LCMT1

protein-coding

leucine carboxyl methyltransferase 1, the group of Protein phosphatase 2 modulatory subunits|7BS protein methyltransferases

Gene summary

LCMT1 catalyzes the methylation of the carboxyl group of the C-terminal leucine residue (leu309) of the catalytic subunit of protein phosphatase-2A (PPP2CA; MIM 176915) (De Baere et al., 1999 [PubMed 10600115]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_016309.3

Inheritance

—

ClinVar variants

U:56B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.53

Max pathogenic AF

—

Genomic locus

chr16:25,111,731-25,178,231

External References & Databases

Ensembl (ENSG00000205629)

Transcript & Mutation Effects

hg38 • Region Span ~66.5 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 LCMT1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 50

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016309.3. 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			1 clinvar			1
missense			52 clinvar	2 clinvar		54
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	56	2	0	58

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 50 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016309.3	RefSeq	NP_057393.2	11	MANE Select
ENST00000399069.8	Ensembl	ENSP00000382021.3	11	MANE Select
NM_001032391.2	RefSeq	NP_001027563.1	9	Standard
ENST00000380962.9	Ensembl	ENSP00000370349.5	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cyclin A/B1/B2 associated events during G2/M transition
G2/M Transition
Mitotic G2-G2/M phases
Cell Cycle
Cell Cycle, Mitotic

Biological Process

G2/M transition of mitotic cell cycle
cellular protein modification process
protein methylation
C-terminal protein methylation
regulation of glucose metabolic process

Molecular Function

protein C-terminal carboxyl O-methyltransferase activity
protein binding
S-adenosylmethionine-dependent methyltransferase activity
protein C-terminal leucine carboxyl O-methyltransferase activity

Cellular Component

nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000399069
Coding exons: 11
Length: 66503
Individuals with no LoFs: 124625
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 124653
p: 0.000112

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.628	160	184	0.870	0.00000965	2181
Missense (PolyPhen)		36	56.115	0.64154		700
Synonymous	-0.0607	70	69.4	1.01	0.00000375	617
Loss of Function	2.01	11	20.9	0.526	0.00000110	241

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00027	0.00019	rare
Latino/Admixed American	0.00020	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00017	0.00017	rare
Finnish	0.00011	0.000093	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.00023	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Methylates the carboxyl group of the C-terminal leucine residue of protein phosphatase 2A catalytic subunits to form alpha-leucine ester residues. {ECO:0000269|PubMed:10600115}.;

Recessive Scores

pRec: 0.102

Intolerance Scores

LoFtool: 0.785
RVIS EVS: -0.49
RVIS percentile EVS: 22.09

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.908

Gene Damage Prediction

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