BRMS1

Summary

BRMS1 (BRMS1 transcriptional repressor and anoikis regulator, HGNC:17262) is a protein-coding gene on chromosome 11q13.2, encoding Breast cancer metastasis-suppressor 1 (Q9HCU9). Transcriptional repressor. It is a selective cancer dependency (DepMap: 19.5% of cell lines).

This gene reduces the metastatic potential, but not the tumorogenicity, of human breast cancer and melanoma cell lines. The protein encoded by this gene localizes primarily to the nucleus and is a component of the mSin3a family of histone deacetylase complexes (HDAC). The protein contains two coiled-coil motifs and several imperfect leucine zipper motifs. Alternative splicing results in two transcript variants encoding different isoforms.

Source: NCBI Gene 25855 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 76 total
• Cancer dependency (DepMap): dependent in 19.5% of screened cell lines
• MANE Select transcript: NM_015399

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17262
Approved symbol	BRMS1
Name	BRMS1 transcriptional repressor and anoikis regulator
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP564A063
Ensembl gene	ENSG00000174744
Ensembl biotype	protein_coding
OMIM	606259
Entrez	25855

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 11 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000359957, ENST00000425825, ENST00000524699, ENST00000525127, ENST00000527375, ENST00000529544, ENST00000530238, ENST00000530756, ENST00000534617, ENST00000877325, ENST00000877326, ENST00000921863, ENST00000921864, ENST00000921865, ENST00000921866, ENST00000961319

RefSeq mRNA: 2 — MANE Select: NM_015399 NM_001024957, NM_015399

CCDS: CCDS44654, CCDS8135

Canonical transcript exons

ENST00000359957 — 10 exons

Exon	Start	End
ENSE00003518949	66338721	66338785
ENSE00003520584	66337339	66337889
ENSE00003543552	66342096	66342241
ENSE00003562224	66340774	66340870
ENSE00003576921	66341206	66341333
ENSE00003619335	66340967	66341046
ENSE00003635583	66341533	66341623
ENSE00003671289	66340121	66340213
ENSE00003790471	66338243	66338282
ENSE00003845047	66344972	66345104

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 95.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.5171 / max 673.7997, expressed in 1780 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120793	24.1341	1825
120791	8.6645	1751
120792	1.8526	1210

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	95.19	gold quality
mucosa of transverse colon	UBERON:0004991	94.28	gold quality
monocyte	CL:0000576	92.87	gold quality
leukocyte	CL:0000738	92.85	gold quality
mononuclear cell	CL:0000842	92.83	gold quality
skin of leg	UBERON:0001511	92.68	gold quality
skin of abdomen	UBERON:0001416	92.52	gold quality
body of stomach	UBERON:0001161	92.10	gold quality
body of pancreas	UBERON:0001150	92.07	gold quality
metanephros cortex	UBERON:0010533	91.61	gold quality
sural nerve	UBERON:0015488	91.42	gold quality
minor salivary gland	UBERON:0001830	91.28	gold quality
transverse colon	UBERON:0001157	91.27	gold quality
esophagus mucosa	UBERON:0002469	91.21	gold quality
blood	UBERON:0000178	90.96	gold quality
left testis	UBERON:0004533	90.96	gold quality
right lobe of thyroid gland	UBERON:0001119	90.94	gold quality
spleen	UBERON:0002106	90.87	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.80	gold quality
lower esophagus mucosa	UBERON:0035834	90.65	gold quality
left lobe of thyroid gland	UBERON:0001120	90.57	gold quality
right testis	UBERON:0004534	90.55	gold quality
gastrocnemius	UBERON:0001388	90.54	gold quality
left adrenal gland	UBERON:0001234	90.45	gold quality
left adrenal gland cortex	UBERON:0035825	90.40	gold quality
upper lobe of left lung	UBERON:0008952	90.39	gold quality
right adrenal gland	UBERON:0001233	90.34	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.32	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.27	gold quality
right adrenal gland cortex	UBERON:0035827	90.26	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: no

Upstream regulators (CollecTRI, top): ARID4A, CASZ1, DNMT1, NFKB, RELA

miRNA regulators (miRDB)

