BCCIP

Summary

BCCIP (BRCA2 and CDKN1A interacting protein, HGNC:978) is a protein-coding gene on chromosome 10q26.2, encoding BRCA2 and CDKN1A-interacting protein (Q9P287). During interphase, required for microtubule organizing and anchoring activities. It is a selective cancer dependency (DepMap: 34.9% of cell lines).

This gene product was isolated on the basis of its interaction with BRCA2 and p21 proteins. It is an evolutionarily conserved nuclear protein with multiple interacting domains. The N-terminal half shares moderate homology with regions of calmodulin and M-calpain, suggesting that it may also bind calcium. Functional studies indicate that this protein may be an important cofactor for BRCA2 in tumor suppression, and a modulator of CDK2 kinase activity via p21. This protein has also been implicated in the regulation of BRCA2 and RAD51 nuclear focus formation, double-strand break-induced homologous recombination, and cell cycle progression. Multiple transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 56647 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 274 total — 1 pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 34.9% of screened cell lines
• MANE Select transcript: NM_078468

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:978
Approved symbol	BCCIP
Name	BRCA2 and CDKN1A interacting protein
Location	10q26.2
Locus type	gene with protein product
Status	Approved
Aliases	BCCIPalpha, TOK-1
Ensembl gene	ENSG00000107949
Ensembl biotype	protein_coding
OMIM	611883
Entrez	56647

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000278100, ENST00000299130, ENST00000368759, ENST00000463330, ENST00000478798, ENST00000901056, ENST00000901057, ENST00000919011, ENST00000919012, ENST00000919013, ENST00000919014, ENST00000919015, ENST00000919016

RefSeq mRNA: 3 — MANE Select: NM_078468 NM_016567, NM_078468, NM_078469

CCDS: CCDS7649, CCDS7650, CCDS7651

Canonical transcript exons

ENST00000278100 — 7 exons

Exon	Start	End
ENSE00000573388	125831420	125831607
ENSE00000728025	125833772	125833946
ENSE00000987849	125823546	125823722
ENSE00001191279	125836104	125836551
ENSE00003486354	125827558	125827638
ENSE00003519282	125830562	125830651
ENSE00003603616	125826591	125826665

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 96.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 101.7845 / max 2814.2941, expressed in 1825 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107570	101.7845	1825

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	96.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.39	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.35	gold quality
ganglionic eminence	UBERON:0004023	96.24	gold quality
parotid gland	UBERON:0001831	96.14	gold quality
gastrocnemius	UBERON:0001388	94.95	gold quality
oocyte	CL:0000023	94.94	gold quality
islet of Langerhans	UBERON:0000006	94.73	gold quality
rectum	UBERON:0001052	94.64	gold quality
calcaneal tendon	UBERON:0003701	94.64	gold quality
muscle of leg	UBERON:0001383	94.62	gold quality
body of pancreas	UBERON:0001150	94.48	gold quality
monocyte	CL:0000576	94.19	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.93	gold quality
cortical plate	UBERON:0005343	93.68	gold quality
pancreas	UBERON:0001264	93.65	gold quality
mononuclear cell	CL:0000842	93.39	gold quality
muscle organ	UBERON:0001630	93.36	gold quality
skeletal muscle organ	UBERON:0014892	93.36	gold quality
leukocyte	CL:0000738	93.25	gold quality
body of stomach	UBERON:0001161	93.25	gold quality
saliva-secreting gland	UBERON:0001044	93.24	gold quality
right testis	UBERON:0004534	93.16	gold quality
gingival epithelium	UBERON:0001949	93.03	gold quality
testis	UBERON:0000473	92.94	gold quality
mucosa of transverse colon	UBERON:0004991	92.67	gold quality
minor salivary gland	UBERON:0001830	92.66	gold quality
popliteal artery	UBERON:0002250	92.64	gold quality
tibial artery	UBERON:0007610	92.64	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)

1 targets.

