LAPTM4B

Chr 8

lysosomal protein transmembrane 4 beta

Also known as: LAPTM4beta, LC27

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
GOFmechanismLOEUF 1.80
Clinical SummaryLAPTM4B
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.80LOEUF
pLI 0.000
Z-score -0.85
OE 1.25 (0.851.80)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.11Z-score
OE missense 1.02 (0.911.16)
176 obs / 171.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.25 (0.851.80)
00.351.4
Missense OE1.02 (0.911.16)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 17 / 13.6Missense obs/exp: 176 / 171.8Syn Z: -0.73
DN
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

LAPTM4B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