14 targeting BRMS1, 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-4481	100.00	66.42	1669
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-6859-3P	97.26	64.69	428
HSA-MIR-6836-3P	97.08	64.99	712
HSA-MIR-345-5P	96.40	66.43	663
HSA-MIR-4485-5P	95.91	59.69	198

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 19.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• BRMS1 functions as a metastasis suppressor in more than one tumor type(i.e., breast carcinoma and cutaneous melanoma)by modifying several metastasis-associated phenotypes. (PMID:11822878)
• BRMS1 has subsequently been shown to suppress metastasis, but not tumorigenicity of human melanoma cells. (PMID:12650606)
• BRMS1 may participate in transcriptional regulation via interaction with the mSin3.HDAC complex (PMID:14581478)
• To further characterize BRMS1-mediated metastasis suppression, proteins differentially expressed between highly metastatic MDA-MB-435 cells & BRMS1-transfected MDA-MB-435 cells were identified. Differential expression was found for 5 proteins. (PMID:15168732)
• Our investigations revealed significantly reduced mRNA expression of metastases suppressor gene BRMS1 in breast cancer brain metastasis. (PMID:15592684)
• Patients with high levels of expression of BRMS1 mRNA have a better prognosis than those with low expression. (PMID:17085653)
• Results show that BRMS1 regulates Osteopontin transcription by abrogating NF-kappaB activation (PMID:17227585)
• Available evidence on the reported functions of the identified proteins supports the emerging role of BRMS1 as negative regulator of the metastasis development. (PMID:17854218)
• The pattern of gene expression associated with BRMS1 expression suggests that metastasis suppression may be mediated by enhanced immune recognition, altered transport, and/or secretion of metastasis-associated proteins. (PMID:17896182)
• Alterations of BRMS1-ARID4A interaction modify gene expression but still suppress metastasis in human breast cancer cells. (PMID:18211900)
• BRMS1 inhibits metastases in multiple organs by blocking several steps in the metastatic cascade. (PMID:18276787)
• OPN downregulation by BRMS1 may be responsible, at least in part, for BRMS1-mediated metastasis suppression by sensitizing cancer cells to stress induced apoptosis. (PMID:18470911)
• Breast cancer metastasis suppressor 1 inhibits SDF-1alpha-induced migration of non-small cell lung cancer by decreasing CXCR4 expression. (PMID:18502034)
• Expression of BRMS1 mRNA in supraglottic cancer is lower than that in adjacent normal mucosa. (PMID:18533556)
• BRMS1 is a potent suppressor of metastasis in multiple organs, and identify two steps in the metastatic process that are sensitive to inhibition by BRMS1. (PMID:18543067)
• BRMS1 is a novel target of epigenetic silencing; and aberrant methylation in the BRMS1 promoter may serve as a cause of loss of its expression. (PMID:18566899)
• Breast cancer metastasis suppressor-1 differentially modulates growth factor signaling (PMID:18664570)
• expression of the characteristic *35 kDa BRMS1 protein is not sufficient to prevent metastasis. The differential expression of alternative splice variants suggests caution should be taken when evaluating BRMS1 mRNA in clinical samples. (PMID:18841483)
• Here, the expression, purification and crystallization of a functional fragment of human BRMS1 that is predicted to be a coiled-coil region are reported (PMID:19052374)
• BRMS1 functions as a metastasis suppressor and may be a prognostic indicator for human non-small cell lung cancer. (PMID:19111386)
• BRMS1 recruits HDAC1 to the NF-kappaB binding site of the uPA promoter, modulates histone acetylation of p65 on the uPA promoter, leading to reduced NF-kappaB binding activity on its consensus sequence, and reduced transactivation of uPA expression. (PMID:19165610)
• Chemosensitivity of breast cancer cells is preserved in the presence of recombinant BRMS1. BRMS1 does not change expression of AKT isoforms or PTEN, implicated in chemoresistance to common drug agents. (PMID:19307053)
• This protein has been found differentially expressed in the Wernicke’s Area from patients with schizophrenia. (PMID:19405953)
• Loss of nuclear BRMS1 was associated with ER-negative cancers and a high rate of proliferation, but was not an independent indicator of prognosis. (PMID:19609101)
• The expression of BRMS1 protein in supraglottic cancer is significantly decreased. Expression has a close relationship with pathologic differentiation and clinical stage and cervical lymph node metastasis. (PMID:19621595)
• BRMS1 expression in breast cancer cells induced reorganization of F-actin and caused alteration in cytoarchitectures (cell topography and ultrastructure). (PMID:20083343)
• Study observed that SNX6 increases BRMS1-dependent transcriptional repression. Moreover, over-expression of SNX6 was capable of diminishing trans-activation in a dose-dependent manner. (PMID:20830743)
• BRMS1 expression was decreased in metastatic melanomas, which resulted in deficient suppression of angiogenesis and contributed to melanoma progression. (PMID:20935672)
• ING4 is induced by BRMS1 and that it inhibits melanoma angiogenesis by suppressing NF-kappaB activity and IL-6 expression. (PMID:21056991)
• SATB1 and BRMS1 might play an important role in the development and lymph node metastasis of ovarian cancer. (PMID:21355308)
• high level of expression and lack of promoter methylation are associated with better overall survival in non-small cell lung cancer patients (PMID:21726917)
• possible link between BRMS1 expression and apoptosis in human breast cancer through a relationship with the expression of genes belonging to the X-chromosome RBM family. (PMID:21737612)
• the enigmatic complexities of BRMS1-mediated metastasis suppression (PMID:21827753)
• These results suggest that the novel regulatory mechanism of BRMS1 by Cul3-SPOP complex is important for breast cancer progression. (PMID:22085717)
• Loss of breast cancer metastasis suppressor 1 promotes ovarian cancer cell metastasis by increasing chemokine receptor 4 expression. (PMID:22200669)
• The loss of BRMS1 expression may be involved in the development and progression of nasal and paranasal sinus carcinomas. (PMID:22239051)
• BRMS1 sensitizes HCC cells to apoptosis through suppressing OPN expression (PMID:22927944)
• Data suggest that low expression of the metastasis suppressor BRMS1 may be an independent prognostic factor for poor prognosis in nasopharyngeal carcinoma (NPC) patients. (PMID:22931099)
• The expression of BRMS1 protein in supraglottic cancer is significantly decreased. BRMS1 gene promotor methylation is related with down-expression of BRMS1 protein. (PMID:23167184)
• Data indicate that mutation of E3 ligase motif not only abolishes BRMS1-induced p300 polyubiquitination and degradation, but importantly, dramatically reduces the metastasis suppressor function of BRMS1. (PMID:23269275)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	brms1	ENSDARG00000051955
mus_musculus	Brms1	ENSMUSG00000080268
rattus_norvegicus	Brms1	ENSRNOG00000020117
drosophila_melanogaster	Brms1	FBGN0030434

Paralogs (2): BRMS1L (ENSG00000100916), SUDS3 (ENSG00000111707)

Protein

Protein identifiers

Breast cancer metastasis-suppressor 1 — Q9HCU9 (reviewed: Q9HCU9)

All UniProt accessions (5): Q9HCU9, E9PJF5, E9PPD1, G5E9I4, H0YCF7

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor. Down-regulates transcription activation by NF-kappa-B by promoting the deacetylation of RELA at ‘Lys-310’. Promotes HDAC1 binding to promoter regions. Down-regulates expression of anti-apoptotic genes that are controlled by NF-kappa-B. Promotes apoptosis in cells that have inadequate adherence to a substrate, a process called anoikis, and may thereby inhibit metastasis. May be a mediator of metastasis suppression in breast carcinoma.

Subunit / interactions. Homohexamer (Potential). Interacts with SNX6, HDAC1 and RELA. Interacts with ARID4A. Identified in mSin3A corepressor complexes together with SIN3A, SIN3B, RBBP4, RBBP7, SAP30, SUDS3, ARID4A, HDAC1 and HDAC2. Interacts with SPOP; this recruits the protein to a ubiquitin ligase complex containing SPOP and CUL3.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expression levels are higher in term placentas than in early placentas. Low levels of expression observed in normal pregnancies and in molar pregnancies.

Post-translational modifications. Ubiquitinated by a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing SPOP, leading to proteasomal degradation.

