RMI1

Summary

RMI1 (RecQ mediated genome instability 1, HGNC:25764) is a protein-coding gene on chromosome 9q21.32, encoding RecQ-mediated genome instability protein 1 (Q9H9A7). Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. It is a selective cancer dependency (DepMap: 69.6% of cell lines).

Predicted to enable nucleotide binding activity. Involved in double-strand break repair via homologous recombination and resolution of DNA recombination intermediates. Located in nuclear body. Part of RecQ family helicase-topoisomerase III complex.

Source: NCBI Gene 80010 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 90 total — 1 likely-pathogenic
• Cancer dependency (DepMap): dependent in 69.6% of screened cell lines
• MANE Select transcript: NM_001358291

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25764
Approved symbol	RMI1
Name	RecQ mediated genome instability 1
Location	9q21.32
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12888, BLAP75
Ensembl gene	ENSG00000178966
Ensembl biotype	protein_coding
OMIM	610404
Entrez	80010

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 19 protein_coding

ENST00000325875, ENST00000445877, ENST00000891301, ENST00000891302, ENST00000891303, ENST00000891304, ENST00000891305, ENST00000915823, ENST00000915824, ENST00000915825, ENST00000915826, ENST00000915827, ENST00000915828, ENST00000915829, ENST00000915830, ENST00000915831, ENST00000915832, ENST00000915833, ENST00000957676

RefSeq mRNA: 5 — MANE Select: NM_001358291 NM_001358291, NM_001358292, NM_001358293, NM_001358294, NM_024945

CCDS: CCDS6669

Canonical transcript exons

ENST00000445877 — 3 exons

Exon	Start	End
ENSE00001268135	83999709	83999797
ENSE00001679630	83980805	83980891
ENSE00001948511	84000951	84004074

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 94.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.0988 / max 107.5606, expressed in 1618 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97099	8.0988	1618

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	94.55	gold quality
secondary oocyte	CL:0000655	94.00	gold quality
choroid plexus epithelium	UBERON:0003911	92.58	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.72	gold quality
bronchial epithelial cell	CL:0002328	87.61	gold quality
ventricular zone	UBERON:0003053	87.56	gold quality
embryo	UBERON:0000922	87.48	gold quality
ganglionic eminence	UBERON:0004023	87.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.66	gold quality
epithelium of bronchus	UBERON:0002031	84.60	gold quality
bronchus	UBERON:0002185	83.91	gold quality
pigmented layer of retina	UBERON:0001782	83.52	gold quality
cortical plate	UBERON:0005343	83.36	gold quality
trabecular bone tissue	UBERON:0002483	82.78	gold quality
endometrium	UBERON:0001295	81.85	gold quality
jejunal mucosa	UBERON:0000399	80.91	gold quality
corpus epididymis	UBERON:0004359	80.90	gold quality
rectum	UBERON:0001052	79.69	gold quality
gingiva	UBERON:0001828	79.35	gold quality
gingival epithelium	UBERON:0001949	79.30	gold quality
colonic mucosa	UBERON:0000317	79.13	gold quality
esophagus squamous epithelium	UBERON:0006920	78.90	gold quality
palpebral conjunctiva	UBERON:0001812	78.87	gold quality
monocyte	CL:0000576	78.82	gold quality
islet of Langerhans	UBERON:0000006	78.70	gold quality
leukocyte	CL:0000738	78.65	gold quality
mononuclear cell	CL:0000842	78.56	gold quality
mucosa of sigmoid colon	UBERON:0004993	78.48	gold quality
amniotic fluid	UBERON:0000173	78.22	gold quality
bone marrow	UBERON:0002371	78.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

64 targeting RMI1, 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-3617-3P	99.98	67.86	918
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-153-5P	99.89	73.86	6317
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-4307	99.82	70.45	3374
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-33A-3P	99.70	70.27	3362

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 69.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 22)

• BLAP75/RMI1 acts by recruiting TOPO IIIalpha to double Holliday junctions (PMID:16537486)
• BLM, Topo IIIalpha, and BLAP75 constitute a dissolvasome complex that processes HR intermediates to limit DNA crossover formation (PMID:16595695)
• BLM is stably associated with RMI1 protein. (PMID:17728255)
• Genetic variant of the human homologous recombination-associated gene RMI1 is associated with acute myeloid leukemia, myelodysplatic syndromes and malignant melanoma (PMID:17900800)
• evolutionarily conserved N-terminal third of BLAP75 mediates complex formation with BLM and Topo IIIalpha and that the DNA binding activity resides in the C-terminal third of this novel protein. (PMID:18390547)
• Individuals carrying genetic variants of the BLM-TOP3A-RMI1 complex have an increased risk of acute myeloid leukemia/myelodysplatic syndromes, malignant melanoma, bladder and breast cancer. (PMID:19432957)
• No evidence was found for an association between RMI1 S455N (rs1982151) and colorectal cancer risk. (PMID:19945966)
• human topoisomerase IIIalpha functions as a decatenase with the assistance of BLM and RMI1 to facilitate the processing of homologous recombination intermediates without crossing over as a mechanism to preserve genome integrity (PMID:20445207)
• Crystal structures of RMI1 and RMI2, two OB-fold regulatory subunits of the BLM complex (PMID:20826342)
• RMI1 is required to promote normal replication fork progression (PMID:22645306)
• two proteins that interact with BLM, RMI1 and RMI2, are phosphorylated upon SAC activation, and, like BLM, RMI1, and RMI2, are phosphorylated in an MPS1-dependent manner. (PMID:24108125)
• The results show that Topo IIIalpha stimulates DNA unwinding by BLM in a manner that is potentiated by RMI1-RMI2, and that the processivity of resection is reliant on the Topo IIIalpha-RMI1-RMI2 complex. (PMID:25200081)
• RMI1 protein level does not change through G1, S and G2 phases, but significantly increases in M phase. (PMID:26556339)
• a model that maps all functionally important structural features for yeast Rmi1 and structure-prediction-based alignment with the recently established crystal structure of the N-terminus of human Rmi1, is proposed. (PMID:26717309)
• RMI1 knockdown cells exhibit accumulation of broken DNAs after being released from hydroxyurea treatment. Moreover, we demonstrate that RMI1 facilitates the recovery from activated checkpoint and resuming the cell cycle after replicative stress. (PMID:29042194)
• The importance of RMI1 in response to DNA double-strand breaks. (PMID:30676768)
• Identification and Bioinformatic Assessment of circRNA Expression After RMI1 Knockdown and Ionizing Radiation Exposure. (PMID:33202158)
• Identification and external validation of a prognostic signature associated with DNA repair genes in gastric cancer. (PMID:33785812)
• Duplex DNA and BLM regulate gate opening by the human TopoIIIalpha-RMI1-RMI2 complex. (PMID:35102151)
• The toposiomerase IIIalpha-RMI1-RMI2 complex orients human Bloom’s syndrome helicase for efficient disruption of D-loops. (PMID:35115525)
• Phenotypic spectrum of BLM- and RMI1-related Bloom syndrome. (PMID:35218564)
• The MRN complex and topoisomerase IIIa-RMI1/2 synchronize DNA resection motor proteins. (PMID:36529288)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rmi1	ENSDARG00000041376
mus_musculus	Rmi1	ENSMUSG00000035367
rattus_norvegicus	Rmi1	ENSRNOG00000019108
caenorhabditis_elegans		WBGENE00011576
caenorhabditis_elegans	rmh-1	WBGENE00019712

Protein

Protein identifiers

RecQ-mediated genome instability protein 1 — Q9H9A7 (reviewed: Q9H9A7)

Alternative names: BLM-associated protein of 75 kDa, FAAP75

All UniProt accessions (2): Q9H9A7, A0A0A0MSU3

UniProt curated annotations — full annotation on UniProt →

Function. Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Promotes TOP3A binding to double Holliday junctions (DHJ) and hence stimulates TOP3A-mediated dissolution. Required for BLM phosphorylation during mitosis. Within the BLM complex, required for BLM and TOP3A stability.

Subunit / interactions. Component of the RMI complex, containing at least TOP3A, RMI1 and RMI2. The RMI complex interacts with BLM. Directly interacts with RMI2 and TOP3A. May bind DHJ. Interacts (via N-terminal region) with BLM; the interaction is direct.

Subcellular location. Nucleus.

Similarity. Belongs to the RMI1 family.

