CETN2

Summary

CETN2 (centrin 2, HGNC:1867) is a protein-coding gene on chromosome Xq28, encoding Centrin-2 (P41208). Plays a fundamental role in microtubule organizing center structure and function.

Caltractin belongs to a family of calcium-binding proteins and is a structural component of the centrosome. The high level of conservation from algae to humans and its association with the centrosome suggested that caltractin plays a fundamental role in the structure and function of the microtubule-organizing center, possibly required for the proper duplication and segregation of the centrosome.

Source: NCBI Gene 1069 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 73 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_004344

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1867
Approved symbol	CETN2
Name	centrin 2
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	CEN2
Ensembl gene	ENSG00000147400
Ensembl biotype	protein_coding
OMIM	300006
Entrez	1069

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000370277, ENST00000493482, ENST00000892144, ENST00000918827

RefSeq mRNA: 1 — MANE Select: NM_004344 NM_004344

CCDS: CCDS14716

Canonical transcript exons

ENST00000370277 — 5 exons

Exon	Start	End
ENSE00000979874	152829149	152829277
ENSE00000979875	152828537	152828674
ENSE00001302515	152829602	152829760
ENSE00001452248	152826994	152827930
ENSE00001452251	152830708	152830757

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.0694 / max 3191.0106, expressed in 1800 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200854	38.0694	1800

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.85	gold quality
epithelium of bronchus	UBERON:0002031	99.58	gold quality
bronchus	UBERON:0002185	99.50	gold quality
right uterine tube	UBERON:0001302	99.41	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.83	gold quality
caput epididymis	UBERON:0004358	98.77	gold quality
germinal epithelium of ovary	UBERON:0001304	98.06	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.03	gold quality
corpus epididymis	UBERON:0004359	97.73	gold quality
epithelium of nasopharynx	UBERON:0001951	97.49	gold quality
cranial nerve II	UBERON:0000941	97.48	gold quality
cauda epididymis	UBERON:0004360	97.22	gold quality
adenohypophysis	UBERON:0002196	96.86	gold quality
pituitary gland	UBERON:0000007	96.69	gold quality
seminal vesicle	UBERON:0000998	96.60	gold quality
nasal cavity epithelium	UBERON:0005384	96.47	gold quality
tibia	UBERON:0000979	96.42	gold quality
hypothalamus	UBERON:0001898	96.32	gold quality
parietal pleura	UBERON:0002400	96.28	gold quality
endometrium	UBERON:0001295	96.21	gold quality
nephron tubule	UBERON:0001231	96.17	gold quality
choroid plexus epithelium	UBERON:0003911	96.11	gold quality
nucleus accumbens	UBERON:0001882	96.07	gold quality
fallopian tube	UBERON:0003889	95.99	gold quality
superior vestibular nucleus	UBERON:0007227	95.90	gold quality
renal glomerulus	UBERON:0000074	95.89	gold quality
smooth muscle tissue	UBERON:0001135	95.82	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	95.75	gold quality
endocervix	UBERON:0000458	95.72	gold quality
caudate nucleus	UBERON:0001873	95.71	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	63.48
E-HCAD-1	yes	33.18
E-MTAB-10287	yes	26.95
E-GEOD-130148	yes	17.24
E-MTAB-6701	yes	15.30
E-MTAB-9388	yes	7.66
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXJ1

miRNA regulators (miRDB)

54 targeting CETN2, 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-8485	100.00	77.57	4731
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-19A-5P	99.36	66.93	1675

Literature-anchored findings (GeneRIF, showing 32)

• required for centriole duplication in mammalian cells (PMID:12176356)
• The solution structure of the long C-terminal fragment of centrin 2 exhibits an open two EF-hand structure, similar to the conformation of related Ca(2+)-saturated regulatory domains. (PMID:12578356)
• structural characterization of the complex formed by the C-terminal domain of Cen2 with a peptide of xeroderma pigmentosum group C protein (PMID:12890685)
• Results describe the self-assembly properties of purified human centrin-2 in vitro. (PMID:15356003)
• Centrin 2 stimulates nucleotide excision repair by interacting with XPC. (PMID:15964821)
• an 18-residue peptide, from the N-terminal unstructured fragment, has a significant affinity for the isolated C-terminal domain, suggesting an active role in the self-assembly of centrin molecules. (PMID:16411764)
• the crystal structure of calcium-loaded full-length centrin-2 complexed with a xeroderma pigmentosum group C peptide; a novel binding motif for centrin (PMID:16627479)
• A complex formed by a Ca2+-bound human centrin 2 with a 17-mer peptide derived from the XPC sequence was crystallized. (PMID:16820684)
• Centrin 2 is highly sensitive to ionizing radiation, which could have important consequences on its biological functions. (PMID:17603931)
• The present data confirm that the in vitro structural features of the centrin/XPC peptide complex are highly relevant to the cellular context. (PMID:17897675)
• CETN2 localizes to the vertebrate nuclear pore and plays a role in mRNA and protein export. (PMID:18172010)
• NMR analysis indicates that the physical interaction between C-XPC and centrin 2 induces only minor conformational changes into XPC, localized around the 17-mer segment (847-863), showed to be critically involved in the centrin binding. (PMID:18177054)
• lower centrin levels in oligoasthnozoospermic males resulted in lower pregnancy percentage in this group after ICSI. (PMID:19179680)
• The nucleocytoplasmic shuttling of centrin-2 depends on the SUMO system. (PMID:19706679)
• The structure of C-HsCen2 [the C-terminal domain of HsCen2 (T94-Y172)] in complex with R17-hSfi1-20 was determined. (PMID:19857500)
• oxidative radicals induce high proportions of irreversible damages (polymerisation) centrin 2 is highly sensitive to ionising radiation. (PMID:20586543)
• Mps1-dependent phosphorylation of Cetn2 stimulates the canonical centriole assembly pathway. (PMID:20980622)
• CDC25B forms a close association with Ctn-2 proteins at the centrosome. (PMID:21091437)
• xeroderma pigmentosum complementation group C expression correlates with a decreased amount of CENTRIN 2 transcript and protein (PMID:21676658)
• The stability of centrin is regulated in part by Aurora A. (PMID:21731694)
• Cen2 influences the binding of RPA and XPA with damaged DNA. (PMID:22809153)
• CDC25B, through activation of a centrosomal pool of CDK2, stabilises the local pool of Mps1 which in turn regulates the level of centrin 2 at the centrosome. (PMID:23840880)
• Data indicate that overexpression of the centrin interactor POC5 leads to the assembly of linear, centrin-dependent structures. (PMID:23844208)
• co-depletion of centrin 2 and PCID2 leads to blocking rather than delaying nuclear protein export, indicating the dominance of the centrin 2 phenotype. (PMID:24291146)
• Centrin2 regulates primary ciliogenesis through controlling CP110 levels. (PMID:25753040)
• Cetn3 inhibits Mps1 autophosphorylation at Thr-676, a known site of T-loop autoactivation, and interferes with Mps1-dependent phosphorylation of Cetn2. The cellular overexpression of Cetn3 attenuates the incorporation of Cetn2 into centrioles and centrosome reduplication, whereas depletion of Cetn3 generates extra centrioles. (PMID:26354417)
• Multidisciplinary approach showed that HsPrp40Ap interacts with centrin in vitro, supporting a coupled functional role for these proteins in pre-mRNA splicing. (PMID:28636910)
• Correlations between loss of expression of three genes: CETN2 (P < 0.001) and ERCC1 (P = 0.01) from the nucleotide excision repair (NER) and NEIL2 (P = 0.04) from the base excision repair (BER) pathways were associated with endocrine treatment resistance in discovery dataset, and subsequently validated in independent patient cohorts. (PMID:29793947)
• The results in this report demonstrate that 14-3-3 epsilon and 14-3-3 gamma form a complex with Centrin2 and that the binding site is located in the N-terminal EF hand in Centrin2, EF1. (PMID:31180055)
• the regulation and control of peptide p22-XPC binding with HsCen2 (PMID:31202846)
• observations indicate that centrin 2 requires calcium-binding capacity for its primary ciliogenesis functions, but not for NER, and suggest that these functions require centrin 2 to be capable of forming complexes with partner proteins. (PMID:31492759)
• High expression of CETN2 is associated with platinum resistance and poor prognosis in epithelial ovarian cancer. (PMID:36527574)

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	cabp2a	ENSDARG00000052016
danio_rerio	cabp2b	ENSDARG00000052277
mus_musculus	Cetn2	ENSMUSG00000031347
rattus_norvegicus	Cetn2	ENSRNOG00000059593
drosophila_melanogaster	TpnC4	FBGN0033027
drosophila_melanogaster	CG13526	FBGN0034774
drosophila_melanogaster	CG5024	FBGN0039373
drosophila_melanogaster	CG17770	FBGN0039374
drosophila_melanogaster	CG30378	FBGN0050378
caenorhabditis_elegans		WBGENE00000285
caenorhabditis_elegans		WBGENE00000287
caenorhabditis_elegans	pat-10	WBGENE00003934
caenorhabditis_elegans		WBGENE00006583
caenorhabditis_elegans		WBGENE00008453
caenorhabditis_elegans	F35C12.3	WBGENE00009408
caenorhabditis_elegans		WBGENE00015264
caenorhabditis_elegans		WBGENE00019352

Paralogs (20): CABP7 (ENSG00000100314), CABP5 (ENSG00000105507), CALML4 (ENSG00000129007), CALM2 (ENSG00000143933), CETN3 (ENSG00000153140), CABP1 (ENSG00000157782), CALM3 (ENSG00000160014), CABP2 (ENSG00000167791), CALML6 (ENSG00000169885), EFCAB3 (ENSG00000172421), EFCAB12 (ENSG00000172771), CABP4 (ENSG00000175544), CETN1 (ENSG00000177143), CALML3 (ENSG00000178363), CALML5 (ENSG00000178372), CALN1 (ENSG00000183166), CALM1 (ENSG00000198668), EFCAB2 (ENSG00000203666), EFCAB7 (ENSG00000203965), EFCAB9 (ENSG00000214360)

Protein

Protein identifiers

Centrin-2 — P41208 (reviewed: P41208)

Alternative names: Caltractin isoform 1

All UniProt accessions (1): P41208

UniProt curated annotations — full annotation on UniProt →

Function. Plays a fundamental role in microtubule organizing center structure and function. Required for centriole duplication and correct spindle formation. Has a role in regulating cytokinesis and genome stability via cooperation with CALM1 and CCP110. Involved in global genome nucleotide excision repair (GG-NER) by acting as component of the XPC complex. Cooperatively with RAD23B appears to stabilize XPC. In vitro, stimulates DNA binding of the XPC:RAD23B dimer. The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, XPA, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single-stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5’-to-3’ direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. As a component of the TREX-2 complex, involved in the export of mRNAs to the cytoplasm through the nuclear pores.

Subunit / interactions. Monomer. Homooligomer. Interacts with SFI1. Interacts with CCP110. Component of the XPC complex composed of XPC, RAD23B and CETN2. Component of the nuclear pore complex (NPC)-associated TREX-2 complex (transcription and export complex 2), composed of at least GANP, 2 copies of ENY2, PCID2, SEM1/DSS1, and either centrin CETN2 or centrin CETN3. The TREX-2 complex also associates with ALYREF/ALY and with the nucleoporin NUP153. Interacts with USP49. Forms a microtubule-associated complex with POC5, POC1B and FAM161A. Interacts with CCDC15.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Nucleus envelope. Nucleus. Nuclear pore complex.

Miscellaneous. Binds two moles of calcium per mole of protein.

Similarity. Belongs to the centrin family.

RefSeq proteins (1): NP_004335* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000629	RNA-helicase_DEAD-box_CS	Conserved_site
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR050145	Centrin_CML-like	Family

Pfam: PF13499

UniProt features (38 total): binding site 10, helix 8, strand 7, domain 4, modified residue 3, region of interest 2, initiator methionine 1, chain 1, cross-link 1, turn 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
2OBH	X-RAY DIFFRACTION	1.8
2GGM	X-RAY DIFFRACTION	2.35
28JS	ELECTRON MICROSCOPY	3.32
8EBX	ELECTRON MICROSCOPY	3.6
8EBT	ELECTRON MICROSCOPY	3.9
28JV	ELECTRON MICROSCOPY	3.91
8EBS	ELECTRON MICROSCOPY	4
8J07	ELECTRON MICROSCOPY	4.1
9PCP	ELECTRON MICROSCOPY	4.3
8EBW	ELECTRON MICROSCOPY	5.6
8EBV	ELECTRON MICROSCOPY	7.1
1M39	SOLUTION NMR
1ZMZ	SOLUTION NMR
2A4J	SOLUTION NMR
2K2I	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P41208-F1	85.51	0.71

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 (10): 45; 47; 52; 150; 152; 154; 156; 161; 41; 43

Post-translational modifications (4): 2, 20, 26, 22

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-5696394	DNA Damage Recognition in GG-NER
R-HSA-5696395	Formation of Incision Complex in GG-NER
R-HSA-8854518	AURKA Activation by TPX2

MSigDB gene sets: 244 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, PAL_PRMT5_TARGETS_UP, WANG_RECURRENT_LIVER_CANCER_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, HSIAO_HOUSEKEEPING_GENES, GOBP_MALE_GAMETE_GENERATION, KAUFFMANN_DNA_REPAIR_GENES, GOCC_MICROTUBULE_ORGANIZING_CENTER, PATIL_LIVER_CANCER, GOBP_NUCLEAR_TRANSPORT, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_NUCLEOTIDE_EXCISION_REPAIR, GOBP_CENTRIOLE_ASSEMBLY, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN

GO Biological Process (11): microtubule cytoskeleton organization (GO:0000226), mitotic cell cycle (GO:0000278), nucleotide-excision repair (GO:0006289), centriole replication (GO:0007099), spermatogenesis (GO:0007283), protein transport (GO:0015031), regulation of cytokinesis (GO:0032465), mRNA transport (GO:0051028), cell division (GO:0051301), DNA repair (GO:0006281), DNA damage response (GO:0006974)

GO Molecular Function (6): calcium ion binding (GO:0005509), microtubule binding (GO:0008017), G-protein beta/gamma-subunit complex binding (GO:0031683), heterotrimeric G-protein binding (GO:0032795), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (18): nucleus (GO:0005634), nucleoplasm (GO:0005654), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), photoreceptor connecting cilium (GO:0032391), ciliary basal body (GO:0036064), nuclear pore nuclear basket (GO:0044615), apical part of cell (GO:0045177), transcription export complex 2 (GO:0070390), XPC complex (GO:0071942), glial cell projection (GO:0097386), 9+2 motile cilium (GO:0097729), nuclear envelope (GO:0005635), nuclear pore (GO:0005643), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
G2/M Transition	2
Centrosome maturation	2
Global Genome Nucleotide Excision Repair (GG-NER)	2
SUMO E3 ligases SUMOylate target proteins	1
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Assembly of the 9+0 primary cilium	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
microtubule organizing center	3
nuclear protein-containing complex	3
protein-containing complex binding	2
intracellular membraneless organelle	2
plasma membrane bounded cell projection	2
cytoskeleton organization	1
microtubule-based process	1
cell cycle	1
mitotic nuclear division	1
DNA repair	1
cell cycle process	1
centrosome duplication	1
centriole assembly	1
developmental process involved in reproduction	1
male gamete generation	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
cytokinesis	1
regulation of cell cycle process	1
regulation of cell division	1
RNA transport	1
cellular process	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
metal ion binding	1
tubulin binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
centriole	1
cytoplasm	1
ciliary transition zone	1
photoreceptor cell cilium	1
cilium	1
nuclear pore	1
nucleotide-excision repair complex	1

Protein interactions and networks

STRING

3110 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CETN2	RAD23B	P54727	996
CETN2	XPC	Q01831	992
CETN2	PCID2	Q5JVF3	986
CETN2	MCM3AP	O60318	981
CETN2	ENY2	Q9NPA8	977
CETN2	SFI1	A8K8P3	968
CETN2	RAD23A	P54725	962
CETN2	PCNT	O95613	884
CETN2	CNTROB	Q8N137	879
CETN2	SEM1	Q6ZVN7	842
CETN2	CEP135	Q66GS9	840
CETN2	PLK4	O00444	832
CETN2	DDB2	Q92466	830
CETN2	CCP110	O43303	820
CETN2	PMPCA	Q10713	816

IntAct

167 interactions, top by confidence:

A	B	Type	Score
POC5	CETN2	psi-mi:“MI:0915”(physical association)	0.920
CETN2	POC5	psi-mi:“MI:0915”(physical association)	0.920
POC5	CETN3	psi-mi:“MI:0914”(association)	0.920
XPC	CETN2	psi-mi:“MI:0407”(direct interaction)	0.900
POC5	CETN3	psi-mi:“MI:0914”(association)	0.770
CETN2	SFI1	psi-mi:“MI:0407”(direct interaction)	0.740
SFI1	CETN2	psi-mi:“MI:0407”(direct interaction)	0.740
CETN2	SFI1	psi-mi:“MI:0914”(association)	0.740
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
XPC	CETN3	psi-mi:“MI:0914”(association)	0.730
XPC	PARP1	psi-mi:“MI:0914”(association)	0.730
CETN2	SGSM1	psi-mi:“MI:0915”(physical association)	0.720
SGSM1	CETN2	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (209): PNMA5 (Two-hybrid), SGSM1 (Two-hybrid), POC5 (Two-hybrid), CETN2 (Affinity Capture-MS), CETN2 (Affinity Capture-MS), CETN2 (Affinity Capture-MS), CETN2 (Affinity Capture-MS), CETN2 (Affinity Capture-MS), CETN2 (Affinity Capture-MS), CETN2 (Affinity Capture-MS), CETN2 (Affinity Capture-MS), CETN2 (Co-fractionation), CETN2 (Co-fractionation), IMPDH2 (Co-fractionation), AP2S1 (Proximity Label-MS)

ESM2 similar proteins: A0A125YHX7, A0A125YZN2, J9W034, O15182, O23184, O35648, O74435, O82659, P02597, P02599, P04352, P05434, P05933, P06704, P27163, P27164, P27482, P41041, P41208, P41209, P41210, P43645, P43646, P49258, P53440, P53441, P54213, P60204, P60205, P60206, P61859, P61860, P61861, Q06827, Q12798, Q24956, Q27177, Q27178, Q27179, Q2TBN3

Diamond homologs: A0A125YHX7, A0A125YZN2, A2WN93, A2WNH1, A2Y609, A3E3H0, A3E4D8, A3E4F9, A4UHC0, A8CEP3, A8I1Q0, J9W034, O15182, O23184, O35648, O60041, O74435, O82018, O82659, O94739, O96102, P02597, P02598, P04352, P04353, P04464, P05419, P05434, P06704, P06787, P07463, P0DH95, P0DH96, P0DH97, P0DH98, P11120, P11121, P13868, P15094, P17928

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
AURKA	up-regulates	CETN2	phosphorylation
CCP110	“up-regulates activity”	CETN2	binding
FOXJ1	“up-regulates quantity by expression”	CETN2	“transcriptional regulation”
PCM1	up-regulates	CETN2	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 112 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
Formation of Incision Complex in GG-NER	6	19.8×	2e-04
Metalloprotease DUBs	5	19.5×	4e-04
Packaging Of Telomere Ends	5	14.3×	1e-03
Recognition and association of DNA glycosylase with site containing an affected purine	5	13.2×	1e-03
Cleavage of the damaged purine	5	13.2×	1e-03
Inhibition of DNA recombination at telomere	6	13.1×	4e-04
Recognition and association of DNA glycosylase with site containing an affected pyrimidine	5	12.0×	2e-03
Cleavage of the damaged pyrimidine	5	12.0×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
nucleotide-excision repair	5	19.5×	1e-03
heterochromatin formation	6	15.6×	6e-04
microtubule cytoskeleton organization	6	7.4×	8e-03
cell division	10	4.7×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	26
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
147548	GRCh38/hg38 Xq28(chrX:151750863-155522304)x1	Pathogenic
3024366	GRCh38/hg38 Xq28(chrX:152819425-152869723)	Likely pathogenic

SpliceAI

553 predictions. Top by Δscore:

