BCAS2

Summary

BCAS2 (BCAS2 pre-mRNA processing factor, HGNC:975) is a protein-coding gene on chromosome 1p13.2, encoding Pre-mRNA-splicing factor SPF27 (O75934). Required for pre-mRNA splicing as component of the activated spliceosome. It is a common-essential gene (DepMap: required in 97.4% of cancer cell lines).

Involved in mRNA splicing, via spliceosome. Located in DNA replication factor A complex and nuclear speck. Part of U2-type catalytic step 2 spliceosome. Implicated in breast cancer.

Source: NCBI Gene 10286 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 24 total
• GTEx eGene: eQTL in 18 tissues, sQTL in 20 (q < 0.05)
• Cancer dependency (DepMap): dependent in 97.4% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.49 (unconstrained)
• MANE Select transcript: NM_005872
• Interaction hub: 1,797 STRING partners (top 9% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:975
Approved symbol	BCAS2
Name	BCAS2 pre-mRNA processing factor
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Aliases	DAM1, SPF27, Snt309
Ensembl gene	ENSG00000116752
Ensembl biotype	protein_coding
OMIM	605783
Entrez	10286

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 11 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000369541

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1

ENST00000369541, ENST00000485021, ENST00000886259, ENST00000886260, ENST00000918497, ENST00000968204, ENST00000968205, ENST00000985642, ENST00000985643, ENST00001077764, ENST00001077765, ENST00001093303, ENST00001093304, ENST00001130733, ENST00001145141

RefSeq mRNA: 1 — MANE Select: NM_005872 NM_005872

CCDS: CCDS874

Canonical transcript exons

ENST00000369541 — 7 exons

Exon	Start	End
ENSE00000784381	114576688	114576758
ENSE00001450297	114567557	114568256
ENSE00001450298	114581499	114581615
ENSE00003489595	114581299	114581391
ENSE00003564914	114569992	114570072
ENSE00003661043	114570700	114570750
ENSE00003685126	114575590	114575751

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 97.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 50.4602 / max 664.7939, expressed in 1810 samples.

Highest expression (Bgee): secondary oocyte, calcaneal tendon, palpebral conjunctiva, cervix squamous epithelium, gluteal muscle.

Genetic regulation across tissues (GTEx eQTL / sQTL)

BCAS2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 18 tissues and its splicing (sQTL) in 20 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 38 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	2.3e-11	-0.24	1:114632222:C:T
Adipose Subcutaneous	sqtl	3.2e-10	-0.49	1:114548544:A:C
Skin Sun Exposed Lower leg	sqtl	4.8e-09	+0.44	1:114659963:T:TG
Nerve Tibial	sqtl	3.1e-06	+0.40	1:114627245:G:A
Thyroid	eqtl	3.3e-06	+0.15	1:114538232:G:C
Artery Tibial	sqtl	3.4e-06	+0.30	1:114567346:T:C
Muscle Skeletal	eqtl	5.7e-05	+0.17	1:114127436:C:T
Skin Not Sun Exposed Suprapubic	sqtl	6.2e-05	-0.30	1:114538313:C:G
Brain Cerebellum	sqtl	6.8e-05	-0.45	1:114576361:C:T
Cells Cultured fibroblasts	sqtl	6.8e-05	-0.41	1:114538313:C:G
Brain Cerebellar Hemisphere	sqtl	7.6e-05	-0.41	1:114537698:C:T
Thyroid	sqtl	1.1e-04	-0.29	1:114538313:C:G
Cells EBV-transformed lymphocytes	eqtl	1.3e-04	+0.15	1:114535926:T:C
Muscle Skeletal	sqtl	1.6e-04	-0.28	1:114537698:C:T
Cells Cultured fibroblasts	eqtl	1.7e-04	+0.10	1:114534373:G:A
Esophagus Muscularis	eqtl	2.5e-04	-0.12	1:114650430:C:T
Whole Blood	eqtl	4.0e-04	-0.12	1:114611407:G:GA
Artery Aorta	sqtl	4.5e-04	-0.25	1:114538232:G:C
Small Intestine Terminal Ileum	eqtl	5.4e-04	+0.22	1:114815619:A:G
Artery Tibial	eqtl	6.0e-04	+0.09	1:114813342:G:A

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
13948	47.1269	1807
13949	3.3333	1483

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.61	gold quality
calcaneal tendon	UBERON:0003701	97.09	gold quality
palpebral conjunctiva	UBERON:0001812	96.98	gold quality
cervix squamous epithelium	UBERON:0006922	96.75	gold quality
gluteal muscle	UBERON:0002000	96.74	gold quality
pons	UBERON:0000988	96.59	gold quality
oocyte	CL:0000023	96.49	gold quality
endothelial cell	CL:0000115	96.29	gold quality
lower esophagus mucosa	UBERON:0035834	95.88	gold quality
islet of Langerhans	UBERON:0000006	95.85	gold quality
parietal pleura	UBERON:0002400	95.75	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.74	gold quality
substantia nigra pars compacta	UBERON:0001965	95.71	gold quality
hair follicle	UBERON:0002073	95.69	gold quality
biceps brachii	UBERON:0001507	95.68	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.54	gold quality
orbitofrontal cortex	UBERON:0004167	95.50	gold quality
parotid gland	UBERON:0001831	95.45	gold quality
heart right ventricle	UBERON:0002080	95.27	gold quality
hypothalamus	UBERON:0001898	95.26	gold quality
pleura	UBERON:0000977	95.21	gold quality
superior vestibular nucleus	UBERON:0007227	95.21	gold quality
tibia	UBERON:0000979	95.20	gold quality
corpus epididymis	UBERON:0004359	95.11	gold quality
sperm	CL:0000019	95.10	gold quality
substantia nigra	UBERON:0002038	95.10	gold quality
ganglionic eminence	UBERON:0004023	94.99	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.97	gold quality
cauda epididymis	UBERON:0004360	94.90	gold quality
midbrain	UBERON:0001891	94.89	gold quality
prefrontal cortex	UBERON:0000451	94.86	gold quality
tongue squamous epithelium	UBERON:0006919	94.85	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.83	gold quality
amygdala	UBERON:0001876	94.79	gold quality
visceral pleura	UBERON:0002401	94.64	gold quality
nucleus accumbens	UBERON:0001882	94.57	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.56	gold quality
triceps brachii	UBERON:0001509	94.53	gold quality
right frontal lobe	UBERON:0002810	94.53	gold quality
mucosa of urinary bladder	UBERON:0001259	94.51	gold quality
squamous epithelium	UBERON:0006914	94.48	gold quality
cervix epithelium	UBERON:0004801	94.46	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.43	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.42	gold quality
postcentral gyrus	UBERON:0002581	94.41	gold quality
cartilage tissue	UBERON:0002418	94.38	gold quality
middle temporal gyrus	UBERON:0002771	94.36	gold quality
male germ cell	CL:0000015	94.35	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.35	gold quality
superior frontal gyrus	UBERON:0002661	94.29	gold quality
lateral globus pallidus	UBERON:0002476	94.23	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.21	gold quality
endometrium	UBERON:0001295	94.20	gold quality
temporal lobe	UBERON:0001871	94.13	gold quality
pigmented layer of retina	UBERON:0001782	94.11	gold quality
putamen	UBERON:0001874	94.11	gold quality
gingiva	UBERON:0001828	94.07	gold quality
amniotic fluid	UBERON:0000173	94.05	gold quality
caudate nucleus	UBERON:0001873	94.02	gold quality
parietal lobe	UBERON:0001872	93.94	gold quality
tendon	UBERON:0000043	93.93	gold quality
myocardium	UBERON:0002349	93.93	gold quality
nasal cavity mucosa	UBERON:0001826	93.92	gold quality
gingival epithelium	UBERON:0001949	93.90	gold quality
entorhinal cortex	UBERON:0002728	93.84	gold quality
spinal cord	UBERON:0002240	93.81	gold quality
forebrain	UBERON:0001890	93.79	gold quality
cortical plate	UBERON:0005343	93.79	gold quality
skeletal muscle tissue	UBERON:0001134	93.77	gold quality
caput epididymis	UBERON:0004358	93.76	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.76	gold quality
telencephalon	UBERON:0001893	93.75	gold quality
epithelium of nasopharynx	UBERON:0001951	93.75	gold quality
esophagus squamous epithelium	UBERON:0006920	93.75	gold quality
gall bladder	UBERON:0002110	93.68	gold quality
adenohypophysis	UBERON:0002196	93.68	gold quality
Ammon’s horn	UBERON:0001954	93.67	gold quality
brain	UBERON:0000955	93.60	gold quality
central nervous system	UBERON:0001017	93.60	gold quality
cerebral cortex	UBERON:0000956	93.59	gold quality
muscle of leg	UBERON:0001383	93.58	gold quality
mammalian vulva	UBERON:0000997	93.57	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.57	gold quality
lower lobe of lung	UBERON:0008949	93.47	gold quality
rectum	UBERON:0001052	93.46	gold quality
embryo	UBERON:0000922	93.44	gold quality
cranial nerve II	UBERON:0000941	93.44	gold quality
muscle organ	UBERON:0001630	93.43	gold quality
popliteal artery	UBERON:0002250	93.42	gold quality
muscle tissue	UBERON:0002385	93.42	gold quality
tibial artery	UBERON:0007610	93.42	gold quality
esophagus mucosa	UBERON:0002469	93.37	gold quality
pituitary gland	UBERON:0000007	93.34	gold quality
gastrocnemius	UBERON:0001388	93.34	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.33	gold quality
adrenal tissue	UBERON:0018303	93.32	gold quality
seminal vesicle	UBERON:0000998	93.30	gold quality
corpus callosum	UBERON:0002336	93.23	gold quality
frontal cortex	UBERON:0001870	93.20	gold quality
nephron tubule	UBERON:0001231	93.17	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-30	no	141.38
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	72.0	low
Frontal cortex	tissue	59.4
Caudate putamen	tissue	58.1
Pons	tissue	56.2
Skeletal muscle	tissue	52.9	medium
Superior colliculi	tissue	52.1
Putamen	tissue	50.7
Thalamus	tissue	49.9
Spinal cord	tissue	49.4
Liver	tissue	47.9	low
Epididymis	tissue	46.9	medium
Midbrain	tissue	46.8
Medulla oblongata	tissue	46.6
Substantia nigra	tissue	45.3
Cerebral cortex	tissue	44.9	medium
Occipital cortex	tissue	44.9
Basal ganglia	tissue	44.0	medium
Cerebellum	tissue	42.6	medium
Prefrontal cortex	tissue	42.5
Periaqueductal gray	tissue	42.4
Hypothalamus	tissue	42.2
Somatosensory cortex	tissue	41.7
Kidney	tissue	41.6	medium
Locus coeruleus	tissue	41.5
Ventral forebrain	tissue	41.5
Septum	tissue	41.3
Hippocampal formation	tissue	40.7
Thyroid gland	tissue	39.7	medium
Motor cortex	tissue	39.6
Entorhinal cortex	tissue	39.3
Parathyroid gland	tissue	38.8	medium
Urinary bladder	tissue	38.8	medium
Retrosplenial and cingulate cortex	tissue	38.6
Adrenal gland	tissue	38.3	medium
Temporal cortex	tissue	38.2
Retina	tissue	37.4
Retrosplenial cortex	tissue	37.1
Heart muscle	tissue	36.8	medium
Lymph node	tissue	35.9	low
Breast	tissue	35.8	low
Postcentral gyrus	tissue	34.7
Choroid plexus	tissue	34.5
Tonsil	tissue	33.9	medium
Prostate	tissue	33.4	low
Endometrium 1	tissue	32.9	low
Ovary	tissue	32.5	medium
Pituitary gland	tissue	31.6
Corpus callosum	tissue	31.6
Insular cortex	tissue	31.6
Amygdala	tissue	30.6
Esophagus	tissue	30.5	medium
Rectum	tissue	30.1	medium
Thymus	tissue	30.1
Adipose tissue	tissue	30.0	not detected
Gallbladder	tissue	29.8	medium
Testis	tissue	29.7	high
Colon	tissue	29.6	low
Olfactory bulb	tissue	29.6
Nucleus accumbens	tissue	29.0
Skin 1	tissue	28.1	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Dorsal spinal cord (49.4), Arcuate nucleus (43.3), Lateral hypothalamic area (43.2), Ventral spinal cord (42.7), Dorsal hippocampus (40.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESRRB

miRNA regulators (miRDB)

Targeting BCAS2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

29 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-1272	99.34	68.79	878
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-100-3P	99.20	67.33	672
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-4751	98.80	64.95	525
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-532-5P	98.43	67.53	760
HSA-MIR-1267	98.24	69.05	837
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-382-5P	96.71	65.90	762
HSA-MIR-6760-3P	96.35	68.31	1001

Functional genomics

gnomAD constraint: pLI 6.78e-09, LOEUF 1.49, missense Z 1.04 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000369541 — one region, missense o/e 0.82. DepMap (CRISPR cell-line fitness): dependent in 97.4% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): UACC-893 (-2.847), HPAF-II (-2.098), RERF-GC-1B (-1.99), C2BBe1 (-1.909), SW 1990 (-1.89), HCC-33 (-1.81), AsPC-1 (-1.793), RCM-1 (-1.787), KLE (-1.785), BICR 31 (-1.713), HT-29 (-1.708), CL-11 (-1.649), DAN-G (-1.641), KP-4 (-1.618), KMS-20 (-1.577).

Literature-anchored findings (GeneRIF, showing 12)

• The BCAS2 gene was amplified in two of 60 primary breast cancer tissues, but not in other cancer cells, providing the first evidence of amplification within this region and indicating that BCAS2 gene codes for a nuclear protein. (PMID:12169396)
• This study suggested that BCAS2 might play an important role in breast cancer development by increasing the estrogen receptor’s function. (PMID:15694360)
• BCAS2 directly interacts with p53 to reduce p53 transcriptional activity by mildly but consistently decreasing p53 protein in the absence of DNA damage. In the presence of DNA damage, BCAS2 prominently reduces p53 protein. (PMID:19903847)
• ERRbeta signalling leads to BCAS2-mediated blockage of the G1/S transition and inhibition of the epithelial to mesenchymal transition through FST-mediated regulation of E-cadherin (PMID:24667650)
• BCAS2 is a novel androgen receptor-interacting protein. (PMID:25461807)
• BCAS2 interacts with HSF4 and negatively regulates its protein stability via ubiquitination. (PMID:26319152)
• These results demonstrate that Aurora B inhibits both direct interaction with the microtubule and oligomerization of the Dam1 complex to drive error correction during mitosis. (PMID:26560693)
• Chromosomal breakpoints involved the BCAS2 gene in 1q31 is associated with Diffuse Large B-Cell Lymphomas. (PMID:27356265)
• Study showed that CDK4 and BCAS2 may be target genes of miR-486 and levels of CDK4 and BCAS2 were both significantly higher in the esophageal cancer tissues and cell lines than levels in the normal tissues and cells. (PMID:29115564)
• BCAS2 is an AF-1 coactivator of ERalpha whose overexpression promotes carcinogenic processes, suggesting an important role in the development of estrogen-receptor positive breast cancer. (PMID:30813351)
• BCAS2, a protein enriched in advanced prostate cancer, interacts with NBS1 to enhance DNA double-strand break repair. (PMID:32963349)
• BCAS2 regulates granulosa cell survival by participating in mRNA alternative splicing. (PMID:37248466)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	bcas2	ENSDARG00000043631
mus_musculus	Bcas2	ENSMUSG00000005687
rattus_norvegicus	Bcas2	ENSRNOG00000018783
drosophila_melanogaster	BCAS2	FBGN0039558
caenorhabditis_elegans		WBGENE00020441

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1915433) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 13 distinct phenotype terms.

Mouse phenotype (MP)	Records
female infertility	2
impaired fertilization	1
abnormal oocyte morphology	1
small ovary	1
impaired ovarian folliculogenesis	1
abnormal oogenesis	1
maternal effect	1
abnormal female meiosis	1
increased primary ovarian follicle number	1
decreased tertiary ovarian follicle number	1
lethality, complete penetrance	1
increased secondary ovarian follicle number	1
decreased superovulation rate	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RAX7	99.1%	Diamond
Xenopus tropicalis	Q6PBE2	86.9%	Diamond
Arabidopsis thaliana	Q949S9	31.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
DENND2C	protein-coding	163259
AMPD1	protein-coding	270
TRIM33	protein-coding	51592

Protein

Protein identifiers

Pre-mRNA-splicing factor SPF27 — O75934 (reviewed: O75934)

Alternative names: Breast carcinoma-amplified sequence 2, DNA amplified in mammary carcinoma 1 protein, Spliceosome-associated protein SPF 27

All UniProt accessions (2): B2R7W3, O75934

UniProt curated annotations — full annotation on UniProt →

Function. Required for pre-mRNA splicing as component of the activated spliceosome. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. The PRP19-CDC5L complex may also play a role in the response to DNA damage (DDR).

Subunit / interactions. Component of the pre-catalytic and catalytic spliceosome complexes. Component of the postcatalytic spliceosome P complex. Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8. Interacts directly in the complex with PRPF19, CDC5L and PLRG1.

Subcellular location. Nucleus. Nucleolus.

Tissue specificity. Ubiquitously expressed.

Similarity. Belongs to the SPF27 family.

RefSeq proteins (1): NP_005863* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008409	SPF27	Family

Pfam: PF05700

UniProt features (20 total): helix 8, strand 3, modified residue 2, sequence conflict 2, initiator methionine 1, chain 1, coiled-coil region 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

26 structures by resolution:

PDB	Title	Method	Resolution (Å)
9S2E	Human intron-lariat spliceosome-Aquarius (ILSaqr)	ELECTRON MICROSCOPY	2.4
8C6J	Human spliceosomal PM5 C* complex	ELECTRON MICROSCOPY	2.8
6ID1	Cryo-EM structure of a human intron lariat spliceosome after Prp43 loaded (ILS2 complex) …	ELECTRON MICROSCOPY	2.86
6ID0	Cryo-EM structure of a human intron lariat spliceosome prior to Prp43 loaded (ILS1 …	ELECTRON MICROSCOPY	2.9
9XTT	Human minor spliceosome branching-completed C complex (after step-I)	ELECTRON MICROSCOPY	2.92
6ICZ	Cryo-EM structure of a human post-catalytic spliceosome (P complex) at 3.0 angstrom	ELECTRON MICROSCOPY	3
8I0T	The cryo-EM structure of human Bact-III complex	ELECTRON MICROSCOPY	3
8I0V	The cryo-EM structure of human post-Bact complex	ELECTRON MICROSCOPY	3
9XU3	Human minor spliceosome exon-ligation-ready C* complex (prior to step-II)	ELECTRON MICROSCOPY	3
9S2F	Human debranched intron spliceosome (DIS)	ELECTRON MICROSCOPY	3.14
6QDV	Human post-catalytic P complex spliceosome	ELECTRON MICROSCOPY	3.3
8I0U	The cryo-EM structure of human Bact-IV complex	ELECTRON MICROSCOPY	3.3
9FMD	Integrative model of the human post-catalytic spliceosome (P-complex)	ELECTRON MICROSCOPY	3.3
8I0W	The cryo-EM structure of human C complex	ELECTRON MICROSCOPY	3.4
8RO2	Integrative Structure of the human intron lariat Spliceosome (ILS’')	ELECTRON MICROSCOPY	3.5
5XJC	Cryo-EM structure of the human spliceosome just prior to exon ligation at 3.6 angstrom	ELECTRON MICROSCOPY	3.6
7W59	The cryo-EM structure of human pre-C*-I complex	ELECTRON MICROSCOPY	3.6
7W5A	The cryo-EM structure of human pre-C*-II complex	ELECTRON MICROSCOPY	3.6
5YZG	The Cryo-EM Structure of Human Catalytic Step I Spliceosome (C complex) at 4.1 angstrom …	ELECTRON MICROSCOPY	4.1
7W5B	The cryo-EM structure of human C* complex	ELECTRON MICROSCOPY	4.3
6FF7	human Bact spliceosome core structure	ELECTRON MICROSCOPY	4.5
7A5P	Human C Complex Spliceosome - Medium-resolution PERIPHERY	ELECTRON MICROSCOPY	5
5Z56	cryo-EM structure of a human activated spliceosome (mature Bact) at 5.1 angstrom.	ELECTRON MICROSCOPY	5.1
5MQF	Cryo-EM structure of a human spliceosome activated for step 2 of splicing (C* complex)	ELECTRON MICROSCOPY	5.9
8CH6	Structure of a late-stage activated spliceosome (BAqr) arrested with a dominant-negative …	ELECTRON MICROSCOPY	5.9
5Z57	Cryo-EM structure of the human activated spliceosome (late Bact) at 6.5 angstrom	ELECTRON MICROSCOPY	6.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75934-F1	89.36	0.70

Human Protein Atlas

Protein class: Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): centrosome; nuclear speckles

Antibody reliability (HPA): IH supported · IF supported

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 (2)

Type	Positions
N-acetylalanine	2
Phosphoserine	94

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 5; 1 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-9918481	Dengue Virus-Host Interactions ⚕	curated
R-HSA-72163	mRNA Splicing - Major Pathway	curated
R-HSA-8953854	Metabolism of RNA	—
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA	—
R-HSA-72172	mRNA Splicing	—

MSigDB gene sets: 189 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_DENTATE_GYRUS_DEVELOPMENT, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, GOBP_OOGENESIS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEUROGENESIS, GOBP_FOREBRAIN_DEVELOPMENT, GOCC_NUCLEAR_REPLICATION_FORK, GOBP_OVARIAN_FOLLICLE_DEVELOPMENT, GOBP_CELL_JUNCTION_ORGANIZATION, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, GOBP_HIPPOCAMPUS_DEVELOPMENT, WANG_LMO4_TARGETS_DN

