LAPTM4B

Chr 8

lysosomal protein transmembrane 4 beta

Also known as: LAPTM4beta, LC27

NCBI Gene: 55353 ENSG00000104341 UniProt: Q86VI4 OMIM: 613296

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.

OMIM 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 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]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.80

LOEUF

GOF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in LAPTM4B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 84

516 rare PASS variants

Rare truncating (LoF)

1 in 630

123 rare PASS variants

Rare synonymous (reference)

1 in 150

236 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LAPTM4B. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 550
South Asian	~43k	1 in 58	1 in 580
Remaining (unassigned)	~30k	1 in 87	1 in 980
European (Finnish)	~27k	1 in 380	1 in 610
Admixed American	~22k	1 in 110	1 in 590
African / African American	~21k	1 in 110	1 in 710
East Asian	~20k	1 in 150	1 in 650
Ashkenazi Jewish	~13k	1 in 400	1 in 700
Middle Eastern	~2,884	1 in 100	1 in 360

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 4 of 7 coding exons well covered in gnomAD exomes; exons 2, 5, 6 marginal. Genomes: all 7.? see exons ↓