NSUN5

protein-coding

NOP2/Sun RNA methyltransferase 5, the group of NOP2/Sun RNA methyltransferase family

Gene summary

This gene encodes a member of an evolutionarily conserved family of proteins that may function as methyltransferases. This gene is located in a larger region of chromosome 7 that is deleted in Williams-Beuren syndrome, a multisystem developmental disorder. There are two pseudogenes for this gene located in the same region of chromosome 7. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

Previous symbols:

WBSCR20
WBSCR20A

MANE transcript

NM_148956.4

Inheritance

—

ClinVar variants

U:80B:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr7:73,302,516-73,308,826

External References & Databases

Ensembl (ENSG00000130305)

Transcript & Mutation Effects

hg38 • Region Span ~6.3 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 NSUN5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 89

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_148956.4. 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			3 clinvar	2 clinvar		5
missense			75 clinvar	12 clinvar		87
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	80	14	0	94

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_148956.4	RefSeq	NP_683759.1	10	MANE Select
ENST00000438747.7	Ensembl	ENSP00000388464.2	10	MANE Select
NM_001168347.3	RefSeq	NP_001161819.1	10	Standard
NM_001168348.3	RefSeq	NP_001161820.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

rRNA base methylation

Molecular Function

RNA binding
methyltransferase activity

Cellular Component

nucleus
nucleolus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000310326
Coding exons: 10
Length: 6351
Individuals with no LoFs: 125636
Homozygous LoFs: 0
Heterozygous LoFs: 112
Defined: 125748
p: 0.000445

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.175	291	300	0.972	0.0000185	2990
Missense (PolyPhen)		94	99.675	0.94307		1061
Synonymous	-0.742	144	133	1.08	0.00000802	1026
Loss of Function	0.466	20	22.4	0.894	0.00000136	224

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00046	0.00046	rare
Ashkenazi Jewish	0.0031	0.0031	notable
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00034	0.00033	rare
South Asian	0.00043	0.00042	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the C(5) position of cytosine 3782 in 28S rRNA. {ECO:0000305|PubMed:23913415}.;

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.914
RVIS EVS: 0.02
RVIS percentile EVS: 55.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.770

Gene Damage Prediction

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