PLLP

Summary

PLLP (plasmolipin, HGNC:18553) is a protein-coding gene on chromosome 16q13, encoding Plasmolipin (Q9Y342). Main component of the myelin sheath that plays an important role in myelin membrane biogenesis and myelination.

Enables identical protein binding activity. Involved in myelin assembly and regulation of transcytosis. Located in myelin sheath and plasma membrane. Biomarker of schizophrenia.

Source: NCBI Gene 51090 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 26 total
• MANE Select transcript: NM_015993

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18553
Approved symbol	PLLP
Name	plasmolipin
Location	16q13
Locus type	gene with protein product
Status	Approved
Aliases	PMLP
Ensembl gene	ENSG00000102934
Ensembl biotype	protein_coding
OMIM	600340
Entrez	51090

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000219207, ENST00000564018, ENST00000564376, ENST00000569059, ENST00000613167, ENST00000896534, ENST00000896535, ENST00000896536, ENST00000938962

RefSeq mRNA: 1 — MANE Select: NM_015993 NM_015993

CCDS: CCDS10777

Canonical transcript exons

ENST00000219207 — 4 exons

Exon	Start	End
ENSE00000685165	57258462	57258584
ENSE00003610209	57261897	57262070
ENSE00003991599	57256097	57257029
ENSE00003991606	57284406	57284672

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 98.96.

FANTOM5 (CAGE): breadth broad, TPM avg 12.6563 / max 1061.1364, expressed in 759 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157517	11.3103	752
157516	1.3459	261

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	98.96	gold quality
middle frontal gyrus	UBERON:0002702	98.78	gold quality
lateral globus pallidus	UBERON:0002476	98.74	gold quality
inferior olivary complex	UBERON:0002127	98.57	gold quality
cranial nerve II	UBERON:0000941	98.24	gold quality
subthalamic nucleus	UBERON:0001906	98.11	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.04	gold quality
nerve	UBERON:0001021	98.02	gold quality
tibial nerve	UBERON:0001323	98.02	gold quality
ventral tegmental area	UBERON:0002691	97.83	gold quality
spinal cord	UBERON:0002240	97.77	gold quality
putamen	UBERON:0001874	97.46	gold quality
medulla oblongata	UBERON:0001896	97.45	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.43	gold quality
dorsal plus ventral thalamus	UBERON:0001897	97.26	gold quality
midbrain	UBERON:0001891	97.23	gold quality
substantia nigra	UBERON:0002038	97.17	gold quality
superior vestibular nucleus	UBERON:0007227	97.07	gold quality
trigeminal ganglion	UBERON:0001675	96.98	gold quality
olfactory bulb	UBERON:0002264	96.87	gold quality
amygdala	UBERON:0001876	96.78	gold quality
dorsal root ganglion	UBERON:0000044	96.76	gold quality
pons	UBERON:0000988	96.58	gold quality
right lung	UBERON:0002167	96.42	gold quality
Ammon’s horn	UBERON:0001954	96.35	gold quality
caudate nucleus	UBERON:0001873	96.27	gold quality
skin of leg	UBERON:0001511	96.00	gold quality
substantia nigra pars compacta	UBERON:0001965	95.73	gold quality
corpus callosum	UBERON:0002336	95.72	gold quality
hypothalamus	UBERON:0001898	95.66	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	1536.98
E-MTAB-3929	yes	477.28
E-MTAB-10287	yes	44.64
E-GEOD-125970	yes	15.98
E-HCAD-9	yes	8.32
E-GEOD-109979	no	71.05
E-MTAB-9067	no	3.79
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting PLLP, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-516A-3P	99.46	67.96	1378

Literature-anchored findings (GeneRIF, showing 3)

• These data support a model in which PLLP functions in myelin biogenesis through organization of myelin liquid-ordered membranes in the Golgi complex. (PMID:26002055)
• Integrative omics analysis identifies biomarkers of idiopathic pulmonary fibrosis. (PMID:35015148)
• Structure of the Myelin Sheath Proteolipid Plasmolipin (PLLP) in a Ganglioside-Containing Lipid Raft. (PMID:37664934)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pllp	ENSDARG00000062756
mus_musculus	Pllp	ENSMUSG00000031775
rattus_norvegicus	Pllp	ENSRNOG00000016558
caenorhabditis_elegans	F28H1.4	WBGENE00017909
caenorhabditis_elegans	F47B3.3	WBGENE00018527

Paralogs (14): CMTM1 (ENSG00000089505), CMTM6 (ENSG00000091317), PLP2 (ENSG00000102007), CMTM3 (ENSG00000140931), CMTM2 (ENSG00000140932), MALL (ENSG00000144063), MAL2 (ENSG00000147676), CMTM7 (ENSG00000153551), MARVELD1 (ENSG00000155254), CMTM5 (ENSG00000166091), CMTM8 (ENSG00000170293), MAL (ENSG00000172005), CMTM4 (ENSG00000183723), CKLF (ENSG00000217555)

Protein

Protein identifiers

Plasmolipin — Q9Y342 (reviewed: Q9Y342)

Alternative names: Plasma membrane proteolipid

All UniProt accessions (4): Q9Y342, A0A087WYE0, H3BN27, J3QLJ3

UniProt curated annotations — full annotation on UniProt →

Function. Main component of the myelin sheath that plays an important role in myelin membrane biogenesis and myelination. Plays an essential function in apical endocytosis. Regulates epithelial development through the regulation of apical endocytosis. Part of the intracellular machinery that mediates basolateral-to-apical transport of ICAM-1, an essential adhesion receptor in epithelial cells, from the subapical compartment in hepatic epithelial cells.

Subunit / interactions. Forms oligomers.

Subcellular location. Cell membrane. Myelin membrane. Apical cell membrane. Golgi apparatus.

Post-translational modifications. Phosphorylated.

Similarity. Belongs to the MAL family.

RefSeq proteins (1): NP_057077* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008253	Marvel	Domain
IPR013295	MAL	Family
IPR050578	MARVEL-CKLF_proteins	Family

Pfam: PF01284

UniProt features (12 total): topological domain 5, transmembrane region 4, chain 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y342-F1	77.09	0.26

Functional residue map

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

Post-translational modifications (1): 9

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 142 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOZGIT_ESR1_TARGETS_DN, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_ENSHEATHMENT_OF_NEURONS, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOBP_REGULATION_OF_ENDOCYTOSIS, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_MYELIN_ASSEMBLY, VECCHI_GASTRIC_CANCER_EARLY_DN, HAN_SATB1_TARGETS_DN

GO Biological Process (5): monoatomic ion transport (GO:0006811), regulation of endocytosis (GO:0030100), myelin assembly (GO:0032288), myelination (GO:0042552), regulation of transcytosis (GO:1904298)

GO Molecular Function (3): structural constituent of myelin sheath (GO:0019911), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (7): Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020), apical plasma membrane (GO:0016324), myelin sheath (GO:0043209), compact myelin (GO:0043218), membrane raft (GO:0045121)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of vesicle-mediated transport	2
myelin sheath	2
transport	1
endocytosis	1
regulation of cellular component organization	1
cellular component assembly involved in morphogenesis	1
myelination	1
axon ensheathment	1
transcytosis	1
regulation of multicellular organismal process	1
structural molecule activity	1
protein binding	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
apical part of cell	1
plasma membrane region	1
membrane microdomain	1

Protein interactions and networks

STRING

596 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLLP	MYADM	Q96S97	915
PLLP	CKLF	Q9UBR5	845
PLLP	OPALIN	Q96PE5	674
PLLP	PLP1	P04400	664
PLLP	MALL	Q13021	647
PLLP	CMTM6	Q9NX76	635
PLLP	BBS2	Q9BXC9	626
PLLP	MAL	P21145	612
PLLP	CMTM7	Q96FZ5	587
PLLP	MOBP	Q13875	575
PLLP	CLDN11	O75508	463
PLLP	MOG	Q16653	458
PLLP	MAG	P20916	449
PLLP	PRR15L	Q9BU68	443
PLLP	CMTM5	Q96DZ9	442

IntAct

141 interactions, top by confidence:

A	B	Type	Score
PLLP	MS4A12	psi-mi:“MI:0915”(physical association)	0.720
MS4A12	PLLP	psi-mi:“MI:0915”(physical association)	0.720
CYSRT1	PLLP	psi-mi:“MI:0915”(physical association)	0.600
PLLP	CYSRT1	psi-mi:“MI:0915”(physical association)	0.600
PLLP	BCL2L13	psi-mi:“MI:0915”(physical association)	0.560
PLLP	AQP6	psi-mi:“MI:0915”(physical association)	0.560
MFF	PLLP	psi-mi:“MI:0915”(physical association)	0.560
GRN	PLLP	psi-mi:“MI:0915”(physical association)	0.560
PACC1	PLLP	psi-mi:“MI:0915”(physical association)	0.560
FRS3	PLLP	psi-mi:“MI:0915”(physical association)	0.560
KRT34	PLLP	psi-mi:“MI:0915”(physical association)	0.560
TRIM59	PLLP	psi-mi:“MI:0915”(physical association)	0.560
CLEC2D	PLLP	psi-mi:“MI:0915”(physical association)	0.560
TMPRSS2	PLLP	psi-mi:“MI:0915”(physical association)	0.560
TNFSF14	PLLP	psi-mi:“MI:0915”(physical association)	0.560
	PLLP	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-2	PLLP	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	PLLP	psi-mi:“MI:0915”(physical association)	0.560
CLEC12B	PLLP	psi-mi:“MI:0915”(physical association)	0.560
CD164L2	PLLP	psi-mi:“MI:0915”(physical association)	0.560
GOLT1A	PLLP	psi-mi:“MI:0915”(physical association)	0.560
TIGIT	PLLP	psi-mi:“MI:0915”(physical association)	0.560
TMEM174	PLLP	psi-mi:“MI:0915”(physical association)	0.560
TMEM167B	PLLP	psi-mi:“MI:0915”(physical association)	0.560
FNDC9	PLLP	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (66): PLLP (Two-hybrid), MS4A12 (Two-hybrid), PLLP (Affinity Capture-RNA), PLLP (Two-hybrid), PLLP (Two-hybrid), PLLP (Proximity Label-MS), PLLP (Proximity Label-MS), PLLP (Two-hybrid), PLLP (Two-hybrid), PLLP (Two-hybrid), PLLP (Two-hybrid), PLLP (Two-hybrid), PLLP (Two-hybrid), PLLP (Two-hybrid), HOXA1 (Two-hybrid)

ESM2 similar proteins: A2VE58, A3KQ86, A6H7B0, A7E3W5, A8MWL6, B2RZ87, O43759, O43760, O43761, O54980, O55100, O55101, O76735, O95473, P07825, P08247, P0DI73, P20488, P22831, P47987, P79826, Q08AU7, Q08DL4, Q28793, Q2YDD6, Q5EBF8, Q5R703, Q5RER2, Q5XGR0, Q5XIT3, Q5YJC1, Q62277, Q62876, Q642A2, Q6RW13, Q7JYV2, Q7TQJ1, Q8BGN8, Q8R191, Q8TBG9

Diamond homologs: A3KQ86, A6H7B0, O09198, P21145, P47987, Q13021, Q1RMP9, Q28296, Q3ZBY0, Q64349, Q6GPN9, Q8IZV2, Q91X49, Q9CZR4, Q9DCU2, Q9Y342, Q8CJ61, A2VE13, Q5RAI2, Q8BI08, Q969L2, Q5BLB7, Q7TQJ1, Q9BSK0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 52 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Class A/1 (Rhodopsin-like receptors)	5	12.4×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1275 predictions. Top by Δscore:

Variant	Effect	Δscore
16:57248640:ATAC:A	donor_gain	1.0000
16:57248641:TACG:T	donor_loss	1.0000
16:57248642:ACGT:A	donor_loss	1.0000
16:57248643:CG:C	donor_loss	1.0000
16:57248644:G:GG	donor_gain	1.0000
16:57248644:GTAAG:G	donor_loss	1.0000
16:57248645:TAAGT:T	donor_loss	1.0000
16:57249763:GCAGA:G	acceptor_gain	1.0000
16:57249764:CA:C	acceptor_loss	1.0000
16:57249764:CAGA:C	acceptor_gain	1.0000
16:57249765:A:AG	acceptor_gain	1.0000
16:57249765:AGATT:A	acceptor_loss	1.0000
16:57249766:G:GA	acceptor_gain	1.0000
16:57249766:GA:G	acceptor_gain	1.0000
16:57249766:GAT:G	acceptor_gain	1.0000
16:57249766:GATT:G	acceptor_gain	1.0000
16:57249766:GATTT:G	acceptor_gain	1.0000
16:57249848:TTACA:T	donor_gain	1.0000
16:57249849:TACA:T	donor_gain	1.0000
16:57249850:ACA:A	donor_gain	1.0000
16:57249851:CA:C	donor_gain	1.0000
16:57249853:G:GG	donor_gain	1.0000
16:57249853:G:T	donor_loss	1.0000
16:57249854:T:A	donor_loss	1.0000
16:57249855:GAGT:G	donor_gain	1.0000
16:57249858:T:G	donor_gain	1.0000
16:57250409:A:AG	acceptor_gain	1.0000
16:57250409:AGGC:A	acceptor_loss	1.0000
16:57250410:G:GA	acceptor_loss	1.0000
16:57250410:G:GG	acceptor_gain	1.0000

AlphaMissense

1163 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:57256991:A:C	S157R	0.987
16:57256991:A:T	S157R	0.987
16:57256993:T:G	S157R	0.987
16:57261977:A:G	W77R	0.984
16:57261977:A:T	W77R	0.984
16:57262052:A:G	W52R	0.983
16:57262052:A:T	W52R	0.983
16:57262064:C:G	G48R	0.977
16:57262064:C:T	G48R	0.977
16:57284529:G:C	F4L	0.977
16:57284529:G:T	F4L	0.977
16:57284531:A:G	F4L	0.977
16:57262004:A:G	W68R	0.974
16:57262004:A:T	W68R	0.974
16:57256999:C:G	G155R	0.973
16:57256999:C:T	G155R	0.973
16:57257020:A:G	C148R	0.972
16:57256998:C:T	G155E	0.970
16:57261993:G:C	F71L	0.970
16:57261993:G:T	F71L	0.970
16:57261995:A:G	F71L	0.970
16:57262064:C:A	G48W	0.967
16:57261908:A:G	W100R	0.966
16:57261908:A:T	W100R	0.966
16:57258537:G:C	F119L	0.965
16:57258537:G:T	F119L	0.965
16:57258539:A:G	F119L	0.965
16:57256979:G:C	S161R	0.962
16:57256979:G:T	S161R	0.962
16:57256981:T:G	S161R	0.962

dbSNP variants (sampled 300 via entrez): RS1000300522 (16:57264602 G>T), RS1000385627 (16:57276175 G>C), RS1000631151 (16:57264320 G>T), RS1000705312 (16:57286252 C>G,T), RS1000966691 (16:57274673 G>A), RS1001017980 (16:57269273 T>G), RS1001054441 (16:57286017 C>T), RS1001492907 (16:57283136 G>A), RS1001631196 (16:57271461 T>C), RS1001745893 (16:57271740 T>A), RS1001899194 (16:57265677 C>A), RS1001901736 (16:57277196 G>A), RS1002070293 (16:57259864 C>T), RS1002497546 (16:57281763 G>A), RS1002569792 (16:57268883 G>A)

Disease associations

OMIM: gene MIM:600340 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002053_3	Sleep duration	3.000000e-06
GCST005752_180	Systemic lupus erythematosus	1.000000e-08
GCST007400_13	Systemic lupus erythematosus	2.000000e-07
GCST008156_124	Hip circumference adjusted for BMI	7.000000e-06
GCST010242_419	HDL cholesterol levels	5.000000e-23

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression, affects expression	4
sodium arsenite	affects methylation, decreases expression, increases expression	3
Calcitriol	increases expression, affects cotreatment	3
Benzo(a)pyrene	decreases expression, increases methylation	2
Estradiol	decreases expression, affects cotreatment, increases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	increases expression, decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
bisphenol A	affects expression	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
cupric chloride	decreases expression	1
hydroquinone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
clothianidin	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases response to substance	1
Cadmium	increases abundance, increases expression	1
Caffeine	increases phosphorylation	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_YA77	IDG-HEK293T-PLLP-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

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