PLBD1

Chr 12

phospholipase B domain containing 1

Also known as: LyLAP, PLBL1

NCBI Gene: 79887 ENSG00000121316 UniProt: Q6P4A8 OMIM: 618486

The protein functions as a lysosomal processive monoaminopeptidase that preferentially cleaves hydrophobic amino acids, particularly leucine residues, and plays a key role in degrading hydrophobic transmembrane domains within lysosomes. Mutations cause neurodegenerative disorders with childhood onset, including developmental delay, intellectual disability, and progressive neurological decline. This follows autosomal recessive inheritance and the gene shows tolerance to loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

Enables aminopeptidase activity. Involved in lysosomal protein catabolic process. Located in lysosome and obsolete extracellular space. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.26

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.26LOEUF

pLI 0.000

Z-score 0.44

OE 0.91 (0.67–1.26)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.78Z-score

OE missense 0.87 (0.79–0.97)

253 obs / 290.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.91 (0.67–1.26)

0≤0.351.4

Missense OE?0.87 (0.79–0.97)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 26 / 28.5Missense obs/exp: 253 / 290.3Syn Z: -0.09

Background carrier burden — how many people carry a rare variant somewhere in PLBD1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 61

657 rare PASS variants

Rare truncating (LoF)

1 in 280

188 rare PASS variants

Rare synonymous (reference)

1 in 220

285 rare PASS variants

Rare missense and truncating variants are carried at similar rates in PLBD1; this gene does not show strong loss-of-function constraint by this measure. 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 120	1 in 300
South Asian	~43k	1 in 93	1 in 430
Remaining (unassigned)	~30k	1 in 66	1 in 230
European (Finnish)	~27k	1 in 210	1 in 4,400
Admixed American	~22k	1 in 99	1 in 190
African / African American	~21k	1 in 65	1 in 580
East Asian	~20k	1 in 110	1 in 250
Ashkenazi Jewish	~13k	1 in 600	≈ 1 in 3,100
Middle Eastern	~2,884	1 in 68	1 in 350

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 10 of 11 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 11.? see exons ↓