PLBD1

Summary

PLBD1 (phospholipase B domain containing 1, HGNC:26215) is a protein-coding gene on chromosome 12p13.1, encoding Lysosomal leucine aminopeptidase (Q6P4A8). Lysosomal processive monoaminopeptidase that preferentially cleaves hydrophobic amino acids, with strong preference for leucine residues.

Predicted to enable phospholipase activity. Predicted to be involved in phospholipid catabolic process. Located in extracellular space.

Source: NCBI Gene 79887 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 80 total — 1 likely-pathogenic
• MANE Select transcript: NM_024829

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26215
Approved symbol	PLBD1
Name	phospholipase B domain containing 1
Location	12p13.1
Locus type	gene with protein product
Status	Approved
Aliases	PLBL1, FLJ22662
Ensembl gene	ENSG00000121316
Ensembl biotype	protein_coding
OMIM	618486
Entrez	79887

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000240617, ENST00000540572, ENST00000541618, ENST00000541800, ENST00000918097, ENST00000918098, ENST00000945093, ENST00000945094, ENST00000945095

RefSeq mRNA: 1 — MANE Select: NM_024829 NM_024829

CCDS: CCDS31751

Canonical transcript exons

ENST00000240617 — 11 exons

Exon	Start	End
ENSE00000541218	14506162	14506268
ENSE00000722241	14506933	14507118
ENSE00000822095	14503661	14503954
ENSE00002235431	14567582	14567883
ENSE00003489620	14511511	14511711
ENSE00003501114	14553193	14553412
ENSE00003548967	14511260	14511400
ENSE00003578518	14535659	14535803
ENSE00003589207	14536570	14536710
ENSE00003659040	14542208	14542291
ENSE00003691396	14540764	14540902

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 99.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.7723 / max 3838.1124, expressed in 1190 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
129831	26.9094	1163
129832	0.9556	421
129833	0.7175	260
129830	0.1326	54
129834	0.0494	35
129835	0.0078	3

Top tissues by expression

286 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.25	gold quality
mononuclear cell	CL:0000842	99.25	gold quality
leukocyte	CL:0000738	99.19	gold quality
trabecular bone tissue	UBERON:0002483	98.73	gold quality
bone marrow	UBERON:0002371	98.63	gold quality
blood	UBERON:0000178	98.40	gold quality
esophagus squamous epithelium	UBERON:0006920	98.09	gold quality
bone element	UBERON:0001474	97.94	gold quality
granulocyte	CL:0000094	97.93	gold quality
epithelium of esophagus	UBERON:0001976	97.47	gold quality
bone marrow cell	CL:0002092	97.17	gold quality
rectum	UBERON:0001052	97.15	gold quality
squamous epithelium	UBERON:0006914	97.01	gold quality
tongue squamous epithelium	UBERON:0006919	96.89	gold quality
gingival epithelium	UBERON:0001949	96.61	gold quality
gingiva	UBERON:0001828	96.54	gold quality
periodontal ligament	UBERON:0008266	96.22	gold quality
oral cavity	UBERON:0000167	95.67	gold quality
mucosa of urinary bladder	UBERON:0001259	95.65	gold quality
cervix epithelium	UBERON:0004801	95.58	gold quality
palpebral conjunctiva	UBERON:0001812	95.57	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.48	gold quality
colonic mucosa	UBERON:0000317	95.42	gold quality
pharyngeal mucosa	UBERON:0000355	94.92	gold quality
mammalian vulva	UBERON:0000997	94.88	gold quality
lower esophagus mucosa	UBERON:0035834	94.46	gold quality
esophagus mucosa	UBERON:0002469	94.36	gold quality
decidua	UBERON:0002450	94.16	gold quality
nasal cavity epithelium	UBERON:0005384	93.83	gold quality
eye	UBERON:0000970	93.81	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-GEOD-149689	yes	691.13
E-MTAB-7008	yes	337.96
E-CURD-122	yes	66.28
E-CURD-112	yes	30.70
E-MTAB-9221	yes	25.84
E-MTAB-6678	yes	24.21
E-MTAB-9067	yes	15.41
E-ANND-3	yes	15.11
E-MTAB-9801	yes	6.92

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting PLBD1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-33B-3P	97.92	67.39	529
HSA-MIR-515-3P	97.92	67.98	506
HSA-MIR-519E-3P	97.92	68.25	508

Literature-anchored findings (GeneRIF, showing 1)

• Peripheral Blood RNA Levels of QSOX1 and PLBD1 Are New Independent Predictors of Left Ventricular Dysfunction After Acute Myocardial Infarction. (PMID:31756302)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	plbd1a	ENSDARG00000063313
danio_rerio	plbd1b	ENSDARG00000076015
mus_musculus	Plbd1	ENSMUSG00000030214
rattus_norvegicus	Plbd1	ENSRNOG00000008933
drosophila_melanogaster	lama	FBGN0016031
caenorhabditis_elegans		WBGENE00008607
caenorhabditis_elegans		WBGENE00021852

Paralogs (1): PLBD2 (ENSG00000151176)

Protein

Protein identifiers

Lysosomal leucine aminopeptidase — Q6P4A8 (reviewed: Q6P4A8)

Alternative names: LAMA-like protein 1, Lamina ancestor homolog 1, Phospholipase B domain-containing protein 1, Phospholipase B-like 1

All UniProt accessions (3): F5GYQ3, F5H053, Q6P4A8

UniProt curated annotations — full annotation on UniProt →

Function. Lysosomal processive monoaminopeptidase that preferentially cleaves hydrophobic amino acids, with strong preference for leucine residues. Plays a key role in the degradation of hydrophobic transmembrane domains within the lysosome.

Subunit / interactions. May form a homodimer, each monomer is composed of a chain A and a chain B.

Subcellular location. Lysosome.

Tissue specificity. Expressed in neutrophils and monocytes.

Post-translational modifications. Proteolytically activated within lysosomes. Undergoes autocatalytic cleavage into an N-terminal A chain and a C-terminal B chain. Both chains A and B remain associated in the mature protein. An additional maturation step involves the removal of a segment spanning residues Leu-209-227-Cys, which occludes the active site.

Induction. Up-regulated in pancreatic ductal adenocarcinoma.

Similarity. Belongs to the Ntn hydrolase family.

RefSeq proteins (1): NP_079105* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007000	PLipase_B-like	Family
IPR043040
IPR043041
IPR043042

Pfam: PF04916

Enzyme classification (BRENDA):

• EC 3.1.1.5 — lysophospholipase (BRENDA: 46 organisms, 226 substrates, 153 inhibitors, 43 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

35 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
LYSOPHOSPHATIDYLCHOLINE	0.022–0.26	5
1-OLEOYL-2-LYSOPHOSPHATIDYLCHOLINE	0.306–0.75	2
1-PALMITOYL LYSOPHOSPHATIDYLCHOLINE	0.0273–0.19	2
1-PALMITOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.0606–0.17	2
PHOSPHATIDYLCHOLINE	0.18–0.63	2
1,2-DIDECANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	1	1
1,2-DIDECANOYLPHOSPHATIDYLCHOLINE	1.1	1
1,2-DIOCTANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	2.9	1
1,2-DIPALMITOYL-SN-GLYCERO-3-PHOSPHOCHOLINE	0.82	1
1,2-DIPALMITOYLPHOSPHATIDYLCHOLINE	0.19	1
1-(4Z,7Z,10Z,13Z,16Z,19Z)-DOCOSAHEXAENOYL-2-LYSO	0.045	1
1-ACYL-2-OLEOYL-PHOSPHATIDYLCHOLINE	1.6	1
1-ARACHIDONOYL-2-LYSOPHOSPHATIDYLCHOLINE	0.0676	1
1-DOCOSAHEXAENOYL LYSOPHOSPHATIDYLCHOLINE	0.045	1
1-HEXANOYL LYSOPHOSPHATIDYLCHOLINE	0.0992	1

Catalyzed reactions (Rhea), 1 shown:

• an N-terminal L-leucyl-L-alpha-aminoacyl-[peptide] + H2O = an N-terminal L-alpha-aminoacyl-[peptide] + L-leucine (RHEA:84791)

UniProt features (25 total): glycosylation site 9, chain 4, sequence variant 3, sequence conflict 3, disulfide bond 2, signal peptide 1, mutagenesis site 1, propeptide 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P4A8-F1	92.07	0.88

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 228 (nucleophile)

Disulfide bonds (2): 470–475, 474–489

Glycosylation sites (9): 308, 366, 366, 411, 526, 526, 71, 71, 308

Mutagenesis-validated functional residues (1):

Position	Phenotype
228	blocks autocatalytic cleavage irrespective of ph.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1482788	Acyl chain remodelling of PC
R-HSA-1482839	Acyl chain remodelling of PE
R-HSA-1482922	Acyl chain remodelling of PI
R-HSA-1483115	Hydrolysis of LPC

MSigDB gene sets: 265 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_CD8A_DC_UP, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_MATURE_CELL, MODULE_453, USF_C, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOLDRATH_ANTIGEN_RESPONSE, GNF2_CD1D, KORKOLA_EMBRYONAL_CARCINOMA_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, COATES_MACROPHAGE_M1_VS_M2_UP, TGACATY_UNKNOWN, KORKOLA_CHORIOCARCINOMA_UP

GO Biological Process (4): phospholipid catabolic process (GO:0009395), lysosomal protein catabolic process (GO:1905146), lipid metabolic process (GO:0006629), lipid catabolic process (GO:0016042)

GO Molecular Function (3): aminopeptidase activity (GO:0004177), glycerophospholipase activity (GO:0004620), hydrolase activity (GO:0016787)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), lysosome (GO:0005764), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	4

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
phospholipid metabolic process	1
lipid catabolic process	1
organophosphate catabolic process	1
lysosome	1
protein catabolic process in the vacuole	1
primary metabolic process	1
lipid metabolic process	1
catabolic process	1
exopeptidase activity	1
phospholipase activity	1
catalytic activity	1
lytic vacuole	1
cytoplasm	1

Protein interactions and networks

STRING

998 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLBD1	JAKMIP2	Q96AA8	462
PLBD1	ZNF831	Q5JPB2	451
PLBD1	PLPP2	O43688	447
PLBD1	SPHKAP	Q2M3C7	437
PLBD1	APOBR	Q0VD83	423
PLBD1	C4BPB	P20851	411
PLBD1	VCAN	P13611	410
PLBD1	LIAS	O43766	402
PLBD1	PLB1	Q6P1J6	402
PLBD1	PLPP3	O14495	395
PLBD1	GRAP2	O75791	379
PLBD1	C7orf57	Q8NEG2	379
PLBD1	TRIM46	Q7Z4K8	377
PLBD1	OR6C70	A6NIJ9	373
PLBD1	DENND11	A4D1U4	368
PLBD1	OR2L3	Q8NG85	368

IntAct

59 interactions, top by confidence:

A	B	Type	Score
ASH2L	KMT2D	psi-mi:“MI:0914”(association)	0.890
LSMEM2	STX7	psi-mi:“MI:0914”(association)	0.740
POLR2L	RCCD1	psi-mi:“MI:0914”(association)	0.640
FTH1	A2ML1	psi-mi:“MI:0914”(association)	0.530
GMCL1	A2ML1	psi-mi:“MI:0914”(association)	0.530
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
CCDC51	TGM5	psi-mi:“MI:0914”(association)	0.530
ZIC1	CTSV	psi-mi:“MI:0914”(association)	0.530
SPICE1	SERPINB2	psi-mi:“MI:0914”(association)	0.530
PLBD1	RANBP2	psi-mi:“MI:0915”(physical association)	0.400
PLBD1	GOT1	psi-mi:“MI:0915”(physical association)	0.400
OR1N1	PLBD1	psi-mi:“MI:0915”(physical association)	0.400
PLBD1		psi-mi:“MI:0915”(physical association)	0.370
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
PI4KA	A2ML1	psi-mi:“MI:0914”(association)	0.350
GPATCH2L	A2ML1	psi-mi:“MI:0914”(association)	0.350
VAV1	CHEK1	psi-mi:“MI:0914”(association)	0.350
ZIC1	IMPA2	psi-mi:“MI:0914”(association)	0.350
IL31RA	DUSP14	psi-mi:“MI:0914”(association)	0.350
SPICE1	ARG1	psi-mi:“MI:0914”(association)	0.350
ATP6V1A		psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
PI4KAP1	A2ML1	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	A2ML1	psi-mi:“MI:0914”(association)	0.350
RIPPLY3	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (101): CCT6B (Affinity Capture-MS), PLBD1 (Affinity Capture-MS), PLBD1 (Affinity Capture-MS), PLBD1 (Affinity Capture-MS), PLBD1 (Affinity Capture-MS), PLBD1 (Affinity Capture-MS), PLBD1 (Affinity Capture-MS), PLBD1 (Affinity Capture-MS), PLBD1 (Affinity Capture-MS), PLBD1 (Affinity Capture-MS), PLBD1 (Affinity Capture-MS), PLBD1 (Affinity Capture-MS), PLBD1 (Affinity Capture-MS), PLBD1 (Synthetic Lethality), PLBD1 (Proximity Label-MS)

ESM2 similar proteins: A0A0P6JG37, A0A383ZFX3, A5A6P2, A6MFL0, A8QL51, A8QL52, F8J2D3, F8S101, G1T7U7, G8XQX1, H0VCJ6, J7H670, O45686, O62146, P0C2D5, P16278, P23780, P81382, P86810, Q02083, Q06K61, Q09551, Q13510, Q17QB3, Q19426, Q2VQV9, Q4JHE2, Q54CS6, Q55BZ5, Q5KTC7, Q5MIX2, Q5R7P4, Q5U2V4, Q5UR76, Q60HH4, Q6L6S1, Q6P4A8, Q6P7S1, Q6STF1, Q6WP39

Diamond homologs: F8J2D3, F8S101, O62146, Q2KIY5, Q3TCN2, Q4QQW8, Q54M94, Q54PS7, Q54ZI6, Q550U9, Q554H5, Q55BJ6, Q55FN1, Q5U2V4, Q6P4A8, Q8NHP8, Q8VCI0, Q9BL07, Q9GL30, Q9XWV2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

80 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	64
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
442150	GRCh37/hg19 12p13.33-11.1(chr12:565369-34835837)x3	Likely pathogenic

SpliceAI

1911 predictions. Top by Δscore:

Variant	Effect	Δscore
12:14503956:T:G	acceptor_loss	1.0000
12:14505652:T:C	donor_gain	1.0000
12:14506159:TA:T	donor_loss	1.0000
12:14506160:A:AG	donor_loss	1.0000
12:14506161:C:G	donor_loss	1.0000
12:14506264:ATAAT:A	acceptor_gain	1.0000
12:14506265:TAAT:T	acceptor_gain	1.0000
12:14506266:AAT:A	acceptor_gain	1.0000
12:14506267:AT:A	acceptor_gain	1.0000
12:14506267:ATCTA:A	acceptor_loss	1.0000
12:14506268:TCTAG:T	acceptor_loss	1.0000
12:14506269:C:CC	acceptor_gain	1.0000
12:14506269:CTAGG:C	acceptor_loss	1.0000
12:14506931:A:AC	donor_gain	1.0000
12:14506932:C:CC	donor_gain	1.0000
12:14511242:A:AC	donor_gain	1.0000
12:14511243:C:CC	donor_gain	1.0000
12:14511243:CGA:C	donor_gain	1.0000
12:14511710:CC:C	acceptor_gain	1.0000
12:14511711:CC:C	acceptor_gain	1.0000
12:14542202:ACGT:A	donor_loss	1.0000
12:14542203:CGTA:C	donor_gain	1.0000
12:14542204:GT:G	donor_loss	1.0000
12:14542205:TACTC:T	donor_loss	1.0000
12:14542206:A:AC	donor_gain	1.0000
12:14542206:ACT:A	donor_gain	1.0000
12:14542206:ACTC:A	donor_gain	1.0000
12:14542206:ACTCC:A	donor_loss	1.0000
12:14542207:C:CC	donor_gain	1.0000
12:14542207:CT:C	donor_gain	1.0000

AlphaMissense

3651 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:14535666:A:C	S279R	0.999
12:14535666:A:T	S279R	0.999
12:14535668:T:G	S279R	0.999
12:14535669:G:C	S278R	0.999
12:14535669:G:T	S278R	0.999
12:14535671:T:G	S278R	0.999
12:14506174:A:C	C489W	0.998
12:14506219:G:C	C474W	0.998
12:14511541:A:G	W339R	0.998
12:14511541:A:T	W339R	0.998
12:14511690:T:A	D289V	0.998
12:14511691:C:G	D289H	0.998
12:14511693:T:A	D288V	0.998
12:14511694:C:G	D288H	0.998
12:14535726:T:A	K259N	0.998
12:14535726:T:G	K259N	0.998
12:14535735:C:A	R256S	0.998
12:14535735:C:G	R256S	0.998
12:14536585:G:C	C228W	0.998
12:14536586:C:T	C228Y	0.998
12:14506162:C:A	K493N	0.997
12:14506162:C:G	K493N	0.997
12:14506175:C:T	C489Y	0.997
12:14506176:A:G	C489R	0.997
12:14506214:C:G	R476P	0.997
12:14506941:C:G	R455P	0.997
12:14507099:A:C	N402K	0.997
12:14507099:A:T	N402K	0.997
12:14511694:C:A	D288Y	0.997
12:14511699:G:A	S286F	0.997

dbSNP variants (sampled 300 via entrez): RS1000014407 (12:14549745 T>G), RS1000031683 (12:14561641 G>A), RS1000043862 (12:14569540 T>C), RS1000070114 (12:14562805 T>G), RS1000155075 (12:14518607 C>T), RS1000193208 (12:14567146 CA>C), RS1000200618 (12:14522734 A>G), RS1000224218 (12:14567549 G>A), RS1000267889 (12:14516805 G>A,C), RS1000325417 (12:14568034 C>A), RS1000358836 (12:14523287 T>A), RS1000381318 (12:14529466 G>A,C), RS1000415416 (12:14554492 T>G), RS1000473855 (12:14531821 C>T), RS1000618699 (12:14548213 T>C)

Disease associations

OMIM: gene MIM:618486 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001651_43	Response to amphetamines	7.000000e-06
GCST004635_23	Testicular germ cell tumor	9.000000e-13
GCST004713_29	Testicular germ cell tumor	3.000000e-08
GCST90002394_365	Monocyte percentage of white cells	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007989	monocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

35 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Particulate Matter	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression, increases abundance	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
Am 580	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
clothianidin	decreases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
bisphenol S	decreases methylation	1
Rosiglitazone	increases expression	1
Gefitinib	affects response to substance	1
Sunitinib	decreases expression	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	affects expression	1
Estradiol	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Tretinoin	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.