PLSCR1

Summary

PLSCR1 (phospholipid scramblase 1, HGNC:9092) is a protein-coding gene on chromosome 3q24, encoding Phospholipid scramblase 1 (O15162). Catalyzes calcium-induced ATP-independent rapid bidirectional and non-specific movement of phospholipids (lipid scrambling or lipid flip-flop) between the inner and outer leaflet of the plasma membrane resulting in collapse of the phospholipid asymmetry which leads to phosphatid….

This gene encodes a phospholipid scramblase family member. The encoded protein is involved in disruption of the asymmetrical distribution of phospholipids between the inner and outer leaflets of the plasma membrane, resulting in externalization of phosphatidylserine. This cell membrane disruption plays an important role in the blood coagulation cascade as well as macrophage clearing of apoptotic cells. The encoded protein has additionally been implicated in gene regulation and interferon-induced antiviral responses.

Source: NCBI Gene 5359 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 46 total
• MANE Select transcript: NM_021105

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9092
Approved symbol	PLSCR1
Name	phospholipid scramblase 1
Location	3q24
Locus type	gene with protein product
Status	Approved
Aliases	MMTRA1B
Ensembl gene	ENSG00000188313
Ensembl biotype	protein_coding
OMIM	604170
Entrez	5359

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 30 protein_coding, 7 nonsense_mediated_decay, 3 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000342435, ENST00000448787, ENST00000462666, ENST00000463777, ENST00000468985, ENST00000469266, ENST00000470496, ENST00000472349, ENST00000477974, ENST00000478267, ENST00000483300, ENST00000484560, ENST00000486631, ENST00000487389, ENST00000488253, ENST00000489775, ENST00000490745, ENST00000493432, ENST00000494568, ENST00000907639, ENST00000907640, ENST00000907641, ENST00000907642, ENST00000907643, ENST00000907644, ENST00000907645, ENST00000907646, ENST00000907647, ENST00000907648, ENST00000907649, ENST00000907650, ENST00000907651, ENST00000929308, ENST00000929309, ENST00000967298, ENST00000967299, ENST00000967300, ENST00000967301, ENST00000967302, ENST00000967303, ENST00000967304, ENST00000967305, ENST00000967306

RefSeq mRNA: 13 — MANE Select: NM_021105 NM_001363872, NM_001363874, NM_001406033, NM_001406034, NM_001406035, NM_001406036, NM_001406037, NM_001406038, NM_001406039, NM_001406040, NM_001406041, NM_001406042, NM_021105

CCDS: CCDS3135, CCDS87153

Canonical transcript exons

ENST00000342435 — 9 exons

Exon	Start	End
ENSE00001851057	146544467	146544607
ENSE00001884022	146515180	146516101
ENSE00003475214	146533470	146533550
ENSE00003514601	146521544	146521705
ENSE00003547587	146536540	146536565
ENSE00003580478	146517006	146517167
ENSE00003583692	146521833	146522053
ENSE00003619173	146525605	146525647
ENSE00003623967	146528614	146528831

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 98.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 69.9371 / max 1295.7705, expressed in 1815 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44936	32.3525	1786
44934	19.3918	1619
44939	10.6580	1774
44935	2.5836	703
44937	2.0539	1118
44933	1.5315	336
44940	0.7779	386
44938	0.3615	184
44929	0.2264	101

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	98.44	gold quality
monocyte	CL:0000576	98.38	gold quality
caput epididymis	UBERON:0004358	98.35	gold quality
mononuclear cell	CL:0000842	98.31	gold quality
gall bladder	UBERON:0002110	98.19	gold quality
germinal epithelium of ovary	UBERON:0001304	98.12	gold quality
pericardium	UBERON:0002407	98.11	gold quality
leukocyte	CL:0000738	98.08	gold quality
esophagus squamous epithelium	UBERON:0006920	98.05	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.01	gold quality
cauda epididymis	UBERON:0004360	97.95	gold quality
colonic mucosa	UBERON:0000317	97.84	gold quality
epithelium of nasopharynx	UBERON:0001951	97.78	gold quality
rectum	UBERON:0001052	97.76	gold quality
vermiform appendix	UBERON:0001154	97.69	gold quality
peritoneum	UBERON:0002358	97.61	gold quality
omental fat pad	UBERON:0010414	97.61	gold quality
bone marrow	UBERON:0002371	97.52	gold quality
colonic epithelium	UBERON:0000397	97.47	gold quality
corpus epididymis	UBERON:0004359	97.44	gold quality
epithelium of esophagus	UBERON:0001976	97.32	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.28	gold quality
caecum	UBERON:0001153	97.27	gold quality
metanephros cortex	UBERON:0010533	97.16	gold quality
upper lobe of left lung	UBERON:0008952	97.07	gold quality
right lung	UBERON:0002167	97.03	gold quality
mucosa of stomach	UBERON:0001199	96.98	gold quality
left ovary	UBERON:0002119	96.96	gold quality
mucosa of urinary bladder	UBERON:0001259	96.95	gold quality
upper lobe of lung	UBERON:0008948	96.95	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-109979	yes	493.09
E-MTAB-7037	yes	405.54
E-HCAD-1	yes	50.38
E-GEOD-125970	yes	18.04
E-CURD-88	yes	12.00
E-GEOD-83139	yes	11.49
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
ITPR1

Upstream regulators (CollecTRI, top): E2F4, FOXO1, SNAI1, STAT1, STAT3

miRNA regulators (miRDB)

66 targeting PLSCR1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-369-3P	99.85	70.52	2264
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-4517	99.76	69.19	1867
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-586	99.65	70.40	2051

Literature-anchored findings (GeneRIF, showing 40)

• Suppression of ovarian carcinoma cell growth in vivo by the interferon-inducible plasma membrane protein, phospholipid scramblase 1. (PMID:11809687)
• PLSCR1 co-localizes with the epidermal growth factor (EGF) receptor in lipid rafts and plays a role in the EGF-induced metabolic or mitogenic response. (PMID:12009895)
• Paper reports studies on PLSCR1 gene knockout mice. PLSCR1-/- mice displayed no hemostatic abnormality. By contrast a defect in hematopoiesis was identified and shown to reflect defective response of hematopoietic precursors to select growth factors. (PMID:12010804)
• expression has a role in the induction of differentiation of human myeloid leukemia cells into granulocytes. (PMID:12031648)
• Trafficking of PLSCR1 to the plasma membrane is dependent upon palmitoylation of the polypeptide; in the absence of palmitoylation, PLSCR1 traffics into the nucleus. (PMID:12564925)
• Identification of domains for PLSCR1 and BACE binding and their colocalization in the Golgi area and endosomal compartments suggest involvement of PLSCR1 in the intracellular distribution and/or recruitment of BACE into the lipid raft. (PMID:12586838)
• phospholipid scramblase 1 plays a role in ischemic injury in the human hippocampus (PMID:12605885)
• PLSCR1, through its interaction with Shc, promotes Src kinase activation through the EGF receptor. (PMID:12871937)
• Higher MmTRA1b mRNA levels were associated with significantly longer overall survival in AML, especially in AML-M4 patients, independent of chromosomal aberrations (PMID:14654079)
• both PLSCR1 and phospholipid flip-flop characterize uropod raft domains of polarized neutrophils (PMID:14766753)
• Data support a mechanism of receptor-mediated nuclear import of PLSCR1 and suggest a potential nuclear function for this plasma membrane protein, mediated through potential interaction with genomic DNA. (PMID:15035622)
• as a protein induced upon PKCdelta activation, PLSCR1 is required for ATRA- and PMA-triggered leukemic cell differentiation (PMID:15308560)
• PLSCR1, which is itself an IFN-stimulated gene-encoded protein, provides a mechanism for amplifying and enhancing the IFN response through increased expression of a select subset of potent antiviral genes (PMID:15308695)
• x-ray crystallography shows that there is a nonclassical nuclear localization signal in PLSCR1 with a unique binding site in importin alpha (PMID:15611084)
• PLSCR1 binds to the promoter region of the IP3R1 gene to enhance its expression (PMID:16091359)
• protein kinase Cdelta and JNK have roles in Ifn-alpha induced expression of phospholipid scramblase 1 through STAT1 (PMID:16260419)
• PR3 externalization depended on PLSCR1 (PMID:17712045)
• PLSCR1 is a novel amplifier of FcepsilonRI signaling that acts selectively on the Lyn-initiated LAT/phospholipase Cgamma1/calcium axis, resulting in potentiation of a selected set of mast cell responses (PMID:18579528)
• the same region of the cytoplasmic domain of PLSCR1 is involved in the binding to CD4 and SLPI (PMID:19333378)
• Results show that binding affinities of the peptides are in the order hPLSCR1>hPLSCR3>hPLSCR2>hPLSCR4 for Ca2+ and in the order hPLSCR1>hPLSCR2>hPLSCR3>hPLSCR4 for Mg2+. (PMID:19540310)
• Monocytes in systemic lupus erythematosus patients had enhanced PLSCR1 mRNA expression, as well as increased fibrin turnover and cell-surface PS exposure. (PMID:20516018)
• PLSCR1 interacts with the tandem repeat region of ECM1a in the dermal epidermal junction zone of human skin. (PMID:20870722)
• Interferon tau induces expression of DDX58 and PLSCR1 via the classical STAT1-mediated cell signaling pathway. (PMID:20926691)
• PLSCR1 might be used as a noninvasive serological diagnostic and prognostic biomarker for CRC. (PMID:20927484)
• PLSCR1 was required for the initial attachment of HCV onto hepatoma cells, where it specifically interacted with entry factor OCLN. We show that PLSCR1 is a novel attachment factor for HCV entry. (PMID:21806988)
• summarizes the mechanisms and roles of PS exposure following platelet activation and discusses the recent identification of TMEM16F and its significance in the scrambling process (PMID:21958383)
• this report identifies PLSCR1 as a protein that physically interacts with Receptor expressed in lymphoid tissues family members and is a potential substrate for phosphorylation by the OSR1 kinase in a RELT-dependent fashion. (PMID:22052202)
• IFNalpha-induced PLSCR1 associates with the cytoskeleton after exposure to alpha-toxin, and cellular depletion of PLSCR1 negates IFN-induced protection from alpha-toxin. (PMID:22264514)
• PLSCR1 inhibited HBV replication through a reduction in the synthesis of viral proteins and DNA replication. (PMID:22342889)
• Phospholipid scramblase 1 expression is enhanced in patients with antiphospholipid syndrome. (PMID:22526829)
• PLSCR1 may play an important role in the IFN-mediated repression of Tax-dependent transactivation during HTLV-1 infection. (PMID:22789739)
• PLSCR1 is overexpressed in colorectal cancer and metastatic liver cancer. Silencing of PLSCR1 by siRNA inhibits the proliferation, adhesion, migration and invasion of tumor cells. (PMID:22893466)
• Calcium-dependent PLSCR-1 activity is required for compensatory endocytosis (but not for exocytosis) in neuroendocrine cells. (PMID:23426682)
• Overexpression of PLSCR1 efficiently represses the Tat-dependent transactivation of the HIV-1 long terminal repeat (LTR) and reduces the nuclear translocation of Tat. (PMID:23501106)
• The C-terminal helix of human PLSCR1 is required for membrane insertion and calcium binding. (PMID:23590222)
• Phospholipid Scramblase 1, an interferon-regulated gene located at 3q23, is regulated by SnoN/SkiL in ovarian cancer cells. (PMID:23621864)
• This is the first biochemical evidence to prove the above hypothesis that hPLSCR1 is activated in heavy metal poisoning, which leads to bidirectional transbilayer movement of phospholipids. (PMID:23659204)
• The data are in agreement with the possibility that PLSCR1 is an integral membrane protein. (PMID:24099740)
• The C-terminal transmembrane domain of human phospholipid scramblase 1 is essential for the protein flip-flop activity and Ca(2)-binding. (PMID:24343571)
• PLSCR1 interacted with ANG in the cell nucleus and regulated rRNA transcription. (PMID:24356419)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
mus_musculus	Plscr1	ENSMUSG00000032369
mus_musculus	Plscr2	ENSMUSG00000032372
mus_musculus	Plscr1l1	ENSMUSG00000074139
rattus_norvegicus	Plscr2	ENSRNOG00000008048
rattus_norvegicus	Plscr1l1	ENSRNOG00000030551
rattus_norvegicus	Plscr2	ENSRNOG00000064984
drosophila_melanogaster	scramb2	FBGN0035390
drosophila_melanogaster	scramb1	FBGN0052056
caenorhabditis_elegans	scrm-6	WBGENE00009753
caenorhabditis_elegans		WBGENE00013052
caenorhabditis_elegans		WBGENE00019530
caenorhabditis_elegans		WBGENE00019531

Paralogs (4): PLSCR4 (ENSG00000114698), PLSCR2 (ENSG00000163746), PLSCR3 (ENSG00000187838), PLSCR5 (ENSG00000231213)

Protein

Protein identifiers

Phospholipid scramblase 1 — O15162 (reviewed: O15162)

Alternative names: Ca(2+)-dependent phospholipid scramblase 1, Erythrocyte phospholipid scramblase, Mg(2+)-dependent nuclease, MmTRA1b

All UniProt accessions (7): C9J0H3, C9J7K9, C9J9P4, C9JE06, O15162, F2Z3F2, H7C5I5

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes calcium-induced ATP-independent rapid bidirectional and non-specific movement of phospholipids (lipid scrambling or lipid flip-flop) between the inner and outer leaflet of the plasma membrane resulting in collapse of the phospholipid asymmetry which leads to phosphatidylserine externalization on the cell surface. Mediates calcium-dependent phosphatidylserine externalization and apoptosis in neurons via its association with TRPC5. Also exhibits magnesium-dependent nuclease activity against double-stranded DNA and RNA but not single-stranded DNA and can enhance DNA decatenation mediated by TOP2A. Negatively regulates FcR-mediated phagocytosis in differentiated macrophages. May contribute to cytokine-regulated cell proliferation and differentiation. May play a role in the antiviral response of interferon (IFN) by amplifying and enhancing the IFN response through increased expression of select subset of potent antiviral genes. Inhibits the functions of viral transactivators, including human T-cell leukemia virus (HTLV)-1 protein Tax, human immunodeficiency virus (HIV)-1 Tat, human hepatitis B virus (HBV) HBx, Epstein-Barr virus (EBV) BZLF1 and human cytomegalovirus IE1 and IE2 proteins through direct interactions. Also mediates the inhibition of influenza virus infection by preventing nuclear import of the viral nucleoprotein/NP. Plays a crucial role as a defense factor against SARS-CoV-2 independently of its scramblase activity by directly targeting nascent viral vesicles to prevent virus-membrane fusion and the release of viral RNA into the host-cell cytosol. (Microbial infection) Acts as an attachment receptor for HCV.

Subunit / interactions. Forms homooligomers in the presence of calcium. Interacts with ABL. Interacts with RELT, RELL1 and RELL2. Interacts with OXSR1 in the presence of RELT. Interacts with TOP2A and TOP2B. Interacts with OCLN. Interacts with TRPC5. Interacts with TRPC1 and TRPC4. Interacts with ILDR1. (Microbial infection) Interacts with hepatitis C virus E1 and E2 glycoproteins. (Microbial infection) Interacts with T-cell leukemia virus (HTLV)-1 protein Tax (via N-terminus); this interaction represses Tax homodimerization. (Microbial infection) Interacts with HIV-1 protein Tat; this interaction represses the Tat-dependent transactivation of the HIV-1 long terminal repeat (LTR) and reduces the nuclear translocation of Tat. (Microbial infection) Interacts with hepatitis B virus protein HBx; this interaction promotes the proteasomal degradation of HBx. (Microbial infection) Interacts with human cytomegalovirus proteins IE1 and IE2. (Microbial infection) Interacts with Epstein Barr virus (EBV) lytic switch protein BZLF1; this interaction negatively regulates the transcriptional regulatory activity of BZLF1 by preventing the formation of the BZLF1-CBP complex. (Microbial infection) Interacts with influenza virus nucleoprotein NP.

Subcellular location. Cell membrane. Nucleus. Cytoplasm. Perinuclear region.

Tissue specificity. Expressed in platelets, erythrocyte membranes, lymphocytes, spleen, thymus, prostate, testis, uterus, intestine, colon, heart, placenta, lung, liver, kidney and pancreas. Not detected in brain and skeletal muscle.

Post-translational modifications. Phosphorylation at Thr-161 by PKC/PKCD increases its phospholipid scramblase activity during both cell stimulation and apoptosis. Phosphorylated by OXSR1 in the presence of RELT. Palmitoylation is required for its phospholipid scramblase activity. Palmitoylation regulates its localization to the cell membrane or the nucleus; trafficking to the cell membrane is dependent upon palmitoylation whereas in the absence of palmitoylation, localizes to the nucleus.

Activity regulation. Activated by Pb(2+) and Hg(2+) ions. Phosphorylation at Thr-161 by PKC/PKCD increases its phospholipid scramblase activity during both cell stimulation and apoptosis.

Cofactor. Magnesium. Can also use zinc with lower efficiency.

Domain organisation. The N-terminal proline-rich domain (PRD) is required for phospholipid scramblase activity. The transmembrane domain is essential for membrane insertion, phospholipid scramblase activity and proper calcium-binding.

Induction. (Microbial infection) Induced by IFNB1/IFN-beta in response to a viral infection. Up-regulated during PMA-induced differentiation of the monocytic cell line THP-1.

Similarity. Belongs to the phospholipid scramblase family.

Isoforms (2)

UniProt ID	Names	Canonical?
O15162-1	1	yes
O15162-2	2

RefSeq proteins (13): NP_001350801, NP_001350803, NP_001392962, NP_001392963, NP_001392964, NP_001392965, NP_001392966, NP_001392967, NP_001392968, NP_001392969, NP_001392970, NP_001392971, NP_066928* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005552	Scramblase	Family

Pfam: PF03803

Enzyme classification (BRENDA):

• EC 7.6.2.1 — P-type phospholipid transporter (BRENDA: 22 organisms, 260 substrates, 62 inhibitors, 53 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.016–2.215	41
P-NITROPHENYL PHOSPHATE	1.17–1.46	3
ACETYL PHOSPHATE	1.03–1.31	2
1-PALMITOYL-2-OLEOYL-SN-GLYCERO-3-PHOSPHO-L-SERI	0.111	1

Catalyzed reactions (Rhea), 3 shown:

• a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl-sn-glycero-3-phosphocholine(out) (RHEA:38571)
• a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) = a 1,2-diacyl-sn-glycero-3-phospho-L-serine(out) (RHEA:38663)
• a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(out) (RHEA:38895)

UniProt features (41 total): mutagenesis site 15, short sequence motif 6, lipid moiety-binding region 5, modified residue 3, region of interest 3, topological domain 2, compositionally biased region 2, splice variant 2, chain 1, transmembrane region 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1Y2A	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15162-F1	70.75	0.39

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 (8): 69, 74, 161, 184, 185, 186, 188, 189

Mutagenesis-validated functional residues (15):

Position	Phenotype
12	60% reduction in nuclease activity; when associated with a-53; a-111; a-211 and a-262.
53	60% reduction in nuclease activity; when associated with a-12; a-111; a-211 and a-262.
69	decrease in phosphorylation.
74	decrease in phosphorylation.
111	60% reduction in nuclease activity; when associated with a-12; a-53; a-211 and a-262.
161	no induction by pkc/prkcd.
184–189	no palmitoylation; constitutively localizes in the nucleus. loss of protection against sars-cov-2-containing vesicles.
211	60% reduction in nuclease activity; when associated with a-12; a-53; a-111 and a-262.
262	60% reduction in nuclease activity; when associated with a-12; a-53; a-111 and a-211.
273	reduces the ca(2+)-dependent phospholipid scrambling.
275	complete inactivation of the ca(2+)-dependent phospholipid scrambling. no effect on its nuclease activity.
277	reduces the ca(2+)-dependent phospholipid scrambling.
279	reduces the ca(2+)-dependent phospholipid scrambling.
281	complete inactivation of the ca(2+)-dependent phospholipid scrambling.
284	reduces the ca(2+)-dependent phospholipid scrambling.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 634 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, MODULE_52, chr3q24, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, LIANG_HEMATOPOIESIS_STEM_CELL_NUMBER_SMALL_VS_HUGE_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOMF_NUCLEASE_ACTIVITY, AMIT_EGF_RESPONSE_60_HELA, GOBP_PLATELET_ACTIVATION, MODULE_45, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS

GO Biological Process (20): phosphatidylserine biosynthetic process (GO:0006659), apoptotic process (GO:0006915), acute-phase response (GO:0006953), response to lead ion (GO:0010288), positive regulation of gene expression (GO:0010628), plasma membrane phospholipid scrambling (GO:0017121), platelet activation (GO:0030168), regulation of mast cell activation (GO:0033003), response to interferon-beta (GO:0035456), negative regulation of viral genome replication (GO:0045071), positive regulation of innate immune response (GO:0045089), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of phagocytosis (GO:0050765), defense response to virus (GO:0051607), regulation of Fc receptor mediated stimulatory signaling pathway (GO:0060368), phosphatidylserine exposure on apoptotic cell surface (GO:0070782), positive regulation of chromosome separation (GO:1905820), positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity (GO:2000373), lipid transport (GO:0006869), symbiont entry into host cell (GO:0046718)

GO Molecular Function (16): magnesium ion binding (GO:0000287), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), virus receptor activity (GO:0001618), DNA binding (GO:0003677), nuclease activity (GO:0004518), epidermal growth factor receptor binding (GO:0005154), calcium ion binding (GO:0005509), zinc ion binding (GO:0008270), hydrolase activity (GO:0016787), SH3 domain binding (GO:0017124), phospholipid scramblase activity (GO:0017128), enzyme binding (GO:0019899), lead ion binding (GO:0032791), CD4 receptor binding (GO:0042609), mercury ion binding (GO:0045340), protein binding (GO:0005515)

GO Cellular Component (11): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), membrane raft (GO:0045121), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
metal ion binding	3
cytoplasm	3
execution phase of apoptosis	2
plasma membrane phospholipid scrambling	2
transition metal ion binding	2
intracellular membrane-bounded organelle	2
nuclear lumen	2
phosphatidylserine metabolic process	1
modified amino acid biosynthetic process	1
glycerophospholipid biosynthetic process	1
programmed cell death	1
apoptotic signaling pathway	1
acute inflammatory response	1
response to metal ion	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
plasma membrane organization	1
phospholipid translocation	1
cell activation	1
blood coagulation	1
regulation of leukocyte activation	1
mast cell activation	1
response to cytokine	1
viral genome replication	1
regulation of viral genome replication	1
negative regulation of viral process	1
positive regulation of response to biotic stimulus	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
innate immune response	1
regulation of innate immune response	1
positive regulation of immune response	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
phagocytosis	1
negative regulation of endocytosis	1
regulation of phagocytosis	1

Protein interactions and networks

STRING

1070 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLSCR1	BACE1	P56817	726
PLSCR1	TRPC5	Q9UL62	679
PLSCR1	STAT1	P42224	605
PLSCR1	PLAC8	Q9NZF1	595
PLSCR1	STAT2	P52630	592
PLSCR1	TLR9	Q9NR96	569
PLSCR1	BACE2	Q9Y5Z0	549
PLSCR1	NAV1	Q8NEY1	547
PLSCR1	RTN3	O95197	546
PLSCR1	RTN2	O75298	544
PLSCR1	SCN2B	O60939	541
PLSCR1	IFNB1	P01574	532
PLSCR1	MX1	P20591	530
PLSCR1	RSAD2	Q8WXG1	526
PLSCR1	IFI44L	Q53G44	516

IntAct

346 interactions, top by confidence:

A	B	Type	Score
PLSCR1	GLRX3	psi-mi:“MI:0915”(physical association)	0.670
EWSR1	PLSCR1	psi-mi:“MI:0915”(physical association)	0.670
PLSCR1	DAZAP2	psi-mi:“MI:0915”(physical association)	0.670
ESR2	PLSCR1	psi-mi:“MI:0915”(physical association)	0.670
SCNM1	PLSCR1	psi-mi:“MI:0915”(physical association)	0.670
PLSCR1	ILF3	psi-mi:“MI:0915”(physical association)	0.670
GLRX3	PLSCR1	psi-mi:“MI:0915”(physical association)	0.670
PLSCR1	EWSR1	psi-mi:“MI:0915”(physical association)	0.670
DAZAP2	PLSCR1	psi-mi:“MI:0915”(physical association)	0.670
PLSCR1	SCNM1	psi-mi:“MI:0915”(physical association)	0.670
ILF3	PLSCR1	psi-mi:“MI:0915”(physical association)	0.670
PLSCR1	ESR2	psi-mi:“MI:0915”(physical association)	0.670
PLSCR1	VPS37C	psi-mi:“MI:0915”(physical association)	0.560
PLSCR1	BCL6B	psi-mi:“MI:0915”(physical association)	0.560
PLSCR1		psi-mi:“MI:0915”(physical association)	0.560
	PLSCR1	psi-mi:“MI:0915”(physical association)	0.560
PLSCR1	FRS3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (213): PLSCR1 (Two-hybrid), PLSCR1 (Two-hybrid), PLSCR1 (Two-hybrid), PLSCR1 (Two-hybrid), PLSCR1 (Two-hybrid), PLSCR1 (Two-hybrid), PLSCR1 (Two-hybrid), RGS3 (Two-hybrid), SMARCC1 (Two-hybrid), STK16 (Two-hybrid), CHRD (Two-hybrid), DAZAP2 (Two-hybrid), GLRX3 (Two-hybrid), FRS3 (Two-hybrid), DEF6 (Two-hybrid)

ESM2 similar proteins: A0PG75, A2A3N6, A7T1N0, A8XKF2, B3H5L1, D4A2Z8, E9PU17, E9PX95, F1S5L4, F4IM84, O08619, O15162, O42857, O75386, P00488, P34751, P41879, P47140, P58195, P58196, P97564, Q05187, Q05B79, Q09306, Q0KHU5, Q28C60, Q3UW68, Q3ZBG9, Q5GJ77, Q5XI69, Q69RI8, Q6DCK1, Q6DNF3, Q6QBQ4, Q6S5G3, Q84M24, Q8IJH8, Q8VHK9, Q9DCW2, Q9FHK8

Diamond homologs: A0PG75, O15162, P58195, P58196, Q3ZBG9, Q6QBQ4, Q9DCW2, Q9JIZ9, Q9JJ00, Q9NRQ2, Q9NRY6, Q9NRY7

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
SRC	“up-regulates activity”	PLSCR1	phosphorylation
ABL1	unknown	PLSCR1	phosphorylation
PRKCD	up-regulates	PLSCR1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 86 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
FRS-mediated FGFR3 signaling	5	64.7×	2e-06
FRS-mediated FGFR4 signaling	5	59.1×	2e-06
FRS-mediated FGFR1 signaling	5	54.4×	2e-06
FRS-mediated FGFR2 signaling	5	52.3×	2e-06
Keratinization	9	11.9×	2e-06
RAF/MAP kinase cascade	5	7.3×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
Ras protein signal transduction	5	17.4×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1141 predictions. Top by Δscore:

Variant	Effect	Δscore
3:146517000:ACTT:A	donor_loss	1.0000
3:146517003:TACA:T	donor_loss	1.0000
3:146517004:A:AC	donor_gain	1.0000
3:146517004:A:T	donor_loss	1.0000
3:146517005:C:CT	donor_gain	1.0000
3:146517005:C:T	donor_loss	1.0000
3:146517005:CA:C	donor_gain	1.0000
3:146517005:CAA:C	donor_gain	1.0000
3:146517005:CAAT:C	donor_gain	1.0000
3:146517005:CAATG:C	donor_gain	1.0000
3:146517032:CAG:C	donor_gain	1.0000
3:146517163:TTAAT:T	acceptor_gain	1.0000
3:146517164:TAAT:T	acceptor_gain	1.0000
3:146517165:AATC:A	acceptor_loss	1.0000
3:146517166:ATC:A	acceptor_loss	1.0000
3:146517168:C:CC	acceptor_gain	1.0000
3:146517168:CT:C	acceptor_loss	1.0000
3:146517169:T:C	acceptor_loss	1.0000
3:146517173:T:C	acceptor_gain	1.0000
3:146517173:T:TC	acceptor_gain	1.0000
3:146516999:GACTT:G	donor_loss	0.9900
3:146517000:A:AC	donor_gain	0.9900
3:146517001:C:CC	donor_gain	0.9900
3:146517165:AAT:A	acceptor_gain	0.9900
3:146517166:AT:A	acceptor_gain	0.9900
3:146533551:C:CC	acceptor_gain	0.9900
3:146533559:C:CT	acceptor_gain	0.9900
3:146533560:A:T	acceptor_gain	0.9900
3:146536538:A:AC	donor_gain	0.9900
3:146536539:C:CC	donor_gain	0.9900

AlphaMissense

2105 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:146517036:T:A	K290N	0.999
3:146517036:T:G	K290N	0.999
3:146517123:C:A	K261N	0.999
3:146517123:C:G	K261N	0.999
3:146521936:C:G	R158T	0.999
3:146516087:A:C	F305L	0.998
3:146516087:A:T	F305L	0.998
3:146516089:A:G	F305L	0.998
3:146517010:A:G	L299P	0.998
3:146517022:C:T	G295D	0.998
3:146517075:A:C	F277L	0.998
3:146517075:A:T	F277L	0.998
3:146517077:A:G	F277L	0.998
3:146517136:C:T	G257D	0.998
3:146517137:C:G	G257R	0.998
3:146521599:A:G	L228P	0.998
3:146521665:A:T	V206D	0.998
3:146521671:C:T	G204D	0.998
3:146521878:T:A	R177S	0.998
3:146521878:T:G	R177S	0.998
3:146521935:T:A	R158S	0.998
3:146521935:T:G	R158S	0.998
3:146521957:C:G	R151P	0.998
3:146521984:G:T	A142E	0.998
3:146525624:C:A	Q112H	0.998
3:146525624:C:G	Q112H	0.998
3:146517023:C:G	G295R	0.997
3:146517037:T:A	K290I	0.997
3:146517038:T:C	K290E	0.997
3:146517136:C:A	G257V	0.997

dbSNP variants (sampled 300 via entrez): RS1000196043 (3:146543990 T>C), RS1000272049 (3:146517787 G>A,T), RS1000359716 (3:146514783 TC>T), RS1000373474 (3:146534607 C>G,T), RS1000544229 (3:146540477 T>A), RS1000560812 (3:146523485 G>A), RS1000573587 (3:146546600 C>A,T), RS1000681084 (3:146528243 A>G), RS1000949258 (3:146515835 T>C), RS1000963420 (3:146516636 T>A), RS1001146186 (3:146522535 C>G,T), RS1001170792 (3:146517902 C>G), RS1001242022 (3:146522281 T>C), RS1001289653 (3:146527746 T>A), RS1001431513 (3:146527109 C>A)

Disease associations

OMIM: gene MIM:604170 | 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
GCST003876_4	Gut microbiota (beta diversity)	5.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Phospholipid scramblases (PLSCR)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	7
Tretinoin	increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Nickel	decreases expression, increases expression	3
Cyclosporine	decreases expression, increases expression	3
bisphenol A	affects expression, affects cotreatment, increases abundance	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Estradiol	affects cotreatment, increases expression	2
Lipopolysaccharides	increases expression, decreases reaction	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression, decreases expression, affects cotreatment	2
ginger extract	affects cotreatment, affects expression, increases abundance	1
methylmercuric chloride	decreases expression	1
apocarotenal	increases expression	1
triphenyl phosphate	affects expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
rottlerin	decreases reaction, 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	affects cotreatment, increases expression	1
NSC668394	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1H0	Abcam A-549 PLSCR1 KO 1	Cancer cell line	Male
CVCL_B2PJ	Abcam A-549 PLSCR1 KO 2	Cancer cell line	Male
CVCL_D7XY	Ubigene A-549 PLSCR1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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