NSUN2

NOP2/Sun RNA methyltransferase 2, the group of NOP2/Sun RNA methyltransferase family

Basic information

Region (hg38): 5:6599238-6633291

Previous symbols: [ "MRT5" ]

Links

ENSG00000037474 ∙ NCBI:54888 ∙ OMIM:610916 ∙ HGNC:25994 ∙ Uniprot:Q08J23 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal recessive 5 (Strong), mode of inheritance: AR
• intellectual disability, autosomal recessive 5 (Moderate), mode of inheritance: AR
• Dubowitz syndrome (Supportive), mode of inheritance: AR
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• intellectual disability, autosomal recessive 5 (Strong), mode of inheritance: AR
• RASopathy (Disputed Evidence), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 5	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	22541559; 22541562; 22577224

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NSUN2 gene.

• not provided (320 variants)
• Inborn genetic diseases (110 variants)
• Intellectual disability, autosomal recessive 5 (90 variants)
• not specified (42 variants)
• Autosomal recessive non-syndromic intellectual disability (2 variants)
• Intellectual disability (2 variants)
• Intellectual Disability, Recessive (2 variants)
• Global developmental delay (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NSUN2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	66	3	75
missense		3	128	2	3	136
nonsense	5	3	1			9
start loss						0
frameshift	10	5	3			18
inframe indel			3			3
splice donor/acceptor (+/-2bp)	2	2				4
splice region			10	12	5	27
non coding			13	68	75	156
Total	17	13	154	136	81

Highest pathogenic variant AF is 0.0000131

Variants in NSUN2

This is a list of pathogenic ClinVar variants found in the NSUN2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-6599304-A-T		Intellectual disability, autosomal recessive 5	Uncertain significance (Jan 13, 2018)
5-6599307-C-T		Intellectual disability, autosomal recessive 5	Uncertain significance (Jan 13, 2018)
5-6599345-A-G		Intellectual disability, autosomal recessive 5	Benign (Jan 12, 2018)
5-6599363-G-A		Intellectual disability, autosomal recessive 5	Benign (Jan 12, 2018)
5-6599379-TG-T		Intellectual Disability, Recessive	Likely benign (Jun 14, 2016)
5-6599394-T-C		Intellectual disability, autosomal recessive 5	Uncertain significance (Feb 16, 2018)
5-6599537-T-C		Intellectual disability, autosomal recessive 5	Uncertain significance (Jan 13, 2018)
5-6599632-G-C		Intellectual disability, autosomal recessive 5	Uncertain significance (Jan 13, 2018)
5-6599724-G-A		Intellectual disability, autosomal recessive 5	Uncertain significance (Jan 12, 2018)
5-6599786-A-G		Intellectual disability, autosomal recessive 5	Uncertain significance (Jan 13, 2018)
5-6599827-C-T		Intellectual disability, autosomal recessive 5	Benign (Sep 11, 2018)
5-6599829-G-T		Intellectual disability, autosomal recessive 5	Uncertain significance (Jan 13, 2018)
5-6599841-C-T		Intellectual disability, autosomal recessive 5	Uncertain significance (Jan 13, 2018)
5-6599876-A-C		Intellectual disability, autosomal recessive 5	Benign/Likely benign (Nov 02, 2018)
5-6599878-G-A		Intellectual disability, autosomal recessive 5	Uncertain significance (Jan 13, 2018)
5-6599904-GCCCCCGCTGCCTTGGGCCTGCTCACCGGGGTGGATGGA-G			Uncertain significance (Jul 12, 2018)
5-6599909-C-T		Intellectual disability, autosomal recessive 5	Likely benign (Jan 13, 2018)
5-6599910-G-A		Intellectual disability, autosomal recessive 5	Uncertain significance (Jan 13, 2018)
5-6599930-C-T		not specified • Intellectual disability, autosomal recessive 5 • Inborn genetic diseases • NSUN2-related disorder	Conflicting classifications of pathogenicity (Feb 01, 2024)
5-6599940-G-T			Uncertain significance (Apr 23, 2023)
5-6599947-C-T		Intellectual disability, autosomal recessive 5	Conflicting classifications of pathogenicity (Nov 01, 2023)
5-6599948-G-A		Intellectual disability, autosomal recessive 5 • Inborn genetic diseases	Uncertain significance (Dec 20, 2023)
5-6599948-G-T		Inborn genetic diseases	Uncertain significance (Dec 27, 2016)
5-6599950-C-G		not specified	Likely benign (Jan 04, 2016)
5-6599950-C-T			Likely benign (Jun 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NSUN2	protein_coding	protein_coding	ENST00000264670	19	34053

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000258	1.00	125707	0	41	125748	0.000163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0340	428	430	0.995	0.0000232	5039
Missense in Polyphen		131	162.89	0.80423		1882
Synonymous	-0.159	165	162	1.02	0.00000936	1417
Loss of Function	3.93	14	41.2	0.340	0.00000215	481

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000462	0.000462
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000441	0.000435
Finnish	0.0000926	0.0000924
European (Non-Finnish)	0.000124	0.000123
Middle Eastern	0.000441	0.000435
South Asian	0.000197	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: RNA methyltransferase that methylates tRNAs, and possibly RNA polymerase III transcripts. Methylates cytosine to 5- methylcytosine (m5C) at positions 34 and 48 of intron-containing tRNA(Leu)(CAA) precursors, and at positions 48, 49 and 50 of tRNA(Gly)(GCC) precursors. May act downstream of Myc to regulate epidermal cell growth and proliferation. Required for proper spindle assembly and chromosome segregation, independently of its methyltransferase activity. {ECO:0000269|PubMed:17071714, ECO:0000269|PubMed:19596847, ECO:0000269|PubMed:22995836}.
• Disease: DISEASE: Mental retardation, autosomal recessive 5 (MRT5) [MIM:611091]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:22541559, ECO:0000269|PubMed:22541562}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: tRNA modification in the nucleus and cytosol;tRNA processing;Metabolism of RNA;Aurora B signaling (Consensus)

Recessive Scores

• pRec: 0.188

Intolerance Scores

• loftool: 0.873
• rvis_EVS: -1
• rvis_percentile_EVS: 8.54

Haploinsufficiency Scores

• pHI: 0.748
• hipred: Y
• hipred_score: 0.756
• ghis: 0.611

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.905

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nsun2
• Phenotype: immune system phenotype; skeleton phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; digestive/alimentary phenotype; vision/eye phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; craniofacial phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: tRNA modification;spermatid development;tRNA methylation;meiotic cell cycle checkpoint;hair follicle maturation;cell division
• Cellular component: nucleus;nucleoplasm;nucleolus;cytoplasm;spindle;chromatoid body
• Molecular function: tRNA binding;RNA binding;methyltransferase activity;tRNA (cytosine-5-)-methyltransferase activity