GO Biological Process (4): RNA splicing, via transesterification reactions (GO:0000375), mRNA splicing, via spliceosome (GO:0000398), RNA splicing (GO:0008380), mRNA processing (GO:0006397)

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

GO Cellular Component (9): Prp19 complex (GO:0000974), nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), nucleolus (GO:0005730), nuclear speck (GO:0016607), U2-type catalytic step 2 spliceosome (GO:0071007), catalytic step 2 spliceosome (GO:0071013), DNA replication factor A complex (GO:0005662)

Reactome top-level categories

4 top-level categories:

Category	Pathways
mRNA Splicing	1
Dengue Virus Infection	1
Processing of Capped Intron-Containing Pre-mRNA	1
Metabolism of RNA	1

GO top-level categories

23 GO namespaces:

Category	Terms
RNA processing	2
nuclear lumen	2
nuclear protein-containing complex	2
RNA splicing	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
binding	1
protein-containing complex	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
ribonucleoprotein complex	1
intracellular membraneless organelle	1
nuclear ribonucleoprotein granule	1
U2-type spliceosomal complex	1
U2 snRNP	1
U6 snRNP	1
catalytic step 2 spliceosome	1
Prp19 complex	1
spliceosomal complex	1
U5 snRNP	1
catalytic complex	1
nuclear replisome	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 14 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
mRNA splicing, via spliceosome	BP	direct assay
U2-type catalytic step 2 spliceosome	CC	direct assay
nuclear speck	CC	direct assay
nucleus	CC	direct assay
spliceosomal complex	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,797 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCAS2	PLRG1	O43660	820
BCAS2	PRPF19	Q9UMS4	811
BCAS2	CDC5L	Q99459	810
BCAS2	SYF2	O95926	645
BCAS2	CWC15	Q9P013	641
BCAS2	CTNNBL1	Q8WYA6	633
BCAS2	PPIL1	Q9Y3C6	631
BCAS2	XAB2	Q9HCS7	609
BCAS2	CDC40	O60508	579
BCAS2	CRNKL1	Q9BZJ0	548
BCAS2	BUD31	P41223	525
BCAS2	BCAS4	Q8TDM0	473
BCAS2	CD2BP2	O95400	465
BCAS2	RBM22	Q9NW64	461
BCAS2	SNW1	Q13573	457

IntAct

Human interaction partners of BCAS2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 68 partners by confidence:

Partner	Interaction type	MIscore	Records
CDC5L	physical association	0.930	6
PRPF19	physical association	0.900	5
GOLGA2	physical association	0.840	9
PLRG1	association	0.790	4
AIMP2	physical association	0.780	12
IKZF3	physical association	0.670	5
HGS	physical association	0.670	4
TCF4	physical association	0.670	4
KRT31	physical association	0.670	3
KRT40	physical association	0.670	3
SNRPC	physical association	0.670	3
PRPF8	physical association	0.630	2
KRT34	physical association	0.560	5
LMO3	physical association	0.560	5
ACY1	physical association	0.560	3
CCDC120	physical association	0.560	3
CCDC17	physical association	0.560	3
ECM1	physical association	0.560	3
EMILIN3	physical association	0.560	3
ENKD1	physical association	0.560	3
FAM86C1P	physical association	0.560	3
GFAP	physical association	0.560	3
HSF2BP	physical association	0.560	3
IFI35	physical association	0.560	3
JPH3	physical association	0.560	3
KLF11	physical association	0.560	3
KRT20	physical association	0.560	3
KRT27	physical association	0.560	3
KRT35	physical association	0.560	3
KRT36	physical association	0.560	3

BioGRID (408 interactions; top human partners by supporting records): CDC5L (Co-fractionation; 20 records), PRPF19 (Co-fractionation; 18 records), PLRG1 (Co-fractionation; 10 records), PRPF8 (Affinity Capture-MS; 7 records), RPA1 (Affinity Capture-Western; 5 records), ESR1 (Affinity Capture-MS; 4 records), MYC (Affinity Capture-MS; 4 records), PPIE (Affinity Capture-MS; 4 records), RPA2 (Affinity Capture-Western; 4 records), SF3B4 (Two-hybrid; 4 records), SNW1 (Affinity Capture-MS; 4 records), CCDC94 (Affinity Capture-MS; 3 records), CTNNBL1 (Co-fractionation; 3 records), CWC15 (Affinity Capture-MS; 3 records), DSN1 (Affinity Capture-MS; 3 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
BCAS2	“form complex”	PRP19-CDC5L	binding

Protein complexes (CORUM) (8)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

8 complexes by size:

Complex	Subunits	Members
Spliceosome, E complex	129	RBM17, DDX39A, GEMIN2, NCBP2, PRPF31, SART3, SF3A2, SNRPA, SRSF7, DDX39B, DHX15, GEMIN5, SCAF4, SMARCB1, SNRPD3, SYNCRIP, U2AF2, HNRNPC, SF3B2, SMARCC2, SFSWAP, USP39, GEMIN6, HNRNPK, RBM42, SF3B1, SF3B4, SNRPG, SRSF6, BCAS2, SMN1, CPSF7, SMARCE1, SRSF8, ARID1A, LSM4, SNRPC, CHD8, FUS, SNRNP70, SRSF11, NUDT21, PBRM1, SNRPB2, SNRPD1, YBX1, SF1, SNRPD2, SRSF2, SRSF5, PPIH, SRSF3, DDX20, SART1, SRSF1, SRSF4, PRPF19, RBM39, RBMXL2, SREK1, PRPF3, SMARCA2, U2AF1, SF3B6, SMARCA1, CPSF1, DDX23, DHX9, RUVBL1, SNRPF, SRRM2, ALYREF, HNRNPA0, HNRNPH1, PCBP2, RBM10, SF3B3, STRAP, HNRNPR, RBM25, ACTBL2, CHERP, SNRPA1, ACTL6A, DDX46, HNRNPL, RBM7, CPSF6, ARID2, DNAJC8, EFTUD2, KHSRP, RUVBL2, SMARCA4, PCBP1, SNRNP40, SNRPE, PRPF4, PRPF8, SF3A1, SF3A3, SNRNP200, ZCCHC8, DDX5, LUC7L3, SMARCC1, HNRNPA2B1, HNRNPD, HTATSF1, LUC7L2, PHF5A, PRPF6, SMARCD1, SNRPB, GEMIN8, U2SURP, NCBP1, GEMIN4, HNRNPU, MTREX, ARID1B, CHD4, HNRNPM, PRPF40A, HNRNPF, SRRT, DDX17, HNRNPA1, PUF60
Spliceosome, A complex	112	RBM39, SAP30BP, CDK11A, CHERP, HNRNPA1, HNRNPK, HNRNPR, HNRNPU, RBM25, SF3A1, DDX46, HNRNPA3, RNPS1, SART1, SF1, SF3A2, SF3B4, SNRPB, ACIN1, CCAR2, DHX9, ELAVL1, ILF2, SF3B3, SRSF5, HNRNPA2B1, CD2BP2, DDX5, PUF60, RBM17, SNRPA1, TCERG1, ZC3H18, SNRPD1, SRSF2, SYNCRIP, ZNF207, CTNNBL1, HSPA8, NCBP2, SF3B2, TRA2B, YBX1, RBM10, SF3A3, SRRM1, SRSF6, SRSF7, SUGP1, DDX42, DNAJC8, EFTUD2, PRCC, SF3B5, SMNDC1, SNRNP200, WBP11, CDC5L, PPP1R8, PRPF6, BCAS2, NCBP1, PRPF19, PRPF3, SNRPD3, SRSF4, U2AF2, HNRNPUL1, NRIP2, PHF5A, RBM5, RBMX, SNRPA, SRRM2, U2AF1, CCAR1, CFAP20, CIRBP, DDX23, SF3B1, SF3B6, SNRPB2, SNRPE, BUB3, DHX15, PCBP1, PPP1CA, PQBP1, SNRNP70, SRSF1, U2SURP, DDX17, SNRPC, SNRPD2, SNRPF, SNRPG, SRRT, SRSF3, SRSF9, AGGF1, FUS, HNRNPC, HTATSF1, ILF3, PLRG1, SEC31B, TRIR, CWC15, HNRNPAB, PNN, PRPF40A, PRPF8
Spliceosome, C complex	39	MAGOH, PPWD1, RBM8A, SNRPF, SNRPG, SYF2, PPIE, SNRPB2, SNRPA1, BCAS2, BUD31, CWC25, SNRPD2, SNRPD3, CASC3, EIF4A3, PRPF19, SNRPD1, SNRPE, YJU2, SRRM2, XAB2, CWC22, RBM22, SNRNP200, AQR, CWC15, EFTUD2, ISY1, PPIG, CDC40, CDC5L, DHX38, PLRG1, PPIL1, PRPF8, SNRPB, SNW1, CRNKL1
★ CDC5L complex	30	SRRM1, SF3B1, SRSF1, CDC5L, DYNC1H1, GCN1, HSPA8, PPP1CA, SF3B2, SCAF8, SNRPA, SRSF2, BZW1, RBMX, SFPQ, SNRPA1, SNRPD3, TCF4, PLRG1, SNRPD2, TOP2A, ILF2, SF3B4, SNRPD1, SFI1, BCAS2, CWC15, PPM1D, PRKDC, PRPF19
CDC5L-PRP19 complex	7	CWC15, HSPA8, PLRG1, PRPF19, BCAS2, CDC5L, CTNNBL1
CDC5L core complex	6	PLRG1, PRPF19, BCAS2, CDC5L, GCN1, HSPA8
PSO4-WRN complex	5	BCAS2, CDC5L, PLRG1, PRPF19, WRN
PSO4 complex	4	BCAS2, CDC5L, PLRG1, PRPF19

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 68 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
Formation of the cornified envelope	9	17.2×	2e-07
Keratinization	11	13.3×	1e-07
mRNA Splicing	5	11.9×	3e-03
mRNA Splicing - Major Pathway	9	10.7×	8e-06
Processing of Capped Intron-Containing Pre-mRNA	5	8.9×	9e-03
Dengue Virus-Host Interactions	7	7.0×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
morphogenesis of an epithelium	8	46.6×	1e-09
intermediate filament organization	10	40.8×	2e-11
epithelial cell differentiation	8	23.8×	2e-07
mRNA splicing, via spliceosome	8	12.4×	2e-05

Disease & clinical

Genetic variants

Variant evidence for BCAS2: 24 ClinVar records (0 pathogenic / likely pathogenic); 4 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	0
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 281):

Position(s)	Effect	Δscore	Sites
1:114568257–114568258	acceptor_loss	1.0000	4
1:114568262	acceptor_gain	1.0000
1:114569990–114569991	donor_loss	1.0000	4
1:114570073–114570074	acceptor_loss	1.0000	3
1:114570698–114570699	donor_loss	1.0000	3
1:114570704	donor_gain	1.0000
1:114575603	donor_gain	1.0000
1:114576762–114576764	acceptor_gain	1.0000	2
1:114581297–114581298	donor_loss	1.0000	5
1:114568258	acceptor_loss	0.9900

AlphaMissense

867 missense substitutions predicted likely pathogenic (of 1,479 scored), across 196 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M84	9	0.908	0.996
D20	8	0.997	0.999
D14	8	0.996	0.999
N123	8	0.993	1.000
H116	8	0.990	0.999
N164	8	0.980	1.000
D99	8	0.979	0.998
N192	8	0.978	0.999
N109	8	0.976	0.999
F61	8	0.956	0.998
N48	8	0.921	0.995
W103	7	0.999	1.000
E39	7	0.998	0.999
W185	7	0.997	1.000
W135	7	0.995	1.000
E69	7	0.988	0.999
Q113	7	0.987	0.999
W165	7	0.983	0.997
Q171	7	0.983	0.999
Q117	7	0.979	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.48e-08
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	3.55e-06
Prostate Adenocarcinoma (TCGA)	unfavorable	0.000658

Disease associations

OMIM: gene MIM:605783 | disease phenotypes:

GWAS associations

4 associations:

Study	Trait	p-value
GCST007576_54	Chronotype	8e-9
GCST002268_9	Autism	3e-8
GCST002268_8	Autism	7e-8
GCST002268_7	Autism	8e-8

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067001 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

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
8.72	Kd	1.891	nM	CHEMBL3752910
8.72	ED50	1.891	nM	CHEMBL3752910
6.02	Kd	953.9	nM	CHEMBL5653589
6.02	ED50	953.9	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147941: Binding affinity to human BCAS2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0019	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147941: Binding affinity to human BCAS2 incubated for 45 mins by Kinobead based pull down assay	kd	0.9539	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Rotenone	decreases expression, increases expression	2
Valproic Acid	increases expression, affects expression	2
Cyclosporine	increases expression	2
dicrotophos	decreases expression	1
deoxynivalenol	increases expression	1
arsenite	increases reaction, affects binding	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
diethyl malate	increases expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arbutin	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Catechin	affects cotreatment, increases expression	1
Diethylstilbestrol	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Gold	decreases expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Methyl Methanesulfonate	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650983	Binding	Binding affinity to human BCAS2 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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for BCAS2 across ~30M SureChEMBL compounds — explore on Sugi Predict.