CENPU

Summary

CENPU (centromere protein U, HGNC:21348) is a protein-coding gene on chromosome 4q35.1, encoding Centromere protein U (Q71F23). Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation.

The centromere is a specialized chromatin domain, present throughout the cell cycle, that acts as a platform on which the transient assembly of the kinetochore occurs during mitosis. All active centromeres are characterized by the presence of long arrays of nucleosomes in which CENPA (MIM 117139) replaces histone H3 (see MIM 601128). MLF1IP, or CENPU, is an additional factor required for centromere assembly (Foltz et al., 2006 [PubMed 16622419]).

Source: NCBI Gene 79682 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 81 total
• MANE Select transcript: NM_024629

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21348
Approved symbol	CENPU
Name	centromere protein U
Location	4q35.1
Locus type	gene with protein product
Status	Approved
Aliases	CENP-U, KLIP1, CENP-50, PBIP1
Ensembl gene	ENSG00000151725
Ensembl biotype	protein_coding
OMIM	611511
Entrez	79682

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000281453, ENST00000502461, ENST00000506535, ENST00000508095, ENST00000510146, ENST00000514781, ENST00000950880

RefSeq mRNA: 1 — MANE Select: NM_024629 NM_024629

CCDS: CCDS3838

Canonical transcript exons

ENST00000281453 — 13 exons

Exon	Start	End
ENSE00001199543	184717136	184717196
ENSE00001199550	184724957	184725062
ENSE00001199561	184694085	184695401
ENSE00001213766	184728918	184729035
ENSE00002026850	184734016	184734096
ENSE00003465376	184730920	184730968
ENSE00003503581	184700820	184700881
ENSE00003545802	184712944	184713013
ENSE00003580634	184702089	184702136
ENSE00003613724	184697647	184697803
ENSE00003628033	184702363	184702441
ENSE00003687467	184710072	184710180
ENSE00003791234	184716397	184716633

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 99.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.4524 / max 325.3243, expressed in 1586 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
55153	16.0989	1546
55154	1.1736	652
55152	0.1799	78

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.03	gold quality
male germ cell	CL:0000015	98.31	gold quality
oocyte	CL:0000023	98.21	gold quality
secondary oocyte	CL:0000655	97.28	gold quality
right testis	UBERON:0004534	97.25	gold quality
left testis	UBERON:0004533	97.24	gold quality
adult organism	UBERON:0007023	96.76	gold quality
trabecular bone tissue	UBERON:0002483	96.27	gold quality
ventricular zone	UBERON:0003053	96.26	gold quality
embryo	UBERON:0000922	96.13	gold quality
testis	UBERON:0000473	95.85	gold quality
ganglionic eminence	UBERON:0004023	95.63	gold quality
bone marrow	UBERON:0002371	94.13	gold quality
amniotic fluid	UBERON:0000173	92.93	gold quality
hair follicle	UBERON:0002073	92.43	gold quality
oral cavity	UBERON:0000167	92.23	gold quality
gingival epithelium	UBERON:0001949	91.69	gold quality
gingiva	UBERON:0001828	90.47	gold quality
oviduct epithelium	UBERON:0004804	90.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.98	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.88	gold quality
bone marrow cell	CL:0002092	89.29	gold quality
lower esophagus mucosa	UBERON:0035834	89.26	gold quality
upper leg skin	UBERON:0004262	89.01	gold quality
mucosa of sigmoid colon	UBERON:0004993	88.74	gold quality
squamous epithelium	UBERON:0006914	88.18	gold quality
esophagus squamous epithelium	UBERON:0006920	87.96	gold quality
rectum	UBERON:0001052	87.62	gold quality
esophagus mucosa	UBERON:0002469	87.62	gold quality
epithelium of esophagus	UBERON:0001976	87.54	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	369.82
E-MTAB-8530	yes	300.48
E-MTAB-10485	yes	263.62
E-MTAB-8884	yes	238.08
E-HCAD-4	yes	146.04
E-GEOD-134144	yes	30.47
E-HCAD-10	yes	25.30
E-CURD-122	yes	22.36
E-HCAD-13	yes	22.11
E-MTAB-9067	yes	20.84
E-HCAD-5	yes	19.37
E-ANND-3	yes	10.78
E-MTAB-6678	yes	7.62
E-GEOD-110499	no	111.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

59 targeting CENPU, 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-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-5582-5P	99.27	71.42	1879

Literature-anchored findings (GeneRIF, showing 23)

• a possible role for MLF1IP deregulation in the genesis of erythroleukemias (PMID:15116101)
• MLF1IP was found in glioblastomas where it was co-localized with MLF1 and nestin. Moreover, it was elevated in the contralateral brain where no tumor cells occurred, suggesting a role in glioma pathogenesis and potentially in other types of malignancies. (PMID:15893739)
• Plk1 self-regulates the Plk1-PBIP1 interaction to timely localize to the kinetochores and promote proper chromosome segregation. (PMID:17081991)
• Deletion mutants of MLF1IP revealed that the N-terminal bipartite nuclear localization signal (NLS) was responsible for nucleolar targeting. (PMID:17595757)
• CENP-U is a novel microtubule binding protein and plays an important role in kinetochore-microtubule attachment through its interaction with Hec1 (PMID:21056971)
• Mammalian polo-like kinase 1-dependent regulation of the PBIP1-CENP-Q complex at kinetochores. (PMID:21454580)
• 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)
• MLF1IP significantly promotes prostate cancer cell proliferation and colony formation and significantly inhibits apoptosis without affecting cell cycle phase arrest in prostate cancer cell lines (PMID:25572810)
• Plk1 regulates the timing of the delocalization and ultimate destruction of the PBIP1.CENP-Q complex. (PMID:25670858)
• This study provides new insights and evidences that MLF1IP over-expression plays important roles in progression of luminal breast cancer. However, the precise cellular mechanisms for MLF1IP in luminal breast cancer need to be further explored. (PMID:27378428)
• MLF1IP promotes normal erythroid proliferation and is involved in the pathogenesis of polycythemia vera. (PMID:28173615)
• In-depth IPA analysis revealed that CENPU was associated with the HMGB1 signaling pathway. qPCR and western blot analysis demonstrated that in the HMGB1 signaling pathway, CENPU knockdown downregulated expression levels of ILB, CXCL8, RAC1 and IL1A (PMID:28677729)
• Centromere protein U promotes cell proliferation, migration and invasion involving Wnt/beta-catenin signaling pathway in non-small cell lung cancer (PMID:30536323)
• CENPU downregulation significantly inhibited LAC cell proliferation, migration and invasion in, which was possibly mediated by PI3K/AKT pathway inactivation (PMID:30849291)
• Centromere protein U (CENPU) enhances angiogenesis in triple-negative breast cancer by inhibiting ubiquitin-proteasomal degradation of COX-2. (PMID:31705927)
• BUB1 and CENP-U, Primed by CDK1, Are the Main PLK1 Kinetochore Receptors in Mitosis. (PMID:33248027)
• Differential requirements for the CENP-O complex reveal parallel PLK1 kinetochore recruitment pathways. (PMID:33596090)
• The lncRNA GATA3-AS1/miR-495-3p/CENPU axis predicts poor prognosis of breast cancer via the PLK1 signaling pathway. (PMID:33902008)
• Bub1 and CENP-U redundantly recruit Plk1 to stabilize kinetochore-microtubule attachments and ensure accurate chromosome segregation. (PMID:34551298)
• Centromere protein U (CENPU) promotes gastric cancer cell proliferation and glycolysis by regulating high mobility group box 2 (HMGB2). (PMID:34872447)
• Abnormal Expression of Centromere Protein U Is Associated with Hepatocellular Cancer Progression. (PMID:34957303)
• Overexpression of MLF1IP promotes colorectal cancer cell proliferation through BRCA1/AKT/p27 signaling pathway. (PMID:35122991)
• Knockdown of CENPU inhibits cervical cancer cell migration and stemness through the FOXM1/Wnt/beta-catenin pathway. (PMID:36608638)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cenpu	ENSDARG00000088924
mus_musculus	Cenpu	ENSMUSG00000031629
rattus_norvegicus	Cenpu	ENSRNOG00000022261

Protein

Protein identifiers

Centromere protein U — Q71F23 (reviewed: Q71F23)

Alternative names: Centromere protein of 50 kDa, Interphase centromere complex protein 24, KSHV latent nuclear antigen-interacting protein 1, MLF1-interacting protein, Polo-box-interacting protein 1

All UniProt accessions (3): Q71F23, D6R9S4, Q09GN1

UniProt curated annotations — full annotation on UniProt →

Function. Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. Plays an important role in the correct PLK1 localization to the mitotic kinetochores. A scaffold protein responsible for the initial recruitment and maintenance of the kinetochore PLK1 population until its degradation. Involved in transcriptional repression.

Subunit / interactions. Component of the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU. The CENPA-NAC complex interacts with the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. Interacts with MLF1. Interacts with PLK1. (Microbial infection) Interacts with the N-terminal domain of Kaposi’s sarcoma-associated herpesvirus latent nuclear antigen (LNA).

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

Tissue specificity. Expressed at high levels in the testis, fetal liver, thymus, bone marrow and at lower levels in the lymph nodes, placenta, colon and spleen. Present in all cell lines examined, including B-cells, T-cells, epithelial cells and fibroblast cells. Expressed at high levels in glioblastoma cell lines.

Post-translational modifications. Phosphorylated by PLK1 at Thr-78, creating a self-tethering site that specifically interacts with the polo-box domain of PLK1.

Similarity. Belongs to the CENP-U/AME1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q71F23-1	1	yes
Q71F23-2	2
Q71F23-3	3

RefSeq proteins (1): NP_078905* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025214	CENP-U	Family

Pfam: PF13097

UniProt features (46 total): modified residue 13, compositionally biased region 6, helix 6, sequence variant 5, mutagenesis site 4, splice variant 3, region of interest 2, coiled-coil region 2, short sequence motif 2, chain 1, cross-link 1, sequence conflict 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
9FJG	X-RAY DIFFRACTION	2
9FJJ	X-RAY DIFFRACTION	2
9FJI	X-RAY DIFFRACTION	2.1
9FJH	X-RAY DIFFRACTION	2.15
28OP	ELECTRON MICROSCOPY	2.7
7R5S	ELECTRON MICROSCOPY	2.83
7PKN	ELECTRON MICROSCOPY	3.2
7XHO	ELECTRON MICROSCOPY	3.29
8K4D	X-RAY DIFFRACTION	3.52
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-Q71F23-F1	66.09	0.30

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 (14): 78, 98, 108, 110, 111, 116, 120, 136, 139, 141, 190, 194, 232, 185

Mutagenesis-validated functional residues (4):

Position	Phenotype
77	insensitive to plk1-induced degradation.
78	insensitive to plk1-induced degradation.
78	failed to enhance the plk1-dependent degradation.

Function

Pathways and Gene Ontology

Reactome pathways

21 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
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-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
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-774815	Nucleosome assembly
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 288 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, IWANAGA_E2F1_TARGETS_INDUCED_BY_SERUM, GOCC_MICROTUBULE_ORGANIZING_CENTER, PATIL_LIVER_CANCER, MODULE_205, ONKEN_UVEAL_MELANOMA_UP, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, PID_PLK1_PATHWAY, MODULE_206, GOCC_CENTROSOME, chr4q35, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP, FUJII_YBX1_TARGETS_DN

GO Biological Process (2): chromosome segregation (GO:0007059), chordate embryonic development (GO:0043009)

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

GO Cellular Component (9): inner kinetochore (GO:0000939), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), centriolar satellite (GO:0034451), chromosome, centromeric region (GO:0000775), kinetochore (GO:0000776), chromosome (GO:0005694), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Cell Cycle	3
Mitotic Prometaphase	2
M Phase	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
RHO GTPase Effectors	1
Nucleosome assembly	1
Mitotic Spindle Checkpoint	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Mitotic Metaphase and Anaphase	1
Cell Cycle, Mitotic	1
Cell Cycle Checkpoints	1
Chromosome Maintenance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membraneless organelle	2
cell cycle process	1
embryo development ending in birth or egg hatching	1
binding	1
kinetochore	1
protein-containing complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
centrosome	1
chromosomal region	1
condensed chromosome, centromeric region	1
supramolecular complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CENPU	CENPQ	Q7L2Z9	998
CENPU	CENPP	Q6IPU0	996
CENPU	CENPN	Q96H22	994
CENPU	CENPO	Q9BU64	994
CENPU	CENPI	Q92674	993
CENPU	CENPH	Q9H3R5	992
CENPU	CENPT	Q96BT3	991
CENPU	CENPM	Q9NSP4	977
CENPU	CENPC	Q03188	970
CENPU	PLK1	P53350	961
CENPU	CENPK	Q9BS16	955
CENPU	CENPA	P49450	948
CENPU	CENPS	Q8N2Z9	931
CENPU	MLF1	P58340	918
CENPU	ITGB3BP	Q13352	913

IntAct

99 interactions, top by confidence:

A	B	Type	Score
CENPU	NUP62	psi-mi:“MI:0915”(physical association)	0.740
NUP62	CENPU	psi-mi:“MI:0915”(physical association)	0.740
SART3	PRPF4	psi-mi:“MI:0914”(association)	0.730
ITGB3BP	CENPU	psi-mi:“MI:0915”(physical association)	0.710
ITGB3BP	CENPU	psi-mi:“MI:0914”(association)	0.710
TFIP11	CENPU	psi-mi:“MI:0915”(physical association)	0.670
CENPU	TFIP11	psi-mi:“MI:0915”(physical association)	0.670
RBM34	RRP8	psi-mi:“MI:0914”(association)	0.640
CENPU	CENPQ	psi-mi:“MI:0915”(physical association)	0.620
PLK1	C1orf226	psi-mi:“MI:0914”(association)	0.560
CENPH	ITGB3BP	psi-mi:“MI:0914”(association)	0.530
FGF3	GTPBP10	psi-mi:“MI:0914”(association)	0.530
ZNF512	ZNF724	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
NUP62	RGPD8	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
RBM4	NVL	psi-mi:“MI:0914”(association)	0.530
RRP8	NVL	psi-mi:“MI:0914”(association)	0.530
KNOP1	DHX15	psi-mi:“MI:0914”(association)	0.530
RPL18A	RRP8	psi-mi:“MI:0914”(association)	0.530
CENPP	ITGB3BP	psi-mi:“MI:0914”(association)	0.530
RPL7A	NVL	psi-mi:“MI:0914”(association)	0.530
ITGB3BP	CENPP	psi-mi:“MI:0914”(association)	0.530
CENPH	PSMD11	psi-mi:“MI:0914”(association)	0.530
CENPU	VIM	psi-mi:“MI:0915”(physical association)	0.400
Ndc80	RRBP1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (180): CENPU (Two-hybrid), CENPU (Two-hybrid), CENPU (Affinity Capture-MS), CENPU (Affinity Capture-MS), CENPU (Affinity Capture-MS), CENPF (Affinity Capture-MS), CENPI (Affinity Capture-MS), GOLGA3 (Affinity Capture-MS), RPL10A (Affinity Capture-MS), NHS (Affinity Capture-MS), PLXNB1 (Affinity Capture-MS), IVNS1ABP (Affinity Capture-MS), FNDC3A (Affinity Capture-MS), ITGB3BP (Affinity Capture-MS), KPNA6 (Affinity Capture-MS)

ESM2 similar proteins: A6H5X4, B1AUS7, D0QMC3, O35368, O60224, O60225, P0C6Y7, P0DOV1, P0DOV2, P23497, P41218, Q15361, Q16384, Q16385, Q16666, Q2KIN0, Q3U827, Q3ZCI6, Q4R7Q1, Q504N7, Q5H9L4, Q5I0E2, Q5I0J8, Q5RAK3, Q5RCZ8, Q5RD14, Q5W0A0, Q62187, Q6K0P9, Q71F23, Q7RTT3, Q7RTT4, Q7RTT5, Q7RTT6, Q86T96, Q8BV49, Q8BVM9, Q8C0V1, Q8C6C7, Q8CGE8

Diamond homologs: Q2KIW5, Q2Z1W2, Q4V8G7, Q71F23, Q8C4M7

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PLK1	down-regulates	CENPU	phosphorylation
CENPU	“form complex”	“CCAN complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 115 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	36.1×	3e-07
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	13	19.4×	2e-11
Peptide chain elongation	12	19.3×	6e-11
Viral mRNA Translation	12	19.3×	6e-11
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	12	19.1×	6e-11
Selenocysteine synthesis	12	18.3×	8e-11
Eukaryotic Translation Termination	12	18.3×	8e-11
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	12	17.9×	9e-11

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	13	23.4×	6e-12
RNA processing	8	17.0×	4e-06
translation	14	14.0×	4e-10
chromosome segregation	8	13.5×	2e-05
ribosomal small subunit biogenesis	5	11.1×	8e-03
rRNA processing	6	8.2×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2075 predictions. Top by Δscore:

Variant	Effect	Δscore
4:184695397:TCATA:T	acceptor_gain	1.0000
4:184695398:CATA:C	acceptor_gain	1.0000
4:184695398:CATAC:C	acceptor_gain	1.0000
4:184695400:TA:T	acceptor_gain	1.0000
4:184695402:C:CC	acceptor_gain	1.0000
4:184710070:A:AC	donor_gain	1.0000
4:184710071:C:CC	donor_gain	1.0000
4:184710071:CTG:C	donor_gain	1.0000
4:184713014:C:CC	acceptor_gain	1.0000
4:184716391:TCTTA:T	donor_loss	1.0000
4:184716392:CTTA:C	donor_loss	1.0000
4:184716393:TTA:T	donor_loss	1.0000
4:184716394:T:TG	donor_loss	1.0000
4:184716395:A:AC	donor_gain	1.0000
4:184716395:A:AT	donor_loss	1.0000
4:184716396:C:CC	donor_gain	1.0000
4:184716482:G:C	donor_gain	1.0000
4:184716630:CTGG:C	acceptor_gain	1.0000
4:184716631:TGG:T	acceptor_gain	1.0000
4:184716632:GG:G	acceptor_gain	1.0000
4:184716634:C:CC	acceptor_gain	1.0000
4:184716636:G:C	acceptor_gain	1.0000
4:184716636:G:GC	acceptor_gain	1.0000
4:184716638:G:C	acceptor_gain	1.0000
4:184716638:G:GC	acceptor_gain	1.0000
4:184717192:CTGAA:C	acceptor_gain	1.0000
4:184717197:C:CC	acceptor_gain	1.0000
4:184724952:AGTAC:A	donor_loss	1.0000
4:184724953:GTACC:G	donor_loss	1.0000
4:184724954:TA:T	donor_loss	1.0000

AlphaMissense

2754 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:184725046:G:C	S77R	0.987
4:184725046:G:T	S77R	0.987
4:184725048:T:G	S77R	0.987
4:184695387:G:C	S386R	0.978
4:184695387:G:T	S386R	0.978
4:184695389:T:G	S386R	0.978
4:184697780:A:G	L337P	0.954
4:184695334:A:G	L404P	0.953
4:184695376:A:G	L390P	0.945
4:184725053:A:G	L75S	0.942
4:184728919:A:C	F71L	0.942
4:184728919:A:T	F71L	0.942
4:184728921:A:G	F71L	0.942
4:184695385:A:G	L387P	0.940
4:184697759:A:G	L344P	0.939
4:184702108:A:G	L302P	0.939
4:184700826:A:G	L327P	0.937
4:184697699:A:G	L364P	0.932
4:184695313:A:G	L411S	0.929
4:184725049:A:C	H76Q	0.925
4:184725049:A:T	H76Q	0.925
4:184695365:C:G	A394P	0.923
4:184697738:A:G	L351P	0.923
4:184725047:C:T	S77N	0.922
4:184695373:A:G	L391S	0.920
4:184702396:A:C	F281L	0.919
4:184702396:A:T	F281L	0.919
4:184702398:A:G	F281L	0.919
4:184725051:G:C	H76D	0.919
4:184695379:G:T	A389D	0.911

dbSNP variants (sampled 300 via entrez): RS10000480 (4:184697941 G>A), RS10000507 (4:184698127 C>T), RS1000084740 (4:184726081 T>A), RS1000138160 (4:184701415 C>T), RS1000178794 (4:184710373 T>C), RS10002618 (4:184735599 A>G,T), RS10002701 (4:184735653 A>G,T), RS1000282440 (4:184702290 TAA>T), RS10002919 (4:184698511 C>T), RS1000353771 (4:184723654 C>A,T), RS1000408303 (4:184716760 T>C,G), RS1000424534 (4:184735374 T>C), RS1000441852 (4:184730451 A>G), RS1000468412 (4:184723378 T>C), RS1000474091 (4:184730644 G>A)

Disease associations

OMIM: gene MIM:611511 | disease phenotypes: MIM:615420

GenCC curated gene-disease

Mondo (1): myopia 22, autosomal dominant (MONDO:0014177)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001455_4	Kawasaki disease	3.000000e-08
GCST004867_17	Systemic lupus erythematosus	8.000000e-07
GCST005312_11	Menopause (age at onset)	1.000000e-16

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004704	age at menopause

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases expression, decreases reaction, increases expression	4
bisphenol A	increases expression, decreases expression	3
Benzo(a)pyrene	increases expression, decreases expression	3
Cyclosporine	decreases expression	3
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	increases expression	2
Cisplatin	affects expression, increases expression	2
Progesterone	decreases expression, increases expression	2
Rotenone	increases expression, decreases expression	2
Tretinoin	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
chromium hexavalent ion	increases abundance, decreases expression	1
deguelin	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	affects expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	increases expression	1
incobotulinumtoxinA	decreases expression	1
NSC 689534	affects binding, decreases expression	1

Clinical trials (associated diseases)

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