CETN1

Summary

CETN1 (centrin 1, HGNC:1866) is a protein-coding gene on chromosome 18p11.32, encoding Centrin-1 (Q12798). Plays a fundamental role in microtubule-organizing center structure and function.

The protein encoded by this gene plays important roles in the determination of centrosome position and segregation, and in the process of microtubule severing. This protein is localized to the centrosome of interphase cells, and redistributes to the region of the spindle poles during mitosis, reflecting the dynamic behavior of the centrosome during the cell cycle.

Source: NCBI Gene 1068 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 33 total — 1 pathogenic
• MANE Select transcript: NM_004066

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1866
Approved symbol	CETN1
Name	centrin 1
Location	18p11.32
Locus type	gene with protein product
Status	Approved
Aliases	CEN1
Ensembl gene	ENSG00000177143
Ensembl biotype	protein_coding
OMIM	603187
Entrez	1068

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000327228

RefSeq mRNA: 1 — MANE Select: NM_004066 NM_004066

CCDS: CCDS11820

Canonical transcript exons

ENST00000327228 — 1 exons

Exon	Start	End
ENSE00001231082	580380	582114

Expression profiles

Bgee: expression breadth broad, 32 present calls, max score 97.30.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2966 / max 316.6617, expressed in 5 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
169052	0.2511	4
169051	0.0455	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.30	gold quality
right testis	UBERON:0004534	97.14	gold quality
testis	UBERON:0000473	93.72	gold quality
sperm	CL:0000019	92.23	gold quality
male germ cell	CL:0000015	91.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.90	gold quality
adult organism	UBERON:0007023	81.70	gold quality
olfactory bulb	UBERON:0002264	78.54	gold quality
type B pancreatic cell	CL:0000169	78.46	gold quality
diaphragm	UBERON:0001103	75.04	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	72.60	gold quality
hair follicle	UBERON:0002073	72.34	gold quality
oocyte	CL:0000023	69.52	gold quality
pancreatic ductal cell	CL:0002079	68.56	silver quality
epithelial cell of pancreas	CL:0000083	67.60	gold quality
mucosa of paranasal sinus	UBERON:0005030	65.20	gold quality
upper arm skin	UBERON:0004263	64.78	gold quality
mucosa of urinary bladder	UBERON:0001259	64.36	gold quality
epithelium of nasopharynx	UBERON:0001951	63.85	gold quality
gingival epithelium	UBERON:0001949	63.84	gold quality
mammary duct	UBERON:0001765	63.49	gold quality
cervix epithelium	UBERON:0004801	63.38	gold quality
secondary oocyte	CL:0000655	63.23	gold quality
ileal mucosa	UBERON:0000331	63.18	silver quality
epithelium of mammary gland	UBERON:0003244	63.02	gold quality
thymus	UBERON:0002370	62.18	gold quality
cervix squamous epithelium	UBERON:0006922	61.70	gold quality
gingiva	UBERON:0001828	61.37	gold quality
cardia of stomach	UBERON:0001162	60.98	gold quality
tongue squamous epithelium	UBERON:0006919	60.97	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	29.55
E-ANND-3	no	1.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting CETN1, 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-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-26A-1-3P	99.64	66.81	788
HSA-MIR-26A-2-3P	99.64	66.82	786
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-888-5P	99.30	70.15	1855
HSA-MIR-590-5P	99.25	70.76	930
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-155-3P	99.03	67.99	924
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-3184-5P	98.56	67.13	1491

Literature-anchored findings (GeneRIF, showing 7)

• These data demonstrate a functional role for CaM binding to CP110 and suggest that CP110 cooperates with CaM and centrin to regulate progression through cytokinesis. (PMID:16760425)
• CETN1 is overexpressed in breast cancer tissue and promotes cells’proliferation, tumor growth and metastasis. (PMID:25261648)
• A chirality change in XPC- and Sfi1-derived peptides affects their affinity for centrin. (PMID:26923803)
• important spectral and hydrodynamic characteristics of human Centrin-1, accounting that HsCentrin-1 has moderate affinity for Ca(2+). Centrin-1 does not gain structure as seen by far- and near-UV circular dichroism, rather there is a loss of ellipticity, though inconsiderable upon binding Ca(2+). (PMID:27235176)
• Conformational scanning of individual EF-hand motifs of calcium sensor protein centrin-1. (PMID:34273620)
• Exome sequencing and functional analyses revealed CETN1 variants leads to impaired cell division and male fertility. (PMID:36048845)
• Human SFI1 and Centrin form a complex critical for centriole architecture and ciliogenesis. (PMID:36125182)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	cetn2	ENSDARG00000101510
mus_musculus	Cetn1	ENSMUSG00000050996
rattus_norvegicus	Cetn1	ENSRNOG00000084288
drosophila_melanogaster	CG17493	FBGN0040010
drosophila_melanogaster	CG31802	FBGN0051802
caenorhabditis_elegans		WBGENE00000285
caenorhabditis_elegans		WBGENE00000287
caenorhabditis_elegans	pat-10	WBGENE00003934
caenorhabditis_elegans		WBGENE00008453
caenorhabditis_elegans	F35C12.3	WBGENE00009408
caenorhabditis_elegans		WBGENE00015264

Paralogs (20): CABP7 (ENSG00000100314), CABP5 (ENSG00000105507), CALML4 (ENSG00000129007), CALM2 (ENSG00000143933), CETN2 (ENSG00000147400), CETN3 (ENSG00000153140), CABP1 (ENSG00000157782), CALM3 (ENSG00000160014), CABP2 (ENSG00000167791), CALML6 (ENSG00000169885), EFCAB3 (ENSG00000172421), EFCAB12 (ENSG00000172771), CABP4 (ENSG00000175544), CALML3 (ENSG00000178363), CALML5 (ENSG00000178372), CALN1 (ENSG00000183166), CALM1 (ENSG00000198668), EFCAB2 (ENSG00000203666), EFCAB7 (ENSG00000203965), EFCAB9 (ENSG00000214360)

Protein

Protein identifiers

Centrin-1 — Q12798 (reviewed: Q12798)

Alternative names: Caltractin isoform 2

All UniProt accessions (2): Q12798, A0A140VJG3

UniProt curated annotations — full annotation on UniProt →

Function. Plays a fundamental role in microtubule-organizing center structure and function. Plays a role in sperm cilia formation.

Subunit / interactions. Monomer. Interacts with CIMAP3. Interacts with USP49.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Cell projection. Cilium.

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

Similarity. Belongs to the centrin family.

RefSeq proteins (1): NP_004057* (*=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 (16 total): binding site 10, domain 4, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12798-F1	86.62	0.69

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

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9613829	Chaperone Mediated Autophagy
R-HSA-9615710	Late endosomal microautophagy
R-HSA-9646399	Aggrephagy

MSigDB gene sets: 101 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_CENTRIOLE_ASSEMBLY, OUELLET_CULTURED_OVARIAN_CANCER_INVASIVE_VS_LMP_DN, WTGAAAT_UNKNOWN, GOCC_CENTROSOME, OCT1_06, GOBP_ORGANELLE_ASSEMBLY, GOBP_CELLULAR_RESPONSE_TO_HEAT, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOCC_NEURON_PROJECTION, GOBP_CENTROSOME_DUPLICATION, GOCC_SPINDLE, GOCC_CENTRIOLE, GOCC_MOTILE_CILIUM

GO Biological Process (4): microtubule cytoskeleton organization (GO:0000226), centriole replication (GO:0007099), cellular response to heat (GO:0034605), cell division (GO:0051301)

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 (11): spindle pole (GO:0000922), nucleus (GO:0005634), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), photoreceptor connecting cilium (GO:0032391), cytoplasm (GO:0005737), microtubule organizing center (GO:0005815), cytoskeleton (GO:0005856), cilium (GO:0005929), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Autophagy	2
Selective autophagy	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
protein-containing complex binding	2
microtubule organizing center	2
intracellular membraneless organelle	2
cytoskeleton organization	1
microtubule-based process	1
cell cycle process	1
centrosome duplication	1
centriole assembly	1
response to heat	1
cellular response to stress	1
cellular process	1
metal ion binding	1
tubulin binding	1
binding	1
cation binding	1
spindle	1
intracellular membrane-bounded organelle	1
centriole	1
cytoplasm	1
ciliary transition zone	1
photoreceptor cell cilium	1
intracellular anatomical structure	1
microtubule cytoskeleton	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

2496 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CETN1	PCNT	O95613	870
CETN1	NIN	Q8N4C6	844
CETN1	PCM1	Q15154	740
CETN1	NUP85	Q9BW27	714
CETN1	POC5	Q8NA72	709
CETN1	SFI1	A8K8P3	693
CETN1	MORN1	Q5T089	677
CETN1	CEP290	O15078	667
CETN1	DCTN2	Q13561	646
CETN1	CEP135	Q66GS9	644
CETN1	CENPA	P49450	643
CETN1	DCTN1	Q14203	635
CETN1	CEP164	Q9UPV0	631
CETN1	PLK4	O00444	620
CETN1	SASS6	Q6UVJ0	618

IntAct

38 interactions, top by confidence:

A	B	Type	Score
CETN1	POC5	psi-mi:“MI:0915”(physical association)	0.850
POC5	CETN1	psi-mi:“MI:0915”(physical association)	0.850
CETN1	SGSM1	psi-mi:“MI:0915”(physical association)	0.780
SGSM1	CETN1	psi-mi:“MI:0915”(physical association)	0.780
XPC	CETN3	psi-mi:“MI:0914”(association)	0.730
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
CETN1	POC5	psi-mi:“MI:0915”(physical association)	0.670
SGSM1	CETN1	psi-mi:“MI:0915”(physical association)	0.660
CETN1	SFI1	psi-mi:“MI:0914”(association)	0.640
SNX9	WASL	psi-mi:“MI:0914”(association)	0.640
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
ZFAND5	CETN1	psi-mi:“MI:0915”(physical association)	0.590
SGSM1	CETN2	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
CETN1	CCP110	psi-mi:“MI:0914”(association)	0.350
USP49	ANKRD28	psi-mi:“MI:0914”(association)	0.350
CALN1	CETN1	psi-mi:“MI:0914”(association)	0.350
CNN3	ATE1	psi-mi:“MI:0914”(association)	0.350
LGALS3BP	ACACB	psi-mi:“MI:0914”(association)	0.350

BioGRID (106): SGSM1 (Two-hybrid), POC5 (Two-hybrid), XPC (Affinity Capture-MS), POC5 (Affinity Capture-MS), SGSM1 (Affinity Capture-MS), KIAA1407 (Affinity Capture-MS), SFI1 (Affinity Capture-MS), SGSM2 (Affinity Capture-MS), EFCAB11 (Affinity Capture-MS), KIF1A (Affinity Capture-MS), TDP1 (Affinity Capture-MS), FBXO16 (Affinity Capture-MS), KIF1B (Affinity Capture-MS), CETN2 (Affinity Capture-MS), TWIST1 (Affinity Capture-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

2 interactions.

A	Effect	B	Mechanism
CCP110	“up-regulates activity”	CETN1	binding
PCM1	up-regulates	CETN1	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	29
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
253646	GRCh37/hg19 18p11.32-11.22(chr18:14316-10784606)x1	Pathogenic

SpliceAI

71 predictions. Top by Δscore:

Variant	Effect	Δscore
18:580607:G:GT	donor_gain	0.6900
18:580643:G:T	donor_gain	0.6900
18:580603:G:GT	donor_gain	0.6400
18:580539:G:GT	donor_gain	0.5800
18:580643:G:GT	donor_gain	0.5800
18:580765:G:T	donor_gain	0.5700
18:580573:G:GA	donor_gain	0.5500
18:580636:G:GA	donor_gain	0.5500
18:580765:G:GT	donor_gain	0.5400
18:580572:T:TA	donor_gain	0.5300
18:580511:G:GT	donor_gain	0.5100
18:580604:A:T	donor_gain	0.5100
18:580635:T:TA	donor_gain	0.5000
18:580926:G:GT	donor_gain	0.5000
18:580511:G:T	donor_gain	0.4900
18:580942:C:G	donor_gain	0.4900
18:580464:T:TA	donor_gain	0.4700
18:580465:G:GA	donor_gain	0.4700
18:580654:G:T	donor_gain	0.4500
18:580733:GCCT:G	donor_gain	0.4400
18:580644:A:T	donor_gain	0.4100
18:581119:A:G	acceptor_gain	0.4100
18:580539:G:T	donor_gain	0.4000
18:580575:C:G	donor_gain	0.4000
18:580615:G:GT	donor_gain	0.3900
18:580755:A:G	donor_gain	0.3900
18:580934:TTCAG:T	donor_gain	0.3900
18:581118:A:AG	acceptor_gain	0.3900
18:580648:C:T	donor_gain	0.3800
18:580718:G:GT	donor_gain	0.3800

AlphaMissense

1165 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:580517:T:C	F37L	0.999
18:580519:T:A	F37L	0.999
18:580519:T:G	F37L	0.999
18:580785:T:C	L126P	0.999
18:580796:G:C	A130P	0.999
18:580736:T:C	F110L	0.998
18:580738:C:A	F110L	0.998
18:580738:C:G	F110L	0.998
18:580745:T:C	F113L	0.998
18:580747:T:A	F113L	0.998
18:580747:T:G	F113L	0.998
18:580833:T:C	L142P	0.998
18:580853:G:C	A149P	0.998
18:580892:T:C	F162L	0.998
18:580894:C:A	F162L	0.998
18:580894:C:G	F162L	0.998
18:580524:T:C	L39P	0.997
18:580575:C:A	A56D	0.997
18:580589:G:C	G61R	0.997
18:580673:T:C	F89L	0.997
18:580675:C:A	F89L	0.997
18:580675:C:G	F89L	0.997
18:580743:T:C	L112P	0.997
18:580770:T:C	I121T	0.997
18:580770:T:G	I121S	0.997
18:580842:T:C	M145T	0.997
18:580842:T:G	M145R	0.997
18:580893:T:C	F162S	0.997
18:580514:G:C	A36P	0.996
18:580566:T:C	L53P	0.996

dbSNP variants (sampled 300 via entrez): RS1001462669 (18:578841 G>A), RS1001827434 (18:579955 G>A), RS1002206172 (18:579635 A>G), RS1002847989 (18:582340 A>C), RS1004119797 (18:579885 T>A,G), RS1005390171 (18:582199 C>T), RS1005462096 (18:581810 CT>C), RS1005926859 (18:581310 T>G), RS1006207018 (18:580997 G>A,C), RS1007931052 (18:578791 G>T), RS1008740468 (18:579645 A>G), RS1009896178 (18:579888 T>A), RS1009976542 (18:580663 C>T), RS1011811204 (18:578598 GT>G,GTT), RS1011968640 (18:581661 G>A)

Disease associations

OMIM: gene MIM:603187 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation	1
butyraldehyde	increases expression	1
CGP 52608	affects binding, increases reaction	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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