PLRG1

protein-coding

pleiotropic regulator 1, the group of WD repeat domain containing|NTC associated proteins|NineTeen complex|Spliceosomal C complex

Gene summary

This gene encodes a core component of the cell division cycle 5-like (CDC5L) complex. The CDC5L complex is part of the spliceosome and is required for pre-mRNA splicing. The encoded protein plays a critical role in alternative splice site selection. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

MANE transcript

NM_002669.4

Inheritance

—

ClinVar variants

U:56B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr4:154,535,005-154,550,400

External References & Databases

Ensembl (ENSG00000171566)

Transcript & Mutation Effects

hg38 • Region Span ~15.4 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 PLRG1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 46

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002669.4. 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			5 clinvar		1 clinvar	6
missense			47 clinvar	2 clinvar		49
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	56	2	1	59

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002669.4	RefSeq	NP_002660.1	15	MANE Select
ENST00000499023.7	Ensembl	ENSP00000424417.1	15	MANE Select
NM_001201564.2	RefSeq	NP_001188493.1	15	Standard
ENST00000302078.10	Ensembl	ENSP00000303191.5	15	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
plrg1	Danio rerio	Structure: post-vent region Quality: truncated abnormal

Gene / Model

Organism

Observed Phenotype

plrg1

Danio rerio

Structure: post-vent region

Quality: truncated

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Spliceosome - Homo sapiens (human)
Metabolism of RNA
mRNA Splicing - Major Pathway
mRNA Splicing
Processing of Capped Intron-Containing Pre-mRNA

Biological Process

mRNA splicing, via spliceosome
protein localization to nucleus
positive regulation of G1/S transition of mitotic cell cycle

Molecular Function

protein binding

Cellular Component

Prp19 complex
fibrillar center
nucleus
nucleoplasm
DNA replication factor A complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000499023
Coding exons: 15
Length: 15430
Individuals with no LoFs: 125690
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125694
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.45	167	283	0.590	0.0000144	3357
Missense (PolyPhen)		48	135.06	0.35539		1603
Synonymous	1.73	76	97.8	0.777	0.00000522	968
Loss of Function	4.89	3	33.5	0.0894	0.00000186	371

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in pre-mRNA splicing as component of the spliceosome (PubMed:28502770, PubMed:28076346). Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing (PubMed:11101529, PubMed:11544257). {ECO:0000269|PubMed:11101529, ECO:0000269|PubMed:11544257, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770}.;

Recessive Scores

pRec: 0.153

Intolerance Scores

LoFtool: 0.346
RVIS EVS: -0.29
RVIS percentile EVS: 33.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.497

Gene Damage Prediction

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