PLAC8

Summary

PLAC8 (placenta associated 8, HGNC:19254) is a protein-coding gene on chromosome 4q21.22, encoding Placenta-specific gene 8 protein (Q9NZF1).

Predicted to enable chromatin binding activity. Predicted to be involved in positive regulation of cold-induced thermogenesis and positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including brown fat cell differentiation; defense response to bacterium; and response to cold. Predicted to be located in azurophil granule lumen and extracellular region.

Source: NCBI Gene 51316 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 13 total
• MANE Select transcript: NM_016619

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19254
Approved symbol	PLAC8
Name	placenta associated 8
Location	4q21.22
Locus type	gene with protein product
Status	Approved
Aliases	onzin, C15
Ensembl gene	ENSG00000145287
Ensembl biotype	protein_coding
OMIM	607515
Entrez	51316

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 20 protein_coding, 2 nonsense_mediated_decay

ENST00000311507, ENST00000411416, ENST00000426923, ENST00000505406, ENST00000509973, ENST00000515389, ENST00000718322, ENST00000718323, ENST00000718328, ENST00000718330, ENST00000718331, ENST00000718332, ENST00000718333, ENST00000718337, ENST00000718338, ENST00000718339, ENST00000718340, ENST00000718341, ENST00000905227, ENST00000905228, ENST00000905229, ENST00000948818

RefSeq mRNA: 3 — MANE Select: NM_016619 NM_001130715, NM_001130716, NM_016619

CCDS: CCDS3601

Canonical transcript exons

ENST00000311507 — 5 exons

Exon	Start	End
ENSE00001237646	83107804	83107950
ENSE00001906597	83090048	83090971
ENSE00002084319	83114666	83114729
ENSE00003664930	83104896	83105020
ENSE00003691032	83094678	83094791

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 99.53.

FANTOM5 (CAGE): breadth broad, TPM avg 51.1269 / max 4281.5230, expressed in 784 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52910	47.3085	631
52911	2.7009	321
52908	0.9322	405
52909	0.1853	68

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.53	gold quality
mucosa of transverse colon	UBERON:0004991	99.50	gold quality
epithelium of bronchus	UBERON:0002031	99.44	gold quality
colonic mucosa	UBERON:0000317	99.38	gold quality
bronchus	UBERON:0002185	99.32	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.27	gold quality
epithelium of nasopharynx	UBERON:0001951	99.20	gold quality
nasopharynx	UBERON:0001728	99.18	gold quality
bone marrow	UBERON:0002371	99.16	gold quality
granulocyte	CL:0000094	98.97	gold quality
ileal mucosa	UBERON:0000331	98.85	gold quality
trabecular bone tissue	UBERON:0002483	98.80	gold quality
bone marrow cell	CL:0002092	98.72	gold quality
rectum	UBERON:0001052	98.55	gold quality
leukocyte	CL:0000738	98.43	gold quality
mononuclear cell	CL:0000842	98.38	gold quality
jejunal mucosa	UBERON:0000399	98.38	gold quality
monocyte	CL:0000576	98.37	gold quality
nasal cavity epithelium	UBERON:0005384	98.31	gold quality
spleen	UBERON:0002106	98.30	gold quality
lower esophagus mucosa	UBERON:0035834	98.20	gold quality
pharyngeal mucosa	UBERON:0000355	98.16	gold quality
blood	UBERON:0000178	97.90	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.67	gold quality
vermiform appendix	UBERON:0001154	96.84	gold quality
esophagus squamous epithelium	UBERON:0006920	96.22	gold quality
epithelium of esophagus	UBERON:0001976	95.19	gold quality
trachea	UBERON:0003126	95.06	gold quality
lymph node	UBERON:0000029	95.01	gold quality
duodenum	UBERON:0002114	94.24	gold quality

Single-cell (SCXA)

Detected in 39 experiment(s), a significant marker in 36.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	2739.02
E-CURD-112	yes	2532.93
E-HCAD-6	yes	2488.58
E-MTAB-8498	yes	2402.61
E-MTAB-9906	yes	2333.62
E-MTAB-10042	yes	2251.38
E-GEOD-125970	yes	2169.87
E-HCAD-1	yes	2076.14
E-HCAD-4	yes	1943.08
E-GEOD-139324	yes	1924.68
E-CURD-79	yes	1919.17
E-MTAB-8884	yes	1849.52
E-MTAB-8410	yes	1833.27
E-MTAB-6653	yes	1797.43
E-CURD-88	yes	1772.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

68 targeting PLAC8, 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-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-30B-3P	99.70	65.76	2325

Literature-anchored findings (GeneRIF, showing 32)

• phorbol 12-myristate 13-acetate(PMA)downregulates onzin expression through PKCepsilon-ERK2 signaling pathway, which favors monocytic differentiation of leukemic cells. (PMID:20072156)
• Data suggest that overexpression of PLAC8 induces apoptosis in some cells (CEM-C7 cells; Jurkat T cells); expression of PLAC8 has anti-apoptosis effect in other cells (adherent cell lines; HEK293T cells; MCF-10A cells). (PMID:22920440)
• expression of retinol-binding protein 4 (RBP4) and placenta-specific 8 increased in the bone tumors of PC3-GFP/PC3-OPG-injected mice. Knockdown of both RBP4 and PLAC8 by siRNA inhibited the growth of PC-3 cells in vitro. (PMID:23708710)
• Excess PLAC8 promotes an unconventional ERK2-dependent EMT in colon cancer. (PMID:24691442)
• Plac8 provides a mechanistic link between primary oncogenic mutations and the induction of autophagy, a central mechanism of metabolic reprogramming, during PDA progression. (PMID:24794439)
• Methylation status of 17 CpG sites in PLAC8 negatively correlated with mRNA expression (PMID:25720387)
• Results establish PLAC8 as a central mediator of tumor progression in PDAC. (PMID:26669866)
• Human oocytes and preimplantation embryos express PLAC8 and the intracellular distribution of PLAC8 protein is dynamic and regulated in an implantation-dependent manner. (PMID:27322877)
• Down-regulated PLAC8 enhances the activity of PI3K/Akt/GSK3B and Wnt/Beta-catenin signaling to promote hepatocellular carcinoma cell proliferation. (PMID:27643556)
• In the current study, we first identified that PLAC8 expression was higher in ccRCC than adjacent non-tumor tissues, suggesting that PLAC8 may be involved in carcinogenesis and malignant progression of ccRCC. KEGG pathway analysis showed that PLAC8 is mainly involved in the immunity- and inflammation-related pathways, such as the NF-kappa B signaling pathway, cytokine-cytokine receptor interaction, and TNF signaling pathw (PMID:28349447)
• PLAC8 is specifically expressed in the interstitial extravillous trophoblast cells (iEVTs) on the fetomaternal interface. Using model systems, including placental villi-decidua co-culture, iEVTs induction by using primary trophoblast cells or explants, etc., we found that PLAC8 promotes invasion and migration of iEVTs. (PMID:29361555)
• Radiation resistance tumors have upregulated Onzin and POU5F1 expression. (PMID:29596836)
• PLAC8 was transcriptionally repressed by KLF4 (PMID:29789534)
• ONZIN overexpression induced CXCL5 upregulation and resulted in increased ERK phosphorylation, which contributed to more aggressive osteosarcoma metastatic phenotypes. (PMID:30041188)
• this study shows that PLAC8 suppresses IL-18 production through regulation of autophagy and is associated with adult Still disease (PMID:30404814)
• PLAC8 may promote the carcinogenesis and epithelial-mesenchymal transition of nasopharyngeal carcinoma via the TGF-beta/Smad pathway. (PMID:30496758)
• Placenta-Specific 8 Is Overexpressed and Regulates Cell Proliferation in Low-Grade Human Pancreatic Neuroendocrine Tumors. (PMID:31018208)
• PLAC8 overexpression correlates with PD-L1 upregulation and acquired resistance to gemcitabine-oxaliplatin in gallbladder carcinoma cells. (PMID:31272718)
• PLCA8 suppresses breast cancer apoptosis by activating the PI3k/AKT/NF-kappaB pathway. (PMID:31448883)
• Expression pattern of placenta specific 8 and keratin 20 in different types of gastrointestinal cancer. (PMID:31974611)
• Plac8-mediated autophagy regulates nasopharyngeal carcinoma cell function via AKT/mTOR pathway. (PMID:32468683)
• [Knockdown of placental-specific protein 8 (PLAC8) inhibits proliferation and promotes apoptosis of human embryonic stem cells]. (PMID:33325361)
• PLAC8 promotes the autophagic activity and improves the growth priority of human trophoblast cells. (PMID:33570788)
• PLAC8 promotes adriamycin resistance via blocking autophagy in breast cancer. (PMID:34117724)
• Placenta-specific 8 (PLAC8) mediates inflammation and mobility of the hPDLCs via MEK/ERK signaling pathway. (PMID:34954560)
• Long noncoding RNA HOXD-AS1 promotes the progression of pancreatic cancer through miR-664b-3p/PLAC8 axis. (PMID:35279480)
• PLAC8 Overexpression Promotes Lung Cancer Cell Growth via Wnt/beta-Catenin Signaling. (PMID:35497881)
• Autophagy-linked plasma and lysosomal membrane protein PLAC8 is a key host factor for SARS-CoV-2 entry into human cells. (PMID:36124427)
• Modification of PLAC8 by UFM1 affects tumorous proliferation and immune response by impacting PD-L1 levels in triple-negative breast cancer. (PMID:36543379)
• PLAC8 contributes to the malignant behaviors of cervical cancer cells by activating the SOX4-mediated AKT pathway. (PMID:36602585)
• Low m6A modification-mediated upregulation of PLAC8 promotes trophoblast cell invasion and migration in preeclampsia. (PMID:37885015)
• Identification of PLAC8 as a Potential Biomarker for the Diagnosis of Interstitial Cystitis. (PMID:38441011)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	plac8.1	ENSDARG00000043729
danio_rerio	plac8.2	ENSDARG00000094438
mus_musculus	Plac8	ENSMUSG00000029322
rattus_norvegicus	Plac8	ENSRNOG00000002217

Paralogs (2): CNFN (ENSG00000105427), PLAC8L1 (ENSG00000173261)

Protein

Protein identifiers

Placenta-specific gene 8 protein — Q9NZF1 (reviewed: Q9NZF1)

Alternative names: Protein C15

All UniProt accessions (3): D6RA24, Q9NZF1, X2BQ60

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Expressed at high levels in plasmacytoid dendritic cells. High expression in spleen, lymph nodes, peripheral blood leukocytes, and bone marrow, with lower expression in thymus, appendix, and fetal liver.

Similarity. Belongs to the cornifelin family.

RefSeq proteins (3): NP_001124187, NP_001124188, NP_057703* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006461	PLAC_motif_containing	Family

Pfam: PF04749

UniProt features (1 total): chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZF1-F1	88.81	0.74

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-9830364	Formation of the nephric duct

MSigDB gene sets: 466 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, MCLACHLAN_DENTAL_CARIES_UP, GOBP_RESPONSE_TO_COLD, GOCC_SECRETORY_GRANULE, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_GROWTH, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, WIELAND_UP_BY_HBV_INFECTION, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_GROWTH, SENESE_HDAC1_AND_HDAC2_TARGETS_DN

GO Biological Process (9): transcription by RNA polymerase II (GO:0006366), positive regulation of cell population proliferation (GO:0008284), response to cold (GO:0009409), negative regulation of multicellular organism growth (GO:0040015), defense response to bacterium (GO:0042742), negative regulation of apoptotic process (GO:0043066), positive regulation of transcription by RNA polymerase II (GO:0045944), brown fat cell differentiation (GO:0050873), positive regulation of cold-induced thermogenesis (GO:0120162)

GO Molecular Function (1): chromatin binding (GO:0003682)

GO Cellular Component (2): extracellular region (GO:0005576), azurophil granule lumen (GO:0035578)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Innate Immune System	1
Kidney development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
response to stress	1
response to temperature stimulus	1
multicellular organism growth	1
regulation of multicellular organism growth	1
negative regulation of developmental growth	1
negative regulation of multicellular organismal process	1
defense response	1
response to bacterium	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
fat cell differentiation	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
binding	1
cellular anatomical structure	1
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1

Protein interactions and networks

STRING

294 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLAC8	C12orf57	Q99622	769
PLAC8	POLR3H	Q9Y535	717
PLAC8	PLSCR1	O15162	595
PLAC8	TBL1XR1	Q9BZK7	570
PLAC8	POLR3F	Q9H1D9	506
PLAC8	NUCLEOLIN	P19338	448
PLAC8	AGRN	O00468	448
PLAC8	CNOT11	Q9UKZ1	447
PLAC8	MIEN1	Q9BRT3	433
PLAC8	APLP1	P51693	419
PLAC8	KRCC1	Q9NPI7	371
PLAC8	CCNL1	Q9UK58	324
PLAC8	NDUFB4	O95168	313
PLAC8	POLR3E	Q9NVU0	305
PLAC8	LGALS1	P09382	271

IntAct

3 interactions, top by confidence:

A	B	Type	Score
PB1	PLAC8	psi-mi:“MI:0915”(physical association)	0.370
PLAC8	COPS5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (28): PLAC8 (Two-hybrid), PLAC8 (Two-hybrid), PLAC8 (Synthetic Growth Defect), RBPMS (Two-hybrid), VAMP5 (Two-hybrid), TRAF1 (Two-hybrid), PLAC8 (Two-hybrid), PLAC8 (Two-hybrid), PLAC8 (Two-hybrid), PLAC8 (Two-hybrid), PLAC8 (Two-hybrid), PLAC8 (Two-hybrid), PLAC8 (Two-hybrid), BAG4 (Two-hybrid), LCE2B (Two-hybrid)

ESM2 similar proteins: A0A1B0GVX0, A2ADU8, A2ADU9, A2Y075, A6QP72, O82232, P34655, P55017, P55018, P56508, P59158, P68178, P68179, Q0DKW8, Q0VBW2, Q22701, Q3ZCB2, Q53GD3, Q54RZ2, Q5REK4, Q5RJI2, Q5TYP8, Q66I68, Q6DK93, Q6DK99, Q6E1M8, Q6E213, Q6GMG8, Q6GZQ0, Q6NUC1, Q6P828, Q6PCW6, Q6ZPD8, Q8H5T6, Q8NG11, Q8QZY6, Q8S5M8, Q91VA1, Q9ARD5, Q9BYD5

Diamond homologs: A1L4L8, Q08EJ0, Q0VBW2, Q3ZCB2, Q5REK4, Q66I68, Q6DK93, Q6DK99, Q6NUC1, Q6PCW6, Q9BYD5, Q9JI48, Q9NZF1, B4FF80, B6TYV8, B6TZ45, D9HP19, D9HP20, D9HP23, D9HP25, D9HP26, D9HP27, P0CW97, P0CW98, Q3EBY6, Q8S8T8, Q9LQU2, Q9LQU4, Q9LS43, Q9LS44, Q9LS45, Q9M815, Q9M9A5, Q9SX24, Q9SX26, B4FUS3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000126862 (4:83107880 T>A), RS1000132028 (4:83093697 T>C), RS1000155333 (4:83115972 CATG>C), RS1000196018 (4:83109351 G>A), RS1000457954 (4:83098398 G>A), RS1000463167 (4:83093391 C>A,G), RS1000491038 (4:83107464 G>A), RS1000573434 (4:83098739 T>G), RS1000829135 (4:83105572 G>A), RS1000969159 (4:83100999 A>C), RS1001113628 (4:83094457 A>C), RS1001178179 (4:83106004 T>A,C), RS1001490080 (4:83093351 G>C), RS1001506975 (4:83112846 T>C), RS10015398 (4:83104341 G>A)

Disease associations

OMIM: gene MIM:607515 | 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
GCST004033_5	QRS interval (sulfonylurea treatment interaction)	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007922	response to sulfonylurea

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
(+)-JQ1 compound	decreases expression	4
Benzo(a)pyrene	decreases methylation, increases expression	3
Tetrachlorodibenzodioxin	affects expression, increases expression	3
Aflatoxin B1	affects expression, increases expression, increases methylation	3
Particulate Matter	decreases expression, increases expression, increases methylation	3
Arsenic	decreases expression, affects cotreatment, increases abundance	2
3,19-(2-bromobenzylidene)andrographolide	decreases response to substance, increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, decreases expression	1
bisphenol A	increases expression	1
diisononyl phthalate	affects cotreatment, decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
methylparaben	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sulforaphane	decreases expression	1
lead nitrate	affects cotreatment, decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	increases expression	1
butylbenzyl phthalate	affects cotreatment, decreases expression	1
cupric chloride	decreases expression	1
ciglitazone	affects binding, increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression	1
phenethyl isothiocyanate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases 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	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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