UIMC1

Summary

UIMC1 (ubiquitin interaction motif containing 1, HGNC:30298) is a protein-coding gene on chromosome 5q35.2, encoding BRCA1-A complex subunit RAP80 (Q96RL1). Ubiquitin-binding protein.

This gene encodes a nuclear protein that interacts with Brca1 (breast cancer 1) in a complex to recognize and repair DNA lesions. This protein binds ubiquitinated lysine 63 of histone H2A and H2AX. This protein may also function as a repressor of transcription. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 51720 — RefSeq curated summary.

At a glance

• Gene–disease (curated): schizophrenia (No Known Disease Relationship, GenCC)
• GWAS associations: 11
• Clinical variants (ClinVar): 118 total — 1 likely-pathogenic
• MANE Select transcript: NM_001199298

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30298
Approved symbol	UIMC1
Name	ubiquitin interaction motif containing 1
Location	5q35.2
Locus type	gene with protein product
Status	Approved
Aliases	RAP80
Ensembl gene	ENSG00000087206
Ensembl biotype	protein_coding
OMIM	609433
Entrez	51720

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 17 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000377227, ENST00000417486, ENST00000428382, ENST00000503273, ENST00000505229, ENST00000505879, ENST00000506128, ENST00000507513, ENST00000509236, ENST00000510376, ENST00000510698, ENST00000511320, ENST00000512031, ENST00000515488, ENST00000890105, ENST00000890106, ENST00000890107, ENST00000890108, ENST00000890109, ENST00000890110, ENST00000924857, ENST00000924858, ENST00000970268, ENST00000970269

RefSeq mRNA: 4 — MANE Select: NM_001199298 NM_001199297, NM_001199298, NM_001317961, NM_016290

CCDS: CCDS4408, CCDS83050

Canonical transcript exons

ENST00000511320 — 15 exons

Exon	Start	End
ENSE00001411826	177006650	177006779
ENSE00002460641	176970742	176970866
ENSE00002526268	176969601	176969706
ENSE00003463033	176968555	176969291
ENSE00003463449	176907114	176907177
ENSE00003520924	176951474	176951577
ENSE00003532032	176958093	176958154
ENSE00003585929	176943335	176943488
ENSE00003601408	176982469	176982623
ENSE00003656042	176906011	176906047
ENSE00003664652	176908523	176908694
ENSE00003664748	176955959	176956035
ENSE00003668468	176975396	176975480
ENSE00003747101	176911311	176911389
ENSE00003844424	176905006	176905492

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 96.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.5483 / max 169.1686, expressed in 1796 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65063	11.0173	1782
65060	1.3038	599
65064	0.8261	450
65059	0.4615	231
65058	0.3525	166
65062	0.2712	100
65061	0.1504	49
65057	0.1161	57
65054	0.0494	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	96.87	gold quality
right testis	UBERON:0004534	96.76	gold quality
sural nerve	UBERON:0015488	96.44	gold quality
testis	UBERON:0000473	95.47	gold quality
calcaneal tendon	UBERON:0003701	94.92	gold quality
monocyte	CL:0000576	94.82	gold quality
mononuclear cell	CL:0000842	94.50	gold quality
leukocyte	CL:0000738	94.28	gold quality
left ovary	UBERON:0002119	94.26	gold quality
granulocyte	CL:0000094	93.97	gold quality
right ovary	UBERON:0002118	93.95	gold quality
colonic epithelium	UBERON:0000397	93.91	gold quality
body of uterus	UBERON:0009853	93.68	gold quality
tibial artery	UBERON:0007610	93.62	gold quality
popliteal artery	UBERON:0002250	93.61	gold quality
endocervix	UBERON:0000458	93.39	gold quality
blood	UBERON:0000178	93.35	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.19	gold quality
right lung	UBERON:0002167	93.13	gold quality
tibial nerve	UBERON:0001323	93.01	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.00	gold quality
lower esophagus	UBERON:0013473	92.98	gold quality
spleen	UBERON:0002106	92.97	gold quality
ectocervix	UBERON:0012249	92.85	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.76	gold quality
aorta	UBERON:0000947	92.75	gold quality
body of pancreas	UBERON:0001150	92.71	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.69	gold quality
cortical plate	UBERON:0005343	92.69	gold quality
ovary	UBERON:0000992	92.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.07

