BABAM1

Summary

BABAM1 (BRISC and BRCA1 A complex member 1, HGNC:25008) is a protein-coding gene on chromosome 19p13.11, encoding BRISC and BRCA1-A complex member 1 (Q9NWV8). Component of the BRCA1-A complex, a complex that specifically recognizes ‘Lys-63’-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs).

Enables identical protein binding activity. Involved in several processes, including DNA repair-dependent chromatin remodeling; mitotic G2 DNA damage checkpoint signaling; and positive regulation of DNA repair. Located in cytosol and nuclear body. Part of BRCA1-A complex and BRISC complex.

Source: NCBI Gene 29086 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 61 total
• MANE Select transcript: NM_014173

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25008
Approved symbol	BABAM1
Name	BRISC and BRCA1 A complex member 1
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20571, HSPC142, NBA1, MERIT40
Ensembl gene	ENSG00000105393
Ensembl biotype	protein_coding
OMIM	612766
Entrez	29086

Gene structure

Transcript identifiers

Ensembl transcripts: 64 — 58 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000359435, ENST00000447614, ENST00000448635, ENST00000594247, ENST00000595393, ENST00000595632, ENST00000596335, ENST00000598188, ENST00000598382, ENST00000598567, ENST00000599057, ENST00000599474, ENST00000601043, ENST00000601171, ENST00000601232, ENST00000601436, ENST00000601938, ENST00000602066, ENST00000863364, ENST00000863365, ENST00000863366, ENST00000863367, ENST00000863368, ENST00000863369, ENST00000863370, ENST00000863371, ENST00000863372, ENST00000863373, ENST00000863374, ENST00000863375, ENST00000863376, ENST00000863377, ENST00000863378, ENST00000922109, ENST00000922110, ENST00000922111, ENST00000922112, ENST00000922113, ENST00000922114, ENST00000922115, ENST00000922116, ENST00000922117, ENST00000922118, ENST00000922119, ENST00000922120, ENST00000922121, ENST00000922122, ENST00000922123, ENST00000922124, ENST00000922125, ENST00000922126, ENST00000922127, ENST00000922128, ENST00000922129, ENST00000922130, ENST00000922131, ENST00000951792, ENST00000951793, ENST00000951794, ENST00000951795, ENST00000951796, ENST00000951797, ENST00000951798, ENST00000951799

RefSeq mRNA: 4 — MANE Select: NM_014173 NM_001033549, NM_001288756, NM_001288757, NM_014173

CCDS: CCDS46012, CCDS74310

Canonical transcript exons

ENST00000598188 — 9 exons

Exon	Start	End
ENSE00001562694	17267443	17267527
ENSE00003208555	17278845	17279337
ENSE00003466182	17276495	17276624
ENSE00003497605	17271597	17271655
ENSE00003510894	17268794	17269091
ENSE00003577614	17276823	17276909
ENSE00003654257	17273904	17274024
ENSE00003660372	17275801	17275825
ENSE00003784720	17274107	17274185

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 97.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 76.4381 / max 371.3286, expressed in 1825 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174473	68.5886	1824
174474	6.3360	1661
174475	1.5135	635

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	97.48	gold quality
right frontal lobe	UBERON:0002810	97.47	gold quality
anterior cingulate cortex	UBERON:0009835	97.39	gold quality
cingulate cortex	UBERON:0003027	97.34	gold quality
granulocyte	CL:0000094	97.20	gold quality
cerebellar hemisphere	UBERON:0002245	97.02	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.99	gold quality
cerebellar cortex	UBERON:0002129	96.96	gold quality
apex of heart	UBERON:0002098	96.94	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.80	gold quality
gastrocnemius	UBERON:0001388	96.75	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.65	gold quality
muscle of leg	UBERON:0001383	96.46	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.40	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.31	gold quality
amygdala	UBERON:0001876	96.31	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.31	gold quality
lower esophagus	UBERON:0013473	96.30	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.30	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.24	gold quality
cerebellum	UBERON:0002037	96.20	gold quality
frontal cortex	UBERON:0001870	96.11	gold quality
ganglionic eminence	UBERON:0004023	96.09	gold quality
neocortex	UBERON:0001950	96.07	gold quality
mucosa of transverse colon	UBERON:0004991	96.02	gold quality
body of stomach	UBERON:0001161	95.98	gold quality
right adrenal gland	UBERON:0001233	95.96	gold quality
right adrenal gland cortex	UBERON:0035827	95.95	gold quality
right atrium auricular region	UBERON:0006631	95.94	gold quality
body of uterus	UBERON:0009853	95.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8060	no	105.71
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting BABAM1, 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-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-18A-5P	99.29	71.05	806
HSA-MIR-18B-5P	99.29	71.05	806
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-4735-3P	99.14	69.85	777
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-6841-3P	98.08	66.54	604
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-5704	94.82	67.46	448

Literature-anchored findings (GeneRIF, showing 12)

• MERIT40 represents a novel factor that links BRCA1-Rap80 complex integrity, DSB recognition, and ubiquitin chain hydrolytic activities to the DNA damage response. (PMID:19261746)
• A stable complex containing MERIT40 acts early in DNA damage response and regulates damage-dependent BRCA1 localization. (PMID:19261748)
• NBA1 is required to maintain BRE and Abra1 abundance and for the recruitment of BRCA1 to sites of DNA damage. In depth bioinformatics analysis revealed that the BRCA1 A complex bears striking similarities to the 19S proteasome complex. (PMID:19261749)
• germline mutations in MERIT40 are rare or absent in familial breast cancer patients. (PMID:19572197)
• Single nucleotide polymorphism in MERIT40 is associated with ovarian cancer. (PMID:20852633)
• NBA1/MERIT40 and BRE interaction is required for the integrity of two distinct deubiquitinating enzyme BRCC36-containing complexes (PMID:21282113)
• findings suggest that germline deleterious mutations in C19orf62 should be rare or absent in familial and nonfamilial breast cancer women (PMID:21431873)
• MERIT40 interacts with ABRAXAS which is adaptor molecule of BRCA1-complex. (PMID:24667604)
• Genetic variants in NBA1 may be an important genetic determinant of triple-negative breast cancer susceptibility. (PMID:26848770)
• Mutation of the RXXPEG motif in the MERIT40 (R28A) disrupted its interaction with TNKS1 and R28A mutant cells displayed multiple mitotic defects including aberrant spindle assembly and chromosome misalignment. (PMID:30571846)
• Phosphoproteomic Analysis Defines BABAM1 as mTORC2 Downstream Effector Promoting DNA Damage Response in Glioblastoma Cells. (PMID:36315652)
• WWOX binds MERIT40 and modulates its function in homologous recombination, implications in breast cancer. (PMID:37248434)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	babam1	ENSDARG00000077526
mus_musculus	Babam1	ENSMUSG00000031820
rattus_norvegicus	Babam1	ENSRNOG00000017071

Protein

Protein identifiers

BRISC and BRCA1-A complex member 1 — Q9NWV8 (reviewed: Q9NWV8)

Alternative names: Mediator of RAP80 interactions and targeting subunit of 40 kDa, New component of the BRCA1-A complex

All UniProt accessions (12): Q9NWV8, J3KQS6, M0QXG9, M0QYV1, M0QZ44, M0R0I0, M0R193, M0R2A4, M0R2I2, M0R2K3, M0R3F4, M0R3H9

UniProt curated annotations — full annotation on UniProt →

Function. Component of the BRCA1-A complex, a complex that specifically recognizes ‘Lys-63’-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes ‘Lys-63’-linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it is required for the complex integrity and its localization at DSBs. Component of the BRISC complex, a multiprotein complex that specifically cleaves ‘Lys-63’-linked ubiquitin in various substrates. In these 2 complexes, it is probably required to maintain the stability of BABAM2 and help the ‘Lys-63’-linked deubiquitinase activity mediated by BRCC3/BRCC36 component. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1. Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and cell surface expression. Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination.

Subunit / interactions. Component of the ARISC complex, at least composed of UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. In the BRCA1-A complex, interacts directly with ABRAXAS1 and BABAM2. Component of the BRISC complex, at least composed of ABRAXAS2, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Identified in a complex with SHMT2 and the other subunits of the BRISC complex.

Subcellular location. Cytoplasm. Nucleus.

Domain organisation. The VWFA-like region is similar to the VWFA domain. Its presence reveals similarities between the structure of the 19S proteasome and the BRCA1-A complexes.

Similarity. Belongs to the BABAM1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NWV8-1	1	yes
Q9NWV8-2	2
Q9NWV8-3	3

RefSeq proteins (4): NP_001028721, NP_001275685, NP_001275686, NP_054892* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026126	BABAM1	Family
IPR036465	vWFA_dom_sf	Homologous_superfamily

UniProt features (42 total): helix 10, strand 9, modified residue 8, splice variant 4, turn 4, sequence conflict 3, region of interest 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8PVY	ELECTRON MICROSCOPY	3.02
8PY2	ELECTRON MICROSCOPY	3.32
6H3C	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NWV8-F1	79.21	0.60

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 (8): 65, 66, 1, 8, 29, 49, 57, 62

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-5689901	Metalloprotease DUBs
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693571	Nonhomologous End-Joining (NHEJ)
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-69473	G2/M DNA damage checkpoint
R-HSA-1640170	Cell Cycle
R-HSA-392499	Metabolism of proteins
R-HSA-5688426	Deubiquitination
R-HSA-5693532	DNA Double-Strand Break Repair
R-HSA-5693538	Homology Directed Repair
R-HSA-5693567	HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)
R-HSA-5693606	DNA Double Strand Break Response
R-HSA-597592	Post-translational protein modification
R-HSA-69481	G2/M Checkpoints
R-HSA-69620	Cell Cycle Checkpoints
R-HSA-73894	DNA Repair

MSigDB gene sets: 191 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_IONIZING_RADIATION, GCM_GSPT1, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, GOBP_CELL_CYCLE_PHASE_TRANSITION, AACYNNNNTTCCS_UNKNOWN, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_MITOTIC_G2_M_TRANSITION_CHECKPOINT, GOBP_STEM_CELL_PROLIFERATION, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_HEMATOPOIETIC_STEM_CELL_PROLIFERATION, GOBP_REGULATION_OF_CELL_CYCLE

GO Biological Process (12): regulation of DNA repair (GO:0006282), double-strand break repair (GO:0006302), mitotic G2 DNA damage checkpoint signaling (GO:0007095), response to ionizing radiation (GO:0010212), mitotic G2/M transition checkpoint (GO:0044818), positive regulation of DNA repair (GO:0045739), cell division (GO:0051301), hematopoietic stem cell proliferation (GO:0071425), DNA repair-dependent chromatin remodeling (GO:0140861), DNA repair (GO:0006281), chromatin organization (GO:0006325), DNA damage response (GO:0006974)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear body (GO:0016604), BRCA1-A complex (GO:0070531), BRISC complex (GO:0070552)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
DNA Double-Strand Break Repair	3
Deubiquitination	1
DNA Double Strand Break Response	1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1
G2/M Checkpoints	1
Post-translational protein modification	1
DNA Repair	1
Homology Directed Repair	1
Metabolism of proteins	1
Cell Cycle Checkpoints	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA repair	3
cellular anatomical structure	3
DNA damage response	2
nuclear protein-containing complex	2
regulation of DNA metabolic process	1
regulation of cellular response to stress	1
mitotic G2 phase	1
mitotic DNA damage checkpoint signaling	1
mitotic G2/M transition checkpoint	1
response to radiation	1
mitotic cell cycle checkpoint signaling	1
negative regulation of G2/M transition of mitotic cell cycle	1
regulation of DNA repair	1
positive regulation of response to stimulus	1
positive regulation of DNA metabolic process	1
cellular process	1
hemopoiesis	1
stem cell proliferation	1
chromatin remodeling	1
DNA metabolic process	1
cellular component organization	1
cellular response to stress	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
nucleoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1370 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BABAM1	BABAM2	Q9NXR7	998
BABAM1	BRCC3	P46736	998
BABAM1	UIMC1	Q96RL1	998
BABAM1	ABRAXAS1	Q6UWZ7	997
BABAM1	ABRAXAS2	Q15018	992
BABAM1	BRCA1	P38398	992
BABAM1	BARD1	Q99728	986
BABAM1	BRCA2	P51587	713
BABAM1	RBBP8	Q99708	710
BABAM1	PSMD4	P55036	669
BABAM1	RAD51	Q06609	656
BABAM1	ANKLE1	Q8NAG6	622
BABAM1	TNKS	O95271	621
BABAM1	RNF8	O76064	621
BABAM1	ABHD8	Q96I13	620

IntAct

84 interactions, top by confidence:

A	B	Type	Score
BABAM2	BABAM1	psi-mi:“MI:0915”(physical association)	0.920
BABAM1	BABAM2	psi-mi:“MI:0915”(physical association)	0.920
BABAM1	BABAM2	psi-mi:“MI:2364”(proximity)	0.920
BRCA1	ABRAXAS1	psi-mi:“MI:0914”(association)	0.860
BABAM1	TRIM27	psi-mi:“MI:0915”(physical association)	0.780
TRIM27	BABAM1	psi-mi:“MI:0915”(physical association)	0.780
BABAM1	TNKS2	psi-mi:“MI:0407”(direct interaction)	0.760
BABAM1	TNKS2	psi-mi:“MI:0915”(physical association)	0.760
BABAM1	TNKS	psi-mi:“MI:0914”(association)	0.640
STK11	KDM4A	psi-mi:“MI:0914”(association)	0.640
DEF6	ARHGAP42	psi-mi:“MI:0914”(association)	0.530
SPATA2	CASK	psi-mi:“MI:0914”(association)	0.530
TNS1	SORBS3	psi-mi:“MI:0914”(association)	0.530
PNOC	CETN3	psi-mi:“MI:0914”(association)	0.530
C9orf85	BRCC3	psi-mi:“MI:0914”(association)	0.530

BioGRID (232): BABAM1 (Affinity Capture-Western), BABAM1 (Two-hybrid), BABAM1 (Affinity Capture-RNA), BABAM1 (Affinity Capture-RNA), BABAM1 (Affinity Capture-MS), BRE (Affinity Capture-MS), SHMT2 (Affinity Capture-MS), TNKS2 (Affinity Capture-MS), TNKS (Affinity Capture-MS), FAM175A (Affinity Capture-MS), UIMC1 (Affinity Capture-MS), BRCC3 (Affinity Capture-MS), FAM175B (Affinity Capture-MS), BABAM1 (Affinity Capture-MS), BABAM1 (Two-hybrid)

ESM2 similar proteins: A0A0R4IES7, A0JN62, A0JNW5, A2AAE1, A2AGL3, A2RSJ4, A2RT67, A2RUS2, A2RV80, B0LPN4, B1H2P5, E7F240, E9Q401, O00507, O94967, P30957, P48553, P51593, Q14161, Q2LD37, Q3TLI0, Q3UHE1, Q3UVG3, Q3UX43, Q5F361, Q5M7Q1, Q5RAQ5, Q5ZJK1, Q658Y4, Q68CL5, Q6BDS2, Q6P6Y1, Q6TEP1, Q6VNB8, Q7TMY8, Q7TSG1, Q7Z6Z7, Q8BHY8, Q8CB44, Q8CGF6

Diamond homologs: B0KWQ2, Q08E57, Q3UI43, Q5M8J0, Q5R7L2, Q5XIJ6, Q6AXK4, Q6DJG6, Q9NWV8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
BABAM1	“form complex”	“BRCA1-A complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 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
DNA Double Strand Break Response	6	56.0×	2e-07
Metalloprotease DUBs	7	41.2×	2e-07
Homology Directed Repair	5	30.3×	3e-05
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	5	30.3×	3e-05
DNA Double-Strand Break Repair	6	29.2×	4e-06
Regulation of PTEN stability and activity	7	25.3×	1e-06
Degradation of AXIN	5	24.3×	8e-05
Nonhomologous End-Joining (NHEJ)	7	23.1×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
mitotic G2/M transition checkpoint	5	61.7×	4e-06
protein K63-linked deubiquitination	5	48.0×	7e-06
response to ionizing radiation	6	37.9×	4e-06
mitotic G2 DNA damage checkpoint signaling	5	34.1×	4e-05
positive regulation of DNA repair	6	33.1×	4e-06
regulation of DNA repair	5	21.2×	3e-04
double-strand break repair	6	18.7×	7e-05
cell division	8	5.7×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1829 predictions. Top by Δscore:

Variant	Effect	Δscore
19:17267478:G:GG	donor_gain	1.0000
19:17267502:G:GT	donor_gain	1.0000
19:17267511:GC:G	donor_gain	1.0000
19:17273899:CCCA:C	acceptor_loss	1.0000
19:17273900:CCA:C	acceptor_loss	1.0000
19:17273902:A:AG	acceptor_gain	1.0000
19:17273902:AGC:A	acceptor_loss	1.0000
19:17273903:G:GA	acceptor_gain	1.0000
19:17273903:GC:G	acceptor_gain	1.0000
19:17273903:GCT:G	acceptor_gain	1.0000
19:17273903:GCTC:G	acceptor_gain	1.0000
19:17273903:GCTCC:G	acceptor_gain	1.0000
19:17274003:G:GA	donor_gain	1.0000
19:17274019:GCC:G	donor_gain	1.0000
19:17274023:GG:G	donor_gain	1.0000
19:17274024:GG:G	donor_gain	1.0000
19:17274025:G:GG	donor_gain	1.0000
19:17274186:G:GG	donor_gain	1.0000
19:17276485:G:A	acceptor_gain	1.0000
19:17276490:T:G	acceptor_gain	1.0000
19:17276492:CA:C	acceptor_loss	1.0000
19:17276493:A:AC	acceptor_loss	1.0000
19:17276493:A:AG	acceptor_gain	1.0000
19:17276493:A:T	acceptor_loss	1.0000
19:17276494:G:GA	acceptor_gain	1.0000
19:17276494:G:GG	acceptor_gain	1.0000
19:17276494:G:T	acceptor_loss	1.0000
19:17276494:GC:G	acceptor_gain	1.0000
19:17276494:GCC:G	acceptor_gain	1.0000
19:17276494:GCCA:G	acceptor_gain	1.0000

AlphaMissense

2175 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:17273964:A:C	K135N	1.000
19:17273964:A:T	K135N	1.000
19:17271603:T:C	C98R	0.999
19:17271607:T:C	L99P	0.999
19:17273954:T:A	V132E	0.999
19:17273957:G:C	R133P	0.999
19:17273962:A:G	K135E	0.999
19:17273963:A:T	K135I	0.999
19:17273989:T:C	F144L	0.999
19:17273990:T:C	F144S	0.999
19:17273991:T:A	F144L	0.999
19:17273991:T:G	F144L	0.999
19:17273992:G:C	A145P	0.999
19:17273996:T:C	L146P	0.999
19:17274022:T:A	W155R	0.999
19:17274022:T:C	W155R	0.999
19:17276560:G:C	R212P	0.999
19:17278951:T:C	L298P	0.999
19:17278954:T:G	L299W	0.999
19:17278970:G:C	Q304H	0.999
19:17278970:G:T	Q304H	0.999
19:17273951:T:C	F131S	0.998
19:17273993:C:A	A145E	0.998
19:17274150:T:C	L170P	0.998
19:17278945:C:A	A296E	0.998
19:17278957:C:A	A300D	0.998
19:17278960:A:G	H301R	0.998
19:17278961:C:A	H301Q	0.998
19:17278961:C:G	H301Q	0.998
19:17278963:C:A	P302H	0.998

dbSNP variants (sampled 300 via entrez): RS1000099339 (19:17267599 C>G), RS1000161036 (19:17272696 G>A), RS1000297918 (19:17272828 C>T), RS1000467902 (19:17266444 G>A,C), RS1000635338 (19:17271721 G>A), RS1000746541 (19:17277895 G>A), RS1001190141 (19:17266249 G>A,T), RS1001205829 (19:17276927 G>A,T), RS1001316027 (19:17272498 C>T), RS1001499308 (19:17265995 C>A), RS1001578444 (19:17277271 G>A), RS1001827974 (19:17265900 C>A,T), RS1001903228 (19:17277573 C>G), RS1002986372 (19:17270445 T>A), RS1003016996 (19:17270296 C>G,T)

Disease associations

OMIM: gene MIM:612766 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000800_1	Ovarian cancer	4.000000e-06
GCST000801_1	Breast cancer	2.000000e-09
GCST001930_7	Breast cancer	9.000000e-13
GCST002748_5	Epithelial ovarian cancer	5.000000e-14
GCST003587_14	Cancer	4.000000e-07
GCST003588_21	Cancer (pleiotropy)	2.000000e-09
GCST003842_19	Breast cancer (estrogen-receptor negative)	1.000000e-12
GCST003845_19	Breast cancer	7.000000e-21
GCST007394_2	Mitochondrial DNA copy number	1.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:1001515	ovarian endometrioid carcinoma
EFO:1001516	ovarian serous carcinoma
EFO:0006312	mitochondrial DNA measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

Binding affinities (BindingDB)

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

Ligand	Measure	Value	Patent
Capzimin	IC50	340 nM	US-10005735: Inhibitors of RPN11

PubChem BioAssay actives

1 with measured affinity, of 1 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
8-sulfanyl-N-[2-(1,3-thiazol-2-yl)ethyl]quinoline-3-carboxamide	1802703: In Vitro BRCC36 Activity Assay from Article 10.1038/nchembio.2326: “Capzimin is a potent and specific inhibitor of proteasome isopeptidase Rpn11.”	ic50	2.3000	uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression	1
coumarin	affects phosphorylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
bisphenol B	increases expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	decreases reaction, affects binding	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Hydrogen Peroxide	increases expression	1
Ivermectin	decreases expression	1
Rotenone	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression, affects cotreatment	1
Vitamin E	increases expression	1
Cyclosporine	increases expression	1
Acrylamide	decreases expression	1
tert-Butylhydroperoxide	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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