NTMT1

protein-coding

N-terminal Xaa-Pro-Lys N-methyltransferase 1, the group of 7BS protein methyltransferases

Gene summary

The METTL11A gene encodes an N-terminal methyltransferase for the RAN (MIM 601179) guanine nucleotide exchange factor regulator of chromosome condensation 1 (RCC1; MIM 179710). METTL11A enzyme alpha-N-methylates other protein targets such as SET (MIM 600960) and RB (MIM 180200).[supplied by OMIM, Nov 2010]

Previous symbols:

C9orf32
METTL11A

MANE transcript

NM_014064.4

Inheritance

—

ClinVar variants

U:35B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr9:129,608,884-129,636,135

External References & Databases

Ensembl (ENSG00000148335)

Transcript & Mutation Effects

hg38 • Region Span ~27.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NTMT1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 29

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014064.4. 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						0
missense			30 clinvar	1 clinvar		31
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	35	1	0	36

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 87 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014064.4	RefSeq	NP_054783.2	3	MANE Select
ENST00000372483.9	Ensembl	ENSP00000361561.4	3	MANE Select
NM_001286796.2	RefSeq	NP_001273725.1	3	Standard
NM_001286797.2	RefSeq	NP_001273726.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

spindle organization
chromosome segregation
histone methylation
N-terminal peptidyl-alanine trimethylation
N-terminal peptidyl-glycine methylation

Molecular Function

protein binding
protein methyltransferase activity
histone methyltransferase activity
N-terminal protein N-methyltransferase activity

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372486
Coding exons: 3
Length: 27047
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125747
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.29	104	148	0.702	0.00000954	1479
Missense (PolyPhen)		38	64.986	0.58474		650
Synonymous	-0.670	75	68.0	1.10	0.00000525	435
Loss of Function	1.45	3	7.19	0.417	3.04e-7	85

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Distributive alpha-N-methyltransferase that methylates the N-terminus of target proteins containing the N-terminal motif [Ala/Gly/Pro/Ser]-Pro-Lys when the initiator Met is cleaved. Specifically catalyzes mono-, di- or tri-methylation of the exposed alpha-amino group of the Ala, Gly or Ser residue in the [Ala/Gly/Ser]-Pro-Lys motif and mono- or di-methylation of Pro in the Pro-Pro-Lys motif. Some of the substrates may be primed by METTL11B-mediated monomethylation (PubMed:24090352). Catalyzes the trimethylation of the N-terminal Gly in CENPA (after removal of Met-1). Responsible for the N-terminal methylation of KLHL31, MYL2, MYL3, RB1, RCC1, RPL23A and SET. Required during mitosis for normal bipolar spindle formation and chromosome segregation via its action on RCC1. {ECO:0000269|PubMed:20481588, ECO:0000269|PubMed:20668449, ECO:0000269|PubMed:24090352, ECO:0000269|PubMed:26543159}.;

Recessive Scores

pRec: 0.124

Intolerance Scores

RVIS EVS: -0.49
RVIS percentile EVS: 22.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N

Gene Damage Prediction

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