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NCOR1, NR6A1, TP53

miRNA regulators (miRDB)

26 targeting UIMC1, 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-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-5694	97.06	67.70	682
HSA-MIR-632	96.08	67.17	798
HSA-MIR-1231	95.10	65.63	663

Literature-anchored findings (GeneRIF, showing 40)

• a novel nuclear protein that interacts with the retinoid-related testis-associated receptor (PMID:12080054)
• Abraxas and RAP80 were required for DNA damage resistance, G(2)-M checkpoint control, and DNA repair. (PMID:17525340)
• data support a model wherein ubiquitin chains at DNA damage sites are used as a targeting mechanism by specific BRCA1 complexes; RAP80 may represent a new class of DNA repair proteins that uses tandem UIM domains as part of its recruitment to DSBs (PMID:17525341)
• identification of receptor-associated protein 80 (RAP80) as a BRCA1-interacting protein in humans (PMID:17525342)
• RAP80/UIMC1, the protein highly expressed in testis, was identified as a new cancer-associated antigen. (PMID:17562356)
• the ubiquitin-interacting motif containing protein RAP80 interacts with BRCA1 and functions in DNA damage repair response (PMID:17621610)
• RAP80 interacts with the SUMO-conjugating enzyme UBC9 and is a novel target for sumoylation (PMID:17698038)
• the human Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage (PMID:18077395)
• Mutational analysis in 168 multiple-case breast/ovarian cancer families, negative for mutations in BRCA1 or BRCA2, suggests that RAP80 does not play an important role as a high penetrance breast cancer susceptibility gene. (PMID:18270812)
• Truncating mutations of the RAP80 gene do not seem to be a cause of familial breast cancer. A novel RAP80 haplotype or rare missense mutations (p.Ala342Thr, p.Met353Thr and p.Tyr575Asp) may be associated with a modest increased risk of breast cancer. (PMID:18306035)
• UV irradiation induces translocation of RAP80 to DNA damage foci that colocalize with gamma-H2AX (PMID:18519686)
• Depletion of RAP80 or RNF8 impairs the translocation of BRCA1 to DNA damage sites and results in defective cell cycle checkpoint control and DSB repair (PMID:18550271)
• it seems unlikely that moderate to highly penetrant alleles of either RAP80 or Abraxas, confer a significantly high relative risk of breast cancer. (PMID:18695986)
• 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)
• critical constitutional mutations in RAP80 abrogate DNA damage responses (DDR) function and may be involved in genetic predisposition to cancer. (PMID:19305427)
• findings show how the sequence between the Rap80 ubiquitin interacting motifs positions the domains for efficient avid polyubiquitin binding across a single K63 linkage, thus defining selectivity (PMID:19328070)
• RAP80 was a significant factor for survival in patients treated according to BRCA1 levels (PMID:19415121)
• Data show that it can function in an autoregulatory loop consisting of RAP80, HDM2, and the p53 master regulatory network, implpying an important role for this loop in genome stability and oncogenesis. (PMID:19433585)
• a model in which the BRCA1-RAP80 complex limits nuclease accessibility to DSBs, thus preventing excessive end resection and potentially deleterious homology-directed DSB repair mechanisms that can impair genome integrity. (PMID:21335604)
• RAP80/BRCA1 complexes suppress excessive double-strand break end processing, HR-type double-strand break repair, and overt chromosomal instability (PMID:21406551)
