PSG6

Summary

PSG6 (pregnancy specific beta-1-glycoprotein 6, HGNC:9523) is a protein-coding gene on chromosome 19q13.31, encoding Pregnancy-specific beta-1-glycoprotein 6 (Q00889).

This gene is a member of the pregnancy-specific glycoprotein (PSG) gene family. The PSG genes are a subgroup of the carcinoembryonic antigen (CEA) family of immunoglobulin-like genes, and are found in a gene cluster at 19q13.1-q13.2 telomeric to another cluster of CEA-related genes. The PSG genes are expressed by placental trophoblasts and released into the maternal circulation during pregnancy, and are thought to be essential for maintenance of normal pregnancy. The protein encoded by this gene contains the Arg-Gly-Asp tripeptide associated with cellular adhesion and recognition. Alternative splicing results in multiple transcript variants and protein isoforms.

Source: NCBI Gene 5675 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 124 total
• MANE Select transcript: NM_001031850

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9523
Approved symbol	PSG6
Name	pregnancy specific beta-1-glycoprotein 6
Location	19q13.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000170848
Ensembl biotype	protein_coding
OMIM	176395
Entrez	5675

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000187910, ENST00000292125, ENST00000402456, ENST00000402603, ENST00000484292, ENST00000594375, ENST00000595062, ENST00000599753, ENST00000601833

RefSeq mRNA: 2 — MANE Select: NM_001031850 NM_001031850, NM_002782

CCDS: CCDS12613, CCDS33038

Canonical transcript exons

ENST00000187910 — 6 exons

Exon	Start	End
ENSE00001932528	42917729	42917894
ENSE00002529616	42907576	42907854
ENSE00003544517	42916125	42916487
ENSE00003624225	42906922	42907176
ENSE00003643687	42910580	42910858
ENSE00003901527	42902086	42902446

Expression profiles

Bgee: expression breadth broad, 36 present calls, max score 95.02.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.9504 / max 2678.9691, expressed in 66 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181226	2.5921	44
181227	0.3351	30
181225	0.0181	4
181224	0.0050	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	95.02	gold quality
decidua	UBERON:0002450	87.23	gold quality
pancreatic ductal cell	CL:0002079	67.73	silver quality
ileal mucosa	UBERON:0000331	67.43	silver quality
stromal cell of endometrium	CL:0002255	67.36	gold quality
upper leg skin	UBERON:0004262	66.39	gold quality
deltoid	UBERON:0001476	62.21	gold quality
adrenal tissue	UBERON:0018303	60.75	gold quality
buccal mucosa cell	CL:0002336	60.35	gold quality
diaphragm	UBERON:0001103	59.36	gold quality
epithelial cell of pancreas	CL:0000083	57.06	gold quality
tibia	UBERON:0000979	54.23	gold quality
quadriceps femoris	UBERON:0001377	54.15	gold quality
nasal cavity epithelium	UBERON:0005384	53.47	gold quality
epithelium of esophagus	UBERON:0001976	53.03	gold quality
jejunal mucosa	UBERON:0000399	52.96	gold quality
smooth muscle tissue	UBERON:0001135	52.86	gold quality
esophagus squamous epithelium	UBERON:0006920	52.75	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
vastus lateralis	UBERON:0001379	52.42	gold quality
myocardium	UBERON:0002349	52.39	gold quality
middle temporal gyrus	UBERON:0002771	52.30	gold quality
male germ cell	CL:0000015	51.80	gold quality
muscle tissue	UBERON:0002385	51.66	gold quality
sperm	CL:0000019	51.62	gold quality
cardiac muscle of right atrium	UBERON:0003379	51.58	gold quality
Brodmann (1909) area 23	UBERON:0013554	51.24	gold quality
left ventricle myocardium	UBERON:0006566	51.17	gold quality
squamous epithelium	UBERON:0006914	50.49	gold quality
upper arm skin	UBERON:0004263	50.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.56
E-MTAB-9801	yes	3.86

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CEBPB, CEBPD, CEBPG, NFKB, RBPJ

