NSUN6

Chr 10AR

NOP2/Sun RNA methyltransferase 6

Also known as: 4933414E04Rik, ARL5B-AS1, MRT82, NOPD1

This gene encodes a cytoplasmic S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates cytosine at position 72 in specific tRNAs including tRNA(Thr) and tRNA(Cys). Biallelic mutations cause autosomal recessive intellectual developmental disorder 82. The gene appears tolerant to loss-of-function variants in the general population (LOEUF 1.479), suggesting that complete loss of function may require biallelic mutations to cause disease.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 82MIM #620779
AR
0
Active trials
30
Pubs (1 yr)
15
P/LP submissions
7%
P/LP missense
1.48
LOEUF
LOF
Mechanism· G2P
Clinical SummaryNSUN6
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 92 VUS of 136 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.48LOEUF
pLI 0.000
Z-score -0.34
OE 1.07 (0.791.48)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.33Z-score
OE missense 1.24 (1.131.37)
292 obs / 234.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.07 (0.791.48)
00.351.4
Missense OE1.24 (1.131.37)
00.61.4
Synonymous OE1.19
01.21.6
LoF obs/exp: 27 / 25.2Missense obs/exp: 292 / 234.8Syn Z: -1.41

ClinVar Variant Classifications

136 submitted variants in ClinVar

Classification Summary

Pathogenic15
VUS92
Likely Benign4
Benign1
15
Pathogenic
92
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
13
0
15
Likely Pathogenic
0
0
0
0
0
VUS
1
78
13
0
92
Likely Benign
0
3
1
0
4
Benign
0
0
1
0
1
Total282280112

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NSUN6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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