• The interaction between MDC1 and RAP80 requires the tandem BRCT domain of MDC1 and the ubiquitin-interacting motifs of RAP80 (PMID:21622030)
• MDC1 is required for the recruitment of RAP80 to DNA double-strand breaks. (PMID:21857162)
• APC/C(Cdc20) or APC/C(Cdh1) complexes regulate RAP80 stability during mitosis to the G(1) phase, and these events are critical for a novel function of RAP80 in mitotic progression. (PMID:22426463)
• a model in which SUMO and Ub modification is coordinated to recruit Rap80 and BRCA1 to DNA damage sites. (PMID:22689573)
• We show that RNF168, its paralog RNF169, RAD18, and the BRCA1-interacting RAP80 protein accumulate at DNA double strand break sites through the use of bipartite modules composed of ubiquitin binding domains. (PMID:22742833)
• Loss of RAP80 abolishes the recruitment of the BRCA1-A complex to DNA lesions in response to DNA damage. (PMID:22792303)
• connect ubiquitin- and SUMO-dependent DSB recognition, revealing that RNF4-synthesized hybrid SUMO-ubiquitin chains are recognized by RAP80 to promote BRCA1 recruitment and DNA repair. (PMID:23211528)
• post-translational phosphorylation of RAP80 by the Cdk1-cyclin B(1) complex is important for RAP80 functional sensitivity to IR and G(2)/M checkpoint control. (PMID:23264621)
• Data indicate that a single point deletion (DeltaE81) in RAP80 abrogates multivalent interactions with polyubiquitin. (PMID:24627472)
• A new role of FANCG in Homologous recombination repair of interstrand crosslinks through K63Ub-mediated interaction with the Rap80-BRCA1 complex. (PMID:25132264)
• patients with low RAP80 expression received gemcitabine/cisplatin, those with intermediate/high RAP80 expression and low/intermediate BRCA1 expression received docetaxel/cisplatin (PMID:25164908)
• Impaired TIP60-mediated H4K16 acetylation accounts for the aberrant chromatin accumulation of 53BP1 and RAP80 in Fanconi anemia pathway-deficient cells. (PMID:26446986)
• Data suggest that RAP80 SIM (SUMO interacting motif) binds SUMO-2; both specificity and affinity are enhanced through phosphorylation of canonical CK2 (casein kinase 2) site within the SIM. (PMID:26719330)
• RAP80 is a critical gatekeeper in impeding epithelial-mesenchymal transition-induced metastasis and malignant phenotypes of cancer as well as preserving DNA integrity. (PMID:26748910)
• TRAIP/RNF206 is required for recruitment of RAP80 to sites of DNA damage.( (PMID:26781088)
• Low RAP80 mRNA expression correlates with sporadic high-grade serous ovarian carcinoma. (PMID:27443420)
• RAP80-BRCA1 complex foci formation is regulated by USP13.USP13 interacts with and deubiquitinates RAP80.RAP80 role in the DNA damage response. (PMID:28569838)
• The RAP80 deficiency reduces the protein level of p32 and p32 dependent mitochondrial translating proteins such as Rieske and COX1. (PMID:28842250)
• RAP80 positively regulated the stability of USP13 to promote cell proliferation of esophageal cancer cells. (PMID:29396516)
• Here we show that in the BRCA1-A complex structure, ABRAXAS integrates the DNA repair protein RAP80 and provides a high-affinity binding site that sequesters the tumor suppressor BRCA1 away from the break site. In the BRISC structure, ABRO1 binds SHMT2alpha, a metabolic enzyme enabling cancer growth in hypoxic environments, which we find prevents BRCC36 from binding and cleaving ubiquitin chains (PMID:31253574)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000091187
mus_musculus	Uimc1	ENSMUSG00000025878
rattus_norvegicus	Uimc1	ENSRNOG00000016891