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), CEACAM3 (ENSG00000170956), PSG9 (ENSG00000183668), CEACAM19 (ENSG00000186567), HEPACAM2 (ENSG00000188175), PSG5 (ENSG00000204941), 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 6 — Q00889 (reviewed: Q00889)

Alternative names: Pregnancy-specific beta-1-glycoprotein 10, Pregnancy-specific beta-1-glycoprotein 12

All UniProt accessions (5): B5MCE1, Q00889, M0QXW0, M0QZA7, M0R314

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Similarity. Belongs to the immunoglobulin superfamily. CEA family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q00889-1	1	yes
Q00889-2	2

RefSeq proteins (2): NP_001027020, NP_002773 (=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 (38 total): sequence variant 15, glycosylation site 7, sequence conflict 5, domain 4, disulfide bond 3, signal peptide 1, chain 1, splice variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q00889-F1	85.55	0.69

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 (3): 168–216, 261–309, 353–393

Glycosylation sites (7): 198, 267, 302, 386, 61, 103, 110

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 47 (showing top): KOBAYASHI_EGFR_SIGNALING_24HR_UP, GOZGIT_ESR1_TARGETS_DN, WANG_LMO4_TARGETS_DN, GNF2_KISS1, GOBP_MULTI_MULTICELLULAR_ORGANISM_PROCESS, MULLIGHAN_NPM1_SIGNATURE_3_DN, MODULE_95, REACTOME_CELL_SURFACE_INTERACTIONS_AT_THE_VASCULAR_WALL, MODULE_112, DASU_IL6_SIGNALING_SCAR_DN, GNF2_TIMP2, MULLIGHAN_NPM1_MUTATED_SIGNATURE_1_DN, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, MODULE_163, ODONNELL_METASTASIS_UP

GO Biological Process (1): female pregnancy (GO:0007565)

GO Molecular Function (0):

GO Cellular Component (1): extracellular region (GO:0005576)

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
multi-organism reproductive process	1
multi-multicellular organism process	1
cellular anatomical structure	1

Protein interactions and networks

STRING

924 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PSG6	CSH1	P01243	788
PSG6	CSH1	P01243	781
PSG6	PAPPA	Q13219	647
PSG6	ALPP	P05187	494
PSG6	AFP	P02771	479
PSG6	PSG8	Q9UQ74	424
PSG6	LGALS1	P09382	419
PSG6	XAGE3	Q8WTP9	418
PSG6	ZNF574	Q6ZN55	405
PSG6	TFPI2	P48307	396
PSG6	BAIAP3	O94812	368
PSG6	SPAST	Q9UBP0	350
PSG6	CGB5	P01233	348
PSG6	ZNF526	Q8TF50	348
PSG6	ISM2	Q6H9L7	343

IntAct

7 interactions, top by confidence:

A	B	Type	Score
PSG3	MGRN1	psi-mi:“MI:0914”(association)	0.530
PSG8	MGRN1	psi-mi:“MI:0914”(association)	0.530
DSCAM	PSG6	psi-mi:“MI:0915”(physical association)	0.400
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350
TADA3	CYTH3	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): PSG6 (Affinity Capture-MS), PSG6 (Affinity Capture-MS), PSG6 (Negative Genetic)

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, A4FUY1, A6QQC6, A8MVW5, D3YXG0, D3ZB51, E9PZ19, O08775, P13595, P13596, P35968

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	102
Likely benign	15
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1128 predictions. Top by Δscore:

Variant	Effect	Δscore
19:42907055:C:A	donor_gain	1.0000
19:42907054:T:TA	donor_gain	0.9900
19:42907173:CCAT:C	acceptor_gain	0.9900
19:42907174:CATC:C	acceptor_gain	0.9900
19:42917723:CCTCA:C	donor_loss	0.9800
19:42917724:CTCA:C	donor_loss	0.9800
19:42917725:TCACC:T	donor_loss	0.9800
19:42917726:CA:C	donor_loss	0.9800
19:42917727:A:T	donor_loss	0.9800
19:42917728:C:G	donor_loss	0.9800
19:42907177:C:CC	acceptor_gain	0.9700
19:42916488:C:CC	acceptor_gain	0.9700
19:42907174:CAT:C	acceptor_gain	0.9600
19:42907176:TC:T	acceptor_loss	0.9600
19:42907178:T:G	acceptor_loss	0.9600
19:42916123:A:AC	donor_gain	0.9600
19:42916124:C:CC	donor_gain	0.9600
19:42907857:G:C	acceptor_gain	0.9500
19:42916486:TG:T	acceptor_gain	0.9500
19:42907037:T:TA	donor_gain	0.9400
19:42910578:A:AC	donor_gain	0.9400
19:42910579:C:CC	donor_gain	0.9400
19:42910859:C:CC	acceptor_gain	0.9400
19:42916484:GATG:G	acceptor_gain	0.9300
19:42907855:C:CC	acceptor_gain	0.9200
19:42916483:TGATG:T	acceptor_gain	0.9200
19:42907853:CG:C	acceptor_gain	0.9100
19:42903722:C:CC	acceptor_gain	0.9000
19:42907574:A:AC	donor_gain	0.9000
19:42907575:C:CC	donor_gain	0.9000

AlphaMissense

2736 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:42910751:A:G	W179R	0.971
19:42910751:A:T	W179R	0.971
19:42916353:A:G	W67R	0.965
19:42916353:A:T	W67R	0.965
19:42910605:A:C	S227R	0.964
19:42910605:A:T	S227R	0.964
19:42910607:T:G	S227R	0.964
19:42907635:C:G	C309S	0.963
19:42907636:A:T	C309S	0.963
19:42910749:C:A	W179C	0.963
19:42910749:C:G	W179C	0.963
19:42907069:A:G	W365R	0.962
19:42907069:A:T	W365R	0.962
19:42907067:C:A	W365C	0.961
19:42907067:C:G	W365C	0.961
19:42916235:A:G	L106P	0.952
19:42910646:A:C	Y214D	0.946
19:42910783:C:G	C168S	0.946
19:42910784:A:T	C168S	0.946
19:42910639:C:G	C216S	0.943
19:42910640:A:T	C216S	0.943
19:42916351:C:A	W67C	0.943
19:42916351:C:G	W67C	0.943
19:42910784:A:G	C168R	0.935
19:42906984:C:G	C393S	0.933
19:42906985:A:T	C393S	0.933
19:42907636:A:G	C309R	0.930
19:42910783:C:T	C168Y	0.930
19:42910782:A:C	C168W	0.925
19:42907105:A:G	C353R	0.924

dbSNP variants (sampled 300 via entrez): RS1000050337 (19:42914864 GAC>G), RS1000054311 (19:42903991 G>A), RS1000074232 (19:42907451 G>A,C,T), RS1000372095 (19:42913427 G>A,C), RS1000489751 (19:42913316 A>C), RS1000587533 (19:42915470 G>A,T), RS1000733722 (19:42910231 G>T), RS1000959556 (19:42915652 G>A,T), RS1001001814 (19:42918128 C>G), RS1001034338 (19:42917967 C>T), RS1001237818 (19:42904225 C>T), RS1001369929 (19:42904168 T>C), RS1001611546 (19:42913475 T>G), RS1001679288 (19:42907487 T>G), RS1001877236 (19:42904469 C>A,T)

Disease associations

OMIM: gene MIM:176395 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
bisphenol F	affects cotreatment, decreases methylation	1
urushiol	increases expression	1
2,4,6-tribromophenol	decreases expression	1
bufotalin	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
sulindac sulfide	decreases expression	1
potassium chromate(VI)	increases expression	1
avobenzone	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
monomethylarsonous acid	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	increases methylation	1
Copper	affects cotreatment, decreases expression	1
Doxorubicin	affects response to substance	1
Formaldehyde	increases expression	1
Lead	increases expression	1
Naled	affects expression	1
Silicon Dioxide	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Crocidolite	increases expression	1
beta-Naphthoflavone	decreases expression	1

Clinical trials (associated diseases)

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