ITGB3BP

Summary

ITGB3BP (integrin subunit beta 3 binding protein, HGNC:6157) is a protein-coding gene on chromosome 1p31.3, encoding Centromere protein R (Q13352). Transcription coregulator that can have both coactivator and corepressor functions.

This gene encodes a transcriptional coregulator that binds to and enhances the activity of members of the nuclear receptor families, thyroid hormone receptors and retinoid X receptors. This protein also acts as a corepressor of NF-kappaB-dependent signaling. This protein induces apoptosis in breast cancer cells through a caspase 2-mediated signaling pathway. This protein is also a component of the centromere-specific histone H3 variant nucleosome associated complex (CENP-NAC) and may be involved in mitotic progression by recruiting the histone H3 variant CENP-A to the centromere. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 23421 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 37 total
• MANE Select transcript: NM_014288

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6157
Approved symbol	ITGB3BP
Name	integrin subunit beta 3 binding protein
Location	1p31.3
Locus type	gene with protein product
Status	Approved
Aliases	NRIF3, HSU37139, TAP20, CENPR
Ensembl gene	ENSG00000142856
Ensembl biotype	protein_coding
OMIM	605494
Entrez	23421

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 12 protein_coding_CDS_not_defined, 8 protein_coding, 1 nonsense_mediated_decay

ENST00000271002, ENST00000371092, ENST00000460251, ENST00000460394, ENST00000461681, ENST00000462285, ENST00000463803, ENST00000465781, ENST00000476508, ENST00000478138, ENST00000478538, ENST00000489099, ENST00000489863, ENST00000492655, ENST00000717656, ENST00000900098, ENST00000900099, ENST00000932587, ENST00000932588, ENST00000955693, ENST00000955694

RefSeq mRNA: 5 — MANE Select: NM_014288 NM_001206739, NM_001347145, NM_001347147, NM_001347148, NM_014288

CCDS: CCDS30736, CCDS55603

Canonical transcript exons

ENST00000271002 — 9 exons

Exon	Start	End
ENSE00001868255	63523129	63523225
ENSE00001900593	63440770	63441103
ENSE00003486286	63454380	63454473
ENSE00003493105	63454890	63454968
ENSE00003528241	63453918	63453974
ENSE00003534292	63508528	63508570
ENSE00003580094	63446806	63446856
ENSE00003610401	63478764	63478833
ENSE00003628191	63490083	63490218

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 97.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.2957 / max 452.2007, expressed in 1760 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12647	13.5619	1700
12648	1.3440	771
12649	0.7117	387
12646	0.5630	317
12650	0.1151	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	97.22	gold quality
calcaneal tendon	UBERON:0003701	95.58	gold quality
secondary oocyte	CL:0000655	94.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.33	gold quality
right uterine tube	UBERON:0001302	93.15	gold quality
ventricular zone	UBERON:0003053	92.82	gold quality
sperm	CL:0000019	91.38	gold quality
ganglionic eminence	UBERON:0004023	90.93	gold quality
embryo	UBERON:0000922	90.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.62	gold quality
right testis	UBERON:0004534	90.50	gold quality
testis	UBERON:0000473	90.23	gold quality
left ovary	UBERON:0002119	90.20	gold quality
left testis	UBERON:0004533	90.00	gold quality
rectum	UBERON:0001052	89.89	gold quality
monocyte	CL:0000576	89.85	gold quality
tendon	UBERON:0000043	89.80	gold quality
ovary	UBERON:0000992	89.72	gold quality
mononuclear cell	CL:0000842	89.56	gold quality
right ovary	UBERON:0002118	89.25	gold quality
leukocyte	CL:0000738	89.17	gold quality
male germ cell	CL:0000015	88.94	gold quality
body of pancreas	UBERON:0001150	88.92	gold quality
gall bladder	UBERON:0002110	88.59	gold quality
body of uterus	UBERON:0009853	88.38	gold quality
bronchial epithelial cell	CL:0002328	88.31	gold quality
right coronary artery	UBERON:0001625	88.16	gold quality
endometrium	UBERON:0001295	88.10	gold quality
lymph node	UBERON:0000029	88.08	gold quality
right lung	UBERON:0002167	88.08	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	37.44
E-GEOD-125970	yes	16.13
E-ANND-3	yes	7.34
E-MTAB-6524	no	174.77

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, ESR1, MTA1

miRNA regulators (miRDB)

