss	0.9500
20:37522664:CA:C	acceptor_loss	0.9500
20:37522665:A:AT	acceptor_loss	0.9500
20:37527140:T:A	donor_gain	0.9500
20:37521401:CAG:C	donor_gain	0.9400
20:37522529:C:G	donor_gain	0.9400
20:37521318:CCATT:C	donor_gain	0.9300
20:37527659:C:A	donor_gain	0.9300
20:37521399:TGCAG:T	donor_gain	0.9200
20:37521400:GCAGG:G	donor_gain	0.9200
20:37522562:G:GT	donor_gain	0.9200
20:37527396:A:C	donor_gain	0.9200
20:37527617:A:C	donor_gain	0.9200
20:37527626:ATCAC:A	donor_loss	0.9200
20:37527627:TCAC:T	donor_loss	0.9200
20:37527628:CA:C	donor_loss	0.9200
20:37527629:ACCTG:A	donor_loss	0.9200
20:37527630:CCTGA:C	donor_loss	0.9200
20:37527631:C:G	donor_loss	0.9200
20:37527658:T:TA	donor_gain	0.9200

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000075729 (20:37519404 CAAAAAAAAAAAAAAAAAAAGAAAAAA>C,CAA,CAAA,CAAAA,CAAAAA,CAAAAAA), RS1000243615 (20:37524736 T>C), RS1000860076 (20:37523589 C>T), RS1000939691 (20:37526451 C>A), RS1000985219 (20:37529208 A>G), RS1001312036 (20:37523894 G>A), RS1001398856 (20:37517105 T>C), RS1001445999 (20:37518377 C>T), RS1001467113 (20:37524558 G>A), RS1001751085 (20:37524284 C>G), RS1001895485 (20:37520105 C>A), RS1002240800 (20:37529166 A>G), RS1002304718 (20:37523008 G>A,C), RS1002450186 (20:37519904 G>A), RS1002636542 (20:37517412 CAAAGT>C)

Disease associations

OMIM: gene MIM:613110 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007843_28	Rheumatoid arthritis	4.000000e-13

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	3
aristolochic acid I	decreases expression, increases expression, decreases reaction	2
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, affects expression	2
Arsenic	increases abundance, affects methylation, affects cotreatment, decreases expression	2
Cisplatin	affects cotreatment, increases expression	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
ochratoxin A	decreases expression	1
resorcinol	increases expression	1
azoxystrobin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression, affects cotreatment	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Decitabine	decreases expression, decreases reaction	1
Vorinostat	decreases expression	1
Leflunomide	decreases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Doxorubicin	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	decreases expression	1

Clinical trials (associated diseases)

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