RefSeq proteins (5): NP_001345220, NP_001345221, NP_001345222, NP_001345223, NP_079221 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013894	RMI1_OB	Domain
IPR032199	RMI1_C	Domain
IPR042470	RMI1_N_C_sf	Homologous_superfamily
IPR044881	RMI1_N_N_sf	Homologous_superfamily
IPR049363	RMI1_N	Domain

Pfam: PF08585, PF16099, PF21000

UniProt features (48 total): helix 20, strand 11, sequence conflict 4, modified residue 4, cross-link 3, sequence variant 2, turn 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
3MXN	X-RAY DIFFRACTION	1.55
7XUV	X-RAY DIFFRACTION	1.6
3NBH	X-RAY DIFFRACTION	2
3NBI	X-RAY DIFFRACTION	2
9PFD	X-RAY DIFFRACTION	2.01
9DHK	X-RAY DIFFRACTION	2.35
9DI4	X-RAY DIFFRACTION	2.7
4CGY	X-RAY DIFFRACTION	2.85
4CHT	X-RAY DIFFRACTION	3.25
4DAY	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H9A7-F1	67.58	0.43

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 (7): 1, 225, 284, 292, 334, 387, 426

Function

Pathways and Gene Ontology

Reactome pathways

32 pathways

ID	Pathway
R-HSA-5685938	HDR through Single Strand Annealing (SSA)
R-HSA-5685942	HDR through Homologous Recombination (HRR)
R-HSA-5693554	Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)
R-HSA-5693568	Resolution of D-loop Structures through Holliday Junction Intermediates
R-HSA-5693579	Homologous DNA Pairing and Strand Exchange
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-5693616	Presynaptic phase of homologous DNA pairing and strand exchange
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-69473	G2/M DNA damage checkpoint
R-HSA-9701192	Defective homologous recombination repair (HRR) due to BRCA1 loss of function
R-HSA-9704331	Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function
R-HSA-9704646	Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function
R-HSA-9709570	Impaired BRCA2 binding to RAD51
R-HSA-9709603	Impaired BRCA2 binding to PALB2
R-HSA-1640170	Cell Cycle
R-HSA-1643685	Disease
R-HSA-212436	Generic Transcription Pathway
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-5693532	DNA Double-Strand Break Repair
R-HSA-5693537	Resolution of D-Loop Structures
R-HSA-5693538	Homology Directed Repair
R-HSA-5693567	HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)
R-HSA-69481	G2/M Checkpoints
R-HSA-69620	Cell Cycle Checkpoints
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-73894	DNA Repair
R-HSA-74160	Gene expression (Transcription)
R-HSA-9675135	Diseases of DNA repair
R-HSA-9675136	Diseases of DNA Double-Strand Break Repair

MSigDB gene sets: 216 (showing top): PID_FANCONI_PATHWAY, GOBP_BEHAVIOR, FISCHER_G1_S_CELL_CYCLE, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, GOBP_RESPONSE_TO_DIETARY_EXCESS, GOBP_GROWTH, GGGTGGRR_PAX4_03, GGCNKCCATNK_UNKNOWN, GOBP_EATING_BEHAVIOR, GOBP_ORGANELLE_FISSION, OCT1_03, GOBP_MULTICELLULAR_ORGANISM_GROWTH, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_DNA_DAMAGE_RESPONSE, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP

GO Biological Process (9): resolution of meiotic recombination intermediates (GO:0000712), double-strand break repair via homologous recombination (GO:0000724), reduction of food intake in response to dietary excess (GO:0002023), DNA replication (GO:0006260), response to glucose (GO:0009749), multicellular organism growth (GO:0035264), glucose homeostasis (GO:0042593), resolution of DNA recombination intermediates (GO:0071139), response to dietary excess (GO:0002021)

GO Molecular Function (2): nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604), RecQ family helicase-topoisomerase III complex (GO:0031422)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	3
Resolution of D-Loop Structures	2
Defective homologous recombination repair (HRR) due to PALB2 loss of function	2
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	2
HDR through Homologous Recombination (HRR)	1
Homologous DNA Pairing and Strand Exchange	1
Regulation of TP53 Activity	1
G2/M Checkpoints	1
Diseases of DNA Double-Strand Break Repair	1
RNA Polymerase II Transcription	1
Generic Transcription Pathway	1
Transcriptional Regulation by TP53	1
DNA Repair	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	2
reciprocal meiotic recombination	1
meiosis I cell cycle process	1
recombinational repair	1
double-strand break repair	1
response to dietary excess	1
eating behavior	1
DNA biosynthetic process	1
response to hexose	1
multicellular organismal process	1
developmental growth	1
carbohydrate homeostasis	1
DNA recombination	1
response to nutrient levels	1
energy homeostasis	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nucleoplasm	1
intracellular membraneless organelle	1
chromosome	1
DNA helicase complex	1

