ICMT

protein-coding

isoprenylcysteine carboxyl methyltransferase, the group of Methyltransferase families

Gene summary

This gene encodes the third of three enzymes that posttranslationally modify isoprenylated C-terminal cysteine residues in certain proteins and target those proteins to the cell membrane. This enzyme localizes to the endoplasmic reticulum. Alternative splicing may result in other transcript variants, but the biological validity of those transcripts has not been determined. [provided by RefSeq, Jul 2008]

MANE transcript

NM_012405.4

Inheritance

—

ClinVar variants

U:35B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr1:6,221,193-6,235,972

External References & Databases

Ensembl (ENSG00000116237)

Transcript & Mutation Effects

hg38 • Region Span ~14.8 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 ICMT variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 32

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012405.4. 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			1 clinvar		1 clinvar	2
missense			33 clinvar			33
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	35	0	1	36

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012405.4	RefSeq	NP_036537.1	5	MANE Select
ENST00000343813.10	Ensembl	ENSP00000343552.5	5	MANE Select
ENST00000474756.1	Ensembl	ENSP00000467999.1	3	Standard
ENST00000489498.5	Ensembl	ENSP00000466222.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Terpenoid backbone biosynthesis - Homo sapiens (human)
Post-translational protein modification
Metabolism of proteins
Gamma carboxylation, hypusine formation and arylsulfatase activation

Biological Process

cellular protein modification process
C-terminal protein methylation
protein targeting to membrane
post-translational protein modification

Molecular Function

protein C-terminal carboxyl O-methyltransferase activity
protein C-terminal S-isoprenylcysteine carboxyl O-methyltransferase activity

Cellular Component

endoplasmic reticulum
endoplasmic reticulum membrane
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000343813
Coding exons: 5
Length: 14780
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125747
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.42	54	132	0.409	0.00000718	1790
Missense (PolyPhen)		9	33.962	0.265		396
Synonymous	0.657	50	56.3	0.889	0.00000338	598
Loss of Function	2.97	2	14.0	0.143	8.01e-7	144

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the post-translational methylation of isoprenylated C-terminal cysteine residues.;

Recessive Scores

pRec: 0.110

Intolerance Scores

LoFtool: 0.0833
RVIS EVS: 0.3
RVIS percentile EVS: 72.01

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.916

Gene Damage Prediction

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