Protein

Protein identifiers

BRCA1-A complex subunit RAP80 — Q96RL1 (reviewed: Q96RL1)

Alternative names: Receptor-associated protein 80, Retinoid X receptor-interacting protein 110, Ubiquitin interaction motif-containing protein 1

All UniProt accessions (5): Q96RL1, D6R9M3, D6RC40, D6RCQ3, D6RDZ5

UniProt curated annotations — full annotation on UniProt →

Function. Ubiquitin-binding protein. Specifically recognizes and binds ‘Lys-63’-linked ubiquitin (PubMed:19328070, Ref.38). Plays a central role in the BRCA1-A complex by specifically binding ‘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. Also weakly binds monoubiquitin but with much less affinity than ‘Lys-63’-linked ubiquitin. May interact with monoubiquitinated histones H2A and H2B; the relevance of such results is however unclear in vivo. Does not bind Lys-48’-linked ubiquitin. May indirectly act as a transcriptional repressor by inhibiting the interaction of NR6A1 with the corepressor NCOR1.

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 the BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. In the BRCA1-A complex, interacts directly with ABRAXAS1. Interacts with UBE2I. Interacts with NR6A1. Interacts with ESR1. Interacts with TSP57. Interacts with TRAIP.

Subcellular location. Nucleus.

Tissue specificity. Expressed in testis, ovary, thymus and heart. Expressed in germ cells of the testis.

Post-translational modifications. Sumoylated. Phosphorylated upon DNA damage by ATM or ATR.

Domain organisation. The tandem UIM domains form a continuous 60 Angstrom-long alpha-helix and mediate binding to ‘Lys-63’-linked ubiquitins. UIM1 and UIM2 bind to the proximal and distal ubiquitin moieties and recognize an ‘Ile-44’-centered hydrophobic patch. Since UIMs don’t interact with the ‘Lys-63’ isopeptide bond the UIM-linker region between the 2 UIM domains determines the selectivity for ‘Lys-63’-linkage, and its length is very important for specificity. The Abraxas-interacting region (AIR) mediates the interaction with ABRAXAS1.

Similarity. Belongs to the RAP80 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q96RL1-1	1	yes
Q96RL1-2	2
Q96RL1-3	3, XHRIP110
Q96RL1-4	4, X2HRIP110
Q96RL1-5	5

RefSeq proteins (4): NP_001186226, NP_001186227, NP_001304890, NP_057374 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003903	UIM_dom	Conserved_site
IPR006642	Rad18_UBZ4	Domain
IPR038868	RAP80	Family
IPR040714	RAP80_UIM	Domain

Pfam: PF18282

UniProt features (99 total): cross-link 18, mutagenesis site 16, region of interest 13, modified residue 13, compositionally biased region 8, sequence conflict 8, splice variant 6, sequence variant 5, binding site 4, domain 2, helix 2, chain 1, short sequence motif 1, zinc finger region 1, strand 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2MKF	SOLUTION NMR
2MKG	SOLUTION NMR
2N9E	SOLUTION NMR
2RR9	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96RL1-F1	55.94	0.13

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 505; 508; 520; 524

Post-translational modifications (31): 29, 44, 46, 101, 140, 205, 379, 402, 419, 466, 627, 653, 677, 20, 31, 75, 90, 188, 245, 382 …

Mutagenesis-validated functional residues (16):

Position	Phenotype
9	does not affect symoylation; when associated with a-19; a-31; a-52 and a-61.
19	does not affect symoylation; when associated with a-9; a-31; a-52 and a-61.
31	does not affect symoylation; when associated with a-9; a-19; a-52 and a-61.
52	does not affect symoylation; when associated with a-9; a-19; a-31 and a-61.
61	does not affect symoylation; when associated with a-9; a-19; a-31 and a-52.
81	strongly reduces ubiquitin binding via uim 1.
88	impairs localization to dna damages sites; when associated with a-92; s-113 and a-117.
92	impairs localization to dna damages sites; when associated with s-88; s-113 and a-117.
97–103	impairs the selectivity for ‘k-63’-linked ubiquitin.
97–103	increases the selectivity for ‘k-63’-linked ubiquitin.
101	slightly impairs the selectivity for ‘k-63’-linked ubiquitin.
113	impairs ubiquitin-binding and localization to dna damages sites; when associated with s-88; a-92 and a-117.
117	impairs ubiquitin-binding and localization to dna damages sites; when associated with s-88; a-92 and s-113.
205	abolishes phosphorylation at this position.
508	abolishes interaction with histone monoubiquitinated h2b without affecting the interaction with h2a.

Function

Pathways and Gene Ontology

Reactome pathways

5 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

MSigDB gene sets: 197 (showing top): GOBP_RESPONSE_TO_IONIZING_RADIATION, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, GOBP_CELL_CYCLE_PHASE_TRANSITION, CACCAGC_MIR138, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_MITOTIC_G2_M_TRANSITION_CHECKPOINT, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_MITOTIC_G2_DNA_DAMAGE_CHECKPOINT_SIGNALING, GOBP_NEGATIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_DNA_DAMAGE_RESPONSE, GOBP_RESPONSE_TO_RADIATION

GO Biological Process (11): 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), negative regulation of DNA-templated transcription (GO:0045892), DNA repair-dependent chromatin remodeling (GO:0140861), DNA repair (GO:0006281), chromatin organization (GO:0006325), DNA damage response (GO:0006974)

GO Molecular Function (7): DNA binding (GO:0003677), zinc ion binding (GO:0008270), histone binding (GO:0042393), ubiquitin-modified histone reader activity (GO:0061649), K63-linked polyubiquitin modification-dependent protein binding (GO:0070530), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604), site of double-strand break (GO:0035861), BRCA1-A complex (GO:0070531)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Deubiquitination	1
DNA Double Strand Break Response	1
DNA Double-Strand Break Repair	1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1
G2/M Checkpoints	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA repair	3
DNA damage response	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
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
chromatin remodeling	1
DNA metabolic process	1
cellular component organization	1
cellular response to stress	1
nucleic acid binding	1
transition metal ion binding	1
protein binding	1
ubiquitin-modified protein reader activity	1
histone reader activity	1
polyubiquitin modification-dependent protein binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nucleoplasm	1
intracellular membraneless organelle	1
site of DNA damage	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

2786 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UIMC1	BRCC3	P46736	999
UIMC1	ABRAXAS1	Q6UWZ7	999
UIMC1	BABAM1	Q9NWV8	998
UIMC1	BABAM2	Q9NXR7	997
UIMC1	BRCA1	P38398	997
UIMC1	BARD1	Q99728	996
UIMC1	MDC1	Q14676	978
UIMC1	TP53BP1	Q12888	949
UIMC1	RNF8	O76064	946
UIMC1	RNF168	Q8IYW5	887
UIMC1	H2AX	P16104	884
UIMC1	RBBP8	Q99708	881
UIMC1	H2AC20	Q16777	874
UIMC1	H2AC19	P20670	874
UIMC1	ABRAXAS2	Q15018	832

IntAct

62 interactions, top by confidence:

A	B	Type	Score
ABRAXAS1	BRCA1	psi-mi:“MI:0914”(association)	0.860
BRCA1	ABRAXAS1	psi-mi:“MI:0914”(association)	0.860
BRCA1	UIMC1	psi-mi:“MI:0914”(association)	0.780
BRCA1	UIMC1	psi-mi:“MI:0403”(colocalization)	0.780
UIMC1	BRCA1	psi-mi:“MI:0914”(association)	0.780
BRCA1	UIMC1	psi-mi:“MI:0915”(physical association)	0.780
UIMC1	BRCA1	psi-mi:“MI:0407”(direct interaction)	0.780
UIMC1	BRCA1	psi-mi:“MI:0915”(physical association)	0.780
ABRAXAS1	UIMC1	psi-mi:“MI:0915”(physical association)	0.680
UIMC1	ABRAXAS1	psi-mi:“MI:0915”(physical association)	0.680
UIMC1	DVL2	psi-mi:“MI:0915”(physical association)	0.670
DVL2	UIMC1	psi-mi:“MI:0915”(physical association)	0.670
BRCA1	BRCA1	psi-mi:“MI:0914”(association)	0.650
COMMD8	VPS26C	psi-mi:“MI:0914”(association)	0.640
BABAM1	TNKS	psi-mi:“MI:0914”(association)	0.640
SPATA2	CASK	psi-mi:“MI:0914”(association)	0.530
UIMC1	TP53BP1	psi-mi:“MI:0403”(colocalization)	0.450
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
UIMC1	RIOX2	psi-mi:“MI:0915”(physical association)	0.400
BLM	UIMC1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (330): UIMC1 (Affinity Capture-Western), FANCG (Reconstituted Complex), HIST2H2AC (Reconstituted Complex), FANCG (FRET), UIMC1 (Affinity Capture-RNA), UIMC1 (Affinity Capture-RNA), UIMC1 (Affinity Capture-RNA), UIMC1 (Affinity Capture-MS), UBC (Reconstituted Complex), UBC (Reconstituted Complex), UBC (Reconstituted Complex), UBC (Reconstituted Complex), UIMC1 (Affinity Capture-MS), UIMC1 (Proximity Label-MS), UIMC1 (Two-hybrid)

ESM2 similar proteins: A0P8Z5, B0KYV5, B1WC58, B2RYR0, F1LR10, F6SNN2, O75128, O75410, P51826, P61590, P61591, P61592, P61593, P61594, Q3USH1, Q501R9, Q5IFK1, Q5PQK4, Q5R8C5, Q5SU73, Q5SWA1, Q5U5Q9, Q6NZF1, Q6P1D7, Q6P7W0, Q6PJW8, Q6Y685, Q6ZSG2, Q6ZVT6, Q7TT79, Q80XI1, Q80XJ2, Q80YR6, Q86T90, Q8BFU3, Q8C9B9, Q8IY92, Q8IYW5, Q8ND24, Q8NEM0

Diamond homologs: A0P8Z5, Q5PQK4, Q5U5Q9, Q96RL1, A0JM80

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
UIMC1	up-regulates	BRCA1	binding
UIMC1	“form complex”	“BRCA1-A complex”	binding
BLM	“up-regulates activity”	UIMC1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 55 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	66.4×	1e-08
Homology Directed Repair	7	50.2×	4e-09
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	7	50.2×	4e-09
Metalloprotease DUBs	6	41.9×	2e-07
DNA Double-Strand Break Repair	7	40.4×	1e-08
Nonhomologous End-Joining (NHEJ)	9	35.1×	3e-10
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	10	34.0×	4e-11
Processing of DNA double-strand break ends	11	29.2×	3e-11

GO biological processes:

GO term	Partners	Fold	FDR
mitotic G2/M transition checkpoint	5	78.7×	4e-07
positive regulation of DNA repair	8	56.2×	4e-10
mitotic G2 DNA damage checkpoint signaling	6	52.2×	3e-07
response to ionizing radiation	6	48.4×	3e-07
cellular response to ionizing radiation	5	40.3×	7e-06
regulation of DNA repair	6	32.5×	2e-06
double-strand break repair	7	27.9×	4e-07
double-strand break repair via homologous recombination	6	18.4×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	83
Likely benign	6
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
546991	NM_001199298.2(UIMC1):c.1677-1G>A	Likely pathogenic

SpliceAI

3297 predictions. Top by Δscore:

Variant	Effect	Δscore
5:176907108:CCTCA:C	donor_loss	1.0000
5:176907109:CTCA:C	donor_loss	1.0000
5:176907110:TCA:T	donor_loss	1.0000
5:176907111:CA:C	donor_loss	1.0000
5:176907112:A:AC	donor_gain	1.0000
5:176907112:ACC:A	donor_loss	1.0000
5:176907113:C:CC	donor_gain	1.0000
5:176907173:TTTTC:T	acceptor_gain	1.0000
5:176907174:TTTC:T	acceptor_gain	1.0000
5:176907175:TTC:T	acceptor_gain	1.0000
5:176907176:TC:T	acceptor_gain	1.0000
5:176907177:CC:C	acceptor_gain	1.0000
5:176907178:C:CC	acceptor_gain	1.0000
5:176907180:G:GC	acceptor_gain	1.0000
5:176907184:C:CT	acceptor_gain	1.0000
5:176907185:A:T	acceptor_gain	1.0000
5:176908519:ATACC:A	donor_loss	1.0000
5:176908520:TACC:T	donor_loss	1.0000
5:176908695:CTAT:C	acceptor_loss	1.0000
5:176908696:T:A	acceptor_loss	1.0000
5:176908699:CCAA:C	acceptor_gain	1.0000
5:176908700:C:T	acceptor_gain	1.0000
5:176908700:CAA:C	acceptor_gain	1.0000
5:176908701:A:T	acceptor_gain	1.0000
5:176908702:A:AC	acceptor_gain	1.0000
5:176911306:CTTA:C	donor_gain	1.0000
5:176911309:A:AC	donor_gain	1.0000
5:176911310:C:CC	donor_gain	1.0000
5:176951475:T:TA	donor_gain	1.0000
5:176951481:T:C	donor_gain	1.0000

AlphaMissense

4752 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:176968923:A:G	W278R	0.995
5:176968923:A:T	W278R	0.995
5:176968835:A:G	L307P	0.994
5:176968909:G:C	F282L	0.994
5:176968909:G:T	F282L	0.994
5:176968911:A:G	F282L	0.994
5:176970762:C:G	A113P	0.994
5:176968908:A:G	C283R	0.993
5:176968880:T:G	Y292S	0.992
5:176968920:C:G	G279R	0.992
5:176943419:A:G	C505R	0.991
5:176968881:A:C	Y292D	0.991
5:176968906:G:C	C283W	0.991
5:176968921:C:A	W278C	0.991
5:176968921:C:G	W278C	0.991
5:176968848:A:C	Y303D	0.990
5:176968881:A:G	Y292H	0.990
5:176968868:A:T	I296N	0.989
5:176968913:G:T	P281Q	0.989
5:176968856:A:G	L300S	0.988
5:176968868:A:C	I296S	0.988
5:176968868:A:G	I296T	0.988
5:176970813:C:G	A96P	0.988
5:176908684:A:G	C563R	0.987
5:176968865:A:G	L297P	0.987
5:176970833:A:G	L89P	0.987
5:176968844:T:G	Q304P	0.986
5:176968827:C:G	A310P	0.985
5:176970837:C:G	A88P	0.985
5:176970839:A:G	L87P	0.985

dbSNP variants (sampled 300 via entrez): RS1000005031 (5:176978043 C>G), RS1000064219 (5:176930603 T>C), RS1000081679 (5:176950955 C>A), RS1000091660 (5:176979802 T>C), RS1000094703 (5:176911490 T>C), RS1000108390 (5:176983653 AC>A), RS1000122813 (5:176923143 G>A), RS1000142406 (5:177011238 T>C), RS1000166821 (5:177001133 A>G), RS1000191865 (5:176972351 G>A), RS1000223470 (5:176963442 A>G), RS1000225962 (5:176950180 A>C), RS1000240271 (5:177023456 A>G), RS1000291104 (5:176985198 G>A), RS1000385841 (5:176989465 G>C,T)

Disease associations

OMIM: gene MIM:609433 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
schizophrenia	No Known Disease Relationship	Unknown

Mondo (2): intellectual disability (MONDO:0001071), schizophrenia (MONDO:0005090)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000403_6	Menarche and menopause (age at onset)	8.000000e-14
GCST001381_15	Menopause (age at onset)	9.000000e-32
GCST001574_7	Activated partial thromboplastin time	6.000000e-88
GCST005312_43	Menopause (age at onset)	2.000000e-11
GCST005312_44	Menopause (age at onset)	1.000000e-33
GCST005863_15	Menopause (age at onset)	9.000000e-14
GCST005956_15	Waist-to-hip ratio adjusted for BMI	1.000000e-07
GCST005957_13	Waist-to-hip ratio adjusted for BMI (age <50)	3.000000e-07
GCST005962_42	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-08
GCST009158_5	Uterine fibroids	1.000000e-11
GCST012226_65	Waist circumference adjusted for body mass index	4.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004704	age at menopause
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases expression, affects cotreatment, increases abundance, affects expression	3
Cyclosporine	increases expression	3
Doxorubicin	increases phosphorylation, decreases expression	2
Ozone	affects cotreatment, increases expression, increases abundance, affects expression	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	increases methylation	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
isobutyl alcohol	increases abundance, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CPG-oligonucleotide	increases expression	1
K 7174	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	affects cotreatment, decreases expression	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Arsenic	increases mutagenesis	1
Benzo(a)pyrene	increases expression	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	increases expression, decreases response to substance	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TW29	HAP1 UIMC1 (-) 1	Cancer cell line	Male
CVCL_TW30	HAP1 UIMC1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety