NSUN2

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

Basic information

Region (hg38): 5:6599239-6633291

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 (359 variants)
Inborn_genetic_diseases (161 variants)
Intellectual_disability,_autosomal_recessive_5 (78 variants)
not_specified (36 variants)
NSUN2-related_disorder (9 variants)
Intellectual_disability (8 variants)
Phenylketonuria (4 variants)
Autosomal_recessive_non-syndromic_intellectual_disability (2 variants)
Intellectual_Disability,_Recessive (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. These statistics are base on transcript: NM_000017755.6. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	120 clinvar	1 clinvar	125
missense	2 clinvar	5 clinvar	184 clinvar	11 clinvar	4 clinvar	206
nonsense	8 clinvar	5 clinvar				13
start loss						0
frameshift	13 clinvar	8 clinvar	4 clinvar			25
splice donor/acceptor (+/-2bp)	3 clinvar	5 clinvar				8
Total	26	23	192	131	5

Highest pathogenic variant AF is 0.000018407

Loading clinvar variants...

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