Target	Regulation
CDKN1A	Unknown

miRNA regulators (miRDB)

31 targeting BCCIP, 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-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-6512-5P	98.76	69.29	1195
HSA-MIR-624-3P	98.37	67.06	1067
HSA-MIR-633	98.35	69.45	1167
HSA-MIR-4329	97.68	66.26	1003
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-6791-3P	97.45	64.31	1123
HSA-MIR-6829-3P	97.45	64.31	1137
HSA-MIR-1243	97.07	65.44	719
HSA-MIR-6839-5P	96.74	68.29	1088
HSA-MIR-4695-3P	96.71	67.21	836
HSA-MIR-378J	96.44	66.20	1020
HSA-MIR-759	96.16	66.77	873
HSA-MIR-6823-3P	95.45	66.14	704
HSA-MIR-2114-3P	95.45	66.11	579
HSA-MIR-6769A-3P	94.91	61.36	412

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 34.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 26)

• In BRCA2, two novel frame shift mutations were identified as 5073-5074delCT and 6866delC. (PMID:11748848)
• BRCA2 germline mutations appear to have a milder clinical phenotype when compared to non-BRCA2 mutations, since survival is higher among breast cancer patients carrying a BRCA2 mutation compared to sporadic breast cancers. (PMID:11754111)
• Unique de novo mutation of BRCA2 has been identified in a woman with early onset breast cancer. (PMID:11836363)
• Overexpression of BCCIP beta delays the G1 to S progression and results in an elevated p21 expression (PMID:14726710)
• BCCIP is critical for BRCA2- and RAD51-dependent responses to DNA damage and homologous recombinational repair. (PMID:15713648)
• BCCIP in maintaining the transactivation activity of wild type p53; down-regulation of BCCIP as a novel mechanism to impair the p53 function in cells harboring wild type p53 (PMID:17135243)
• suggest an essential role of BCCIP in the maintenance of genomic integrity (PMID:17452982)
• BCCIP-dependent repair of double strand breaks by homologous recombination is an early RAD51 response to ionizing radiation-induced DNA damage. (PMID:18413737)
• LYRIC/AEG-1 is a negative regulator of BCCIPalpha, promoting proteasomal degradation either through direct interaction, or potentially through an indirect mechanism involving downstream effects of the NF-kappaB signaling pathway. (PMID:18440304)
• BCCIP is phosphorylated by the Src tyrosine kinase and dephosphorylated by the PTPmu tyrosine phosphatase; neurite outgrowth assays suggest that BCCIP and PTPmu are in a common signal transduction pathway. (PMID:18773424)
• BCCIP protein expression was not detectable in approximately 45% of all astrocytic tumors. (PMID:19653894)
• regulation of p21 intracellular distribution is a new mechanism for BCCIP to modulate p21 functions (PMID:19713748)
• Results indicate that BCCIP germ line mutations are unlikely to be a major contributor to familial breast/ovarian cancer risk in our population. (PMID:23911796)
• The BCCIPbeta, but not BCCIPalpha, interacts with EIF6 and RPL23/UL14 and stabilizes the latter. (PMID:25150171)
• the existence of both INO80 and YY1 is required for recruiting the INO80/YY1 complex to BCCIP promoter region. Our findings strongly indicate that BCCIP is a potential target gene of the INO80/YY1 complex. (PMID:27535137)
• we demonstrate that BCCIPbeta induces a conformational change within the RAD51 filament that promotes release of ADP to help maintain an active presynaptic filament. Our findings reveal a functional role for BCCIPbeta as a RAD51 accessory factor in HR. (PMID:27694622)
• Expression of BCCIP beta was notably higher in tumor tissues of esophageal squamous cell carcinoma (ESCC) and Eca 109 cells. In vitro studies such as starvation and refeeding assay along with BCCIP beta-shRNA transfection assay demonstrated that BCCIP beta expression promoted proliferation of ESCC cells. (PMID:27995408)
• this study identifies BCCIP as a novel factor critical for microtubule regulation and explicates a mechanism utilized by BCCIP in tumor suppression. (PMID:28394342)
• BCCIPbeta, as a S7 modulator, contributes to the regulation of ribosomal and extraribosomal functions of S7 and has implications in cell growth and tumor development. (PMID:28510697)
• We analyzed the BCCIP protein level in 470 cases of human breast cancer to determine the associations between BCCIP and 53BP1, p53, and subtypes of breast cancer. We further constructed a unique BCCIP knockdown mouse model to determine whether a partial BCCIP deficiency leads to spontaneous breast cancer formation (PMID:29047390)
• BCCIP stabilized YY1 protein in colorectal cancer cells.Transcriptional regulation of BCCIP was associated with its ability to stabilize YY1.BCCIP promoter region contains YY1 binding site (CCGCCATC).BCCIP binds to and activates its promoter in a YY1-dependent fashion. (PMID:29932276)
• BCCIPbeta facilitates p53 ubiquitination via binding with E6 protein in high-risk HPV positive head and neck squamous cell carcinoma. (PMID:32736693)
• BCCIP is required for nucleolar recruitment of eIF6 and 12S pre-rRNA production during 60S ribosome biogenesis. (PMID:33245766)
• Structure of human BCCIP and implications for binding and modification of partner proteins. (PMID:33452718)
• Overexpression of BCCIP predicts an unfavorable prognosis and promotes the proliferation and migration of lung adenocarcinoma. (PMID:34297484)
• Expression and Significance of BCCIP and Glutathione Peroxidase 4 in Clear Cell Renal Cell Carcinoma. (PMID:38342812)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	bccip	ENSDARG00000004948
mus_musculus	Bccip	ENSMUSG00000030983
rattus_norvegicus	Bccip	ENSRNOG00000018066
drosophila_melanogaster	CG9286	FBGN0038183
caenorhabditis_elegans		WBGENE00022851

Protein

Protein identifiers

BRCA2 and CDKN1A-interacting protein — Q9P287 (reviewed: Q9P287)

Alternative names: P21- and CDK-associated protein 1, Protein TOK-1

All UniProt accessions (1): Q9P287

UniProt curated annotations — full annotation on UniProt →

Function. During interphase, required for microtubule organizing and anchoring activities. During mitosis, required for the organization and stabilization of the spindle pole. Isoform 2/alpha is particularly important for the regulation of microtubule anchoring, microtubule stability, spindle architecture and spindle orientation, compared to isoform 1/beta. May promote cell cycle arrest by enhancing the inhibition of CDK2 activity by CDKN1A. May be required for repair of DNA damage by homologous recombination in conjunction with BRCA2. May not be involved in non-homologous end joining (NHEJ).

Subunit / interactions. Interacts with BRCA2, CDKN1A and MTDH/LYRIC. Isoform 2/alpha, but not isoform 1/beta, interacts with DCTN1/p150-glued and ACTR1A/ARP1. Both isoform 1 and isoform 2 interact with alpha-, beta- and gamma-tubulins. Interacts with TENT5C; the interaction has no effect on TENT5C poly(A) polymerase function.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Spindle pole Cytoplasm. Spindle pole.

Tissue specificity. Expressed at high levels in testis and skeletal muscle and at lower levels in brain, heart, kidney, liver, lung, ovary, pancreas, placenta, and spleen.

Miscellaneous. HT1080 cells that constitutively express low levels of BCCIP display increased levels of spontaneous single-stranded DNA and double-strand breaks.

Similarity. Belongs to the BCP1 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9P287-1	1, Beta	yes
Q9P287-2	2, Alpha
Q9P287-3	3
Q9P287-4	4

RefSeq proteins (3): NP_057651, NP_510868, NP_510869 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025602	BCP1_family	Family

Pfam: PF13862

UniProt features (36 total): helix 11, strand 9, region of interest 3, splice variant 3, modified residue 3, sequence conflict 2, turn 2, chain 1, sequence variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7KYS	X-RAY DIFFRACTION	2.2
7KYQ	X-RAY DIFFRACTION	3.06
8EXF	X-RAY DIFFRACTION	3.22
8EXE	X-RAY DIFFRACTION	3.5
8EQB	ELECTRON MICROSCOPY	6.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P287-F1	79.67	0.59

Antibody-complex structures (SAbDab): 1 — 8EQB

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 (3): 42, 112, 281

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 217 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_MICROTUBULE_ANCHORING, GOBP_SPINDLE_LOCALIZATION, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_NEUROGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, WEI_MYCN_TARGETS_WITH_E_BOX

GO Biological Process (9): regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0000079), establishment of mitotic spindle orientation (GO:0000132), microtubule cytoskeleton organization (GO:0000226), DNA repair (GO:0006281), mitotic spindle organization (GO:0007052), microtubule anchoring (GO:0034453), neuroendocrine cell differentiation (GO:0061101), mitotic spindle assembly (GO:0090307), DNA damage response (GO:0006974)

GO Molecular Function (6): DNA binding (GO:0003677), RNA binding (GO:0003723), tubulin binding (GO:0015631), kinase regulator activity (GO:0019207), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), nuclear cyclin-dependent protein kinase holoenzyme complex (GO:0019908), mitotic spindle pole (GO:0097431), spindle pole (GO:0000922), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
mitotic cell cycle	2
nucleic acid binding	2
microtubule organizing center	2
intracellular membraneless organelle	2
cyclin-dependent protein serine/threonine kinase activity	1
regulation of protein serine/threonine kinase activity	1
establishment of mitotic spindle localization	1
establishment of spindle orientation	1
cytoskeleton organization	1
microtubule-based process	1
DNA metabolic process	1
DNA damage response	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
microtubule cytoskeleton organization	1
neuron differentiation	1
neuroepithelial cell differentiation	1
mitotic sister chromatid segregation	1
mitotic spindle organization	1
spindle assembly	1
mitotic nuclear division	1
cellular response to stress	1
cytoskeletal protein binding	1
kinase activity	1
enzyme regulator activity	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
centriole	1
cytoplasm	1
cyclin-dependent protein kinase holoenzyme complex	1
nucleus	1
nuclear protein-containing complex	1
spindle pole	1
mitotic spindle	1
spindle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2248 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCCIP	BRCA2	P51587	994
BCCIP	CDKN1A	P38936	976
BCCIP	DHX32	Q7L7V1	960
BCCIP	UROS	P10746	929
BCCIP	MTDH	Q86UE4	925
BCCIP	RAD51	Q06609	787
BCCIP	DHX15	O43143	639
BCCIP	TENT5A	Q96IP4	602
BCCIP	SLC9B1	Q4ZJI4	541
BCCIP	BRCA1	P38398	540
BCCIP	CDK2	P24941	522
BCCIP	ZBTB16	Q05516	508
BCCIP	H1-0	P07305	497
BCCIP	GRWD1	Q9BQ67	486
BCCIP	NOL7	Q9UMY1	479

IntAct

95 interactions, top by confidence:

A	B	Type	Score
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
BCCIP	RPL23	psi-mi:“MI:0915”(physical association)	0.830
RPL23	BCCIP	psi-mi:“MI:0915”(physical association)	0.830
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
	BCCIP	psi-mi:“MI:0915”(physical association)	0.560
BCCIP		psi-mi:“MI:0915”(physical association)	0.560
BCCIP	FCF1	psi-mi:“MI:0915”(physical association)	0.560
BCCIP	ZNF19	psi-mi:“MI:0915”(physical association)	0.560
BCCIP	MRPS9	psi-mi:“MI:0915”(physical association)	0.560
RALY	BCCIP	psi-mi:“MI:0915”(physical association)	0.560
PDGFB	BCCIP	psi-mi:“MI:0915”(physical association)	0.560
CPAP	BCCIP	psi-mi:“MI:0915”(physical association)	0.560
ZNF19	BCCIP	psi-mi:“MI:0915”(physical association)	0.560
ZNF138	BCCIP	psi-mi:“MI:0915”(physical association)	0.560
RPL38	BCCIP	psi-mi:“MI:0915”(physical association)	0.560
MRPS9	BCCIP	psi-mi:“MI:0915”(physical association)	0.560
BCCIP	EIF6	psi-mi:“MI:0914”(association)	0.560
MARCKSL1	NMT2	psi-mi:“MI:0914”(association)	0.530

BioGRID (224): BCCIP (Two-hybrid), CCDC33 (Two-hybrid), BCCIP (Affinity Capture-MS), RPL23 (Affinity Capture-MS), EIF6 (Affinity Capture-MS), PAPD4 (Affinity Capture-MS), BCCIP (Two-hybrid), BCCIP (Two-hybrid), BCCIP (Co-fractionation), BCCIP (Co-fractionation), BCCIP (Co-fractionation), BCCIP (Co-fractionation), BCCIP (Co-fractionation), CRCP (Co-fractionation), POLR1C (Co-fractionation)

ESM2 similar proteins: A0A1S4F550, A0A2B4SJZ1, A0A903V9Z8, C0HMB7, I7GVL4, O36307, O36405, O50917, O57199, O57571, O77763, P01579, P07611, P09807, P13776, P15628, P20147, P21030, P22622, P27737, P28027, P28341, P34431, P34566, P42160, P46402, P52473, P54890, Q01048, Q01479, Q12079, Q17F11, Q1PD52, Q1PDC9, Q1WM28, Q21738, Q5MIU2, Q5UQ37, Q62574, Q6UY68

Diamond homologs: O64885, O74907, Q2H137, Q2U600, Q4HZK7, Q4PA45, Q4WVS2, Q5AXW5, Q6BII5, Q6FY61, Q9P287, Q2NL37, Q5BJJ7, Q6GL92, Q6GNI0, Q9CWI3, Q9VFR0, Q06338, Q59PE7, Q6C7K5, Q756K9, Q7S8R3, Q61GH1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 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
Peptide chain elongation	8	17.5×	1e-06
Viral mRNA Translation	8	17.5×	1e-06
Formation of a pool of free 40S subunits	9	17.4×	8e-07
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	8	17.3×	1e-06
Selenocysteine synthesis	8	16.6×	1e-06
Eukaryotic Translation Termination	8	16.6×	1e-06
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	8	16.2×	1e-06
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	8	16.2×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	9	22.5×	2e-07
translation	8	11.1×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	176
Likely benign	71
Benign	6

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
253439	GRCh37/hg19 10q26.12-26.2(chr10:122239239-128203032)x1	Pathogenic

SpliceAI

1439 predictions. Top by Δscore:

Variant	Effect	Δscore
10:125823720:GAG:G	donor_gain	1.0000
10:125823721:AGG:A	donor_loss	1.0000
10:125823722:GGT:G	donor_loss	1.0000
10:125823723:G:GG	donor_gain	1.0000
10:125823723:GTG:G	donor_loss	1.0000
10:125826585:TTACA:T	acceptor_loss	1.0000
10:125826586:TACAG:T	acceptor_loss	1.0000
10:125826588:CA:C	acceptor_loss	1.0000
10:125826589:A:AG	acceptor_gain	1.0000
10:125826589:A:AT	acceptor_loss	1.0000
10:125826590:G:GG	acceptor_gain	1.0000
10:125826590:GGAA:G	acceptor_gain	1.0000
10:125826661:AGCAG:A	donor_loss	1.0000
10:125826662:GCAGG:G	donor_loss	1.0000
10:125826663:CAGGT:C	donor_loss	1.0000
10:125826664:AG:A	donor_loss	1.0000
10:125826665:GG:G	donor_loss	1.0000
10:125826666:GTATT:G	donor_loss	1.0000
10:125826667:T:G	donor_loss	1.0000
10:125827556:A:AG	acceptor_gain	1.0000
10:125827557:G:GC	acceptor_gain	1.0000
10:125827557:GC:G	acceptor_gain	1.0000
10:125827557:GCT:G	acceptor_gain	1.0000
10:125827557:GCTT:G	acceptor_gain	1.0000
10:125827557:GCTTT:G	acceptor_gain	1.0000
10:125827636:AAGGT:A	donor_loss	1.0000
10:125827639:G:GG	donor_gain	1.0000
10:125827639:GT:G	donor_loss	1.0000
10:125827640:T:A	donor_loss	1.0000
10:125830555:A:AG	acceptor_gain	1.0000