20 targeting ITGB3BP, 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-4692	100.00	67.32	2066
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-2276-3P	98.76	67.75	1384
HSA-MIR-6804-3P	98.72	64.82	852
HSA-MIR-548Q	98.71	65.35	563
HSA-MIR-7111-3P	97.80	66.75	1467
HSA-MIR-299-3P	97.73	66.67	773
HSA-MIR-3907	96.76	65.04	662
HSA-MIR-4491	96.53	66.20	935
HSA-MIR-4657	96.53	66.57	895
HSA-MIR-6847-3P	96.50	67.30	582
HSA-MIR-4772-5P	95.60	68.04	617

Literature-anchored findings (GeneRIF, showing 10)

• The presence of various isoforms and the relationship between subcellular localization and integrin-activating function of beta(3)-endonexin is described. (PMID:11864709)
• This protein downregulates urokinase-type plasminogen activator receptor promoter activity. (PMID:12244126)
• Results suggest that breast cancer cells contain a novel “death switch” that can be specifically triggered by NRIF3 or death domain 1. (PMID:15082778)
• Metastasis-associated protein 1 interacts with NRIF3, an estrogen-inducible nuclear receptor coregulator (PMID:15254226)
• findings suggest that NRIF3-Ser28 is a physiologic target of Pak1 signaling and contributes to the enhanced NRIF3 co-activator activity, leading to coordinated potentiation of ERalpha transactivation (PMID:18521086)
• Data propose that CENP-P/O/R/Q/U self-assembles on kinetochores with varying stoichiometry and undergoes a pre-mitotic maturation step that could be important for kinetochores switching into the correct conformation for microtubule-attachment. (PMID:23028590)
• The beta3-endonexin can act as a novel anti-angiogenic factor specifically in the response to hypoxia due to its negative impact on the activation of HIF-1. (PMID:24386901)
• Identification of genes in hepatocellular carcinoma induced by non-alcoholic fatty liver disease. (PMID:32623384)
• Integrated profiling identifies ITGB3BP as prognostic biomarker for hepatocellular carcinoma. (PMID:33974527)
• beta3-Endonexin interacts with ninein in vascular endothelial cells to promote angiogenesis. (PMID:34118594)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Itgb3bp	ENSMUSG00000028549
rattus_norvegicus	Itgb3bp	ENSRNOG00000009116

Protein

Protein identifiers

Centromere protein R — Q13352 (reviewed: Q13352)

Alternative names: Beta-3-endonexin, Integrin beta-3-binding protein, Nuclear receptor-interacting factor 3

All UniProt accessions (1): Q13352

UniProt curated annotations — full annotation on UniProt →

Function. Transcription coregulator that can have both coactivator and corepressor functions. Isoform 1, but not other isoforms, is involved in the coactivation of nuclear receptors for retinoid X (RXRs) and thyroid hormone (TRs) in a ligand-dependent fashion. In contrast, it does not coactivate nuclear receptors for retinoic acid, vitamin D, progesterone receptor, nor glucocorticoid. Acts as a coactivator for estrogen receptor alpha. Acts as a transcriptional corepressor via its interaction with the NFKB1 NF-kappa-B subunit, possibly by interfering with the transactivation domain of NFKB1. Induces apoptosis in breast cancer cells, but not in other cancer cells, via a caspase-2 mediated pathway that involves mitochondrial membrane permeabilization but does not require other caspases. May also act as an inhibitor of cyclin A-associated kinase. Also acts a component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex.

Subunit / interactions. Homodimer; mediated by the coiled coil domain. Isoform 3, but not other isoforms, interacts with the cytoplasmic tail of integrin ITGB3. The relevance of the interaction with ITGB3 is however uncertain, since isoform 3 is mainly nuclear. Interacts with CCNA2 and MTA1. Interacts with NFKB1 NF-kappa-B subunit. Component of the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. The CENPA-CAD complex interacts with the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU. Interacts with TASOR.

Subcellular location. Nucleus. Chromosome. Centromere. Kinetochore Nucleus Nucleus. Cytoplasm Cytoplasm.

Tissue specificity. Widely expressed. Expressed in spleen, thymus, prostate, ovary, small intestine and white blood cells. Highly expressed in testis and colon. Isoform 4 is expressed in platelets, lymphocytes and granulocytes.

Domain organisation. The DD1 domain (also called RepD1 domain) mediates the corepressor function and is essential in the triggering of apoptosis. Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif, a motif known to be important for the association with nuclear receptors. Such motif, which is required for an efficient association with nuclear receptors, is however not essential. Contains one Leu-Xaa-Xaa-Ile-Leu (LXXIL) motif, which is essential for the association with nuclear receptors.

Induction. By estrogen.

Isoforms (5)

UniProt ID	Names	Canonical?
Q13352-1	1	yes
Q13352-2	2, Long, EnL, En-L
Q13352-3	3, Short, EnS, En-S
Q13352-4	4
Q13352-5	5

RefSeq proteins (5): NP_001193668, NP_001334074, NP_001334076, NP_001334077, NP_055103* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009601	CENP-R	Family

Pfam: PF06729

UniProt features (30 total): mutagenesis site 7, helix 5, splice variant 4, modified residue 3, short sequence motif 3, region of interest 2, cross-link 2, chain 1, sequence variant 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
28OP	ELECTRON MICROSCOPY	2.7
7R5S	ELECTRON MICROSCOPY	2.83
7PKN	ELECTRON MICROSCOPY	3.2
7XHO	ELECTRON MICROSCOPY	3.29
9TAW	ELECTRON MICROSCOPY	3.54
7PB8	X-RAY DIFFRACTION	3.68
7XHN	ELECTRON MICROSCOPY	3.71
9TAX	ELECTRON MICROSCOPY	4.5
7R5V	ELECTRON MICROSCOPY	4.55
7QOO	ELECTRON MICROSCOPY	4.6
7YYH	ELECTRON MICROSCOPY	8.9
7YWX	ELECTRON MICROSCOPY	12
9TAY	ELECTRON MICROSCOPY	15.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13352-F1	72.76	0.23

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 (5): 71, 8, 22, 17, 28

Mutagenesis-validated functional residues (7):

Position	Phenotype
9	decreased interaction with nuclear receptors.
28	loss of repressor function.
63–66	abolishes localization to nucleus.
63–65	abolishes localization to nucleus.
89	abolishes dimerization, but not interactions with nuclear receptors; when associated with r-96.
96	abolishes dimerization, but not interactions with nuclear receptors; when associated with r-89.
172–176	abolishes interaction with nuclear receptors.

Function

Pathways and Gene Ontology

Reactome pathways

25 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-205043	NRIF signals cell death from the nucleus
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-606279	Deposition of new CENPA-containing nucleosomes at the centromere
R-HSA-68877	Mitotic Prometaphase
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation
R-HSA-141424	Amplification of signal from the kinetochores
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-193704	p75 NTR receptor-mediated signalling
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-204998	Cell death signalling via NRAGE, NRIF and NADE
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-68882	Mitotic Anaphase
R-HSA-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-69618	Mitotic Spindle Checkpoint
R-HSA-69620	Cell Cycle Checkpoints
R-HSA-73886	Chromosome Maintenance
R-HSA-73887	Death Receptor Signaling
R-HSA-774815	Nucleosome assembly
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 289 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GNF2_MSH2, GOBP_REGULATION_OF_EPITHELIAL_CELL_APOPTOTIC_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, AREB6_01, MEF2_02, PAX2_01, PUJANA_CHEK2_PCC_NETWORK, MUELLER_PLURINET, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_APOPTOTIC_PROCESS, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, BRN2_01, GATA6_01, GNF2_RFC3

GO Biological Process (9): regulation of DNA-templated transcription (GO:0006355), apoptotic process (GO:0006915), chromosome segregation (GO:0007059), cell adhesion (GO:0007155), signal transduction (GO:0007165), CENP-A containing chromatin assembly (GO:0034080), positive regulation of epithelial cell proliferation (GO:0050679), cell division (GO:0051301), negative regulation of epithelial cell apoptotic process (GO:1904036)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (9): inner kinetochore (GO:0000939), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), chromosome, centromeric region (GO:0000775), kinetochore (GO:0000776), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Mitotic Prometaphase	2
M Phase	2
Amplification of signal from the kinetochores	1
Cell death signalling via NRAGE, NRIF and NADE	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
Nucleosome assembly	1
Mitotic Spindle Checkpoint	1
Death Receptor Signaling	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
p75 NTR receptor-mediated signalling	1
Mitotic Metaphase and Anaphase	1
Cell Cycle, Mitotic	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cellular process	3
intracellular membraneless organelle	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell cycle process	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
chromatin organization	1
kinetochore assembly	1
protein localization to CENP-A containing chromatin	1
positive regulation of cell population proliferation	1
epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
negative regulation of apoptotic process	1
epithelial cell apoptotic process	1
regulation of epithelial cell apoptotic process	1
binding	1
kinetochore	1
protein-containing complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
chromosomal region	1
condensed chromosome, centromeric region	1
supramolecular complex	1

Protein interactions and networks

STRING

1045 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITGB3BP	CENPQ	Q7L2Z9	980
ITGB3BP	CENPP	Q6IPU0	973
ITGB3BP	CENPO	Q9BU64	972
ITGB3BP	CENPL	Q8N0S6	956
ITGB3BP	CENPK	Q9BS16	941
ITGB3BP	CENPH	Q9H3R5	917
ITGB3BP	CENPU	Q71F23	913
ITGB3BP	CENPI	Q92674	910
ITGB3BP	CENPS	Q8N2Z9	897
ITGB3BP	CENPT	Q96BT3	879
ITGB3BP	CENPN	Q96H22	857
ITGB3BP	CENPM	Q9NSP4	851
ITGB3BP	CENPW	Q5EE01	833
ITGB3BP	ITGB3	P05106	828
ITGB3BP	CENPC	Q03188	739

IntAct

176 interactions, top by confidence:

A	B	Type	Score
ITGB3BP	CENPU	psi-mi:“MI:0915”(physical association)	0.710
ITGB3BP	CENPU	psi-mi:“MI:0914”(association)	0.710
ITGB3BP	ARFIP2	psi-mi:“MI:0915”(physical association)	0.670
ITGB3BP	CERT1	psi-mi:“MI:0915”(physical association)	0.670
ARFIP2	ITGB3BP	psi-mi:“MI:0915”(physical association)	0.670
ITGB3BP	PIH1D2	psi-mi:“MI:0915”(physical association)	0.670
ITGB3BP	KIFC3	psi-mi:“MI:0915”(physical association)	0.560
KIFC3	ITGB3BP	psi-mi:“MI:0915”(physical association)	0.560
SNAPC5	ITGB3BP	psi-mi:“MI:0915”(physical association)	0.560
USHBP1	ITGB3BP	psi-mi:“MI:0915”(physical association)	0.560
PBX3	ITGB3BP	psi-mi:“MI:0915”(physical association)	0.560
MSGN1	ITGB3BP	psi-mi:“MI:0915”(physical association)	0.560
PIK3R3	ITGB3BP	psi-mi:“MI:0915”(physical association)	0.560
HSF2BP	ITGB3BP	psi-mi:“MI:0915”(physical association)	0.560
ITGB3BP	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
USP20	ITGB3BP	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (116): ITGB3BP (Two-hybrid), ITGB3BP (Two-hybrid), ARFIP2 (Two-hybrid), UBR7 (Two-hybrid), PIH1D2 (Two-hybrid), ITGB3BP (Affinity Capture-MS), ITGB3BP (Affinity Capture-MS), CENPU (Affinity Capture-MS), CENPQ (Affinity Capture-MS), ITGB3BP (Two-hybrid), ARFIP2 (Two-hybrid), ATP5J (Affinity Capture-MS), FANCD2 (Affinity Capture-MS), FLNB (Affinity Capture-MS), CENPI (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTZ2, A3RM20, A4UHQ4, A6H7E2, A6NGH7, A9JSR5, B0BK70, O55527, O74982, P04861, P04862, P06747, P0C137, P0C139, P0C142, P14253, P14254, P33493, P35940, P40167, P69479, P69480, P69738, Q0GBX8, Q13352, Q14BK3, Q2T9U9, Q2YDE5, Q32L17, Q3UYG1, Q4KLZ4, Q4VKV6, Q5I0J4, Q5RE16, Q66HB6, Q6AXY9, Q810N5, Q8IR45, Q8IYM0, Q8NCU1

Diamond homologs: Q13352, Q1T763, Q5U1Z7, Q9CQ82

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PAK1	up-regulates	ITGB3BP	phosphorylation
ITGB3BP	“form complex”	“CCAN complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 87 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
Nucleosome assembly	6	51.0×	6e-07
Chromosome Maintenance	6	22.7×	6e-05
Amplification of signal from the kinetochores	5	17.6×	1e-03
Deposition of new CENPA-containing nucleosomes at the centromere	6	17.0×	2e-04
Mitotic Spindle Checkpoint	5	14.2×	2e-03
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	5	10.4×	5e-03
Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide	5	9.5×	6e-03
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	5	8.7×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
chromosome segregation	6	12.9×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

6258 predictions. Top by Δscore:

Variant	Effect	Δscore
1:63370902:G:GT	donor_gain	1.0000
1:63370926:G:GG	donor_gain	1.0000
1:63402339:TATGT:T	donor_gain	1.0000
1:63402340:ATGT:A	donor_gain	1.0000
1:63402342:GT:G	donor_gain	1.0000
1:63402344:G:GG	donor_gain	1.0000
1:63406315:A:AG	acceptor_gain	1.0000
1:63406316:G:GA	acceptor_gain	1.0000
1:63428926:A:AG	acceptor_gain	1.0000
1:63428927:G:GA	acceptor_gain	1.0000
1:63428927:GT:G	acceptor_gain	1.0000
1:63428927:GTAT:G	acceptor_gain	1.0000
1:63429018:A:AG	acceptor_gain	1.0000
1:63429078:G:GT	donor_gain	1.0000
1:63436821:A:AG	acceptor_gain	1.0000
1:63436822:G:GG	acceptor_gain	1.0000
1:63453913:CTTA:C	donor_loss	1.0000
1:63453914:TTA:T	donor_loss	1.0000
1:63453915:TACCT:T	donor_loss	1.0000
1:63453916:A:AC	donor_gain	1.0000
1:63453916:ACC:A	donor_loss	1.0000
1:63453917:C:CC	donor_gain	1.0000
1:63453917:C:CG	donor_loss	1.0000
1:63453973:CA:C	acceptor_gain	1.0000
1:63453975:C:CC	acceptor_gain	1.0000
1:63454378:A:AC	donor_gain	1.0000
1:63454379:C:CC	donor_gain	1.0000
1:63454791:A:AC	donor_gain	1.0000
1:63454792:C:CC	donor_gain	1.0000
1:63454792:CT:C	donor_gain	1.0000

AlphaMissense

1173 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:63454382:A:G	L142P	0.911
1:63446828:G:C	F171L	0.901
1:63446828:G:T	F171L	0.901
1:63446830:A:G	F171L	0.901
1:63508561:T:A	R5S	0.879
1:63508561:T:G	R5S	0.879
1:63490157:C:A	G37V	0.867
1:63446837:G:C	S168R	0.855
1:63446837:G:T	S168R	0.855
1:63446839:T:G	S168R	0.855
1:63490157:C:T	G37E	0.853
1:63508564:T:A	K4N	0.850
1:63508564:T:G	K4N	0.850
1:63490158:C:G	G37R	0.815
1:63490158:C:T	G37R	0.815
1:63446826:A:G	L172P	0.803
1:63454473:C:G	A112P	0.803
1:63490160:G:A	T36I	0.775
1:63508556:A:G	L7P	0.774
1:63490170:A:G	S33P	0.767
1:63454903:A:G	L107S	0.748
1:63490141:A:C	S42R	0.736
1:63490141:A:T	S42R	0.736
1:63490143:T:G	S42R	0.736
1:63454451:A:G	L119P	0.733
1:63523129:G:A	P2L	0.725
1:63446829:A:G	F171S	0.723
1:63490135:A:C	F44L	0.718
1:63490135:A:T	F44L	0.718
1:63490137:A:G	F44L	0.718

dbSNP variants (sampled 300 via entrez): RS1000001649 (1:63490895 C>T), RS1000075589 (1:63448434 G>A), RS1000079448 (1:63489454 A>G), RS1000161071 (1:63511313 T>C), RS1000173057 (1:63465988 T>C), RS1000200423 (1:63451569 CA>C), RS1000250370 (1:63455864 G>T), RS1000304429 (1:63456204 T>C), RS1000334029 (1:63469606 G>A), RS1000423529 (1:63489837 C>A), RS1000446936 (1:63495367 G>A), RS1000477088 (1:63502621 G>A), RS1000488326 (1:63463235 G>A,T), RS1000507141 (1:63524125 G>A), RS1000531456 (1:63448743 A>G)

Disease associations

OMIM: gene MIM:605494 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002397_633	Mean spheric corpuscular volume	1.000000e-12

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects reaction, decreases reaction, decreases expression, affects binding, affects folding	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
bisphenol AF	affects binding, affects folding, affects reaction, decreases reaction	2
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	2
Valproic Acid	affects expression, decreases methylation	2
Cyclosporine	decreases expression, increases expression	2
Particulate Matter	increases abundance, affects expression, increases reaction, decreases expression	2
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
methylselenic acid	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
nickel chloride	increases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
2,3-dimethoxy-1,4-naphthoquinone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
ICG 001	decreases expression	1
Dasatinib	decreases expression	1
Irinotecan	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Troglitazone	decreases expression	1

Clinical trials (associated diseases)

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