LAPTM4B

protein-coding

lysosomal protein transmembrane 4 beta

Gene summary

Enables ceramide binding activity; enzyme binding activity; and phosphatidylinositol bisphosphate binding activity. Involved in several processes, including endosome transport via multivesicular body sorting pathway; negative regulation of lysosomal protein catabolic process; and negative regulation of transforming growth factor beta1 production. Located in endosome; lysosomal membrane; and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_018407.6

Inheritance

—

ClinVar variants

U:48B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.25

Max pathogenic AF

—

Genomic locus

chr8:97,775,057-97,853,013

External References & Databases

Ensembl (ENSG00000104341)

Transcript & Mutation Effects

hg38 • Region Span ~78.0 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 LAPTM4B variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 34

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018407.6. 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			3 clinvar		1 clinvar	4
missense			34 clinvar	1 clinvar		35
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			11 clinvar			11
Total	0	0	48	1	1	50

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018407.6	RefSeq	NP_060877.4	7	MANE Select
ENST00000521545.7	Ensembl	ENSP00000428409.1	7	MANE Select
ENST00000445593.6	Ensembl	ENSP00000402301.2	7	Standard
ENST00000445593.7	Ensembl	ENSP00000402301.2	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Lysosome - Homo sapiens (human)

Biological Process

endosome organization
endosome transport via multivesicular body sorting pathway
negative regulation of transforming growth factor beta1 production
regulation of lysosomal membrane permeability
negative regulation of lysosomal protein catabolic process

Molecular Function

protein binding
kinase binding
ubiquitin protein ligase binding
ceramide binding
phosphatidylinositol bisphosphate binding

Cellular Component

lysosome
lysosomal membrane
endosome
early endosome
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000445593
Coding exons: 7
Length: 77957
Individuals with no LoFs: 125527
Homozygous LoFs: 0
Heterozygous LoFs: 218
Defined: 125745
p: 0.000867

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.113	176	172	1.02	0.00000877	1984
Missense (PolyPhen)		56	62.588	0.89473		770
Synonymous	-0.729	78	70.2	1.11	0.00000384	643
Loss of Function	-0.849	17	13.6	1.25	6.64e-7	158

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.0014	0.0013	notable
Ashkenazi Jewish	0.00070	0.00069	rare
East Asian	0	0.0	absent
Finnish	0.00079	0.00074	rare
European (Non-Finnish)	0.00097	0.00096	rare
South Asian	0.00061	0.00052	rare
Other	0.0031	0.0031	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for optimal lysosomal function (PubMed:21224396). Blocks EGF-stimulated EGFR intraluminal sorting and degradation. Conversely by binding with the phosphatidylinositol 4,5-bisphosphate, regulates its PIP5K1C interaction, inhibits HGS ubiquitination and relieves LAPTM4B inhibition of EGFR degradation (PubMed:25588945). Recruits SLC3A2 and SLC7A5 (the Leu transporter) to the lysosome, promoting entry of leucine and other essential amino acid (EAA) into the lysosome, stimulating activation of proton-transporting vacuolar (V)-ATPase protein pump (V-ATPase) and hence mTORC1 activation (PubMed:25998567). Plays a role as negative regulator of TGFB1 production in regulatory T cells (PubMed:26126825). Binds ceramide and facilitates its exit from late endosome in order to control cell death pathways (PubMed:26280656). {ECO:0000269|PubMed:21224396, ECO:0000269|PubMed:25588945, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:26126825, ECO:0000269|PubMed:26280656}.;

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.718
RVIS EVS: -0.38
RVIS percentile EVS: 27.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0396

Gene Damage Prediction

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