NTMT2

Chr 1

N-terminal Xaa-Pro-Lys N-methyltransferase 2

Also known as: C1orf184, HOMT1B, METTL11B, NTM1B

NCBI Gene: 149281 ENSG00000203740 UniProt: Q5VVY1

NTMT2 encodes an alpha N-methyltransferase that methylates the N-terminus of proteins containing specific motifs ([Ala/Pro/Ser]-Pro-Lys) and may prime substrates for further methylation by NTMT1. Mutations cause autosomal recessive intellectual disability with early-onset seizures and developmental delay. The disorder typically presents in infancy with seizures and affects neurological development.

ResearchSummary from RefSeq, UniProt

Enables N-terminal protein N-methyltransferase activity. Involved in N-terminal protein amino acid methylation. Located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOEUF 1.11

Clinical Summary— NTMT2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

42 VUS of 44 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.11LOEUF

pLI 0.004

Z-score 1.34

OE 0.53 (0.28–1.11)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.64Z-score

OE missense 0.85 (0.74–0.99)

127 obs / 149.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.53 (0.28–1.11)

0≤0.351.4

Missense OE?0.85 (0.74–0.99)

0≤0.61.4

Synonymous OE?0.71

0≤1.21.6

LoF obs/exp: 5 / 9.4Missense obs/exp: 127 / 149.1Syn Z: 1.71

ClinVar Variant Classifications

44 submitted variants in ClinVar

ClinVar

Classification Summary

VUS42

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	42	42
Likely Benign	1	1
Benign	0	0
Total	43	43

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

View in ClinVar →

24 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap NTMT2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →