LAMP2

Chr XXLD

lysosome associated membrane protein 2

Also known as: CD107b, DND, LAMP-2, LAMPB, LGP-96, LGP110

NCBI Gene: 3920 ENSG00000005893 UniProt: P13473

The protein encoded by this gene is a member of a family of membrane glycoproteins. This glycoprotein provides selectins with carbohydrate ligands. It may play a role in tumor cell metastasis. It may also function in the protection, maintenance, and adhesion of the lysosome. Alternative splicing of this gene results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Danon diseaseMIM #300257

XLD

Active trials

Pathogenic / LP

385

ClinVar variants

154

Pubs (1 yr)

0.8

Missense Z

0.64

LOEUF

Clinical Summary— LAMP2

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Gene-Disease Validity (ClinGen)

Danon disease · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

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ClinVar Variants

82 Pathogenic / Likely Pathogenic· 143 VUS of 385 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

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GeneReview available — LAMP2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint

0.64LOEUF

pLI 0.267

Z-score 2.42

OE 0.25 (0.11–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint

0.84Z-score

OE missense 0.80 (0.69–0.94)

116 obs / 144.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios

LoF OE0.25 (0.11–0.64)

0≤0.351.4

Missense OE0.80 (0.69–0.94)

0≤0.61.4

Synonymous OE0.81

0≤1.21.6

LoF obs/exp: 3 / 12.1Missense obs/exp: 116 / 144.4Syn Z: 1.06

GOF

Badonyi & Marsh 2024 ↗

0.5771th %ile

GOF

0.6638th %ile

LOF

0.3842th %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

385 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic68

Likely Pathogenic14

VUS143

Likely Benign130

Benign21

Conflicting9

Pathogenic

Likely Pathogenic

143

VUS

130

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	26	2	40	0	68
Likely Pathogenic	5	3	5	1	14
VUS	3	112	23	5	143
Likely Benign	0	8	66	56	130
Benign	0	2	18	1	21
Conflicting	—				9
Total	34	127	152	63	385

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

View in ClinVar →

LAMP2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

LAMP2-related Danon disease

definitive

Monoallelic X HeterozygousLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure, Decreased Gene Product Level

Dev. DisordersCardiac

G2P ↗

splice region variantstart lostmissense variantstop gained NMD triggeringsplice donor variant NMD triggeringframeshift variant NMD triggeringsplice acceptor variant NMD triggering

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org