Domain organisation. Contains an N-terminal anti-parallel coiled coil formed by two BRMS1 chains; this region can form homohexamers.

Similarity. Belongs to the BRMS1 family.

RefSeq proteins (2): NP_001020128, NP_056214* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013907	Sds3	Family

Pfam: PF08598

UniProt features (8 total): compositionally biased region 2, cross-link 2, chain 1, region of interest 1, coiled-coil region 1, helix 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2XUS	X-RAY DIFFRACTION	1.91
4AUV	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCU9-F1	79.23	0.52

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): 184, 242

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-3214815	HDACs deacetylate histones
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-1643685	Disease
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-5663205	Infectious disease
R-HSA-9679506	SARS-CoV Infections
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 138 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, ELVIDGE_HYPOXIA_DN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_REGULATION_OF_PROTEIN_DEACETYLATION, GOBP_MACROMOLECULE_DEACYLATION, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, chr11q13, BROWNE_HCMV_INFECTION_24HR_UP, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, FREAC3_01, GOBP_NEGATIVE_REGULATION_OF_NF_KAPPAB_TRANSCRIPTION_FACTOR_ACTIVITY, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA, GOBP_NEGATIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_MAINTENANCE_OF_CELL_NUMBER

GO Biological Process (12): negative regulation of transcription by RNA polymerase II (GO:0000122), apoptotic process (GO:0006915), negative regulation of cell migration (GO:0030336), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), obsolete negative regulation of NF-kappaB transcription factor activity (GO:0032088), regulation of apoptotic process (GO:0042981), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of protein deacetylation (GO:0090312), negative regulation of stem cell population maintenance (GO:1902455), positive regulation of stem cell population maintenance (GO:1902459), positive regulation of anoikis (GO:2000210), regulation of gene expression (GO:0010468)

GO Molecular Function (3): histone deacetylase binding (GO:0042826), NF-kappaB binding (GO:0051059), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Sin3-type complex (GO:0070822)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Chromatin modifying enzymes	1
SARS-CoV Infections	1
Chromatin organization	1
Disease	1
Viral Infection Pathways	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
stem cell population maintenance	2
regulation of stem cell population maintenance	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
apoptotic process	1
regulation of programmed cell death	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
protein deacetylation	1
positive regulation of protein modification process	1
regulation of protein deacetylation	1
negative regulation of developmental process	1
negative regulation of multicellular organismal process	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
positive regulation of apoptotic process	1
anoikis	1
regulation of anoikis	1
gene expression	1
regulation of macromolecule biosynthetic process	1
enzyme binding	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
histone deacetylase complex	1
nuclear chromosome	1

Protein interactions and networks

STRING

972 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BRMS1	ARID4A	P29374	976
BRMS1	HDAC1	Q13547	900
BRMS1	SAP30	O75446	880
BRMS1	ARID4B	Q4LE39	842
BRMS1	SIN3A	Q96ST3	829
BRMS1	ING1	Q9UK53	824
BRMS1	ING2	Q9H160	752
BRMS1	SIN3B	O75182	735
BRMS1	SAP18	O00422	730
BRMS1	SINHCAF	Q9NP50	692
BRMS1	RBBP4	P31149	671
BRMS1	PHF12	Q96QT6	652
BRMS1	NME1	P15531	643
BRMS1	SAP30L	Q9HAJ7	641
BRMS1	RBBP7	Q16576	604

IntAct

113 interactions, top by confidence:

A	B	Type	Score
HDAC1	KDM1A	psi-mi:“MI:0914”(association)	0.910
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
POLR2E	POLR3A	psi-mi:“MI:0914”(association)	0.870
PRPS1	PRPSAP2	psi-mi:“MI:0914”(association)	0.840
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
BRMS1	HDAC1	psi-mi:“MI:0915”(physical association)	0.830
HDAC1	BRMS1	psi-mi:“MI:0915”(physical association)	0.830
BRMS1	HDAC1	psi-mi:“MI:0914”(association)	0.830
BRMS1	NMI	psi-mi:“MI:0915”(physical association)	0.790
NMI	BRMS1	psi-mi:“MI:0915”(physical association)	0.790
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
HDAC2	BRMS1	psi-mi:“MI:0915”(physical association)	0.720
BRMS1	HDAC2	psi-mi:“MI:0915”(physical association)	0.720
BRMS1	CEP70	psi-mi:“MI:0915”(physical association)	0.670
CEP70	BRMS1	psi-mi:“MI:0915”(physical association)	0.670
BRMS1	SMARCE1	psi-mi:“MI:0915”(physical association)	0.650
SMARCE1	BRMS1	psi-mi:“MI:0915”(physical association)	0.650
FOXK2	DVL2	psi-mi:“MI:0914”(association)	0.640

BioGRID (157): BRMS1 (Two-hybrid), CEP70 (Two-hybrid), BRMS1 (Affinity Capture-Western), SNX6 (Two-hybrid), BRMS1 (Reconstituted Complex), BRMS1 (FRET), E2F1 (Two-hybrid), SUDS3 (Two-hybrid), SIN3A (Affinity Capture-Western), SIN3B (Affinity Capture-Western), SAP30 (Affinity Capture-Western), HDAC1 (Affinity Capture-Western), HDAC2 (Affinity Capture-Western), RBBP7 (Affinity Capture-Western), RBBP4 (Affinity Capture-Western)

ESM2 similar proteins: A0PJP4, A2VDP1, A4FV29, A4II71, E9PSK7, F1RCP1, O00472, O60271, Q0IHE5, Q15545, Q1LZE0, Q28DG8, Q2HJG8, Q2TBQ7, Q3U1T3, Q498D5, Q4R5A5, Q4V8V1, Q58A65, Q5DTM8, Q5EA95, Q5M7T3, Q5PSV4, Q5R6Y9, Q5R7L9, Q5RHQ8, Q5VTR2, Q5ZKF4, Q5ZLL9, Q5ZLS3, Q62739, Q68CZ1, Q6AZT4, Q6DC03, Q6R1L1, Q7ZXA8, Q8BXG3, Q8CG73, Q8IZC4, Q8K0Q5

Diamond homologs: A4FV29, A4II71, Q1LZE0, Q3U1T3, Q4V8V1, Q5M7T3, Q5PSV4, Q5ZLL9, Q6AZT4, Q99N20, Q9HCU9

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
BRMS1	“down-regulates quantity by destabilization”	EP300	ubiquitination
BRMS1	“up-regulates activity”	KDM1A	binding
SPOP	“down-regulates quantity”	BRMS1	ubiquitination
CSNK2A1	“down-regulates quantity by destabilization”	BRMS1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 94 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
Notch-HLH transcription pathway	6	32.2×	2e-06
Regulation of TP53 Activity through Acetylation	5	30.1×	4e-05
Regulation of PTEN gene transcription	8	18.8×	2e-06
NOTCH1 Intracellular Domain Regulates Transcription	6	18.8×	4e-05
Negative epigenetic regulation of rRNA expression	5	17.1×	3e-04
Constitutive Signaling by NOTCH1 PEST Domain Mutants	6	15.5×	9e-05
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	6	15.5×	9e-05
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	8	15.4×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of stem cell population maintenance	11	93.6×	2e-17
positive regulation of stem cell population maintenance	12	45.9×	7e-15
negative regulation of gene expression, epigenetic	6	26.8×	9e-06
negative regulation of transforming growth factor beta receptor signaling pathway	11	21.2×	6e-10
negative regulation of cell migration	12	14.9×	4e-09
chromatin remodeling	10	8.1×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1694 predictions. Top by Δscore:

Variant	Effect	Δscore
11:66340769:CTTA:C	donor_loss	1.0000
11:66340770:TTA:T	donor_loss	1.0000
11:66340771:TACCA:T	donor_loss	1.0000
11:66340772:A:AC	donor_gain	1.0000
11:66340772:A:T	donor_loss	1.0000
11:66340773:C:CA	donor_gain	1.0000
11:66340773:CCA:C	donor_gain	1.0000
11:66340867:CACT:C	acceptor_gain	1.0000
11:66340869:CT:C	acceptor_gain	1.0000
11:66340870:TCTGG:T	acceptor_loss	1.0000
11:66340871:C:CC	acceptor_gain	1.0000
11:66340871:C:T	acceptor_loss	1.0000
11:66340968:T:TA	donor_gain	1.0000
11:66341531:A:AC	donor_gain	1.0000
11:66341532:C:CC	donor_gain	1.0000
11:66341532:CTT:C	donor_gain	1.0000
11:66341534:T:TA	donor_gain	1.0000
11:66342090:GCTCA:G	donor_loss	1.0000
11:66342091:CTCAC:C	donor_loss	1.0000
11:66342092:TCA:T	donor_loss	1.0000
11:66342093:CACCG:C	donor_loss	1.0000
11:66342094:A:AC	donor_gain	1.0000
11:66342095:C:CC	donor_gain	1.0000
11:66342104:T:A	donor_gain	1.0000
11:66342240:CT:C	acceptor_gain	1.0000
11:66342241:TC:T	acceptor_loss	1.0000
11:66342242:C:CC	acceptor_gain	1.0000
11:66342242:C:CG	acceptor_loss	1.0000
11:66342243:T:A	acceptor_loss	1.0000
11:66337895:CATA:C	acceptor_gain	0.9900

AlphaMissense

1618 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:66338728:A:T	I229N	0.999
11:66338741:C:G	D225H	0.999
11:66338764:A:T	L217H	0.999
11:66338740:T:A	D225V	0.998
11:66338740:T:G	D225A	0.998
11:66338764:A:G	L217P	0.998
11:66338771:A:C	Y215D	0.998
11:66338776:A:T	I213N	0.998
11:66341209:C:G	A119P	0.998
11:66341550:G:C	F71L	0.998
11:66341550:G:T	F71L	0.998
11:66341552:A:G	F71L	0.998
11:66338728:A:C	I229S	0.997
11:66338728:A:G	I229T	0.997
11:66338739:G:C	D225E	0.997
11:66338739:G:T	D225E	0.997
11:66338740:T:C	D225G	0.997
11:66341262:T:G	Y101S	0.997
11:66341319:C:G	R82P	0.997
11:66341542:A:G	L74P	0.997
11:66338732:C:G	A228P	0.996
11:66338738:A:G	W226R	0.996
11:66338738:A:T	W226R	0.996
11:66338749:A:T	I222N	0.996
11:66338776:A:C	I213S	0.996
11:66340830:A:G	L160P	0.996
11:66340971:A:G	L145P	0.996
11:66340984:C:G	A141P	0.996
11:66341551:A:G	F71S	0.996
11:66341563:A:G	L67P	0.996

dbSNP variants (sampled 300 via entrez): RS1000154130 (11:66337457 C>A,G), RS1000835117 (11:66339081 G>A), RS1001682340 (11:66337565 C>T), RS1001721048 (11:66342743 C>G), RS1002110441 (11:66341713 A>G), RS1002743634 (11:66344231 A>C), RS1002755052 (11:66344542 C>T), RS1004060281 (11:66338872 C>A,T), RS1004521001 (11:66341961 G>A), RS1004875942 (11:66341356 T>A), RS1005262491 (11:66343230 T>C), RS1005335041 (11:66341571 C>A,T), RS1005518751 (11:66339143 C>G,T), RS1005624729 (11:66342832 C>T), RS1005841023 (11:66337462 G>C)

Disease associations

OMIM: gene MIM:606259 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001241_12	Bipolar disorder	2.000000e-07
GCST008103_21	Bipolar disorder	2.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Air Pollutants	affects expression, increases abundance	2
Smoke	decreases expression, affects expression, increases abundance	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
butyraldehyde	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression	1
licochalcone B	increases expression	1
Temozolomide	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	increases phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Lead	affects expression	1
Ozone	affects expression, increases abundance	1
Piroxicam	affects cotreatment, decreases expression	1
Selenium	increases expression	1
Dronabinol	decreases expression	1
Vitamin E	increases expression	1
Metribolone	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1LQ	Abcam K-562 BRMS1 KO	Cancer cell line	Female
CVCL_D2IB	Abcam Raji BRMS1 KO	Cancer cell line	Male
CVCL_UQ22	Abcam Jurkat BRMS1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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