BRK1

Summary

BRK1 (BRICK1 subunit of SCAR/WAVE actin nucleating complex, HGNC:23057) is a protein-coding gene on chromosome 3p25.3, encoding Protein BRICK1 (Q8WUW1). Involved in regulation of actin and microtubule organization. It is a selective cancer dependency (DepMap: 32.0% of cell lines).

Enables identical protein binding activity. Contributes to small GTPase binding activity. Involved in Rac protein signal transduction and positive regulation of cellular component organization. Located in extracellular exosome. Part of SCAR complex.

Source: NCBI Gene 55845 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 128 total — 10 pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 32.0% of screened cell lines
• MANE Select transcript: NM_018462

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23057
Approved symbol	BRK1
Name	BRICK1 subunit of SCAR/WAVE actin nucleating complex
Location	3p25.3
Locus type	gene with protein product
Status	Approved
Aliases	MDS027, HSPC300
Ensembl gene	ENSG00000254999
Ensembl biotype	protein_coding
OMIM	611183
Entrez	55845

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000530758, ENST00000916415

RefSeq mRNA: 1 — MANE Select: NM_018462 NM_018462

CCDS: CCDS54553

Canonical transcript exons

ENST00000530758 — 3 exons

Exon	Start	End
ENSE00002146984	10126269	10127190
ENSE00002188501	10125626	10125708
ENSE00002271926	10115675	10115819

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 99.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 179.5757 / max 1037.7844, expressed in 1828 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35273	179.5757	1828

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.31	gold quality
upper arm skin	UBERON:0004263	99.27	gold quality
adult organism	UBERON:0007023	99.01	gold quality
islet of Langerhans	UBERON:0000006	98.99	gold quality
right testis	UBERON:0004534	98.89	gold quality
monocyte	CL:0000576	98.88	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.87	gold quality
lower esophagus	UBERON:0013473	98.86	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.86	gold quality
leukocyte	CL:0000738	98.84	gold quality
right coronary artery	UBERON:0001625	98.84	gold quality
left coronary artery	UBERON:0001626	98.84	gold quality
popliteal artery	UBERON:0002250	98.84	gold quality
tibial artery	UBERON:0007610	98.84	gold quality
left testis	UBERON:0004533	98.82	gold quality
aorta	UBERON:0000947	98.78	gold quality
smooth muscle tissue	UBERON:0001135	98.77	gold quality
descending thoracic aorta	UBERON:0002345	98.77	gold quality
coronary artery	UBERON:0001621	98.76	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.76	gold quality
thoracic aorta	UBERON:0001515	98.73	gold quality
mucosa of stomach	UBERON:0001199	98.72	gold quality
ascending aorta	UBERON:0001496	98.72	gold quality
cortical plate	UBERON:0005343	98.63	gold quality
body of uterus	UBERON:0009853	98.63	gold quality
esophagus	UBERON:0001043	98.59	gold quality
left uterine tube	UBERON:0001303	98.59	gold quality
ectocervix	UBERON:0012249	98.57	gold quality
endocervix	UBERON:0000458	98.55	gold quality
skin of abdomen	UBERON:0001416	98.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8205	no	1188.36
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NRF1, SP1

miRNA regulators (miRDB)

66 targeting BRK1, 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-188-3P	100.00	68.76	1240
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-510-3P	99.54	70.06	2965

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 32.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 6)

• Von Hippel-Lindau (VHL) locus deletion of the HSPC300 actin regulator gene greatly lowers risk of clear cell renal cell carcinoma development in Spanish VHL syndrome patients studied. (PMID:17311301)
• higher expression in primary lung tumours with lymph node metastases and also in tumours from patients with more advanced disease (PMID:19576655)
• Growing body of evidence suggesting that patients with VHL syndrome caused by large VHL deletions that include C3orf10 may be designated as having a specific subtype (Type 1B) of the disorder. (PMID:19764026)
• Data show that Brk1 downregulation results in defective directional migration and invasive growth in renal cell carcinoma cells as well as in other tumor cell types. (PMID:20861187)
• We verified that NRF-1 positively regulates FAM134C and ENOX1, and negatively regulates C3orf10 in human neuroblastoma IMR-32 cells and primary rat cortical neurons. (PMID:23939472)
• Sp1 transcriptionally regulates BRK1 expression in non-small cell lung cancer cells. (PMID:24680773)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Brk1	ENSMUSG00000033940
rattus_norvegicus	Brk1	ENSRNOG00000010184
drosophila_melanogaster	HSPC300	FBGN0061198

Protein

Protein identifiers

Protein BRICK1 — Q8WUW1 (reviewed: Q8WUW1)

All UniProt accessions (1): Q8WUW1

UniProt curated annotations — full annotation on UniProt →

Function. Involved in regulation of actin and microtubule organization. Part of a WAVE complex that activates the Arp2/3 complex. As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes.

Subunit / interactions. Homotrimer when in free form. Directly interacts with WASF2. Component of the WAVE1 complex composed of ABI2, CYFIP1 or CYFIP2, BRK1, NCKAP1 and WASF1/WAVE1. Within the complex, a heterodimer containing NCKAP1 and CYFIP1 interacts with a heterotrimer formed by WAVE1, ABI2 and BRK1.

Subcellular location. Cytoplasm. Cytoskeleton.

Similarity. Belongs to the BRK1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WUW1-1	1	yes
Q8WUW1-2	2

RefSeq proteins (1): NP_060932* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033378	BRICK1	Family

UniProt features (6 total): initiator methionine 1, chain 1, coiled-coil region 1, modified residue 1, splice variant 1, helix 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
3P8C	X-RAY DIFFRACTION	2.29
4N78	X-RAY DIFFRACTION	2.43
7USC	ELECTRON MICROSCOPY	3
7USD	ELECTRON MICROSCOPY	3
7USE	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WUW1-F1	94.15	0.87

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 (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

23 pathways

ID	Pathway
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-5663213	RHO GTPases Activate WASPs and WAVEs
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9664422	FCGR3A-mediated phagocytosis
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-194138	Signaling by VEGF
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-5663205	Infectious disease
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9658195	Leishmania infection
R-HSA-9664407	Parasite infection
R-HSA-9664417	Leishmania phagocytosis
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3
R-HSA-9824443	Parasitic Infection Pathways

MSigDB gene sets: 164 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, REACTOME_INNATE_IMMUNE_SYSTEM, TGCGCANK_UNKNOWN, GOBP_REGULATION_OF_ACTIN_NUCLEATION, GOMF_GTPASE_BINDING, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_LAMELLIPODIUM_ASSEMBLY, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION

GO Biological Process (11): in utero embryonic development (GO:0001701), actin filament organization (GO:0007015), regulation of actin polymerization or depolymerization (GO:0008064), positive regulation of lamellipodium assembly (GO:0010592), Rac protein signal transduction (GO:0016601), positive regulation of protein-containing complex assembly (GO:0031334), fibroblast proliferation (GO:0048144), positive regulation of fibroblast proliferation (GO:0048146), cell motility (GO:0048870), positive regulation of Arp2/3 complex-mediated actin nucleation (GO:2000601), actin cytoskeleton organization (GO:0030036)

GO Molecular Function (4): identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), protein binding (GO:0005515), small GTPase binding (GO:0031267)

GO Cellular Component (6): cytosol (GO:0005829), cytoskeleton (GO:0005856), lamellipodium (GO:0030027), SCAR complex (GO:0031209), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
RHO GTPase cycle	3
Signaling by Rho GTPases	2
Fcgamma receptor (FCGR) dependent phagocytosis	1
Signaling by VEGF	1
RHO GTPase Effectors	1
Leishmania phagocytosis	1
Immune System	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Innate Immune System	1
Disease	1
Signal Transduction	1
Parasitic Infection Pathways	1
Leishmania infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cytoplasm	2
cellular anatomical structure	2
chordate embryonic development	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
actin polymerization or depolymerization	1
regulation of actin filament length	1
regulation of actin filament organization	1
regulation of lamellipodium assembly	1
lamellipodium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
positive regulation of lamellipodium organization	1
small GTPase-mediated signal transduction	1
regulation of protein-containing complex assembly	1
positive regulation of cellular component biogenesis	1
positive regulation of cellular component organization	1
protein-containing complex assembly	1
cell population proliferation	1
positive regulation of cell population proliferation	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
cellular process	1
Arp2/3 complex-mediated actin nucleation	1
regulation of Arp2/3 complex-mediated actin nucleation	1
positive regulation of actin nucleation	1
cytoskeleton organization	1
actin filament-based process	1
protein binding	1
GTPase binding	1
intracellular membraneless organelle	1
cell leading edge	1
plasma membrane bounded cell projection	1
protein-containing complex	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1230 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BRK1	ABI2	Q9NYB9	999
BRK1	NCKAP1	Q9Y2A7	999
BRK1	CYFIP2	Q96F07	999
BRK1	WASF1	Q92558	998
BRK1	CYFIP1	Q7L576	998
BRK1	ABI1	Q8IZP0	997
BRK1	WASF2	Q9Y6W5	996
BRK1	NCKAP1L	P55160	995
BRK1	WAS	P42768	899
BRK1	NCK1	P16333	892
BRK1	WASF3	Q9UPY6	882
BRK1	ABI3	Q9P2A4	858
BRK1	WASL	O00401	758
BRK1	NCK2	O43639	714
BRK1	BAIAP2	Q9UQB8	650

IntAct

298 interactions, top by confidence:

A	B	Type	Score
ABI2	BRK1	psi-mi:“MI:0915”(physical association)	0.910
ABI2	CYFIP1	psi-mi:“MI:0915”(physical association)	0.870
BRK1	NDEL1	psi-mi:“MI:0915”(physical association)	0.830
HSBP1	BRK1	psi-mi:“MI:0915”(physical association)	0.740
BRK1	RNF20	psi-mi:“MI:0915”(physical association)	0.740
BRK1	MRFAP1	psi-mi:“MI:0915”(physical association)	0.720
DTNBP1	BRK1	psi-mi:“MI:0915”(physical association)	0.670
BRK1	DTNBP1	psi-mi:“MI:0915”(physical association)	0.670
BRK1	A2M	psi-mi:“MI:0915”(physical association)	0.560
BRK1	DBH	psi-mi:“MI:0915”(physical association)	0.560
BRK1	DCTN1	psi-mi:“MI:0915”(physical association)	0.560
DMWD	BRK1	psi-mi:“MI:0915”(physical association)	0.560
BRK1	DNM2	psi-mi:“MI:0915”(physical association)	0.560
	BRK1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (152): DTNBP1 (Two-hybrid), BRK1 (Affinity Capture-MS), BRK1 (Affinity Capture-MS), BRK1 (Two-hybrid), BRK1 (Affinity Capture-MS), BRK1 (Affinity Capture-MS), BRK1 (Affinity Capture-MS), BRK1 (Two-hybrid), BRK1 (Affinity Capture-MS), BRK1 (Affinity Capture-MS), BRK1 (Affinity Capture-MS), BRK1 (Affinity Capture-MS), BRK1 (Affinity Capture-MS), BRK1 (Affinity Capture-MS), BRK1 (Affinity Capture-MS)

ESM2 similar proteins: A2BD66, A7TLF1, C5DMF2, C5DUB3, F4K657, O01901, O14330, O44445, O94376, P47822, P62505, P69851, P87297, Q22756, Q23679, Q54X65, Q61BU1, Q626S1, Q6BER6, Q6C5U8, Q6CDG5, Q6CER3, Q6CGR3, Q6CKH5, Q6CSY9, Q6CT76, Q6CTB9, Q6CVF3, Q6FN16, Q6FP96, Q6FRP0, Q6FVV1, Q6IQ86, Q6P7G6, Q74Z51, Q754U2, Q755V6, Q759Q6, Q75EX7, Q84VA7

Diamond homologs: A2BD66, Q54X65, Q6IQ86, Q6P7G6, Q84VA7, Q8RW98, Q8WUW1, Q91VR8, Q94JY4

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
BRK1	“form complex”	“WRC complex”	binding
BRK1	“up-regulates activity”	NHS	binding
NRF1	“down-regulates quantity by repression”	BRK1	“transcriptional regulation”
BRK1	down-regulates	Neurite_outgrowth
BRK1	“form complex”	“WAVE complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 74 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
RHO GTPases Activate WASPs and WAVEs	5	30.5×	2e-04
FCGR3A-mediated phagocytosis	5	18.0×	1e-03
Regulation of actin dynamics for phagocytic cup formation	5	17.7×	1e-03
VEGFA-VEGFR2 Pathway	5	13.4×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	0
Uncertain significance	16
Likely benign	1
Benign	94

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
144845	GRCh38/hg38 3p25.3(chr3:9896061-10220962)x1	Pathogenic
1456081	NC_000003.11:g.(?10070342)(10191719_?)del	Pathogenic
253501	GRCh37/hg19 3p25.3(chr3:10128763-10188569)x1	Pathogenic
3062688	GRCh37/hg19 3p25.3(chr3:10167355-10209588)x1	Pathogenic
4682579	GRCh37/hg19 3p25.3(chr3:10128635-10222177)x1	Pathogenic
665653	NC_000003.12:g.(?10052377)(10149975_?)del	Pathogenic
833032	NC_000003.12:g.(?10072861)(10150035_?)del	Pathogenic
833211	NC_000003.12:g.(?10052377)(10150035_?)del	Pathogenic
997719	NC_000003.11:g.10160443_10184298del	Pathogenic
997720	NC_000003.11:g.10167511_10193484del	Pathogenic

SpliceAI

551 predictions. Top by Δscore:

Variant	Effect	Δscore
3:10115758:G:GT	donor_gain	1.0000
3:10115838:G:T	donor_gain	1.0000
3:10118966:GAATA:G	donor_gain	1.0000
3:10125707:GGGTG:G	donor_loss	1.0000
3:10125708:GGTG:G	donor_loss	1.0000
3:10125709:G:T	donor_loss	1.0000
3:10125710:TGAG:T	donor_loss	1.0000
3:10125711:GAGT:G	donor_loss	1.0000
3:10115758:G:T	donor_gain	0.9900
3:10115771:A:G	donor_gain	0.9900
3:10115815:GTTCG:G	donor_gain	0.9900
3:10115816:T:G	donor_gain	0.9900
3:10115819:GG:G	donor_loss	0.9900
3:10115820:G:GG	donor_gain	0.9900
3:10115820:GT:G	donor_loss	0.9900
3:10115821:T:G	donor_loss	0.9900
3:10118971:G:GG	donor_gain	0.9900
3:10125625:GATAT:G	acceptor_gain	0.9900
3:10125707:GG:G	donor_gain	0.9900
3:10125708:GG:G	donor_gain	0.9900
3:10125709:G:GG	donor_gain	0.9900
3:10115744:G:GT	donor_gain	0.9800
3:10118968:ATA:A	donor_gain	0.9800
3:10125625:GAT:G	acceptor_gain	0.9800
3:10118967:AATA:A	donor_gain	0.9700
3:10125621:CTCA:C	acceptor_loss	0.9700
3:10125622:TCAG:T	acceptor_loss	0.9700
3:10125623:CA:C	acceptor_loss	0.9700
3:10125625:G:GT	acceptor_loss	0.9700
3:10125713:G:C	donor_loss	0.9700

AlphaMissense

488 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:10115747:T:A	W16R	1.000
3:10115747:T:C	W16R	1.000
3:10115749:G:C	W16C	1.000
3:10115749:G:T	W16C	1.000
3:10115804:T:C	F35L	1.000
3:10115806:T:A	F35L	1.000
3:10115806:T:G	F35L	1.000
3:10115748:G:C	W16S	0.999
3:10115757:G:C	R19P	0.999
3:10115808:T:C	L36P	0.999
3:10115816:T:C	F39L	0.999
3:10115818:C:A	F39L	0.999
3:10115818:C:G	F39L	0.999
3:10125703:G:C	A66P	0.999
3:10115805:T:C	F35S	0.998
3:10115805:T:G	F35C	0.998
3:10115808:T:A	L36H	0.998
3:10115817:T:C	F39S	0.998
3:10125634:T:C	C43R	0.998
3:10125635:G:A	C43Y	0.998
3:10125636:T:G	C43W	0.998
3:10125649:G:C	A48P	0.998
3:10125656:T:C	L50P	0.998
3:10125668:T:C	L54S	0.998
3:10125677:T:C	L57P	0.998
3:10115744:G:C	D15H	0.997
3:10115745:A:T	D15V	0.997
3:10115798:G:C	A33P	0.997
3:10115817:T:G	F39C	0.997
3:10125638:G:C	R44P	0.997

dbSNP variants (sampled 300 via entrez): RS1000731039 (3:10119970 A>ACC), RS1000790312 (3:10113819 C>T), RS1000836748 (3:10126574 C>A,G,T), RS1000844037 (3:10117877 A>C), RS1000996624 (3:10124523 T>C), RS1001110736 (3:10124847 G>A), RS1001295153 (3:10118287 A>G,T), RS1001403772 (3:10124702 A>G), RS1001595164 (3:10124226 G>A), RS1001928876 (3:10125360 C>G,T), RS1001951626 (3:10125193 C>A,G,T), RS1002404029 (3:10125920 A>G), RS1002818711 (3:10120118 C>T), RS1002858659 (3:10123385 C>T), RS1002975306 (3:10114283 C>A,T)

Disease associations

OMIM: gene MIM:611183 | disease phenotypes: MIM:606217, MIM:193300, MIM:263400, MIM:227650

GenCC curated gene-disease

Mondo (4): atrioventricular septal defect, susceptibility to, 2 (MONDO:0011650), von Hippel-Lindau disease (MONDO:0008667), Chuvash polycythemia (MONDO:0009892), Fanconi anemia (MONDO:0019391)

Orphanet (3): Chuvash erythrocytosis (Orphanet:238557), Von Hippel-Lindau disease (Orphanet:892), Fanconi anemia (Orphanet:84)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008403_37	Arterial stiffness index	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004517	arterial stiffness measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D005199	Fanconi Anemia	C15.378.050.085.080.280; C15.378.190.223.500.500.280; C16.320.077.280; C18.452.284.280
D006623	von Hippel-Lindau Disease	C10.562.925; C14.907.077.925; C16.131.077.245.750; C16.320.184.750
C565249	Atrioventricular Septal Defect, Partial, with Heterotaxy Syndrome (supp.)
C563918	Erythrocytosis, Familial, 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3758062 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	3
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Diuron	decreases expression	1
Estradiol	decreases expression	1
Ivermectin	decreases expression	1
Smoke	decreases expression	1
Zinc	decreases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	decreases expression	1
Lactic Acid	decreases expression	1
Genistein	increases expression	1
Particulate Matter	decreases expression, increases abundance	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
CHEMBL3762160	Binding	Inhibition of BRK (unknown origin) at 100 nM	4-Aminoindazolyl-dihydrofuro[3,4-d]pyrimidines as non-covalent inhibitors of mutant epidermal growth factor receptor tyrosine kinase. — Bioorg Med Chem Lett

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1LI	Abcam HeLa BRK1 KO	Cancer cell line	Female
CVCL_SF72	HAP1 BRK1 (-) 1	Cancer cell line	Male
CVCL_SF73	HAP1 BRK1 (-) 2	Cancer cell line	Male
CVCL_SF74	HAP1 BRK1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07405164	PHASE3	RECRUITING	Extension Study for Participants in Studies That Include Belzutifan (MK-6482-043/LITESPARK-043)
NCT06519786	PHASE3	UNKNOWN	Safety and Efficacy of Metformin for Treatment of Cytopenia in Children and Adolescents With Fanconi Anemia
NCT00052013	PHASE2	COMPLETED	Treatment of Von Hippel-Lindau (VHL)-Related Hemangioblastoma With PTK787/ZK 222584
NCT00330564	PHASE2	TERMINATED	Evaluation of Sunitinib Malate in Patients With Von Hippel-Lindau Syndrome (VHL) Who Have VHL Lesions to Follow
NCT01168440	PHASE2	COMPLETED	Study of Sunitinib in Patients With Von Hippel-Lindau (VHL) Disease
NCT01266070	PHASE2	TERMINATED	TKI 258 in Von Hippel-Lindau Syndrome (VHL)
NCT01436227	PHASE2	COMPLETED	Pazopanib Hydrochloride in Treating Patients With Von Hippel-Lindau Syndrome
NCT01967537	PHASE2	COMPLETED	Evaluation of 68Gallium-DOTATATE PET/CT for Detecting Neuroendocrine Tumors
NCT03108066	PHASE2	COMPLETED	MK-3795 (PT2385) for the Treatment of Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma (MK-3795-003)
NCT03401788	PHASE2	ACTIVE_NOT_RECRUITING	A Phase 2 Study of Belzutifan (PT2977, MK-6482) for the Treatment of Von Hippel Lindau (VHL) Disease-Associated Renal Cell Carcinoma (RCC) (MK-6482-004)
NCT04074135	PHASE2	RECRUITING	Natural History and Management of Von Hippel-Lindau (VHL) Associated Pancreatic Neuroendocrine Tumors
NCT04924075	PHASE2	RECRUITING	Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Solid Tumors With HIF-2α Related Genetic Alterations (MK-6482-015)
NCT05810246	PHASE2	UNKNOWN	68Ga-NY104 PET/CT in Von Hippel-Lindau Disease
NCT07167329	PHASE2	RECRUITING	Real-World Effectiveness and Pharmacogenetics of Belzutifan in VHL Syndrome: The BELIEVE-VHL Trial
NCT00000603	PHASE2	COMPLETED	Cord Blood Stem Cell Transplantation Study (COBLT)
NCT00001749	PHASE2	COMPLETED	Medical Treatment for Diamond Blackfan Anemia
NCT00004787	PHASE2	COMPLETED	Phase II Pilot Study of Granulocyte Colony-Stimulating Factor for Inherited Bone Marrow Failure Syndromes
NCT00053989	PHASE2	COMPLETED	NMA Allogeneic Hematopoietic Cell Transplant in Hematologic Cancer/Disorders
NCT00084695	PHASE2	UNKNOWN	Umbilical Cord Blood for Stem Cell Transplantation in Treating Young Patients With Malignant or Nonmalignant Diseases
NCT00258427	PHASE2	COMPLETED	Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia
NCT00453388	PHASE2	COMPLETED	Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant, Mycophenolate Mofetil, and Cyclosporine in Treating Patients With Fanconi Anemia
NCT01071239	PHASE2	COMPLETED	Hematopoietic Stem Cell Transplant for Fanconi Anemia
NCT02143830	PHASE2	RECRUITING	HSCT for Patients With Fanconi Anemia Using Risk-Adjusted Chemotherapy
NCT02931071	PHASE2	COMPLETED	Clinical Phase II Trial to Evaluate CD34+ Cells Mobilization and Collection in Patients With Fanconi Anemia for Subsequent Transduction With a Lentiviral Vector Carring FANCA Gene. FANCOSTEM-1
NCT03206086	PHASE2	ACTIVE_NOT_RECRUITING	Eltrombopag for People With Fanconi Anemia
NCT03398824	PHASE2	COMPLETED	Pilot Study of Metformin for Patients With Fanconi Anemia
NCT03476330	PHASE2	COMPLETED	Quercetin Chemoprevention for Squamous Cell Carcinoma in Patients With Fanconi Anemia
NCT03579875	PHASE2	RECRUITING	Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders
NCT03600909	PHASE2	TERMINATED	A Study of the Effect of Blood Stem Cell Transplant After Chemotherapy Alone in Patients With Fanconi Anemia
NCT04232085	PHASE2	RECRUITING	Regenerative Medicine to Restore Hematopoiesis and Immune Function in Immunodeficiencies and Inherited Bone Marrow Failures
NCT06045052	PHASE2	COMPLETED	Eltrombopag for Treatment of Fanconi Anemia
NCT00089765	PHASE1	COMPLETED	Ranibizumab Injections to Treat Retinal Tumors in Patients With Von Hippel-Lindau Syndrome
NCT02108002	PHASE1	COMPLETED	Effect of Vorinostat on Nervous System Hemangioblastomas in Von Hippel-Lindau Disease (Missense Mutation Only)
NCT05843305	PHASE1	UNKNOWN	A Study of BPI-452080 in Subjects With Solid Tumors
NCT00001399	PHASE1	COMPLETED	Gene Therapy for the Treatment of Fanconi’s Anemia Type C
NCT00005896	PHASE1	UNKNOWN	Phase I Pilot Study of CD34 Enriched, Fanconi’s Anemia Complementation Group C Gene Transduced Autologous Peripheral Blood Stem Cell Transplantation in Patients With Fanconi’s Anemia
NCT00006127	PHASE1	UNKNOWN	Phase I Study of Amifostine in Patients With Bone Marrow Failure Related to Fanconi’s Anemia
NCT00093743	PHASE1	COMPLETED	Low-Dose Total-Body Irradiation and Fludarabine Phosphate Followed by Unrelated Donor Stem Cell Transplant in Treating Patients With Fanconi Anemia
NCT00243399	PHASE1	COMPLETED	Oxandrolone for the Treatment of Bone Marrow Aplasia in Fanconi Anemia
NCT00272857	PHASE1	COMPLETED	Bone Marrow Cell Gene Transfer in Individuals With Fanconi Anemia