PLBD2

Summary

PLBD2 (phospholipase B domain containing 2, HGNC:27283) is a protein-coding gene on chromosome 12q24.13, encoding Putative aminopeptidase PLBD2 (Q8NHP8). Putative aminopeptidase.

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

Source: NCBI Gene 196463 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 96 total
• MANE Select transcript: NM_173542

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27283
Approved symbol	PLBD2
Name	phospholipase B domain containing 2
Location	12q24.13
Locus type	gene with protein product
Status	Approved
Aliases	PLBL2, p76
Ensembl gene	ENSG00000151176
Ensembl biotype	protein_coding
OMIM	620097
Entrez	196463

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000280800, ENST00000545182, ENST00000547163, ENST00000548997, ENST00000900704, ENST00000900705, ENST00000929636, ENST00000929637, ENST00000929638, ENST00000929639, ENST00000966959, ENST00000966960

RefSeq mRNA: 2 — MANE Select: NM_173542 NM_001159727, NM_173542

CCDS: CCDS53834, CCDS9168

Canonical transcript exons

ENST00000280800 — 12 exons

Exon	Start	End
ENSE00001103861	113369116	113369209
ENSE00001201972	113387744	113387906
ENSE00001201977	113386937	113387089
ENSE00001201981	113385212	113385283
ENSE00001201986	113384851	113384946
ENSE00001201991	113384105	113384265
ENSE00001201997	113380745	113380842
ENSE00001202000	113374793	113375007
ENSE00001202021	113388459	113391629
ENSE00002421093	113358587	113358890
ENSE00003653478	113374474	113374574
ENSE00003675985	113372649	113372807

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 98.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.2863 / max 547.0475, expressed in 1818 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128171	45.3817	1816
128172	0.8029	412
128173	0.1017	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	98.36	gold quality
left adrenal gland	UBERON:0001234	98.35	gold quality
adrenal cortex	UBERON:0001235	98.30	gold quality
left adrenal gland cortex	UBERON:0035825	98.30	gold quality
right adrenal gland	UBERON:0001233	98.25	gold quality
adrenal gland	UBERON:0002369	97.16	gold quality
dorsal root ganglion	UBERON:0000044	94.55	gold quality
stromal cell of endometrium	CL:0002255	93.61	gold quality
right ovary	UBERON:0002118	93.29	gold quality
left ovary	UBERON:0002119	93.29	gold quality
right testis	UBERON:0004534	93.18	gold quality
left testis	UBERON:0004533	93.06	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.71	gold quality
descending thoracic aorta	UBERON:0002345	92.29	gold quality
decidua	UBERON:0002450	92.18	gold quality
substantia nigra pars compacta	UBERON:0001965	92.16	gold quality
upper arm skin	UBERON:0004263	91.95	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.73	gold quality
right coronary artery	UBERON:0001625	91.52	gold quality
thoracic aorta	UBERON:0001515	91.32	gold quality
left ventricle myocardium	UBERON:0006566	91.24	gold quality
ascending aorta	UBERON:0001496	91.21	gold quality
islet of Langerhans	UBERON:0000006	91.07	gold quality
trigeminal ganglion	UBERON:0001675	90.91	gold quality
cardiac muscle of right atrium	UBERON:0003379	90.91	gold quality
testis	UBERON:0000473	90.87	gold quality
left coronary artery	UBERON:0001626	90.67	gold quality
coronary artery	UBERON:0001621	90.66	gold quality
right atrium auricular region	UBERON:0006631	90.59	gold quality
hypothalamus	UBERON:0001898	90.54	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

81 targeting PLBD2, 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-432-3P	100.00	67.86	705
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-377-5P	99.70	65.28	712

Literature-anchored findings (GeneRIF, showing 1)

• describe the identification of p76 by MS and we analyze several of its biochemical characteristics (PMID:17105447)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	plbd2	ENSDARG00000114245
mus_musculus	Plbd2	ENSMUSG00000029598
rattus_norvegicus	Plbd2	ENSRNOG00000001385
caenorhabditis_elegans		WBGENE00012544

Paralogs (1): PLBD1 (ENSG00000121316)

Protein

Protein identifiers

Putative aminopeptidase PLBD2 — Q8NHP8 (reviewed: Q8NHP8)

Alternative names: 76 kDa protein, LAMA-like protein 2, Lamina ancestor homolog 2, Phospholipase B domain-containing protein 2

All UniProt accessions (2): Q8NHP8, H0YIX0

UniProt curated annotations — full annotation on UniProt →

Function. Putative aminopeptidase.

Subunit / interactions. The 32 kDa and 45 kDa fragment, generated through proteolytic cleavage, remain associated in the mature form of the protein. Interacts with IGF2R.

Subcellular location. Lysosome lumen.

Tissue specificity. Ubiquitously expressed, with highest levels in heart, brain and liver.

Post-translational modifications. The p76 protein is synthesized as a 80 kDa precursor which is then processed into a N-terminal 32 kDa form and a C-terminal 45 kDa form. Glycosylated; contains mannose 6-phosphate sugars.

Similarity. Belongs to the Ntn hydrolase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NHP8-1	1	yes
Q8NHP8-2	2

RefSeq proteins (2): NP_001153199, NP_775813* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007000	PLipase_B-like	Family
IPR043040
IPR043041
IPR043042

Pfam: PF04916

UniProt features (17 total): glycosylation site 6, chain 3, disulfide bond 2, sequence variant 2, signal peptide 1, splice variant 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NHP8-F1	92.27	0.86

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): 244 (nucleophile)

Disulfide bonds (2): 142–152, 492–495

Glycosylation sites (6): 515, 88, 110, 231, 436, 465

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 94 (showing top): AP1_01, AP1_Q4_01, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, TGCTGAY_UNKNOWN, LIAO_METASTASIS, TGANTCA_AP1_C, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_CATABOLIC_PROCESS, NFE2_01, AP1FJ_Q2, GOCC_LYSOSOMAL_LUMEN, GOCC_VACUOLAR_LUMEN, chr12q24, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, MATSUDA_NATURAL_KILLER_DIFFERENTIATION

GO Biological Process (3): phospholipid catabolic process (GO:0009395), lipid metabolic process (GO:0006629), lipid catabolic process (GO:0016042)

GO Molecular Function (3): glycerophospholipase activity (GO:0004620), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (4): extracellular region (GO:0005576), lysosomal lumen (GO:0043202), extracellular exosome (GO:0070062), lysosome (GO:0005764)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phospholipid metabolic process	1
lipid catabolic process	1
organophosphate catabolic process	1
primary metabolic process	1
lipid metabolic process	1
catabolic process	1
phospholipase activity	1
binding	1
catalytic activity	1
cellular anatomical structure	1
lysosome	1
vacuolar lumen	1
extracellular vesicle	1
lytic vacuole	1

Protein interactions and networks

STRING

646 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLBD2	RALBP1	Q15311	542
PLBD2	ARL6IP6	Q8N6S5	518
PLBD2	RFTN2	Q52LD8	489
PLBD2	OR8G5	Q8NG78	470
PLBD2	GRB2	P29354	466
PLBD2	PLB1	Q6P1J6	464
PLBD2	SIAE	Q9HAT2	457
PLBD2	RNASET2	O00584	443
PLBD2	HEMK2	Q9Y5N5	435
PLBD2	LYPD3	O95274	433
PLBD2	ACP3	P15309	412
PLBD2	GLG1	Q92896	410
PLBD2	H2AC1	Q96QV6	410
PLBD2	AIP	O00170	405
PLBD2	PATE1	Q8WXA2	400

IntAct

24 interactions, top by confidence:

A	B	Type	Score
PLBD2	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
Shoc2	GABPB1	psi-mi:“MI:0914”(association)	0.350
CHORDC1	SSR3	psi-mi:“MI:0914”(association)	0.350
ZWINT	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
TFG	NCOA4	psi-mi:“MI:0914”(association)	0.350
STRAP	RAPH1	psi-mi:“MI:0914”(association)	0.350
Ankrd26	TBC1D31	psi-mi:“MI:0914”(association)	0.350
Cep44	SSR3	psi-mi:“MI:0914”(association)	0.350
MYH11	TBC1D31	psi-mi:“MI:0914”(association)	0.350
ECPAS		psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
NME1-NME2	SART1	psi-mi:“MI:0914”(association)	0.350
RIN3		psi-mi:“MI:0914”(association)	0.350
HNRNPH1	VWA8	psi-mi:“MI:0914”(association)	0.350
IPO5	C11orf98	psi-mi:“MI:0914”(association)	0.350
IGF2R	MANBA	psi-mi:“MI:0914”(association)	0.350
SKP1	RNASET2	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (52): PLBD2 (Co-fractionation), PLBD2 (Co-fractionation), PLBD2 (Affinity Capture-MS), PLBD2 (Affinity Capture-MS), PLBD2 (Affinity Capture-MS), PLBD2 (Affinity Capture-MS), PLBD2 (Affinity Capture-MS), PLBD2 (Affinity Capture-MS), PLBD2 (Affinity Capture-MS), PLBD2 (Affinity Capture-MS), PLBD2 (Affinity Capture-MS), PLBD2 (Affinity Capture-RNA), PLBD2 (Affinity Capture-RNA), PLBD2 (Affinity Capture-MS), PLBD2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0P6JG37, A0A383ZFX3, A5A6P2, F1N2K1, F8J2D3, F8S101, G1T7U7, H0VCJ6, O45686, O77695, P08236, P68827, Q02083, Q09551, Q0P5H1, Q13510, Q17QB3, Q2KIY5, Q3TCN2, Q4QQW8, Q5KTC7, Q5R5N6, Q5R748, Q5RDY9, Q5U2V4, Q5VSG8, Q60HH4, Q642A7, Q69ZQ1, Q6NSJ0, Q6P1J0, Q6P4A8, Q6P7S1, Q6T3U3, Q6T3U4, Q6W3E9, Q6W3F0, Q75UG4, Q7Z4N8, Q8C7K6

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1788 predictions. Top by Δscore:

Variant	Effect	Δscore
12:113358889:GG:G	donor_gain	1.0000
12:113358890:GG:G	donor_gain	1.0000
12:113358890:GGTAA:G	donor_loss	1.0000
12:113369110:CTCCA:C	acceptor_loss	1.0000
12:113369111:TCCAG:T	acceptor_loss	1.0000
12:113369112:CCA:C	acceptor_loss	1.0000
12:113369113:CAGGT:C	acceptor_loss	1.0000
12:113369114:A:AG	acceptor_gain	1.0000
12:113369114:AG:A	acceptor_gain	1.0000
12:113369114:AGGT:A	acceptor_gain	1.0000
12:113369114:AGGTG:A	acceptor_gain	1.0000
12:113369115:G:GA	acceptor_gain	1.0000
12:113369115:GG:G	acceptor_gain	1.0000
12:113369115:GGT:G	acceptor_gain	1.0000
12:113369115:GGTG:G	acceptor_gain	1.0000
12:113369115:GGTGG:G	acceptor_gain	1.0000
12:113369206:GGAG:G	donor_gain	1.0000
12:113369207:GAGG:G	donor_gain	1.0000
12:113369210:G:GG	donor_gain	1.0000
12:113369210:G:T	donor_loss	1.0000
12:113369211:T:A	donor_loss	1.0000
12:113372647:A:AG	acceptor_gain	1.0000
12:113372648:G:GA	acceptor_gain	1.0000
12:113372648:GCTC:G	acceptor_gain	1.0000
12:113372766:G:GT	donor_gain	1.0000
12:113372804:CCAGG:C	donor_loss	1.0000
12:113372808:G:GG	donor_gain	1.0000
12:113374469:CCTA:C	acceptor_loss	1.0000
12:113374470:CTA:C	acceptor_loss	1.0000
12:113374472:A:AT	acceptor_loss	1.0000

AlphaMissense

3832 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:113374973:G:C	K275N	0.995
12:113374973:G:T	K275N	0.995
12:113385270:A:C	S425R	0.994
12:113385272:C:A	S425R	0.994
12:113385272:C:G	S425R	0.994
12:113372672:C:A	N136K	0.993
12:113372672:C:G	N136K	0.993
12:113384258:A:C	S371R	0.993
12:113384260:C:A	S371R	0.993
12:113384260:C:G	S371R	0.993
12:113388540:T:A	W562R	0.993
12:113388540:T:C	W562R	0.993
12:113374496:T:C	L189P	0.991
12:113372728:T:C	L155P	0.990
12:113374962:C:A	R272S	0.990
12:113387906:G:C	K534N	0.990
12:113387906:G:T	K534N	0.990
12:113388542:G:C	W562C	0.990
12:113388542:G:T	W562C	0.990
12:113374505:T:C	L192P	0.989
12:113380786:T:C	S301P	0.989
12:113384864:T:A	W378R	0.989
12:113384864:T:C	W378R	0.989
12:113387827:G:C	R508P	0.989
12:113369117:T:A	W98R	0.988
12:113369117:T:C	W98R	0.988
12:113372689:G:A	C142Y	0.988
12:113374885:C:A	A246D	0.988
12:113380787:C:T	S301F	0.988
12:113380796:G:A	G304D	0.988

dbSNP variants (sampled 300 via entrez): RS1000071535 (12:113364805 G>A,T), RS1000244651 (12:113364145 G>T), RS1000302217 (12:113365375 A>G), RS1000334826 (12:113377871 G>A,C), RS1000367197 (12:113382397 A>G), RS1000437495 (12:113371137 T>G), RS1000491327 (12:113371404 A>G), RS1000543851 (12:113376744 G>C), RS1000717695 (12:113364362 T>C), RS1000736052 (12:113370151 C>T), RS1001044295 (12:113359844 A>G), RS1001177718 (12:113364347 C>T), RS1001293940 (12:113364749 A>G), RS1001744645 (12:113386866 C>T), RS1001765044 (12:113381629 C>A,T)

Disease associations

OMIM: gene MIM:620097 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_2	Body mass index	9.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression, affects cotreatment	2
bisphenol A	decreases expression	2
Smoke	decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cadmium Chloride	increases abundance, increases palmitoylation, increases expression, decreases reaction	2
sodium arsenite	decreases expression	1
cobaltous chloride	decreases secretion	1
2-bromopalmitate	increases abundance, increases palmitoylation, decreases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
bisphenol B	increases expression	1
abrine	decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Cadmium	increases abundance, increases palmitoylation, decreases reaction	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	increases methylation	1
Gold Compounds	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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