LACTB

protein-coding

lactamase beta, the group of Serine beta lactamase family

Gene summary

This gene encodes a mitochondrially-localized protein that has sequence similarity to prokaryotic beta-lactamases. Many of the residues responsible for beta-lactamase activity are not conserved in this protein, suggesting it may have a different enzymatic function. Increased expression of the related mouse gene was found to be associated with obesity. Alternative splicing results in multiple transcript variants encoding different protein isoforms. [provided by RefSeq, Dec 2013]

Previous symbols:

MRPL56

MANE transcript

NM_032857.5

Inheritance

—

ClinVar variants

P:1U:78B:5

Top phenotype

Abnormality of neuronal migration

gnomAD constraint

pLI —, LoF o/e 0.61

Max pathogenic AF

—

Genomic locus

chr15:63,121,833-63,142,061

External References & Databases

Ensembl (ENSG00000103642)

Transcript & Mutation Effects

hg38 • Region Span ~20.2 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 LACTB variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 75

not providedTotal: 4

Abnormality of neuronal migrationTotal: 1

Hypercholesterolemia, familial, 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032857.5. 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			74 clinvar	1 clinvar	3 clinvar	78
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	1	0	78	1	4	84

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_032857.5	RefSeq	NP_116246.2	6	MANE Select
ENST00000261893.9	Ensembl	ENSP00000261893.4	6	MANE Select
NM_001288585.2	RefSeq	NP_001275514.1	5	Standard
NM_171846.4	RefSeq	NP_741982.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis
lipid metabolic process
regulation of lipid metabolic process

Molecular Function

peptidase activity
identical protein binding

Cellular Component

mitochondrion
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000261893
Coding exons: 6
Length: 20262
Individuals with no LoFs: 125722
Homozygous LoFs: 0
Heterozygous LoFs: 26
Defined: 125748
p: 0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.26	207	265	0.782	0.0000131	3499
Missense (PolyPhen)		67	93.288	0.7182		1123
Synonymous	1.43	81	99.1	0.817	0.00000510	1063
Loss of Function	1.60	12	19.6	0.611	9.12e-7	286

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00028	0.00027	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000090	0.000088	rare
South Asian	0.000072	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Mitochondrial serine protease that acts as a regulator of mitochondrial lipid metabolism (PubMed:28329758). Acts by decreasing protein levels of PISD, a mitochondrial enzyme that converts phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn), thereby affecting mitochondrial lipid metabolism (PubMed:28329758). It is unclear whether it acts directly by mediating proteolysis of PISD or by mediating proteolysis of another lipid metabolism protein (PubMed:28329758). Acts as a tumor suppressor that has the ability to inhibit proliferation of multiple types of breast cancer cells: probably by promoting decreased levels of PISD, thereby affecting mitochondrial lipid metabolism (PubMed:28329758). {ECO:0000269|PubMed:28329758}.;

Recessive Scores

pRec: 0.124

Intolerance Scores

LoFtool: 0.464
RVIS EVS: 0.13
RVIS percentile EVS: 63.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0483

Gene Damage Prediction

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