AlphaMissense

2118 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:125830625:A:C	S129R	0.995
10:125830627:C:A	S129R	0.995
10:125830627:C:G	S129R	0.995
10:125836201:G:C	R291P	0.995
10:125833839:A:C	S223R	0.990
10:125833841:T:A	S223R	0.990
10:125833841:T:G	S223R	0.990
10:125833914:T:C	F248L	0.989
10:125833916:T:A	F248L	0.989
10:125833916:T:G	F248L	0.989
10:125826606:T:C	F61L	0.986
10:125826608:T:A	F61L	0.986
10:125826608:T:G	F61L	0.986
10:125836167:T:A	W280R	0.986
10:125836167:T:C	W280R	0.986
10:125836169:G:C	W280C	0.982
10:125836169:G:T	W280C	0.982
10:125830617:G:A	G126D	0.979
10:125831604:T:C	L199P	0.979
10:125831557:A:C	R183S	0.978
10:125831557:A:T	R183S	0.978
10:125833844:G:C	K224N	0.978
10:125833844:G:T	K224N	0.978
10:125826658:T:C	L78P	0.976
10:125827592:T:C	L92P	0.974
10:125827627:A:C	S104R	0.970
10:125827629:T:A	S104R	0.970
10:125827629:T:G	S104R	0.970
10:125831568:T:A	V187D	0.970
10:125836107:G:C	A260P	0.969

dbSNP variants (sampled 300 via entrez): RS1000341279 (10:125851359 C>G), RS1000479301 (10:125838787 G>A), RS1000536201 (10:125838068 T>G), RS1000778407 (10:125848735 G>A), RS1000824898 (10:125849090 A>G), RS1000844451 (10:125850154 A>T), RS1000902172 (10:125832036 G>A,C), RS1001027732 (10:125821901 TA>T), RS1001185946 (10:125829922 A>G), RS1001223011 (10:125827973 A>G), RS1001245889 (10:125830326 G>A), RS1001479687 (10:125825097 G>A,T), RS1001522867 (10:125839664 T>A), RS1001551319 (10:125827284 A>G), RS1001552568 (10:125843001 C>T)

Disease associations

OMIM: gene MIM:611883 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST90002390_500	Mean corpuscular hemoglobin	9.000000e-16
GCST90002392_552	Mean corpuscular volume	1.000000e-13
GCST90002403_233	Red blood cell count	3.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067087 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.80	Kd	1592	nM	CHEMBL5653589
5.80	ED50	1592	nM	CHEMBL5653589

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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147943: Binding affinity to human BCCIP incubated for 45 mins by Kinobead based pull down assay	kd	1.5917	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, increases expression	3
bisphenol A	decreases expression	2
aristolochic acid I	increases expression	1
afuresertib	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression, increases abundance	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
CPG-oligonucleotide	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Troglitazone	decreases expression	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	increases expression	1
Cisplatin	decreases expression, increases reaction	1
Coal	decreases expression, increases abundance	1
Copper	affects binding, decreases expression	1
Dactinomycin	increases secretion, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	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
CHEMBL5650985	Binding	Binding affinity to human BCCIP 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.