PLP2

Summary

PLP2 (proteolipid protein 2, HGNC:9087) is a protein-coding gene on chromosome Xp11.23, encoding Proteolipid protein 2 (Q04941). May play a role in cell differentiation in the intestinal epithelium.

This gene encodes an integral membrane protein that localizes to the endoplasmic reticulum in colonic epithelial cells. The encoded protein can multimerize and may function as an ion channel. A polymorphism in the promoter of this gene may be linked to an increased risk of X-linked cognitive disability. A pseudogene of this gene is found on chromosome 5.

Source: NCBI Gene 5355 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 46 total
• GTEx eGene: eQTL in 45 tissues, sQTL in 9 (q < 0.05)
• MANE Select transcript: NM_002668

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9087
Approved symbol	PLP2
Name	proteolipid protein 2
Location	Xp11.23
Locus type	gene with protein product
Status	Approved
Aliases	A4, A4-LSB, MGC126187
Ensembl gene	ENSG00000102007
Ensembl biotype	protein_coding
OMIM	300112
Entrez	5355

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 nonsense_mediated_decay

MANE Select: ENST00000376327

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1

ENST00000376327, ENST00000376322, ENST00000879549, ENST00000935268, ENST00000983336, ENST00001092619, ENST00001132492

RefSeq mRNA: 1 — MANE Select: NM_002668 NM_002668

CCDS: CCDS14319

Canonical transcript exons

ENST00000376327 — 5 exons

Exon	Start	End
ENSE00000670265	49174335	49174425
ENSE00000670267	49173388	49173483
ENSE00000670269	49173129	49173281
ENSE00001470203	49174672	49175235
ENSE00003851018	49171898	49172096

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 99.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 190.9998 / max 3605.2796, expressed in 1788 samples.

Highest expression (Bgee): gingival epithelium, gingiva, skin of abdomen, descending thoracic aorta, esophagus mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PLP2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 45 tissues and its splicing (sQTL) in 9 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 54 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	5.0e-131	-0.94	X:49171812:C:A
Artery Tibial	eqtl	7.4e-66	-0.84	X:49171812:C:A
Nerve Tibial	eqtl	1.0e-60	-0.97	X:49171812:C:A
Adipose Subcutaneous	eqtl	1.0e-50	-0.96	X:49171812:C:A
Thyroid	eqtl	2.2e-47	-1.06	X:49171812:C:A
Artery Aorta	eqtl	2.0e-41	-0.97	X:49171812:C:A
Lung	eqtl	7.3e-40	-1.09	X:49171812:C:A
Adipose Visceral Omentum	eqtl	5.0e-37	-1.00	X:49171812:C:A
Testis	eqtl	1.8e-34	-0.93	X:49171812:C:A
Spleen	eqtl	3.3e-34	-1.39	X:49171812:C:A
Cells Cultured fibroblasts	eqtl	2.5e-32	-0.52	X:49171812:C:A
Heart Atrial Appendage	eqtl	1.4e-31	-0.98	X:49171812:C:A
Muscle Skeletal	eqtl	3.3e-31	-0.70	X:49171812:C:A
Heart Left Ventricle	eqtl	8.5e-30	-0.75	X:49171812:C:A
Colon Sigmoid	eqtl	5.3e-29	-0.89	X:49171812:C:A
Skin Not Sun Exposed Suprapubic	eqtl	5.7e-28	-0.47	X:49171812:C:A
Esophagus Muscularis	eqtl	2.7e-26	-0.82	X:49171812:C:A
Brain Putamen basal ganglia	eqtl	4.8e-24	-0.83	X:49171812:C:A
Cells EBV-transformed lymphocytes	eqtl	1.5e-23	-1.30	X:49171812:C:A
Pituitary	eqtl	2.3e-23	-0.89	X:49171812:C:A

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
196320	114.5359	1777
196319	39.8478	1717
196321	36.6161	1681

Top tissues by expression

showing 100 of 287 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
gingival epithelium	UBERON:0001949	99.43	gold quality
gingiva	UBERON:0001828	99.35	gold quality
skin of abdomen	UBERON:0001416	99.24	gold quality
descending thoracic aorta	UBERON:0002345	99.20	gold quality
esophagus mucosa	UBERON:0002469	99.17	gold quality
skin of leg	UBERON:0001511	99.16	gold quality
right coronary artery	UBERON:0001625	99.13	gold quality
thoracic aorta	UBERON:0001515	99.10	gold quality
ascending aorta	UBERON:0001496	99.09	gold quality
zone of skin	UBERON:0000014	99.08	gold quality
aorta	UBERON:0000947	99.05	gold quality
nipple	UBERON:0002030	99.05	gold quality
popliteal artery	UBERON:0002250	99.04	gold quality
tibial artery	UBERON:0007610	99.04	gold quality
upper leg skin	UBERON:0004262	99.03	gold quality
body of pancreas	UBERON:0001150	99.00	gold quality
tongue squamous epithelium	UBERON:0006919	98.98	gold quality
lower esophagus mucosa	UBERON:0035834	98.97	gold quality
pharyngeal mucosa	UBERON:0000355	98.96	gold quality
penis	UBERON:0000989	98.95	gold quality
vagina	UBERON:0000996	98.92	gold quality
mammalian vulva	UBERON:0000997	98.92	gold quality
esophagus	UBERON:0001043	98.91	gold quality
skin of hip	UBERON:0001554	98.88	gold quality
left coronary artery	UBERON:0001626	98.87	gold quality
mucosa of stomach	UBERON:0001199	98.80	gold quality
left adrenal gland cortex	UBERON:0035825	98.78	gold quality
monocyte	CL:0000576	98.76	gold quality
left adrenal gland	UBERON:0001234	98.76	gold quality
right adrenal gland	UBERON:0001233	98.72	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.72	gold quality
leukocyte	CL:0000738	98.71	gold quality
coronary artery	UBERON:0001621	98.70	gold quality
esophagus squamous epithelium	UBERON:0006920	98.70	gold quality
mononuclear cell	CL:0000842	98.69	gold quality
granulocyte	CL:0000094	98.68	gold quality
mucosa of transverse colon	UBERON:0004991	98.64	gold quality
lower esophagus	UBERON:0013473	98.62	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.62	gold quality
epithelium of esophagus	UBERON:0001976	98.60	gold quality
adrenal cortex	UBERON:0001235	98.55	gold quality
oral cavity	UBERON:0000167	98.54	gold quality
squamous epithelium	UBERON:0006914	98.52	gold quality
right adrenal gland cortex	UBERON:0035827	98.51	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.50	gold quality
left uterine tube	UBERON:0001303	98.47	gold quality
ectocervix	UBERON:0012249	98.40	gold quality
body of uterus	UBERON:0009853	98.39	gold quality
transverse colon	UBERON:0001157	98.32	gold quality
upper arm skin	UBERON:0004263	98.30	gold quality
bone marrow	UBERON:0002371	98.22	gold quality
sigmoid colon	UBERON:0001159	98.19	gold quality
endocervix	UBERON:0000458	98.17	gold quality
adrenal gland	UBERON:0002369	98.16	gold quality
bone marrow cell	CL:0002092	98.10	gold quality
rectum	UBERON:0001052	98.10	gold quality
hair follicle	UBERON:0002073	98.01	gold quality
blood	UBERON:0000178	98.00	gold quality
tendon of biceps brachii	UBERON:0008188	97.98	gold quality
uterine cervix	UBERON:0000002	97.92	gold quality
cervix epithelium	UBERON:0004801	97.84	gold quality
colon	UBERON:0001155	97.79	gold quality
large intestine	UBERON:0000059	97.76	gold quality
right ovary	UBERON:0002118	97.76	gold quality
mouth mucosa	UBERON:0003729	97.74	gold quality
pancreas	UBERON:0001264	97.73	gold quality
upper lobe of left lung	UBERON:0008952	97.68	gold quality
endometrium epithelium	UBERON:0004811	97.67	gold quality
upper lobe of lung	UBERON:0008948	97.60	gold quality
right lung	UBERON:0002167	97.58	gold quality
left ovary	UBERON:0002119	97.57	gold quality
minor salivary gland	UBERON:0001830	97.54	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.53	gold quality
islet of Langerhans	UBERON:0000006	97.47	gold quality
adenohypophysis	UBERON:0002196	97.46	gold quality
saphenous vein	UBERON:0007318	97.46	gold quality
smooth muscle tissue	UBERON:0001135	97.44	gold quality
right atrium auricular region	UBERON:0006631	97.43	gold quality
trabecular bone tissue	UBERON:0002483	97.36	gold quality
body of stomach	UBERON:0001161	97.33	gold quality
intestine	UBERON:0000160	97.21	gold quality
pituitary gland	UBERON:0000007	97.18	gold quality
omental fat pad	UBERON:0010414	97.14	gold quality
adrenal tissue	UBERON:0018303	97.14	gold quality
peritoneum	UBERON:0002358	97.13	gold quality
body of tongue	UBERON:0011876	97.11	gold quality
tibial nerve	UBERON:0001323	97.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.01	gold quality
urinary bladder	UBERON:0001255	97.00	gold quality
colonic mucosa	UBERON:0000317	96.99	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.99	gold quality
fundus of stomach	UBERON:0001160	96.97	gold quality
synovial joint	UBERON:0002217	96.96	gold quality
myometrium	UBERON:0001296	96.89	gold quality
cardiac atrium	UBERON:0002081	96.85	gold quality
urethra	UBERON:0000057	96.81	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.79	gold quality
trachea	UBERON:0003126	96.59	gold quality
ovary	UBERON:0000992	96.54	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.54	gold quality

Single-cell (SCXA)

Detected in 23 experiment(s), a significant marker in 19.

Experiment	Marker?	Max mean expression
E-MTAB-7407	yes	589.97
E-CURD-112	yes	465.65
E-MTAB-6701	yes	89.92
E-CURD-114	yes	72.29
E-HCAD-4	yes	67.75
E-HCAD-6	yes	62.05
E-GEOD-125970	yes	24.91
E-MTAB-10042	yes	16.56
E-MTAB-9467	yes	16.38
E-HCAD-10	yes	15.30
E-MTAB-9067	yes	15.21
E-MTAB-8498	yes	13.38
E-CURD-122	yes	13.32
E-CURD-46	yes	10.15
E-GEOD-135922	yes	9.98

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skin 1	tissue	368.8	low
Bone marrow	tissue	338.5	medium
Esophagus	tissue	257.1	low
Vagina	tissue	256.9	low
Smooth muscle	tissue	146.2	low
Tonsil	tissue	138.7	low
Urinary bladder	tissue	133.4	low
Colon	tissue	132.9	medium
Rectum	tissue	122.4	medium
Adrenal gland	tissue	112.9	medium
Seminal vesicle	tissue	98.6	low
Pancreas	tissue	97.6	low
Pituitary gland	tissue	93.3
Stomach 1	tissue	86.0	medium
Appendix	tissue	82.6	medium
Cervix	tissue	81.2	medium
Small intestine	tissue	80.6	high
Lung	tissue	79.3	medium
Spinal cord	tissue	79.3
Ovary	tissue	73.5	not detected
Thymus	tissue	72.6
Endometrium 1	tissue	72.1	low
Skeletal muscle	tissue	67.8	low
Duodenum	tissue	66.8	high
Heart muscle	tissue	66.5	low
Breast	tissue	62.5	medium
Adipose tissue	tissue	59.4	medium
Fallopian tube	tissue	58.5	low
Placenta	tissue	57.1	low
Lymph node	tissue	56.0	low
Prostate	tissue	53.4	low
Gallbladder	tissue	49.8	high
Tongue	tissue	49.7
Salivary gland	tissue	49.1	low
Medulla oblongata	tissue	46.7
Substantia nigra	tissue	44.1
Epididymis	tissue	40.3	low
Hypothalamus	tissue	39.1
Midbrain	tissue	38.9
Pons	tissue	36.7
Corpus callosum	tissue	36.2
Periaqueductal gray	tissue	35.8
Parathyroid gland	tissue	35.2	low
Spleen	tissue	34.1	low
Superior colliculi	tissue	32.1
Thalamus	tissue	30.6
Septum	tissue	29.3
Choroid plexus	tissue	28.3
Hippocampal formation	tissue	26.3
Amygdala	tissue	26.2
Putamen	tissue	21.9
Ventral forebrain	tissue	21.5
Basal ganglia	tissue	20.1	medium
Cerebral cortex	tissue	19.2	medium
Motor cortex	tissue	19.2
Temporal cortex	tissue	19.2
Prefrontal cortex	tissue	19.1
Testis	tissue	18.9	high
Kidney	tissue	18.9	high
Entorhinal cortex	tissue	18.1

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (301.1), Ventral spinal cord (79.3), Dorsal spinal cord (75.9), White matter (36.2), Subiculum (26.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PLP2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 38 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-1273H-3P	99.29	67.55	980
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-4777-3P	99.15	68.92	626
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-3164	99.02	68.39	1071
HSA-MIR-6820-3P	99.02	68.50	1035
HSA-MIR-1843	98.97	66.07	838

Functional genomics

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000376327 — one region, missense o/e 1.03.

Literature-anchored findings (GeneRIF, showing 16)

• PLP2/A4 has a role in the chemotactic processes via CCR1 (PMID:15474493)
• PLP2 is expressed abundantly in the pyramidal cells of hippocampus and granular cells of the cerebellum in the brains of a cohort of males with probable X-linked mental retardation. (PMID:17416750)
• This work ascribes a critical function to PLP2 for viral ligase activity and underlines the power of non-lethal haploid genetic screens in human cells to identify the genes involved in pathogen manipulation of the host immune system. (PMID:24278019)
• PLP2 and RAB5C are binding partners of TPD52. (PMID:24604726)
• PLP2 specifically binds to phosphatidylinositol 3 kinase to activate the protein kinase B pathway to enhance cell proliferation, adhesion, and invasion in melanoma cells. (PMID:26287415)
• Up-regulation of miR-422a attenuated microsphere formation, proliferation and tumor formation of breast cancer stem cells via suppressing the PLP2 expression. (PMID:29509055)
• Higher PLP2 immunohistochemistry staining significantly correlated with more advanced tumor grades and poorer prognosis in human gliomas. (PMID:30373180)
• Reduced expression of proteolipid protein 2 increases ER stress-induced apoptosis and autophagy in glioblastoma. (PMID:31778016)
• MiR-765 functions as a tumour suppressor and eliminates lipids in clear cell renal cell carcinoma by downregulating PLP2. (PMID:31901870)
• PLP2 Expression as a Prognostic and Therapeutic Indicator in High-Risk Multiple Myeloma. (PMID:32596309)
• CD45RO(-)CD8(+) T cell-derived exosomes restrict estrogen-driven endometrial cancer development via the ERbeta/miR-765/PLP2/Notch axis. (PMID:33859750)
• PLP2 drives collective cell migration via ZO-1-mediated cytoskeletal remodeling at the leading edge in human colorectal cancer cells. (PMID:34409455)
• PLP2-derived peptide Rb4 triggers PARP-1-mediated necrotic death in murine melanoma cells. (PMID:35190586)
• Structural basis of plp2-mediated cytoskeletal protein folding by TRiC/CCT. (PMID:36921056)
• Low Expression of A3C and PLP2 Indicating a Favorable Prognosis in Human Gliomas. (PMID:37715423)
• Reduced Proteolipid Protein 2 promotes endoplasmic reticulum stress-related apoptosis and increases drug sensitivity in acute myeloid leukemia. (PMID:38085372)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	plp2b	ENSDARG00000036630
danio_rerio	plp2a	ENSDARG00000042972
mus_musculus	Plp2	ENSMUSG00000031146
mus_musculus	Plp2rt	ENSMUSG00000057762
rattus_norvegicus	Plp2	ENSRNOG00000039496
rattus_norvegicus	Plp2l1	ENSRNOG00000055728
caenorhabditis_elegans	F28H1.4	WBGENE00017909
caenorhabditis_elegans	F47B3.3	WBGENE00018527

Paralogs (14): CMTM1 (ENSG00000089505), CMTM6 (ENSG00000091317), PLLP (ENSG00000102934), CMTM3 (ENSG00000140931), CMTM2 (ENSG00000140932), MALL (ENSG00000144063), MAL2 (ENSG00000147676), CMTM7 (ENSG00000153551), MARVELD1 (ENSG00000155254), CMTM5 (ENSG00000166091), CMTM8 (ENSG00000170293), MAL (ENSG00000172005), CMTM4 (ENSG00000183723), CKLF (ENSG00000217555)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1298382) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 6 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased susceptibility to ischemic brain injury	1
increased neuron apoptosis	1
abnormal endoplasmic reticulum morphology	1
increased fibroblast apoptosis	1
increased endoplasmic reticulum stress	1
abnormal Golgi vesicle transport	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Oryctolagus cuniculus	Q95MN6	88.2%	Diamond
Bos taurus	Q6Y1E2	87.5%	Diamond
Ovis aries	Q28597	82.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PRICKLE3	protein-coding	4007
SYP	protein-coding	6855
CACNA1F	protein-coding	778
MAGIX	protein-coding	79917
WDR45	protein-coding	11152
GPKOW	protein-coding	27238
SYP-AS1	ncRNA	100873921
CCDC22	protein-coding	28952
FOXP3	protein-coding	50943

Protein

Protein identifiers

Proteolipid protein 2 — Q04941 (reviewed: Q04941)

Alternative names: Differentiation-dependent protein A4, Intestinal membrane A4 protein

All UniProt accessions (1): Q04941

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in cell differentiation in the intestinal epithelium.

Subcellular location. Membrane.

Tissue specificity. Enriched in colonic mucosa. The expression of A4 follows a gradient along the crypto-villus axis with the most abundant message occurring in the lower half of the crypt.

Isoforms (2)

UniProt ID	Names	Canonical?
Q04941-1	1	yes
Q04941-2	2

RefSeq proteins (1): NP_002659* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008253	Marvel	Domain
IPR050578	MARVEL-like	Family

Pfam: PF01284

UniProt features (10 total): transmembrane region 4, glycosylation site 2, chain 1, domain 1, splice variant 1, sequence variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q04941-F1	78.76	0.22

Human Protein Atlas

Protein class: Transporters, Transporter channels and pores, Predicted membrane proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH approved

Functional residue map

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

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	18, 108

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 314 (showing top): RNGTGGGC_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, HORIUCHI_WTAP_TARGETS_DN, GOBP_RESPONSE_TO_PEPTIDE, XU_GH1_AUTOCRINE_TARGETS_UP, JAEGER_METASTASIS_DN, MODULE_151, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, HSIAO_HOUSEKEEPING_GENES, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN, TTGGGAG_MIR150

GO Biological Process (4): monoatomic ion transport (GO:0006811), chemotaxis (GO:0006935), cytokine-mediated signaling pathway (GO:0019221), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (3): monoatomic ion transmembrane transporter activity (GO:0015075), chemokine binding (GO:0019956), protein binding (GO:0005515)

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

20 GO namespaces:

Category	Terms
transport	1
response to chemical	1
taxis	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
monoatomic ion transport	1
transmembrane transport	1
transmembrane transporter activity	1
monoatomic ion transmembrane transport	1
cytokine binding	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 11 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
plasma membrane	CC	direct assay
chemokine binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 610 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLP2	PLP1	P04400	974
PLP2	PDCL2	Q8N4E4	898
PLP2	PDC	P20941	888
PLP2	PDCL3	Q9H2J4	865
PLP2	SUCLG2	Q96I99	747
PLP2	TUBB2A	Q13885	639
PLP2	CGA	P01215	630
PLP2	TUBB	P05218	618
PLP2	TCP1	P17987	613
PLP2	ZUP1	Q96AP4	519
PLP2	SH2D3C	Q8N5H7	509
PLP2	PPP1CA	P08129	492
PLP2	ISG15	P05161	477
PLP2	IRF3	Q14653	457
PLP2	SH2D3A	Q9BRG2	453

IntAct

Human interaction partners of PLP2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 68 partners by confidence:

Partner	Interaction type	MIscore	Records
TMEM79	physical association	0.670	4
CCR1	physical association	0.660	3
TMPRSS2	physical association	0.600	4
ARFIP2	physical association	0.560	5
PACC1	physical association	0.560	5
AQP3	physical association	0.560	3
AQP8	physical association	0.560	3
ASGR2	physical association	0.560	3
ATP5PF	physical association	0.560	3
BIK	physical association	0.560	3
BNIP3	physical association	0.560	3
CD53	physical association	0.560	3
CD79A	physical association	0.560	3
CERS4	physical association	0.560	3
CIAO2A	physical association	0.560	3
CLDN5	physical association	0.560	3
CPLX4	physical association	0.560	3
CRB3	physical association	0.560	3
CREB3L1	physical association	0.560	3
CYB561	physical association	0.560	3
CYBC1	physical association	0.560	3
CYBRD1	physical association	0.560	3
DARS2	physical association	0.560	3
DNAJC1	physical association	0.560	3
EBP	physical association	0.560	3
ELOVL5	physical association	0.560	3
EVI2A	physical association	0.560	3
FAM209A	physical association	0.560	3
FAM210B	physical association	0.560	3
FATE1	physical association	0.560	3

BioGRID (123 interactions; top human partners by supporting records): LACC1 (Affinity Capture-MS; 2 records), AQP2 (Two-hybrid), AQP3 (Two-hybrid), AQP6 (Two-hybrid), AQP8 (Two-hybrid), ARFIP2 (Two-hybrid), ARL13B (Two-hybrid), ASGR2 (Two-hybrid), ATP5J (Two-hybrid), BIK (Two-hybrid), BNIP3 (Two-hybrid), C17orf62 (Two-hybrid), C9orf72 (Affinity Capture-MS), CCDC155 (Two-hybrid), CCR1 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for PLP2: 46 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	2
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 413):

Position(s)	Effect	Δscore	Sites
X:49172074	donor_gain	1.0000
X:49173380	acceptor_gain	1.0000
X:49173386–49173387	acceptor_loss	1.0000	4
X:49173613	donor_gain	1.0000
X:49173668	donor_gain	1.0000
X:49174325	acceptor_gain	1.0000
X:49174333–49174334	acceptor_loss	1.0000	6
X:49174426–49174427	donor_loss	1.0000	5
X:49173127–49173128	acceptor_loss	0.9900	5
X:49173255	donor_gain	0.9900

AlphaMissense

256 missense substitutions predicted likely pathogenic (of 974 scored), across 87 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D84	8	0.912	0.955
D128	8	0.888	0.923
F125	7	0.910	0.952
W80	7	0.884	0.983
F19	7	0.868	0.948
F42	7	0.854	0.962
E31	6	0.873	0.956
M57	6	0.867	0.956
K24	6	0.856	0.950
E56	6	0.822	0.921
G115	5	0.932	0.968
G25	5	0.886	0.983
Y95	5	0.851	0.954
G118	5	0.833	0.984
C16	5	0.764	0.938
C12	5	0.699	0.832
F64	5	0.693	0.716
C35	4	0.942	0.981
S83	4	0.880	0.974
F85	4	0.858	0.870

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	1.7e-05
Lung Adenocarcinoma (validation)	unfavorable	2.07e-05
Glioblastoma Multiforme (validation)	unfavorable	0.000335
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000369

Disease associations

OMIM: gene MIM:300112 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST90002401_293	Platelet distribution width	9e-10

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067398 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	9
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression, increases expression	3
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
entinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	increases methylation, affects methylation, increases expression	2
Cadmium	decreases reaction, increases abundance, increases palmitoylation, decreases expression	2
Doxorubicin	decreases expression, affects expression	2
Tretinoin	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
salinomycin	decreases expression	1
beta-lapachone	increases expression	1
methylparaben	increases expression	1
sodium arsenite	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
cadmium acetate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CD 437	decreases expression	1
deguelin	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
dorsomorphin	increases expression, affects cotreatment	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	increases expression	1
Temozolomide	decreases expression	1
Decitabine	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Atrazine	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652069	Binding	Binding affinity to human PLP2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TE70	HAP1 PLP2 (-) 1	Cancer cell line	Male
CVCL_TE71	HAP1 PLP2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PLP2 across ~30M SureChEMBL compounds — explore on Sugi Predict.