GeneBe

PCM1

protein-coding

pericentriolar material 1

Gene summary

The protein encoded by this gene is a component of centriolar satellites, which are electron dense granules scattered around centrosomes. Inhibition studies show that this protein is essential for the correct localization of several centrosomal proteins, and for anchoring microtubules to the centrosome. Chromosomal aberrations involving this gene are associated with papillary thyroid carcinomas and a variety of hematological malignancies, including atypical chronic myeloid leukemia and T-cell lymphoma. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

MANE transcript

NM_006197.4

Inheritance

—

ClinVar variants

U:449B:42

Top phenotype

PCM1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.45

Max pathogenic AF

—

Genomic locus

chr8:17,922,842-18,029,948

External References & Databases

Ensembl (ENSG00000078674)NCBI Gene (5108)OMIM (600299)HGNC:8727GenCCUniProt (Q15154)AlphaFoldClinVar (PCM1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~107.1 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PCM1 variants in ClinVar

6 Conditions Cataloged
not specifiedTotal: 409
not providedTotal: 34
PCM1-related disorderTotal: 15
EBV-positive nodal T- and NK-cell lymphomaTotal: 1
Congenital heart diseaseTotal: 1
Thyroid cancer, nonmedullary, 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006197.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
4
clinvar
10
clinvar
5
clinvar
 19
missense
422
clinvar
24
clinvar
2
clinvar
 448
nonsense
6
clinvar
1
clinvar
 7
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
17
clinvar
 17
Total00449357491
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 168 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_006197.4RefSeqNP_006188.437MANE Select
ENST00000325083.13EnsemblENSP00000327077.837MANE Select
NM_001315507.2RefSeqNP_001302436.237Standard
NM_001315508.2RefSeqNP_001302437.234Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
pcm1Danio rerio

Structure: whole organism

Quality: curved lateral

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Prader-Willi and Angelman Syndrome
  • Regulation of PLK1 Activity at G2/M Transition
  • Recruitment of mitotic centrosome proteins and complexes
  • Loss of Nlp from mitotic centrosomes
  • Loss of proteins required for interphase microtubule organization from the centrosome

Biological Process

  • G2/M transition of mitotic cell cycle
  • neuron migration
  • centrosome cycle
  • regulation of G2/M transition of mitotic cell cycle
  • interkinetic nuclear migration

Molecular Function

  • protein binding
  • identical protein binding

Cellular Component

  • pericentriolar material
  • cytoplasm
  • centrosome
  • centriole
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000325083
Coding exons
37
Length
105130
Individuals with no LoFs
124562
Homozygous LoFs
1
Heterozygous LoFs
92
Defined
124655
p
0.000373
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-6.1614749421.560.000046713318
Missense (PolyPhen)497352.831.40865218
Synonymous-7.264913251.510.00001643568
Loss of Function5.024396.10.4470.000004761314

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000270.00026rare
Latino/Admixed American0.000700.00055rare
Ashkenazi Jewish0.000300.00030rare
East Asian0.000240.00022rare
Finnish0.000420.00042rare
European (Non-Finnish)0.000360.00035rare
South Asian0.000480.00046rare
Other0.000180.00017rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Required for centrosome assembly and function (PubMed:12403812, PubMed:15659651, PubMed:16943179). Essential for the correct localization of several centrosomal proteins including CEP250, CETN3, PCNT and NEK2 (PubMed:12403812, PubMed:15659651). Required to anchor microtubules to the centrosome (PubMed:12403812, PubMed:15659651). Involved in the biogenesis of cilia (PubMed:20551181, PubMed:24121310). {ECO:0000269|PubMed:12403812, ECO:0000269|PubMed:15659651, ECO:0000269|PubMed:16943179, ECO:0000269|PubMed:20551181, ECO:0000269|PubMed:24121310}.;
Disease
DISEASE: Note=A chromosomal aberration involving PCM1 is found in papillary thyroid carcinomas (PTCs) (PubMed:10980597). Translocation t(8;10)(p21.3;q11.2) with RET links the protein kinase domain of RET to the major portion of PCM1 (PubMed:10980597). {ECO:0000269|PubMed:10980597}.; DISEASE: Note=A chromosomal aberration involving PCM1 is found in a variety of hematological malignancies including atypical chronic myeloid leukemia (atypical CML) and T-cell lymphoma (PubMed:15805263, PubMed:16034466, PubMed:16091753, PubMed:16769584, PubMed:16424865). Translocation t(8;9)(p22;p24) with JAK2 links the protein kinase domain of JAK2 to the major portion of PCM1 (PubMed:15805263, PubMed:16034466, PubMed:16091753, PubMed:16769584, PubMed:16424865). {ECO:0000269|PubMed:15805263, ECO:0000269|PubMed:16034466, ECO:0000269|PubMed:16091753, ECO:0000269|PubMed:16424865, ECO:0000269|PubMed:16769584}.;

Recessive Scores

pRec
0.135

Intolerance Scores

LoFtool
0.819
RVIS EVS
-0.32
RVIS percentile EVS
30.93

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
S
Essential (gene trap)
H
Indispensability pred.
E
Indispensability score
0.987

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium
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