PWP2

protein-coding

PWP2 small subunit processome component, the group of WD repeat domain containing|UTPb subcomplex

Gene summary

Enables RNA binding activity. Involved in ribosomal small subunit biogenesis. Located in nucleolus. Part of small-subunit processome. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

PWP2H

MANE transcript

NM_005049.3

Inheritance

—

ClinVar variants

U:179B:13

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr21:44,107,373-44,131,181

External References & Databases

Ensembl (ENSG00000241945)

Transcript & Mutation Effects

hg38 • Region Span ~23.8 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 PWP2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 175

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005049.3. 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			4 clinvar	3 clinvar	3 clinvar	10
missense			167 clinvar	6 clinvar	1 clinvar	174
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	179	9	4	192

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005049.3	RefSeq	NP_005040.2	21	MANE Select
ENST00000291576.12	Ensembl	ENSP00000291576.6	21	MANE Select
ENST00000456705.1	Ensembl	ENSP00000411749.1	6	Standard
ENST00000862525.1	Ensembl	ENSP00000532584.1	21	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
pwp2h	Danio rerio	Structure: intestinal bulb epithelium Quality: decreased length abnormal

Gene / Model

Organism

Observed Phenotype

pwp2h

Danio rerio

Structure: intestinal bulb epithelium

Quality: decreased length

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ribosome biogenesis in eukaryotes - Homo sapiens (human)
rRNA processing
Metabolism of RNA
rRNA modification in the nucleus and cytosol
rRNA processing in the nucleus and cytosol

Biological Process

ribosomal small subunit assembly
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)
rRNA processing

Molecular Function

RNA binding

Cellular Component

nucleoplasm
small-subunit processome
Pwp2p-containing subcomplex of 90S preribosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000291576
Coding exons: 21
Length: 23893
Individuals with no LoFs: 125713
Homozygous LoFs: 0
Heterozygous LoFs: 35
Defined: 125748
p: 0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.325	549	571	0.962	0.0000360	5989
Missense (PolyPhen)		162	187.6	0.86354		1995
Synonymous	-1.32	271	245	1.11	0.0000176	1820
Loss of Function	4.18	14	43.9	0.319	0.00000222	490

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0.00025	0.00020	rare
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00015	0.00012	rare
South Asian	0.00024	0.00023	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.116

Intolerance Scores

LoFtool: 0.456
RVIS EVS: -0.56
RVIS percentile EVS: 19.07

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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