Variant	Effect	Δscore
X:152827927:TTTC:T	acceptor_gain	1.0000
X:152827929:TC:T	acceptor_gain	1.0000
X:152827929:TCC:T	acceptor_loss	1.0000
X:152827930:CC:C	acceptor_gain	1.0000
X:152827931:C:CC	acceptor_gain	1.0000
X:152827931:CT:C	acceptor_loss	1.0000
X:152828533:AAAC:A	donor_loss	1.0000
X:152828534:AAC:A	donor_loss	1.0000
X:152828535:A:AT	donor_loss	1.0000
X:152828536:C:CA	donor_loss	1.0000
X:152828670:TCAGA:T	acceptor_gain	1.0000
X:152828671:CAGA:C	acceptor_gain	1.0000
X:152828671:CAGAC:C	acceptor_gain	1.0000
X:152828672:AGAC:A	acceptor_loss	1.0000
X:152828673:GA:G	acceptor_gain	1.0000
X:152828673:GAC:G	acceptor_loss	1.0000
X:152828675:C:CC	acceptor_gain	1.0000
X:152828676:T:C	acceptor_gain	1.0000
X:152828676:T:TC	acceptor_gain	1.0000
X:152828680:CAAG:C	acceptor_gain	1.0000
X:152828681:A:T	acceptor_gain	1.0000
X:152828683:G:GC	acceptor_gain	1.0000
X:152828689:C:CT	acceptor_gain	1.0000
X:152829144:CTT:C	donor_loss	1.0000
X:152829145:TTACC:T	donor_loss	1.0000
X:152829146:TACC:T	donor_loss	1.0000
X:152829147:A:AC	donor_gain	1.0000
X:152829147:AC:A	donor_gain	1.0000
X:152829148:C:CA	donor_loss	1.0000
X:152829148:C:CG	donor_gain	1.0000

AlphaMissense

1167 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:152828589:A:G	L126P	1.000
X:152827874:G:C	F162L	0.999
X:152827874:G:T	F162L	0.999
X:152827876:A:G	F162L	0.999
X:152827915:C:G	A149P	0.999
X:152827926:A:G	M145T	0.999
X:152828541:A:G	L142P	0.999
X:152828578:C:G	A130P	0.999
X:152828631:A:G	L112P	0.999
X:152828636:G:C	F110L	0.999
X:152828636:G:T	F110L	0.999
X:152828638:A:G	F110L	0.999
X:152829259:C:G	G61R	0.999
X:152829606:A:G	L53P	0.999
X:152829648:A:G	L39P	0.999
X:152829653:A:C	F37L	0.999
X:152829653:A:T	F37L	0.999
X:152829655:A:G	F37L	0.999
X:152827875:A:G	F162S	0.998
X:152827914:G:T	A149D	0.998
X:152827926:A:C	M145R	0.998
X:152827926:A:T	M145K	0.998
X:152828577:G:T	A130D	0.998
X:152828604:A:C	I121S	0.998
X:152828604:A:G	I121T	0.998
X:152828627:A:C	F113L	0.998
X:152828627:A:T	F113L	0.998
X:152828629:A:G	F113L	0.998
X:152828637:A:G	F110S	0.998
X:152829173:A:C	F89L	0.998

dbSNP variants (sampled 300 via entrez): RS1000558690 (X:152829957 T>C), RS1001835163 (X:152830793 C>T), RS1002119269 (X:152830638 C>T), RS1003387272 (X:152832440 C>T), RS1004567373 (X:152828684 T>C), RS1006292813 (X:152830873 A>C), RS1007411122 (X:152831281 C>A,T), RS1007526088 (X:152831901 C>T), RS1008879206 (X:152826891 G>A), RS1009475432 (X:152831934 T>C), RS1009880128 (X:152832374 A>G), RS1010472262 (X:152830530 C>A), RS1010782797 (X:152830040 C>A), RS1014517942 (X:152827996 T>A,G), RS1015034932 (X:152830887 C>A,G)

Disease associations

OMIM: gene MIM:300006 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): autism spectrum disorder (MONDO:0005258)

Orphanet (1): NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST011353_5	Serum alkaline phosphatase levels	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
bisphenol A	affects expression	1
trichostatin A	affects expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
potassium chromate(VI)	decreases expression	1
periodate-oxidized adenosine	affects expression	1
2,3-dimethoxy-1,4-naphthoquinone	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
chloropicrin	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
K 7174	decreases expression	1
scriptaid	affects expression	1
abrine	decreases expression	1
quinocetone	increases expression	1
MRK 003	decreases expression	1
bisphenol S	increases expression, affects cotreatment	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Dimethylnitrosamine	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Hydrogen Peroxide	affects expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0A1	Ubigene HeLa CETN2 KO	Cancer cell line	Female
CVCL_E1TP	HAP1 CETN2 (-) 1	Cancer cell line	Male
CVCL_E1TQ	HAP1 CETN2 (-) 2	Cancer cell line	Male
CVCL_E1TR	HAP1 CETN2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder