LAPTM4B

Chr 8

lysosomal protein transmembrane 4 beta

Also known as: LAPTM4beta, LC27

NCBI Gene: 55353 ENSG00000104341 UniProt: Q86VI4

The LAPTM4B protein is required for optimal lysosomal function and regulates lysosomal membrane permeability, while also controlling EGFR degradation and facilitating ceramide transport from late endosomes. Mutations in LAPTM4B cause autosomal recessive cerebral atrophy with pontocerebellar hypoplasia, a severe neurodevelopmental disorder affecting brain development with onset in infancy or early childhood. The gene shows low constraint against loss-of-function variants, consistent with recessive inheritance where both copies must be affected to cause disease.

ResearchSummary from RefSeq, UniProt

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 macromolecule metabolic process; and regulation of lysosomal membrane permeability. Located in several cellular components, including endosome; lysosomal membrane; and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.80

Clinical Summary— LAPTM4B

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

49 VUS of 87 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.80LOEUF

pLI 0.000

Z-score -0.85

OE 1.25 (0.85–1.80)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.11Z-score

OE missense 1.02 (0.91–1.16)

176 obs / 171.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.25 (0.85–1.80)

0≤0.351.4

Missense OE?1.02 (0.91–1.16)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 17 / 13.6Missense obs/exp: 176 / 171.8Syn Z: -0.73

This gene — mechanism propensity

0.5870th %ile

GOF

0.6638th %ile

LOF

0.4528th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

87 submitted variants in ClinVar

ClinVar

Classification Summary

VUS49

Likely Benign4

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	33	16	0	49
Likely Benign	1	3	0	4
Benign	0	2	1	3
Total	34	21	1	56

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

35 pathogenic / likely-pathogenic (of 37) ClinVar copy-number / structural variants overlap LAPTM4B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →