CMBL

protein-coding

carboxymethylenebutenolidase homolog

Gene summary

CMBL (EC 3.1.1.45) is a cysteine hydrolase of the dienelactone hydrolase family that is highly expressed in liver cytosol. CMBL preferentially cleaves cyclic esters, and it activates medoxomil-ester prodrugs in which the medoxomil moiety is linked to an oxygen atom (Ishizuka et al., 2010 [PubMed 20177059]).[supplied by OMIM, Apr 2010]

MANE transcript

NM_138809.4

Inheritance

—

ClinVar variants

U:49B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr5:10,275,875-10,307,902

External References & Databases

Ensembl (ENSG00000164237)

Transcript & Mutation Effects

hg38 • Region Span ~32.0 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 CMBL variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 46

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138809.4. 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			2 clinvar	1 clinvar	1 clinvar	4
missense			45 clinvar	3 clinvar		48
nonsense					1 clinvar	1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	49	4	2	55

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138809.4	RefSeq	NP_620164.1	5	MANE Select
ENST00000296658.4	Ensembl	ENSP00000296658.3	5	MANE Select
ENST00000873539.1	Ensembl	ENSP00000543598.1	5	Standard
ENST00000873540.1	Ensembl	ENSP00000543599.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Phase I - Functionalization of compounds
Biological oxidations
Metabolism

Biological Process

xenobiotic metabolic process

Molecular Function

hydrolase activity

Cellular Component

cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000296658
Coding exons: 5
Length: 32152
Individuals with no LoFs: 125525
Homozygous LoFs: 0
Heterozygous LoFs: 222
Defined: 125747
p: 0.000883

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.375	149	137	1.09	0.00000708	1620
Missense (PolyPhen)		50	46.564	1.0738		577
Synonymous	-0.0795	50	49.3	1.01	0.00000286	438
Loss of Function	1.28	8	13.0	0.617	7.47e-7	143

Population LoF Frequency

Population	CAF	p-value	Status
African	0.010	0.010	notable
Latino/Admixed American	0.00061	0.00061	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00065	0.00065	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cysteine hydrolase. Can convert the prodrug olmesartan medoxomil into its pharmacologically active metabolite olmerstatan, an angiotensin receptor blocker, in liver and intestine. May also activate beta-lactam antibiotics faropenem medoxomil and lenampicillin. {ECO:0000269|PubMed:20177059}.;

Recessive Scores

pRec: 0.0862

Intolerance Scores

LoFtool: 0.736
RVIS EVS: 0.15
RVIS percentile EVS: 64.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.874

Gene Damage Prediction

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