Protein interactions and networks

STRING

1221 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RMI1	RMI2	Q96E14	999
RMI1	TOP3A	Q13472	999
RMI1	BLM	P54132	993
RMI1	DNA2	P51530	987
RMI1	FANCM	Q8IYD8	973
RMI1	WRN	Q14191	910
RMI1	FAAP24	Q9BTP7	888
RMI1	ERCC6L	Q2NKX8	880
RMI1	EXO1	Q9UQ84	867
RMI1	MUS81	Q96NY9	858
RMI1	RAD52	P43351	850
RMI1	RAD51	Q06609	846
RMI1	RECQL	P46063	834
RMI1	GEN1	Q17RS7	796
RMI1	RECQL4	O94761	768

IntAct

67 interactions, top by confidence:

A	B	Type	Score
RPA2	RPA1	psi-mi:“MI:0914”(association)	0.960
RPA1	RPA2	psi-mi:“MI:0914”(association)	0.960
TOP3A	RMI1	psi-mi:“MI:0407”(direct interaction)	0.940
RMI1	TOP3A	psi-mi:“MI:0914”(association)	0.940
RPA3	RPA2	psi-mi:“MI:0914”(association)	0.930
RMI1	BLM	psi-mi:“MI:0914”(association)	0.930
RMI1	BLM	psi-mi:“MI:0915”(physical association)	0.930
BLM	RMI1	psi-mi:“MI:0915”(physical association)	0.930
RMI1	BLM	psi-mi:“MI:0403”(colocalization)	0.930
BLM	TOP3A	psi-mi:“MI:0914”(association)	0.890
BLM	TOP3A	psi-mi:“MI:0403”(colocalization)	0.890
RMI2	BLM	psi-mi:“MI:0914”(association)	0.830
RMI1	RMI2	psi-mi:“MI:0407”(direct interaction)	0.790
RMI1	RMI2	psi-mi:“MI:0915”(physical association)	0.790

BioGRID (82): RMI1 (Affinity Capture-MS), RMI1 (Affinity Capture-Western), RMI1 (Affinity Capture-Western), RMI1 (Affinity Capture-MS), RMI1 (Co-crystal Structure), RMI1 (Affinity Capture-MS), RMI1 (Affinity Capture-MS), TOP3A (Affinity Capture-MS), DCAF15 (Affinity Capture-MS), RMI1 (Affinity Capture-MS), RMI1 (Affinity Capture-MS), RMI1 (Affinity Capture-MS), RMI1 (Affinity Capture-MS), DCAF15 (Affinity Capture-MS), RMI1 (Affinity Capture-MS)

ESM2 similar proteins: A2RVA7, A4IF98, F6UH96, O08901, O60566, O75113, P14629, P62283, P62285, P62286, P62287, P62289, P62290, P62291, P62292, P62293, P62294, P62297, Q08DB0, Q0P4I1, Q0VA42, Q17RS7, Q2TA20, Q32NQ8, Q4R7I0, Q5F3D1, Q5I2W8, Q5R789, Q5T5J6, Q5ZHV8, Q6A037, Q6DDH2, Q6DJS0, Q6NZY4, Q6XV80, Q7Y1C4, Q7Y1C5, Q7ZVM9, Q7ZXG4, Q7ZXT3

Diamond homologs: A4IF98, Q2HJG4, Q5ZHV8, Q5ZMS6, Q66HC1, Q6DDH2, Q6NRP6, Q6NYG6, Q6P1U3, Q7ZVM9, Q91W18, Q9D4G9, Q9H7E2, Q9H9A7, O18870, O75940, Q16637, Q3T045, Q4QQU6, Q4R4F8, Q58EK5, Q5R591, Q6DEY1, Q8BGT7, P91399, Q8HYB8, Q9W6S8, O02771, O35876, P97801, Q5RE18, Q5XUX6, Q7XRV0, Q7ZV80, A9CPT4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 37 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
Impaired BRCA2 binding to RAD51	8	95.0×	7e-13
HDR through Single Strand Annealing (SSA)	8	90.1×	7e-13
Impaired BRCA2 binding to PALB2	5	87.8×	3e-08
Presynaptic phase of homologous DNA pairing and strand exchange	8	83.7×	1e-12
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	5	81.3×	4e-08
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	5	81.3×	4e-08
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	5	81.3×	4e-08
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	5	75.7×	5e-08

