PCNT

Summary

PCNT (pericentrin, HGNC:16068) is a protein-coding gene on chromosome 21q22.3, encoding Pericentrin (O95613). Integral component of the filamentous matrix of the centrosome involved in the initial establishment of organized microtubule arrays in both mitosis and meiosis. It is a selective cancer dependency (DepMap: 11.0% of cell lines).

The protein encoded by this gene binds to calmodulin and is expressed in the centrosome. It is an integral component of the pericentriolar material (PCM). The protein contains a series of coiled-coil domains and a highly conserved PCM targeting motif called the PACT domain near its C-terminus. The protein interacts with the microtubule nucleation component gamma-tubulin and is likely important to normal functioning of the centrosomes, cytoskeleton, and cell-cycle progression. Mutations in this gene cause Seckel syndrome-4 and microcephalic osteodysplastic primordial dwarfism type II. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5116 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephalic osteodysplastic primordial dwarfism type II (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 4,079 total — 226 pathogenic, 118 likely-pathogenic
• Phenotypes (HPO): 102
• Cancer dependency (DepMap): dependent in 11.0% of screened cell lines
• MANE Select transcript: NM_006031

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16068
Approved symbol	PCNT
Name	pericentrin
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	KEN, KIAA0402, PCN, PCNTB, SCKL4
Ensembl gene	ENSG00000160299
Ensembl biotype	protein_coding
OMIM	605925
Entrez	5116

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 11 retained_intron, 7 protein_coding, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000359568, ENST00000418394, ENST00000465356, ENST00000466474, ENST00000480896, ENST00000482575, ENST00000483844, ENST00000490468, ENST00000695525, ENST00000695526, ENST00000695527, ENST00000695528, ENST00000695529, ENST00000695530, ENST00000695531, ENST00000695532, ENST00000695533, ENST00000695534, ENST00000695535, ENST00000695536, ENST00000695537, ENST00000695558, ENST00000703224, ENST00000703225, ENST00000703226

RefSeq mRNA: 2 — MANE Select: NM_006031 NM_001315529, NM_006031

CCDS: CCDS33592, CCDS93109

Canonical transcript exons

ENST00000359568 — 47 exons

Exon	Start	End
ENSE00001740168	46324156	46324282
ENSE00001851890	46346128	46346208
ENSE00003460972	46388742	46388884
ENSE00003464323	46381694	46381840
ENSE00003484112	46366584	46367139
ENSE00003505517	46356974	46357191
ENSE00003570581	46349684	46349820
ENSE00003581236	46363480	46363934
ENSE00003595154	46355452	46355626
ENSE00003613496	46353987	46354068
ENSE00003613544	46349012	46349186
ENSE00003627023	46346743	46346998
ENSE00003634961	46353104	46353326
ENSE00003636169	46351429	46351540
ENSE00003678564	46385832	46385983
ENSE00003689424	46347457	46347512
ENSE00003964170	46326377	46326589
ENSE00003964189	46334397	46334768
ENSE00003988406	46416069	46416839
ENSE00003988407	46445284	46445769
ENSE00003988408	46428395	46428590
ENSE00003988409	46436979	46437081
ENSE00003988410	46401551	46401721
ENSE00003988411	46397265	46397494
ENSE00003988412	46398235	46398255
ENSE00003988413	46398014	46398130
ENSE00003988414	46389199	46389431
ENSE00003988416	46390670	46390832
ENSE00003988417	46431529	46432215
ENSE00003988418	46435904	46436148
ENSE00003988420	46421970	46422124
ENSE00003988423	46440083	46440202
ENSE00003988424	46425831	46425971
ENSE00003988425	46430010	46430232
ENSE00003988426	46411189	46412067
ENSE00003988428	46412837	46412992
ENSE00003988429	46427622	46427795
ENSE00003988431	46443810	46443948
ENSE00003988432	46440855	46441084
ENSE00003988433	46444694	46444821
ENSE00003988434	46430507	46430657
ENSE00003988435	46438164	46438337
ENSE00003988436	46391164	46391376
ENSE00003988437	46418204	46418306
ENSE00003988439	46442497	46442573
ENSE00003988440	46399590	46399796
ENSE00003988441	46402331	46402483

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 98.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.1005 / max 849.0739, expressed in 1770 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189706	9.7360	1703
189707	2.9796	1258
189710	1.2840	53
189709	0.0689	24
189708	0.0223	14
189719	0.0098	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	98.33	gold quality
body of tongue	UBERON:0011876	98.03	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.65	gold quality
muscle of leg	UBERON:0001383	97.48	gold quality
diaphragm	UBERON:0001103	96.69	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.51	gold quality
gluteal muscle	UBERON:0002000	96.18	gold quality
triceps brachii	UBERON:0001509	96.03	gold quality
muscle organ	UBERON:0001630	95.84	gold quality
tongue	UBERON:0001723	94.79	gold quality
biceps brachii	UBERON:0001507	94.74	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.15	gold quality
middle temporal gyrus	UBERON:0002771	94.08	gold quality
skeletal muscle tissue	UBERON:0001134	93.60	gold quality
right testis	UBERON:0004534	93.54	gold quality
left testis	UBERON:0004533	93.46	gold quality
sural nerve	UBERON:0015488	93.18	gold quality
pituitary gland	UBERON:0000007	92.38	gold quality
adenohypophysis	UBERON:0002196	92.34	gold quality
tendon of biceps brachii	UBERON:0008188	92.08	gold quality
superior surface of tongue	UBERON:0007371	92.02	gold quality
right frontal lobe	UBERON:0002810	91.86	gold quality
apex of heart	UBERON:0002098	91.68	gold quality
testis	UBERON:0000473	91.60	gold quality
vastus lateralis	UBERON:0001379	91.38	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.33	gold quality
primary visual cortex	UBERON:0002436	91.30	gold quality
heart left ventricle	UBERON:0002084	91.06	gold quality
cardiac ventricle	UBERON:0002082	90.93	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.53
E-CURD-112	no	218.05

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

13 targeting PCNT, 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-4668-5P	99.79	70.58	3782
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-6516-5P	98.42	70.19	1551
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-3189-3P	96.80	66.34	896
HSA-MIR-371B-3P	94.48	66.59	345

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• CG-NAP and kendrin provide sites for microtubule nucleation in the mammalian centrosome by anchoring gamma-TuRC (PMID:12221128)
• results confirm that MT1-MMP cleaves pericentrin-2 in humans but not in mice and that mouse models of cancer probably cannot be used to critically examine MT1-MMP functionality (PMID:16251193)
• Elevated levels of PCNT2 might be implicated in the pathophysiology of bipolar disorder. (PMID:17884020)
• Mutations in PCNT cause Seckel syndrome with defective ATR-dependent DNA damage signaling. (PMID:18157127)
• study found that biallelic loss-of-function mutations in the centrosomal pericentrin (PCNT) gene on chromosome 21q22.3 cause microcephalic osteodysplastic primordial dwarfism type II (MOPD II) in 25 patients (PMID:18174396)
• Upregulation of pericentrin is associated with increased angiogenesis and prostate tumor cell proliferation (PMID:18701509)
• These findings suggest that the DISC1-kendrin interaction plays a key role in the microtubule dynamics. (PMID:18955030)
• The association of PCNT2 and DBZ with schizophrenia and bipolar disorder in a case-control study of Japanese cohorts, was examined. (PMID:19191256)
• results suggest that genetic variations in the PCNT gene may play a significant role in the etiology of major depressive disorder in the Japanese population (PMID:19448849)
• Results show that a lack of microcephalin or pericentrin results in a loss of Chk1 from centrosomes with subsequently deregulated activation of centrosomal cyclin B-Cdk1. (PMID:19546241)
• Microcephalic osteodysplastic primordial dwarfism type II is a genetically homogeneous condition due to loss-of-function of pericentrin. (PMID:19643772)
• Results found no significant association between the pericentrin gene and schizophrenia in the Japanese population. This gene may not play a major role independently in the etiology of SZ. (PMID:19937158)
• The NESs and NLS of pericentrin are essential for its subcellular localization and nucleocytoplasmic trafficking during the cell cycle.(Pericentrin) (PMID:20567258)
• these results suggest that kendrin anchors Nek2A and suppresses its kinase activity at the centrosomes, and thus, is involved in the mechanism to prevent premature centrosome splitting during interphase. (PMID:20599736)
• Data suggest that pericentrin may regulate the intracellular distribution and secretion of insulin. (PMID:20676397)
• Severe insulin resistance and premature diabetes are common features of PCNT deficiency but are not congenital. (PMID:21270239)
• PCNT has a crucial role in tooth development; teeth of a patient with a novel homozygous mutation p.Glu1154X are probably the smallest ever reported. (PMID:21567919)
• The pericentrin (PCNT), a PCM protein, was specifically phosphorylated by PLK1 during mitosis. (PMID:22184200)
• Kendrin is a novel and crucial substrate for separase at the centrosome, protecting the engaged centrioles from premature disengagement and thereby blocking reduplication until the cell passes through mitosis. (PMID:22542101)
• Expression of RRP1B, PCNT, KIF21A and ADRB2 in leucocytes of Down’s syndrome subjects, was analyzed. (PMID:22552340)
• The pericentrin B cleavage is essential for timely centriole disengagement and duplication. (PMID:22722493)
• Che-1 depletion abolishes the ability of Chk1 to bind pericentrin and to localize at centrosomes, which, in its turn, deregulates the activation of centrosomal cyclin B-Cdk1 and advances entry into mitosis. (PMID:23798705)
• Data suggest that changes in the expression levels of PCNT in DS subjects may be involved into the molecular mechanism of Down’s syndrome. (PMID:23979692)
• PCNT gene mutation is associated with hematological abnormalities in patients with microcephalic osteodysplastic primordial dwarfism type II. (PMID:24106199)
• The CEP215-pericentrin interaction is required for centrosome maturation and subsequent bipolar spindle formation during mitosis. (PMID:24466316)
• Cep68 degradation allows Cep215 removal from peripheral pericentriolar material (PCM) preventing centriole separation following disengagement, PCNT cleavage mediates Cep215 removal from core of the PCM to inhibit centriole disengagement and duplication (PMID:25503564)
• we identified two novel mutations in the PCNT gene associated with Microcephalic osteodysplastic primordial dwarfism type II and intracranial aneurysms (PMID:26231886)
• PCNT has to be phosphorylated by PLK1 to be a suitable substrate of separase. (PMID:26647647)
• Here, the authors show that PCNT is delivered co-translationally to centrosomes during early mitosis by cytoplasmic dynein, as evidenced by centrosomal enrichment of PCNT mRNA, its translation near centrosomes, and requirement of intact polysomes for PCNT mRNA localization. (PMID:29708497)
• CRISPR/Cas9-mediated knockout of Syne-2 in cell culture led to an overexpression and mislocalization of Pcnt and to ciliogenesis defects. This suggests that the Pcnt-Syne-2 complex is important for ciliogenesis and outer segment formation during retinal development and plays a role in nuclear migration. (PMID:30054381)
• High pericentrin expression is associated with Disruptive Cilia Formation in down syndrome. (PMID:30100262)
• We identified 2 different variants in exon 38 from the PCNT gene shared between affected members from 2 different families with either intracranial aneurysms or subarachnoid hemorrhages (PMID:30413633)
• We also find that Cep57 binds to the well-conserved PACT domain of pericentrin. (PMID:30804344)
• Deletion of PCNT in HeLa cells had little effect on interphase centrosomes. However, centrioles in PCNT-deleted mitotic cells prematurely separated and frequently amplified, revealing that centrioles are limited within the spindle poles by PCNT during mitosis. (PMID:30814333)
• Critical homozygous or compound heterozygous variants in PCNT are a known cause of microcephalic osteodysplastic primordial dwarfism type II accompanied by mandibular hypoplasia, which is similar to the maxillofacial phenotype. (PMID:31311520)
• Centrosome amplification is a frequent event in circulating tumor cells from subjects with metastatic breast cancer. (PMID:32255253)
• Microcephalic osteodysplastic primordial dwarfism type II: Additional nine patients with implications on phenotype and genotype correlation. (PMID:32267100)
• Novel PCNT variants in MOPDII with attenuated growth restriction and pachygyria. (PMID:32557621)
• Microcephalic osteodysplastic primordial dwarfism type II and pachygyria: Morphometric analysis in a 2-year-old girl. (PMID:32744776)
• Centriole-independent mitotic spindle assembly relies on the PCNT-CDK5RAP2 pericentriolar matrix. (PMID:33170211)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pcnt	ENSDARG00000033012
mus_musculus	Pcnt	ENSMUSG00000001151
rattus_norvegicus	Pcnt	ENSRNOG00000001276

Paralogs (1): AKAP9 (ENSG00000127914)

Protein

Protein identifiers

Pericentrin — O95613 (reviewed: O95613)

Alternative names: Kendrin, Pericentrin-B

All UniProt accessions (9): O95613, A0A8Q3SHV6, A0A8Q3SHY5, A0A8Q3SHZ3, A0A8Q3SHZ8, A0A8Q3SI04, A0A8V8TQ91, A0A8V8TQT6, H7C2A3

UniProt curated annotations — full annotation on UniProt →

Function. Integral component of the filamentous matrix of the centrosome involved in the initial establishment of organized microtubule arrays in both mitosis and meiosis. Plays a role, together with DISC1, in the microtubule network formation. Is an integral component of the pericentriolar material (PCM). May play an important role in preventing premature centrosome splitting during interphase by inhibiting NEK2 kinase activity at the centrosome.

Subunit / interactions. Interacts with CHD3. Interacts with CHD4; the interaction regulates centrosome integrity. Interacts with DISC1 and PCM1. Binds calmodulin. Interacts with CDK5RAP2; the interaction is leading to centrosomal localization of PCNT and CDK5RAP2. Interacts with isoform 1 of NEK2. Interacts with CEP131. Interacts with CCDC13. Interacts with CEP68. Interacts with ATF5; the ATF5:PCNT:polyglutamylated tubulin (PGT) tripartite unites the mother centriole and the pericentriolar material (PCM) in the centrosome.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Tissue specificity. Expressed in all tissues tested, including placenta, liver, kidney and thymus.

Post-translational modifications. Cleaved during mitotis which leads to removal of CDK5RAP2 from the centrosome and promotes centriole disengagement and subsequent centriole separation. The C-terminal fragment is rapidly degraded following cleavage. Ubiquitinated by TRIM43; leading to proteasomal degradation.

Disease relevance. Microcephalic osteodysplastic primordial dwarfism 2 (MOPD2) [MIM:210720] Adults with this rare inherited condition have an average height of 100 centimeters and a brain size comparable to that of a 3-month-old baby, but are of near-normal intelligence. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Composed of a coiled-coil central region flanked by non-helical N- and C-terminals.

Isoforms (2)

UniProt ID	Names	Canonical?
O95613-1	1	yes
O95613-2	2

RefSeq proteins (2): NP_001302458, NP_006022* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019528	PACT_domain	Domain
IPR028745	AKAP9/Pericentrin	Family

Pfam: PF10495

UniProt features (94 total): sequence variant 29, modified residue 19, region of interest 12, sequence conflict 12, compositionally biased region 8, coiled-coil region 6, mutagenesis site 5, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for O95613 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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 (19): 44, 188, 191, 610, 682, 1245, 1653, 1712, 2044, 2177, 2192, 2225, 2226, 2327, 2352, 2355, 2477, 2486, 3302

Mutagenesis-validated functional residues (5):

Position	Phenotype
2231	produces non-cleavable protein which remains on centrosomes in late mitosis until its levels eventually drop in cells un
2232	stabilizes the c-terminal fragment produced by cleavage.
3196–3197	decrease in calmodulin binding.
3203	decrease in calmodulin binding.
3208–3209	decrease in calmodulin binding.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
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-8854518	AURKA Activation by TPX2
R-HSA-9613829	Chaperone Mediated Autophagy
R-HSA-9615710	Late endosomal microautophagy
R-HSA-9646399	Aggrephagy

MSigDB gene sets: 465 (showing top): MODULE_451, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, NKX25_02, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_MICROTUBULE_NUCLEATION, LHX3_01, YY1_Q6, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_TRANSPORT, YY1_02, DACOSTA_UV_RESPONSE_VIA_ERCC3_TTD_DN, GOBP_CILIUM_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION

GO Biological Process (6): microtubule cytoskeleton organization (GO:0000226), microtubule nucleation (GO:0007020), mitotic spindle organization (GO:0007052), signal transduction (GO:0007165), cilium assembly (GO:0060271), positive regulation of intracellular protein transport (GO:0090316)

GO Molecular Function (3): calmodulin binding (GO:0005516), molecular adaptor activity (GO:0060090), protein binding (GO:0005515)

GO Cellular Component (10): centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), microtubule (GO:0005874), membrane (GO:0016020), centriolar satellite (GO:0034451), sperm midpiece (GO:0097225), cytoplasm (GO:0005737), microtubule organizing center (GO:0005815), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
G2/M Transition	2
Centrosome maturation	2
Autophagy	2
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Assembly of the 9+0 primary cilium	1
Selective autophagy	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
binding	2
microtubule organizing center	2
intracellular membraneless organelle	2
microtubule cytoskeleton	2
cytoskeleton organization	1
microtubule-based process	1
microtubule cytoskeleton organization	1
microtubule polymerization	1
mitotic cell cycle	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
intracellular protein transport	1
positive regulation of intracellular transport	1
regulation of intracellular protein transport	1
positive regulation of protein transport	1
protein binding	1
molecular_function	1
centriole	1
cytoplasm	1
polymeric cytoskeletal fiber	1
centrosome	1
sperm flagellum	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3425 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCNT	NIN	Q8N4C6	976
PCNT	CNTLN	Q9NXG0	969
PCNT	DISC1	Q9NRI5	963
PCNT	CDK5RAP2	Q96SN8	942
PCNT	DYNC1LI1	Q9Y6G9	922
PCNT	NUP85	Q9BW27	919
PCNT	ERC2	O15083	906
PCNT	CEP290	O15078	901
PCNT	CEP192	Q8TEP8	896
PCNT	CNTROB	Q8N137	892
PCNT	CETN2	P41208	884
PCNT	PLK4	O00444	882
PCNT	CETN1	Q12798	870
PCNT	NEDD1	Q8NHV4	853
PCNT	CPAP	Q9HC77	852

IntAct

186 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
CEP290	CCP110	psi-mi:“MI:0403”(colocalization)	0.890
ODAD1	HGS	psi-mi:“MI:0914”(association)	0.850
CALM1	CEP290	psi-mi:“MI:0403”(colocalization)	0.810
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
PCM1	PCNT	psi-mi:“MI:0914”(association)	0.710
PCNT	PCM1	psi-mi:“MI:0914”(association)	0.710
PCNT	PCM1	psi-mi:“MI:0915”(physical association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
IKBIP	SNAPIN	psi-mi:“MI:0914”(association)	0.670
DISC1	PCNT	psi-mi:“MI:0915”(physical association)	0.670
PCNT	DISC1	psi-mi:“MI:0915”(physical association)	0.670
PCNT	DISC1	psi-mi:“MI:0403”(colocalization)	0.670
MIS18A	DCTN6	psi-mi:“MI:0914”(association)	0.640
LPXN	PCNT	psi-mi:“MI:0914”(association)	0.640
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
BIRC7	HTRA2	psi-mi:“MI:0914”(association)	0.640
PCNT	YBX1	psi-mi:“MI:0915”(physical association)	0.560
YBX1	PCNT	psi-mi:“MI:0915”(physical association)	0.560
YBX1	PCNT	psi-mi:“MI:0403”(colocalization)	0.560
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
MZT1	PCNT	psi-mi:“MI:0914”(association)	0.530

BioGRID (323): PCNT (Affinity Capture-MS), PCNT (Affinity Capture-MS), PCNT (Affinity Capture-MS), PCNT (Affinity Capture-MS), PCNT (Affinity Capture-MS), PCNT (Affinity Capture-MS), PCNT (Affinity Capture-MS), PCNT (Affinity Capture-MS), PCNT (Affinity Capture-MS), PCNT (Affinity Capture-Western), PCNT (Proximity Label-MS), PCNT (Proximity Label-MS), PCNT (Proximity Label-MS), PCNT (Proximity Label-MS), PCNT (Proximity Label-MS)

ESM2 similar proteins: A2AM05, A6NDK9, A6NDN3, A7MC22, A9QT41, B1AJZ9, O88522, O95613, P0CB05, P0CG33, P48725, Q0KK56, Q14789, Q14980, Q19UN5, Q28628, Q2KJ21, Q2TAC2, Q5DU05, Q5U4E6, Q60952, Q66HR5, Q6AY97, Q6PHN1, Q6TMG5, Q70FJ1, Q7TME2, Q80VM7, Q861Q8, Q8CGU1, Q8K389, Q8K3K8, Q8N283, Q8N998, Q8R5M4, Q8TBY8, Q8VDC1, Q91VW5, Q95KA2, Q95KU9

Diamond homologs: O95613, P48725, Q28628, Q70FJ1, Q99996

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PCNT	“up-regulates activity”	CDK5RAP2	binding
PCM1	up-regulates	PCNT	relocalization
CEP68	“up-regulates activity”	PCNT	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 180 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
Loss of Nlp from mitotic centrosomes	10	13.6×	4e-07
Loss of proteins required for interphase microtubule organization from the centrosome	10	13.6×	4e-07
AURKA Activation by TPX2	10	13.0×	4e-07
Centrosome maturation	6	13.0×	4e-04
Recruitment of mitotic centrosome proteins and complexes	11	12.8×	2e-07
RHOU GTPase cycle	5	11.9×	2e-03
Anchoring of the basal body to the plasma membrane	12	11.6×	2e-07
Recruitment of NuMA to mitotic centrosomes	11	11.0×	4e-07

GO biological processes:

GO term	Partners	Fold	FDR
substantia nigra development	6	14.0×	1e-03
non-motile cilium assembly	7	12.9×	1e-03
centrosome cycle	5	10.7×	7e-03
positive regulation of transcription elongation by RNA polymerase II	5	9.6×	1e-02
endocytosis	9	5.5×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

4079 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	226
Likely pathogenic	118
Uncertain significance	1339
Likely benign	1802
Benign	244

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1174802	NM_006031.6(PCNT):c.2818dup (p.Ala940fs)	Pathogenic
127247	NM_006031.6(PCNT):c.196G>T (p.Gly66Ter)	Pathogenic
1323422	NM_006031.6(PCNT):c.3465-1G>C	Pathogenic
1323423	NM_006031.6(PCNT):c.4655C>A (p.Ser1552Ter)	Pathogenic
1323425	NM_006031.6(PCNT):c.9700+1G>A	Pathogenic
1323427	NM_006031.6(PCNT):c.7511del (p.Lys2504fs)	Pathogenic
1332726	NM_006031.6(PCNT):c.1444C>T (p.Gln482Ter)	Pathogenic
1338241	NM_006031.6(PCNT):c.2347dup (p.Gln783fs)	Pathogenic
1338242	NM_006031.6(PCNT):c.4004-2A>G	Pathogenic
1343402	NM_006031.6(PCNT):c.5059_5060del (p.Asn1687fs)	Pathogenic
1357587	NM_006031.6(PCNT):c.1550dup (p.Gln518fs)	Pathogenic
1418248	NM_006031.6(PCNT):c.8544del (p.Ala2849fs)	Pathogenic
1443277	NM_006031.6(PCNT):c.1637del (p.Gln546fs)	Pathogenic
1451665	NM_006031.6(PCNT):c.2980C>T (p.Arg994Ter)	Pathogenic
1453798	NM_006031.6(PCNT):c.1519C>T (p.Arg507Ter)	Pathogenic
1455235	NM_006031.6(PCNT):c.3019_3020del (p.Leu1007fs)	Pathogenic
1459287	NM_006031.6(PCNT):c.7026dup (p.Asp2343Ter)	Pathogenic
1459821	NM_006031.6(PCNT):c.307C>T (p.Gln103Ter)	Pathogenic
159565	NM_006031.6(PCNT):c.1468C>T (p.Gln490Ter)	Pathogenic
159580	NM_006031.6(PCNT):c.2984_2994del (p.Ala995fs)	Pathogenic
159621	NM_006031.6(PCNT):c.5578G>T (p.Glu1860Ter)	Pathogenic
159663	NM_006031.6(PCNT):c.7796del (p.Leu2599fs)	Pathogenic
159677	NM_006031.6(PCNT):c.8868dup (p.Ala2957fs)	Pathogenic
159681	NM_006031.6(PCNT):c.8917C>T (p.Arg2973Ter)	Pathogenic
1805459	NM_006031.6(PCNT):c.8695C>T (p.Gln2899Ter)	Pathogenic
1878985	NM_006031.6(PCNT):c.6899del (p.His2300fs)	Pathogenic
1901606	NM_006031.6(PCNT):c.8461C>T (p.Gln2821Ter)	Pathogenic
1915818	NM_006031.6(PCNT):c.8542del (p.Glu2848fs)	Pathogenic
1917141	NM_006031.6(PCNT):c.1670_1671del (p.Val557fs)	Pathogenic
2007969	NM_006031.6(PCNT):c.8959del (p.Arg2987fs)	Pathogenic

SpliceAI

9553 predictions. Top by Δscore:

Variant	Effect	Δscore
21:46326366:T:G	acceptor_gain	1.0000
21:46326373:GCA:G	acceptor_loss	1.0000
21:46326375:A:AG	acceptor_gain	1.0000
21:46326375:AGCTT:A	acceptor_gain	1.0000
21:46326376:G:GG	acceptor_gain	1.0000
21:46326376:GC:G	acceptor_gain	1.0000
21:46326376:GCT:G	acceptor_gain	1.0000
21:46326376:GCTT:G	acceptor_gain	1.0000
21:46326376:GCTTG:G	acceptor_gain	1.0000
21:46326519:G:GT	donor_gain	1.0000
21:46326570:G:GT	donor_gain	1.0000
21:46326585:CTCAG:C	donor_loss	1.0000
21:46326586:TCAG:T	donor_loss	1.0000
21:46326587:CAG:C	donor_loss	1.0000
21:46326588:AGGTA:A	donor_loss	1.0000
21:46326589:GGTAG:G	donor_loss	1.0000
21:46326590:G:GA	donor_loss	1.0000
21:46326591:T:G	donor_loss	1.0000
21:46334393:TTA:T	acceptor_loss	1.0000
21:46334394:TA:T	acceptor_loss	1.0000
21:46334395:A:AG	acceptor_gain	1.0000
21:46334395:A:G	acceptor_loss	1.0000
21:46334395:AGCC:A	acceptor_gain	1.0000
21:46334395:AGCCG:A	acceptor_gain	1.0000
21:46334396:G:GG	acceptor_gain	1.0000
21:46334396:GC:G	acceptor_gain	1.0000
21:46334396:GCC:G	acceptor_gain	1.0000
21:46334396:GCCG:G	acceptor_gain	1.0000
21:46334396:GCCGG:G	acceptor_gain	1.0000
21:46334765:AAAG:A	donor_loss	1.0000

AlphaMissense

21856 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:46440907:T:C	L3149P	0.998
21:46440928:T:C	L3156P	0.998
21:46440948:T:C	F3163L	0.998
21:46440950:C:A	F3163L	0.998
21:46440950:C:G	F3163L	0.998
21:46440898:G:C	R3146T	0.997
21:46440899:A:C	R3146S	0.997
21:46440899:A:T	R3146S	0.997
21:46440901:A:T	K3147I	0.997
21:46440920:G:C	K3153N	0.997
21:46440920:G:T	K3153N	0.997
21:46440924:T:C	Y3155H	0.997
21:46440925:A:G	Y3155C	0.997
21:46441075:C:A	A3205E	0.997
21:46441084:G:C	R3208T	0.997
21:46398050:T:C	F1495L	0.996
21:46398052:C:A	F1495L	0.996
21:46398052:C:G	F1495L	0.996
21:46440894:T:C	F3145L	0.996
21:46440896:T:A	F3145L	0.996
21:46440896:T:G	F3145L	0.996
21:46440898:G:T	R3146I	0.996
21:46440903:G:C	A3148P	0.996
21:46440917:A:C	Q3152H	0.996
21:46440917:A:T	Q3152H	0.996
21:46440924:T:G	Y3155D	0.996
21:46442504:T:C	F3211L	0.996
21:46442506:T:A	F3211L	0.996
21:46442506:T:G	F3211L	0.996
21:46440885:G:C	A3142P	0.995

dbSNP variants (sampled 300 via entrez): RS1000002238 (21:46421789 C>G), RS1000022244 (21:46357549 C>T), RS1000048352 (21:46356482 C>T), RS1000052484 (21:46352587 C>T), RS1000096465 (21:46424763 C>T), RS1000107250 (21:46323809 G>A,T), RS1000116573 (21:46357264 C>T), RS1000122467 (21:46357601 AT>A,ATT), RS1000133806 (21:46336555 C>T), RS1000145935 (21:46442204 C>T), RS1000151669 (21:46392306 G>A,C), RS1000171355 (21:46375757 C>T), RS1000178439 (21:46393430 CT>C), RS1000180517 (21:46407536 G>T), RS1000181582 (21:46338815 C>G)

Disease associations

OMIM: gene MIM:605925 | disease phenotypes: MIM:210720

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephalic osteodysplastic primordial dwarfism type II	Definitive	Autosomal recessive
Moyamoya disease	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
microcephalic osteodysplastic primordial dwarfism type II	Definitive	AR

Mondo (7): microcephalic osteodysplastic primordial dwarfism type II (MONDO:0008872), vascular dementia (MONDO:0004648), cystic kidney disease (MONDO:0002473), intellectual disability (MONDO:0001071), microcephaly (MONDO:0001149), megacolon (MONDO:0001273), Moyamoya disease (MONDO:0016820)

Orphanet (2): Microcephalic osteodysplastic primordial dwarfism type II (Orphanet:2637), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

102 total (30 of 102 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000047	Hypospadias
HP:0000055	Abnormal female external genitalia morphology
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000278	Retrognathia
HP:0000293	Full cheeks
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000363	Abnormal earlobe morphology
HP:0000369	Low-set ears
HP:0000387	Absent earlobe
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000430	Underdeveloped nasal alae
HP:0000431	Wide nasal bridge
HP:0000444	Convex nasal ridge
HP:0000448	Prominent nose
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000540	Hypermetropia
HP:0000582	Upslanted palpebral fissure
HP:0000682	Abnormal dental enamel morphology
HP:0000691	Microdontia
HP:0000774	Narrow chest
HP:0000826	Precocious puberty
HP:0000882	Hypoplastic scapulae
HP:0000890	Long clavicles
HP:0000944	Abnormal metaphysis morphology
HP:0000957	Cafe-au-lait spot

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006979_186	Heel bone mineral density	4.000000e-10
GCST007665_8	Treatment resistant depression	5.000000e-06
GCST008758_85	Pre-treatment viral load in HIV-1 infection	1.000000e-16
GCST011914_1	S100 calcium-binding protein levels	1.000000e-300

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0009854	treatment resistant depression
EFO:0010125	viral load
EFO:0600012	S100 calcium-binding protein B measurement

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D015140	Dementia, Vascular	C10.228.140.300.400; C10.228.140.300.510.800.500; C10.228.140.380.230; C10.228.140.695.500; C14.907.137.126.372.500; C14.907.253.560.350.500; F03.615.400.350
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D052177	Kidney Diseases, Cystic	C12.050.351.968.419.403; C12.200.777.419.403; C12.950.419.403
D008531	Megacolon	C06.405.469.158.701
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D009072	Moyamoya Disease	C10.228.140.300.200.600; C10.228.140.300.510.200.737; C14.907.137.615; C14.907.253.123.620; C14.907.253.560.200.737
C565898	Microcephalic Osteodysplastic Primordial Dwarfism, Type II (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects cotreatment, decreases methylation	1
arsenite	decreases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
fatostatin	affects localization	1
Gefitinib	decreases response to substance	1
Fulvestrant	decreases methylation, affects cotreatment	1
Vorinostat	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Arsenic	affects methylation	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tretinoin	decreases expression	1

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2A2	Abcam HeLa PCNT KO	Cancer cell line	Female
CVCL_B3DL	Abcam HEK293T PCNT KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00165763	PHASE4	COMPLETED	Efficacy and Safety of Donepezil Hydrochloride (Aricept) in Vascular Dementia
NCT00847860	PHASE4	COMPLETED	Cilostazol Verse Asprin for Vascular Dementia in Poststroke Patients With White Matter Lesions
NCT00947531	PHASE4	COMPLETED	A Clinical Trial to Evaluate the Safety and Efficacy of 20 ml Cerebrolysin in Patients With Vascular Dementia
NCT00950430	PHASE4	ENROLLING_BY_INVITATION	Imaging of Brain Amyloid Plaques in the Aging Population
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT04205578	PHASE3	UNKNOWN	NBP in Patients With Moyamoya Disease of High Risk for Ischemic Cerebrovascular Events
NCT00099216	PHASE3	COMPLETED	Efficacy and Safety of Rivastigmine Capsules in Patients With Probable Vascular Dementia
NCT00130338	PHASE3	COMPLETED	Rivastigmine Capsules in Patients With Probable Vascular Dementia
NCT00209456	PHASE3	COMPLETED	Dopamine Transporter Scintigraphy Imaging (DAT-Imaging) in Patients With Lewy Body Dementia
NCT00249158	PHASE3	COMPLETED	A Study of the Effectiveness and Safety of Risperidone in the Treatment of Behavioral Disturbances in Patients With Dementia
NCT00261573	PHASE3	COMPLETED	A Study of the Safety and Effectiveness of Galantamine Versus Placebo in the Treatment of Patients With Vascular Dementia or Mixed Dementia
NCT00621647	PHASE3	COMPLETED	Seroquel- Agitation Associated With Dementia
NCT02453932	PHASE3	COMPLETED	Efficacy and Safety of Tianzhi Granule in Mild to Moderate Vascular Dementia
NCT03682185	PHASE3	COMPLETED	The Healthy Patterns Sleep Study
NCT03789760	PHASE3	COMPLETED	The Clinical Trial of Chinese Herbal Medicine (SaiLuoTong) Capsule
NCT03804229	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Butylphthalide Soft Capsule for the Treatment of Vascular Dementia
NCT03986424	PHASE3	COMPLETED	Local Study of Akatinol Memantine in VaD in Russia
NCT04552041	PHASE3	COMPLETED	Prospekta in the Treatment of Cognitive, Behavioral and Psychiatric Disorders in Patients With Vascular Dementia.
NCT04705051	PHASE3	TERMINATED	Long-term Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) With Venglustat
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT01466543	PHASE2	UNKNOWN	Effect of Zydena (Udenafil) on Cerebral Blood Flow and Peripheral Blood Viscosity
NCT01475578	PHASE2	COMPLETED	Study of STA-1 Capsule in Patients With Vascular Dementia (Marrow-Sea Deficiency)
NCT01608217	PHASE2	COMPLETED	Delta-THC in Dementia
NCT01761227	PHASE2	COMPLETED	Efficacy and Safety of Fufangdanshen Tablets in Mild to Moderate Vascular Dementia
NCT01953705	PHASE2	UNKNOWN	n-3 PUFA for Vascular Cognitive Aging
NCT01965756	PHASE2	COMPLETED	Effect of Insulin Sensitizer Metformin on AD Biomarkers
NCT01978730	PHASE2	UNKNOWN	The Clinical Trial of Chinese Herbal Medicine SaiLuoTong Capsule
NCT02467413	PHASE2	WITHDRAWN	BAC in Patient With Alzheimer’s Disease or Vascular Dementia
NCT03230071	PHASE2	COMPLETED	Efficacy and Safety of TMBCZG in Mild to Moderate Vascular Dementia
NCT04109963	PHASE2	UNKNOWN	Trial of Remote Ischemic Pre-conditioning in Vascular Cognitive Impairment
NCT05371639	PHASE2	UNKNOWN	Efficacy and Safety of Tian Ma Bian Chun Zhi Gan Tablets in Mild to Moderate Vascular Dementia
NCT02684435	PHASE2	COMPLETED	Contrast-enhanced Ultrasound of the Kidney
NCT03196076	PHASE2	COMPLETED	Contrast-enhanced Ultrasound for Complex Kidney Lesion Diagnosis in Patients With CKD Extension
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability