PSG5

Summary

PSG5 (pregnancy specific beta-1-glycoprotein 5, HGNC:9522) is a protein-coding gene on chromosome 19q13.31, encoding Pregnancy-specific beta-1-glycoprotein 5 (Q15238).

The human pregnancy-specific glycoproteins (PSGs) are a group of molecules that are mainly produced by the placental syncytiotrophoblasts during pregnancy. PSGs comprise a subgroup of the carcinoembryonic antigen (CEA) family, which belongs to the immunoglobulin superfamily. For additional general information about the PSG gene family, see PSG1 (MIM 176390).

Source: NCBI Gene 5673 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 48 total
• MANE Select transcript: NM_002781

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9522
Approved symbol	PSG5
Name	pregnancy specific beta-1-glycoprotein 5
Location	19q13.31
Locus type	gene with protein product
Status	Approved
Aliases	FL-NCA-3, PSG
Ensembl gene	ENSG00000204941
Ensembl biotype	protein_coding
OMIM	176394
Entrez	5673

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000342951, ENST00000366175, ENST00000401942, ENST00000401992, ENST00000404580, ENST00000407356, ENST00000407568, ENST00000489220, ENST00000599214, ENST00000599812, ENST00000600817

RefSeq mRNA: 2 — MANE Select: NM_002781 NM_001130014, NM_002781

CCDS: CCDS12617

Canonical transcript exons

ENST00000342951 — 6 exons

Exon	Start	End
ENSE00001330348	43175870	43176148
ENSE00001557913	43167743	43168203
ENSE00001564066	43186342	43186536
ENSE00003009702	43175215	43175469
ENSE00003143425	43170055	43170138
ENSE00003536747	43184782	43185147

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 95.93.

FANTOM5 (CAGE): breadth broad, TPM avg 4.6291 / max 663.8296, expressed in 275 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181238	4.0776	264
181237	0.5515	114

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	95.93	gold quality
decidua	UBERON:0002450	88.39	gold quality
buccal mucosa cell	CL:0002336	87.56	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.26	gold quality
stromal cell of endometrium	CL:0002255	81.45	gold quality
endothelial cell	CL:0000115	79.40	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.32	gold quality
diaphragm	UBERON:0001103	76.89	gold quality
olfactory bulb	UBERON:0002264	72.25	gold quality
cervix squamous epithelium	UBERON:0006922	72.19	gold quality
type B pancreatic cell	CL:0000169	72.16	gold quality
vena cava	UBERON:0004087	71.85	gold quality
adrenal tissue	UBERON:0018303	71.43	gold quality
hair follicle	UBERON:0002073	70.19	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	70.18	gold quality
mucosa of urinary bladder	UBERON:0001259	69.56	gold quality
cardia of stomach	UBERON:0001162	68.58	silver quality
oocyte	CL:0000023	68.56	gold quality
male germ cell	CL:0000015	68.27	silver quality
sperm	CL:0000019	67.65	silver quality
nasal cavity epithelium	UBERON:0005384	67.55	gold quality
corpus callosum	UBERON:0002336	67.41	gold quality
saphenous vein	UBERON:0007318	66.94	silver quality
pons	UBERON:0000988	66.85	silver quality
cerebellar vermis	UBERON:0004720	66.74	silver quality
body of tongue	UBERON:0011876	66.25	gold quality
gingival epithelium	UBERON:0001949	66.21	gold quality
pericardium	UBERON:0002407	65.95	silver quality
Brodmann (1909) area 46	UBERON:0006483	65.91	gold quality
pharyngeal mucosa	UBERON:0000355	65.87	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	6.98
E-ANND-3	yes	3.74

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, KLF4, KLF6, RXRA, SP1, ZNF362

miRNA regulators (miRDB)

39 targeting PSG5, 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-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-1244	99.33	68.38	832
HSA-MIR-7158-5P	99.25	67.95	796
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-4635	98.74	67.63	1339
HSA-MIR-508-3P	98.66	69.62	887
HSA-MIR-8060	98.61	66.93	1187

Literature-anchored findings (GeneRIF, showing 4)

• Strong synergic activity of KLF4 and Sp1 on the PSG-5 promoter. (PMID:16563348)
• the mRNA expression of PREGNANCY-SPECIFIC BETA-1-GLYCOPROTEIN is up-regulated in cells circulating within blood from women with preeclampsia, and is positively correlated with cliical severity (PMID:17978129)
• esults are consistent with a regulatory role of lysine acetylation on PSG expression through a relaxed chromatin state and an increase in the transcriptional activity of Sp1 and KLF6 following an augmented Sp1 acetylation and KLF6 nuclear localization. (PMID:23418492)
• show that human PSG1 binds alphaIIbbeta3 and inhibits the platelet - fibrinogen interaction. Unexpectedly, however, the KGD is not critical as multiple PSG1 domains independently bind and inhibit alphaIIbbeta3 function (PMID:23469002)

Cross-species orthologs

0 orthologs

Paralogs (24): CEACAM21 (ENSG00000007129), CEACAM7 (ENSG00000007306), CEACAM1 (ENSG00000079385), CEACAM6 (ENSG00000086548), CEACAM4 (ENSG00000105352), CEACAM5 (ENSG00000105388), PSG8 (ENSG00000124467), CEACAM8 (ENSG00000124469), HEPACAM (ENSG00000165478), PSG6 (ENSG00000170848), CEACAM3 (ENSG00000170956), PSG9 (ENSG00000183668), CEACAM19 (ENSG00000186567), HEPACAM2 (ENSG00000188175), CEACAM18 (ENSG00000213822), CEACAM16 (ENSG00000213892), VSTM5 (ENSG00000214376), PSG3 (ENSG00000221826), PSG7 (ENSG00000221878), PSG1 (ENSG00000231924), PSG2 (ENSG00000242221), PSG11 (ENSG00000243130), PSG4 (ENSG00000243137), CEACAM20 (ENSG00000273777)

Protein

Protein identifiers

Pregnancy-specific beta-1-glycoprotein 5 — Q15238 (reviewed: Q15238)

Alternative names: Fetal liver non-specific cross-reactive antigen 3

All UniProt accessions (4): E7EQY3, E9PC55, Q15238, M0R1G9

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Synthesized by syncytiotrophoblast of the placenta.

Similarity. Belongs to the immunoglobulin superfamily. CEA family.

RefSeq proteins (2): NP_001123486, NP_002772* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050831	CEA_cell_adhesion	Family

Pfam: PF07686, PF13895, PF13927

UniProt features (22 total): sequence conflict 6, sequence variant 4, glycosylation site 4, domain 3, disulfide bond 2, signal peptide 1, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9PBH	X-RAY DIFFRACTION	2.13

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15238-F1	85.87	0.70

Functional residue map

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

Disulfide bonds (2): 169–217, 261–301

Glycosylation sites (4): 104, 111, 175, 210

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-202733	Cell surface interactions at the vascular wall

MSigDB gene sets: 56 (showing top): GOBP_HETEROPHILIC_CELL_CELL_ADHESION, GOBP_CELL_CELL_ADHESION, GNF2_KISS1, GOBP_MULTI_MULTICELLULAR_ORGANISM_PROCESS, GNF2_CDKN1C, HENDRICKS_SMARCA4_TARGETS_UP, REACTOME_CELL_SURFACE_INTERACTIONS_AT_THE_VASCULAR_WALL, MODULE_47, MODULE_342, GNF2_TIMP2, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_WITH_LMP1_UP, CHICAS_RB1_TARGETS_GROWING, CHICAS_RB1_TARGETS_CONFLUENT, ATM_DN.V1_UP, BMI1_DN.V1_UP

GO Biological Process (2): heterophilic cell-cell adhesion (GO:0007157), female pregnancy (GO:0007565)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), cell surface (GO:0009986)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell-cell adhesion	1
multi-organism reproductive process	1
multi-multicellular organism process	1
binding	1

Protein interactions and networks

STRING

1182 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSG5	CSH1	P01243	666
PSG5	CSH1	P01243	663
PSG5	SDHC	Q99643	603
PSG5	LGALS4	P56470	581
PSG5	PAPPA	Q13219	507
PSG5	ESR1	P03372	503
PSG5	SDHB	P21912	491
PSG5	RARA	P10276	449
PSG5	GAPDH	P00354	435
PSG5	AR	P10275	422
PSG5	ACTB	P02570	421
PSG5	SLCO6A1	Q86UG4	419
PSG5	ESR2	Q92731	418
PSG5	ADCY10	Q96PN6	415
PSG5	KLF6	Q99612	414

IntAct

11 interactions, top by confidence:

A	B	Type	Score
PSG5	TIE1	psi-mi:“MI:0915”(physical association)	0.540
PSG5	TIE1	psi-mi:“MI:0407”(direct interaction)	0.540
TIE1	PSG5	psi-mi:“MI:0407”(direct interaction)	0.540
PDGFRA	PSG5	psi-mi:“MI:0915”(physical association)	0.400
PSG5	TNFRSF12A	psi-mi:“MI:0915”(physical association)	0.400
PSG5	NLGN3	psi-mi:“MI:0915”(physical association)	0.370
NLGN3	PSG5	psi-mi:“MI:0915”(physical association)	0.370
PSG5	PRPF40A	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (4): PSG5 (Affinity Capture-MS), PSG5 (Two-hybrid), PSG5 (Two-hybrid), TIE1 (Reconstituted Complex)

ESM2 similar proteins: A0A0K2S4Q6, A6NI73, O75019, O75022, O75023, O76036, P0C191, P11464, P11465, P13688, P31997, P40199, P59901, Q00887, Q00888, Q00889, Q08708, Q0V881, Q15238, Q16557, Q28110, Q496F6, Q5M7U7, Q5SQ64, Q6GTX8, Q6ISS4, Q6MG56, Q6PI73, Q863H2, Q863H3, Q8C567, Q8IYS5, Q8MHY9, Q8MJZ2, Q8N149, Q8N423, Q8N6C8, Q8VBT3, Q95JB9, Q96LA5

Diamond homologs: A0A0B4J1L0, D3ZQE1, E9QA28, O75871, P06731, P11464, P11465, P13688, P16573, P31809, P31997, P40198, P40199, Q00887, Q00888, Q00889, Q13046, Q14002, Q15238, Q16557, Q2WEN9, Q3KPI0, Q3UKK2, Q61400, Q63111, Q810J1, Q925P2, Q9D2Z1, Q9UQ72, Q9UQ74, Q0E9H9, Q6UY09, A8MTB9, A0A140LHF2, Q8BFR2, Q8N475, Q9PWR4, P35329, Q4VAH7, Q7TPB4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1067 predictions. Top by Δscore:

Variant	Effect	Δscore
19:43173874:CCCA:C	acceptor_gain	0.9900
19:43173877:A:C	acceptor_gain	0.9900
19:43175348:C:A	donor_gain	0.9900
19:43184780:A:AC	donor_gain	0.9900
19:43184781:C:CC	donor_gain	0.9900
19:43173873:CCCCA:C	acceptor_gain	0.9800
19:43173875:CCA:C	acceptor_gain	0.9800
19:43173876:CA:C	acceptor_gain	0.9800
19:43173883:A:AC	acceptor_gain	0.9800
19:43176149:C:CC	acceptor_gain	0.9800
19:43185148:C:CC	acceptor_gain	0.9800
19:43168200:CTGT:C	acceptor_gain	0.9700
19:43170144:A:C	acceptor_gain	0.9700
19:43173876:C:T	acceptor_gain	0.9700
19:43173883:A:C	acceptor_gain	0.9700
19:43175347:T:TA	donor_gain	0.9700
19:43176147:CA:C	acceptor_gain	0.9700
19:43184825:A:AC	donor_gain	0.9700
19:43170139:C:CC	acceptor_gain	0.9600
19:43170144:A:AC	acceptor_gain	0.9600
19:43175868:A:AC	donor_gain	0.9600
19:43175869:C:CC	donor_gain	0.9600
19:43176151:G:C	acceptor_gain	0.9600
19:43185143:TGATG:T	acceptor_gain	0.9600
19:43185146:TG:T	acceptor_gain	0.9600
19:43186336:CCTCA:C	donor_loss	0.9600
19:43186337:CTCA:C	donor_loss	0.9600
19:43186338:TCACC:T	donor_loss	0.9600
19:43186339:CACCT:C	donor_loss	0.9600
19:43186340:A:AT	donor_loss	0.9600

AlphaMissense

2142 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:43185013:A:G	W67R	0.975
19:43185013:A:T	W67R	0.975
19:43175929:C:G	C217S	0.969
19:43175930:A:T	C217S	0.969
19:43185011:C:A	W67C	0.962
19:43185011:C:G	W67C	0.962
19:43175360:C:A	W273C	0.961
19:43175360:C:G	W273C	0.961
19:43175362:A:G	W273R	0.956
19:43175362:A:T	W273R	0.956
19:43184892:A:G	L107P	0.955
19:43175895:A:C	S228R	0.954
19:43175895:A:T	S228R	0.954
19:43175897:T:G	S228R	0.954
19:43175930:A:G	C217R	0.954
19:43176039:C:A	W180C	0.954
19:43176039:C:G	W180C	0.954
19:43176073:C:G	C169S	0.949
19:43176074:A:T	C169S	0.949
19:43175398:A:G	C261R	0.948
19:43175278:A:G	C301R	0.947
19:43175277:C:G	C301S	0.944
19:43175278:A:T	C301S	0.944
19:43176041:A:G	W180R	0.942
19:43176041:A:T	W180R	0.942
19:43176074:A:G	C169R	0.942
19:43184896:A:G	S106P	0.941
19:43175396:G:C	C261W	0.936
19:43175264:G:C	N305K	0.932
19:43175264:G:T	N305K	0.932

dbSNP variants (sampled 300 via entrez): RS1000044394 (19:43185968 T>C), RS1000114742 (19:43176415 G>C), RS1000264496 (19:43172437 G>T), RS1000419314 (19:43168512 G>A,C,T), RS1000562489 (19:43186103 A>G,T), RS1000699945 (19:43172235 A>C), RS1000760822 (19:43167565 T>G), RS1000848078 (19:43182583 G>C), RS1000879115 (19:43182460 A>G), RS1001005482 (19:43171443 A>C), RS1001043425 (19:43179110 C>A,T), RS1001165318 (19:43186183 G>A,T), RS1001357315 (19:43182847 G>C,T), RS1001825449 (19:43188230 G>A,T), RS1001858642 (19:43171948 G>T)

Disease associations

OMIM: gene MIM:176394 | 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
GCST011706_5	Cerebral microbleeds (lobar)	5.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010059	cerebral microbleeds

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance	3
Arsenic	increases expression, decreases expression, increases abundance	2
bufotalin	increases expression	1
sodium arsenate	increases expression, increases abundance	1
potassium chromate(VI)	increases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Alitretinoin	affects binding, increases activity, affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Chromium	increases expression	1
Copper	affects binding, increases expression	1
Diclofenac	increases expression	1
Disulfiram	affects binding, increases expression	1
Lucanthone	increases expression	1
Methylcholanthrene	affects binding, increases reaction	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Okadaic Acid	decreases expression	1
beta-Naphthoflavone	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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