PRC1

protein-coding

protein regulator of cytokinesis 1

Gene summary

This gene encodes a protein that is involved in cytokinesis. The protein is present at high levels during the S and G2/M phases of mitosis but its levels drop dramatically when the cell exits mitosis and enters the G1 phase. It is located in the nucleus during interphase, becomes associated with mitotic spindles in a highly dynamic manner during mitosis, and localizes to the cell mid-body during cytokinesis. This protein has been shown to be a substrate of several cyclin-dependent kinases (CDKs). It is necessary for polarizing parallel microtubules and concentrating the factors responsible for contractile ring assembly. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

MANE transcript

NM_003981.4

Inheritance

—

ClinVar variants

U:94B:3

Top phenotype

Familial cancer of breast

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr15:90,966,040-90,995,629

External References & Databases

Ensembl (ENSG00000198901)

Transcript & Mutation Effects

hg38 • Region Span ~29.6 kb

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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 PRC1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 91

Familial cancer of breastTotal: 3

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003981.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	1 clinvar		3
missense			90 clinvar	2 clinvar		92
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	94	3	0	97

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 71 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003981.4	RefSeq	NP_003972.2	15	MANE Select
ENST00000394249.8	Ensembl	ENSP00000377793.3	15	MANE Select
NM_001267580.2	RefSeq	NP_001254509.2	13	Standard
NM_199413.3	RefSeq	NP_955445.2	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signal Transduction
RHO GTPases activate CIT
RHO GTPase Effectors
Signaling by Rho GTPases
TNFalpha

Biological Process

mitotic spindle elongation
microtubule bundle formation
positive regulation of cell population proliferation
regulation of cytokinesis
cell division

Molecular Function

protein binding
microtubule binding
kinesin binding
protein kinase binding

Cellular Component

spindle pole
nucleus
spindle
cytosol
spindle microtubule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000394249
Coding exons: 15
Length: 29590
Individuals with no LoFs: 125684
Homozygous LoFs: 0
Heterozygous LoFs: 64
Defined: 125748
p: 0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.283	332	347	0.957	0.0000193	4066
Missense (PolyPhen)		72	90.638	0.79437		1163
Synonymous	-0.688	133	123	1.08	0.00000649	1149
Loss of Function	3.58	19	44.9	0.424	0.00000287	453

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00027	0.00027	rare
South Asian	0.00039	0.00039	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Key regulator of cytokinesis that cross-links antiparrallel microtubules at an average distance of 35 nM. Essential for controlling the spatiotemporal formation of the midzone and successful cytokinesis. Required for KIF14 localization to the central spindle and midbody. Required to recruit PLK1 to the spindle. Stimulates PLK1 phosphorylation of RACGAP1 to allow recruitment of ECT2 to the central spindle. Acts as an oncogene for promoting bladder cancer cells proliferation, apoptosis inhibition and carcinogenic progression (PubMed:17409436). {ECO:0000269|PubMed:12082078, ECO:0000269|PubMed:15297875, ECO:0000269|PubMed:15625105, ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:17409436, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:20691902, ECO:0000269|PubMed:9885575}.;

Recessive Scores

pRec: 0.155

Intolerance Scores

LoFtool: 0.934
RVIS EVS: -0.2
RVIS percentile EVS: 39.11

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.900

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium