NOP2

protein-coding

NOP2 nucleolar protein, the group of NOP2/Sun RNA methyltransferase family

Gene summary

Enables rRNA (cytosine-C5-)-methyltransferase activity. Involved in positive regulation of cell population proliferation; regulation of signal transduction by p53 class mediator; and ribosome biogenesis. Located in nucleolus. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

NOL1

MANE transcript

NM_001258308.2

Inheritance

—

ClinVar variants

U:127B:13

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chr12:6,556,863-6,568,691

External References & Databases

Ensembl (ENSG00000111641)

Transcript & Mutation Effects

hg38 • Region Span ~11.8 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 NOP2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 124

not providedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001258308.2. 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			121 clinvar	7 clinvar	4 clinvar	132
nonsense			2 clinvar			2
start loss						0
frameshift					1 clinvar	1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	127	7	6	140

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 66 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001258308.2	RefSeq	NP_001245237.1	15	MANE Select
ENST00000322166.10	Ensembl	ENSP00000313272.6	15	MANE Select
NM_001033714.3	RefSeq	NP_001028886.1	15	Standard
NM_001258309.2	RefSeq	NP_001245238.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Imatinib and Chronic Myeloid Leukemia
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors
rRNA processing
Gene expression (Transcription)
Generic Transcription Pathway

Biological Process

ribosomal large subunit assembly
regulation of transcription by RNA polymerase II
positive regulation of cell population proliferation
rRNA base methylation
regulation of signal transduction by p53 class mediator

Molecular Function

RNA binding
protein binding
rRNA (cytosine-C5-)-methyltransferase activity

Cellular Component

nucleoplasm
nucleolus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000382421
Coding exons: 16
Length: 11829
Individuals with no LoFs: 124635
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 124638
p: 0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.638	431	470	0.917	0.0000261	5436
Missense (PolyPhen)		110	167.49	0.65677		1832
Synonymous	1.31	157	179	0.876	0.00000926	1702
Loss of Function	5.38	2	37.6	0.0532	0.00000232	392

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000066	0.000065	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in ribosomal large subunit assembly (PubMed:24120868). S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the C(5) position of cytosine 4447 in 28S rRNA (Probable). May play a role in the regulation of the cell cycle and the increased nucleolar activity that is associated with the cell proliferation (Probable). {ECO:0000269|PubMed:24120868, ECO:0000305, ECO:0000305|PubMed:23913415}.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.702
RVIS EVS: 0.38
RVIS percentile EVS: 75.63

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.451

Gene Damage Prediction

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