NSUN6

protein-coding

NOP2/Sun RNA methyltransferase 6, the group of NOP2/Sun RNA methyltransferase family

Gene summary

Enables tRNA (cytidine-N5)-methyltransferase activity and tRNA binding activity. Involved in tRNA C5-cytosine methylation. Located in cytoplasm. Implicated in autosomal recessive intellectual developmental disorder 82. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

NOPD1
ARL5B-AS1

MANE transcript

NM_182543.5

Inheritance

ClinVar variants

P:4U:92B:4

Top phenotype

Intellectual developmental disorder, autosomal recessive 82

gnomAD constraint

pLI —, LoF o/e 1.07

Max pathogenic AF

—

Genomic locus

chr10:18,545,561-18,659,285

External References & Databases

Ensembl (ENSG00000241058)

Transcript & Mutation Effects

hg38 • Region Span ~113.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder, autosomal recessive 82STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0968944

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Intellectual developmental disorder, autosomal recessive 82AR

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 37226891

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NSUN6 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 81

Intellectual developmental disorder, autosomal recessive 82Total: 4

not providedTotal: 3

NSUN6-related conditionTotal: 1

Developmental and epileptic encephalopathy, 83Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_182543.5. 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			2
missense	1 clinvar		85 clinvar	4 clinvar		90
nonsense						0
start loss						0
frameshift	1 clinvar	2 clinvar				3
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	2	2	92	4	0	100

Highest pathogenic variant AF is 0.00012887998

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_182543.5	RefSeq	NP_872349.1	11	MANE Select
ENST00000377304.7	Ensembl	ENSP00000366519.4	11	MANE Select
NM_001351115.2	RefSeq	NP_001338044.1	11	Standard
NM_001351116.2	RefSeq	NP_001338045.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

tRNA modification in the nucleus and cytosol
tRNA processing
Metabolism of RNA

Biological Process

tRNA modification
tRNA methylation

Molecular Function

tRNA binding
tRNA (cytosine-5-)-methyltransferase activity

Cellular Component

cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377304
Coding exons: 11
Length: 106062
Individuals with no LoFs: 125556
Homozygous LoFs: 0
Heterozygous LoFs: 190
Defined: 125746
p: 0.000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.33	292	235	1.24	0.0000112	3029
Missense (PolyPhen)		98	79.276	1.2362		978
Synonymous	-1.41	102	85.5	1.19	0.00000412	908
Loss of Function	-0.339	27	25.2	1.07	0.00000131	325

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0024	0.0023	notable
Latino/Admixed American	0.00063	0.00055	rare
Ashkenazi Jewish	0.0024	0.0024	notable
East Asian	0.0019	0.0019	notable
Finnish	0.00032	0.00032	rare
European (Non-Finnish)	0.00042	0.00041	rare
South Asian	0.00055	0.00052	rare
Other	0.00082	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May have S-adenosyl-L-methionine-dependent methyl- transferase activity. {ECO:0000305}.;

Recessive Scores

pRec: 0.0991

Intolerance Scores

LoFtool: 0.729
RVIS EVS: -0.2
RVIS percentile EVS: 38.98

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.159

Gene Damage Prediction

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