GO biological processes:

GO term	Partners	Fold	FDR
DNA recombination	5	51.1×	4e-06
double-strand break repair via homologous recombination	9	42.6×	6e-11
telomere maintenance	5	40.5×	7e-06
DNA replication	5	25.0×	4e-05
DNA repair	12	23.2×	1e-11
DNA damage response	7	11.3×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	63
Likely benign	14
Benign	6

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1183963	NM_001358291.2(RMI1):c.1284_1288del (p.Lys428fs)	Likely pathogenic

SpliceAI

444 predictions. Top by Δscore:

Variant	Effect	Δscore
9:83999707:A:AG	acceptor_gain	1.0000
9:83999708:G:GG	acceptor_gain	1.0000
9:83999794:CGTGG:C	donor_loss	1.0000
9:83999795:GTG:G	donor_gain	1.0000
9:83999796:TGG:T	donor_loss	1.0000
9:83999798:G:A	donor_loss	1.0000
9:83999798:G:GG	donor_gain	1.0000
9:83999799:TAA:T	donor_loss	1.0000
9:83980500:TA:T	donor_loss	0.9900
9:83980501:A:G	donor_loss	0.9900
9:83980502:CCTAT:C	donor_loss	0.9900
9:83980505:ATAGG:A	donor_gain	0.9900
9:83999704:CCCA:C	acceptor_loss	0.9900
9:83999705:CCA:C	acceptor_loss	0.9900
9:83999707:A:AC	acceptor_loss	0.9900
9:83999707:AG:A	acceptor_gain	0.9900
9:83999707:AGG:A	acceptor_gain	0.9900
9:83999708:GG:G	acceptor_gain	0.9900
9:83999708:GGG:G	acceptor_gain	0.9900
9:83999708:GGGC:G	acceptor_gain	0.9900
9:83999708:GGGCC:G	acceptor_gain	0.9900
9:83999796:TG:T	donor_gain	0.9900
9:83999797:GG:G	donor_gain	0.9900
9:84000948:CAG:C	acceptor_loss	0.9900
9:83999701:T:G	acceptor_gain	0.9800
9:83999793:TCGTG:T	donor_gain	0.9800
9:83999794:CGTG:C	donor_gain	0.9800
9:83999795:GTGG:G	donor_gain	0.9800
9:83999796:TGGT:T	donor_gain	0.9800
9:84000949:A:AG	acceptor_gain	0.9700

AlphaMissense

2734 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:84001152:T:A	W56R	0.999
9:84001152:T:C	W56R	0.999
9:84001062:T:A	W26R	0.997
9:84001062:T:C	W26R	0.997
9:84001064:G:C	W26C	0.995
9:84001064:G:T	W26C	0.995
9:84001027:T:C	L14P	0.994
9:84001076:T:G	C30W	0.993
9:84001156:T:C	L57P	0.993
9:84001396:T:C	L137P	0.992
9:84001153:G:C	W56S	0.991
9:84001154:G:C	W56C	0.990
9:84001154:G:T	W56C	0.990
9:84001484:A:C	K166N	0.990
9:84001484:A:T	K166N	0.990
9:84001074:T:C	C30R	0.988
9:84001083:T:A	W33R	0.988
9:84001083:T:C	W33R	0.988
9:84001428:G:A	G148R	0.988
9:84001428:G:C	G148R	0.988
9:84001477:G:A	G164D	0.988
9:84001045:T:A	V20D	0.987
9:84001407:G:C	D141H	0.986
9:84001411:G:A	G142E	0.986
9:84001411:G:T	G142V	0.986
9:84001429:G:A	G148E	0.985
9:84001483:A:T	K166I	0.985
9:84001063:G:C	W26S	0.984
9:84001150:A:C	Q55P	0.984
9:84001159:T:C	L58P	0.984

dbSNP variants (sampled 300 via entrez): RS1000504878 (9:83992683 G>A), RS1000539971 (9:83980362 T>A,C,G), RS1000565209 (9:83986990 T>TA), RS1000711743 (9:83998109 A>G), RS1000822740 (9:83992191 T>G), RS1000911319 (9:83980510 C>A), RS1000936495 (9:83996997 G>A), RS1001014611 (9:83985495 T>C), RS1001042464 (9:83985065 T>A), RS1001106953 (9:83981167 A>G), RS1001263428 (9:83989674 AAAAAT>A), RS1001294064 (9:83990666 A>G), RS1001311579 (9:84003745 T>C), RS1001354172 (9:84000832 T>C), RS1001367087 (9:83991252 G>A)

Disease associations

OMIM: gene MIM:610404 | disease phenotypes: MIM:114500

GenCC curated gene-disease

Mondo (1): colorectal cancer (MONDO:0005575)

Orphanet (1): NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667)

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST000635_17	Response to statin therapy	6.000000e-06
GCST002114_2	Molar-incisor hypomineralization	2.000000e-06
GCST002541_72	Menarche (age at onset)	2.000000e-09
GCST003993_31	Menarche (age at onset)	1.000000e-11
GCST006613_135	Triglycerides	2.000000e-08
GCST007294_144	Body fat distribution (trunk fat ratio)	5.000000e-19
GCST007294_83	Body fat distribution (trunk fat ratio)	7.000000e-17
GCST007295_107	Body fat distribution (leg fat ratio)	2.000000e-13
GCST007295_11	Body fat distribution (leg fat ratio)	2.000000e-06
GCST007295_92	Body fat distribution (leg fat ratio)	6.000000e-18
GCST007323_81	Risk-taking tendency (4-domain principal component model)	3.000000e-10
GCST007327_114	Smoking status (ever vs never smokers)	2.000000e-09
GCST007603_8	Smoking initiation	2.000000e-08
GCST90002409_30	Childhood body mass index	3.000000e-06
GCST90020028_334	Hip circumference adjusted for BMI	2.000000e-08

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0005321	molar-incisor hypomineralization
EFO:0004703	age at menarche
EFO:0004530	triglyceride measurement
EFO:0004341	body fat distribution
EFO:0008579	risk-taking behaviour
EFO:0004318	smoking behavior
EFO:0005670	smoking initiation
EFO:0004340	body mass index
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
uranyl acetate	affects expression	1
N(4)-hydroxycytidine	increases expression	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
picoxystrobin	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Calcitriol	decreases expression, affects cotreatment	1
Coumestrol	affects cotreatment, increases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Dimethyl Sulfoxide	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Paraquat	decreases expression	1
Testosterone	decreases expression, affects cotreatment	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00114829	PHASE4	UNKNOWN	Preoperative Assessment of Colon Tumor
NCT00114842	PHASE4	COMPLETED	Magnetic Resonance (MR) Colonography With Fecal Tagging
NCT00114946	PHASE4	TERMINATED	A Study to Compare Two Avastin-Based Treatment Regimens for the Treatment of Metastatic Colorectal Cancer
NCT00122720	PHASE4	COMPLETED	The Effect of Darbepoetin Upon Rehabilitation for Colorectal Cancer Surgery
NCT00129870	PHASE4	TERMINATED	CONCEPT: Comparison of Oxaliplatin vs Conventional Methods With Calcium/Magnesium in First-Line Metastatic Colorectal Cancer
NCT00138060	PHASE4	COMPLETED	Toxicity/Benefit Ratio Optimization of Chemotherapy in Colorectal Cancer (CRC) Patients by Determination of Individual Genotypic Determinants
NCT00216424	PHASE4	TERMINATED	Capecitabine (Xeloda) and Radiation for Patients With Rectosigmoid Carcinoma
NCT00327093	PHASE4	TERMINATED	Elaboration of a Model for Predicting Efficacy of Monoclonal Antibodies (Cetuximab and Bevacizumab) in Patients With Colorectal Cancer and Liver Metastases
NCT00332943	PHASE4	COMPLETED	MR Colonography With Fecal Tagging. Barium vs. BariumFerumoxsil
NCT00441311	PHASE4	COMPLETED	Dissemination of Colorectal Cancer Screening to Primary Care Physicians
NCT00460837	PHASE4	WITHDRAWN	Comparison of Bowel Preparation in Virtual Colonoscopy (VC) - Patient Experience
NCT00473980	PHASE4	COMPLETED	Preoperative Non-steroidal Anti-inflammatory Drugs(NSAID) to Colorectal Cancer Patients
NCT00488904	PHASE4	COMPLETED	Omega-3 Fatty Acids and Postoperative Complications After Colorectal Surgery
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00502671	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) as Adjuvant Monotherapy in Patients With Colon Cancer.
NCT00559676	PHASE4	COMPLETED	Study of Biomarkers in Patients Undergoing Chemotherapy for Metastatic Colorectal Cancer
NCT00577031	PHASE4	COMPLETED	OBELIX Study: A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Cancer of the Colon or Rectum.
NCT00626054	PHASE4	COMPLETED	Comparison of Two Methods of Administration of a PEG Solution
NCT00812864	PHASE4	COMPLETED	Pharmacokinetic Study of Capecitabine in Elderly Cancer Patient (≥ 75 Years)
NCT00868569	PHASE4	UNKNOWN	Transhepatic Arterial Chemotherapy (TAC) Versus Transcatheter Arterial Chemoembolization (TACE) Plus Folfox4 as the Treatment of Unresectable Liver Metastasis of Colorectal Cancer
NCT00868816	PHASE4	COMPLETED	Oxaliplatine Based Adjuvant Chemotherapy for Stage II/III Colorectal Cancer: 8 Cycles Versus 12 Cycles
NCT00874406	PHASE4	UNKNOWN	Preoperative Transhepatic Arterial Chemotherapy (TAC) in the Treatment of Liver Metastasis of Resectable Colorectal Cancer
NCT00928928	PHASE4	COMPLETED	Oxidative Stress Markers in Open and Laparoscopic Colectomy for Cancer
NCT00942461	PHASE4	COMPLETED	Inflammatory Response in Laparoscopic and Open Colectomy
NCT01023633	PHASE4	UNKNOWN	OPTIMOX1 in Chinese mCRC Patients
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01315990	PHASE4	UNKNOWN	FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema
NCT01493713	PHASE4	COMPLETED	Correlation Between RECIST, Morphologic Response by CT- Histopathologic Response in Hepatic Metastasis Secondary to Colorectal Cancer
NCT01609660	PHASE4	COMPLETED	Impact of Probiotics on the Intestinal Microbiota
NCT01641458	PHASE4	COMPLETED	Pharmacology-driven Dosing of Fluoropyrimidines in Cancer Patients
NCT01689792	PHASE4	COMPLETED	A Multi-centre Study Comparing the Polyp Detection Rate of Two Different Types of Bowel Preparation: a 2-litre Solution (MOVIPREP®) Versus a Hyperosmotic and Stimulant Combined Low Volume Bowel Preparation (Sodium Picosulfate and Magnesium Citrate)
NCT01695772	PHASE4	COMPLETED	A Study of Bevacizumab Plus 5-Flurouracil (5-FU) Based Doublet Chemotherapy as Neoadjuvant Therapy for Participants With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer
NCT01695863	PHASE4	COMPLETED	Efficacy and Patient Satisfaction of Miralax and Gatorade Versus Movi Prep
NCT01706822	PHASE4	TERMINATED	Radial Reload Laparoscopic LAR Case Series
NCT01740947	PHASE4	TERMINATED	Does Administration of Antibiotics in Patients Undergoing Surgery for Colorectal Cancer Result in Less Complications and Better Prognosis?
NCT01831310	PHASE4	COMPLETED	Nutrition for Colorectal Cancer Patients and Neutrophil Functions
NCT01841294	PHASE4	UNKNOWN	NK Activity Modulation Induced by Intravenous Lidocaine During Colorectal Laparoscopic Surgery
NCT01959061	PHASE4	UNKNOWN	Efficacy and Safety of Raltitrexed-based Transarterial Chemoembolisation(TACE)for Colorectal Cancer Liver Metastases
NCT02032953	PHASE4	UNKNOWN	Enhancing the Anabolic Effect of Perioperative Nutrition With Insulin While Maintaining Normoglycemia
NCT02567331	PHASE4	COMPLETED	A Study of Capecitabine (Xeloda) in Patients With Metastatic Colorectal Cancer