PGRMC1

Summary

PGRMC1 (progesterone receptor membrane component 1, HGNC:16090) is a protein-coding gene on chromosome Xq24, encoding Membrane-associated progesterone receptor component 1 (O00264). Component of a progesterone-binding protein complex.

This gene encodes a putative membrane-associated progesterone steroid receptor. The protein is expressed predominantly in the liver and kidney.

Source: NCBI Gene 10857 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cataract (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 57 total — 1 pathogenic, 2 likely-pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006667

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16090
Approved symbol	PGRMC1
Name	progesterone receptor membrane component 1
Location	Xq24
Locus type	gene with protein product
Status	Approved
Aliases	HPR6.6
Ensembl gene	ENSG00000101856
Ensembl biotype	protein_coding
OMIM	300435
Entrez	10857

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000217971, ENST00000535419, ENST00000875291, ENST00000875292

RefSeq mRNA: 2 — MANE Select: NM_006667 NM_001282621, NM_006667

CCDS: CCDS14576, CCDS65313

Canonical transcript exons

ENST00000217971 — 3 exons

Exon	Start	End
ENSE00000675684	119240309	119240464
ENSE00001037750	119243151	119244466
ENSE00001455681	119236285	119236691

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 113.3504 / max 1069.3421, expressed in 1822 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197384	78.8258	1817
197385	30.1200	1809
197383	4.4046	1577

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
seminal vesicle	UBERON:0000998	99.36	gold quality
caput epididymis	UBERON:0004358	99.34	gold quality
adrenal tissue	UBERON:0018303	99.33	gold quality
corpus epididymis	UBERON:0004359	99.27	gold quality
cauda epididymis	UBERON:0004360	99.21	gold quality
bronchial epithelial cell	CL:0002328	99.19	gold quality
pons	UBERON:0000988	99.10	gold quality
endometrium	UBERON:0001295	99.06	gold quality
upper leg skin	UBERON:0004262	99.05	gold quality
middle temporal gyrus	UBERON:0002771	99.04	gold quality
substantia nigra pars compacta	UBERON:0001965	98.97	gold quality
jejunal mucosa	UBERON:0000399	98.96	gold quality
nephron tubule	UBERON:0001231	98.96	gold quality
germinal epithelium of ovary	UBERON:0001304	98.94	gold quality
subthalamic nucleus	UBERON:0001906	98.87	gold quality
superior vestibular nucleus	UBERON:0007227	98.86	gold quality
mammalian vulva	UBERON:0000997	98.84	gold quality
trigeminal ganglion	UBERON:0001675	98.84	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.76	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.75	gold quality
liver	UBERON:0002107	98.74	gold quality
right lobe of liver	UBERON:0001114	98.70	gold quality
left adrenal gland	UBERON:0001234	98.66	gold quality
hypothalamus	UBERON:0001898	98.66	gold quality
epithelium of bronchus	UBERON:0002031	98.60	gold quality
left adrenal gland cortex	UBERON:0035825	98.60	gold quality
adrenal cortex	UBERON:0001235	98.59	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.59	gold quality
spinal cord	UBERON:0002240	98.58	gold quality
monocyte	CL:0000576	98.57	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-GEOD-124472	yes	1642.45
E-MTAB-9154	yes	1563.32
E-MTAB-10287	yes	1163.95
E-HCAD-4	yes	37.59
E-CURD-122	yes	19.62
E-MTAB-9221	yes	18.27
E-MTAB-8142	yes	12.18
E-CURD-112	yes	8.48
E-HCAD-1	yes	5.06
E-GEOD-36552	no	370.00
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, NR1H3

miRNA regulators (miRDB)

93 targeting PGRMC1, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548AW	99.99	72.57	3559
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-507	99.97	70.11	1915
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 40)

• Hpr6.6 regulates cell death through a novel oxidative damage response pathway. (PMID:14523988)
• The expression of a novel progesterone-binding protein (hmPR2/PGMRC2) was investigated. Transcripts of this protein have been detected in human sperm. (PMID:15702432)
• Hpr6 homologues regulate cytochrome P450 proteins implicated in hormone, steroid and xenobiotic chemical metabolism; Hpr6 expression linked to cancer progression and cellular survival (PMID:15970648)
• Our findings support a model in which Hpr6 binds to heme and regulates susceptibility to damaging agents (PMID:16234411)
• These findings demonstrate that PGRMC1 is required for P450 activity and suggest that interindividual variation in PGRMC1 function may impact multiple biochemical pathways and drug metabolism. (PMID:17276356)
• PGRMC1 may be involved in sterol metabolism or homeostasis and cell survival [review] (PMID:18249431)
• PGRMC1 plays an important role in promoting ovarian cancer cell viability and that attenuating PGRMC1’s action makes the ovarian cancer cells more sensitive to cisplatin. (PMID:18319313)
• The aim of this study was to assess the expression, localization and hormonal regulation of two novel P(4) receptor candidates, P(4) receptor membrane component (PGRMC) 1 and PGRMC2, as well as the PGRMC1 partner Serpine 1 mRNA binding protein (SERBP1). (PMID:18440126)
• The results demonstrate the first demonstration of mPR expression in human epithelial ovarian tumors. (PMID:18479732)
• These findings suggest that mutant or reduced levels of PGMRC1 may cause premature ovarian failure through impaired activation of the microsomal cytochrome P450 and increased apoptosis of ovarian cells. (PMID:18782852)
• PGRMC1 is expressed in ER-negative mammary ductule basal epithelial cells. High levels of ER or PGRMC1 are mutually exclusive in individual cells. PGRMC1 phosphorylation may be involved in clinical differences among breast tumors of differing ER status. (PMID:18922159)
• In human GL cells PGRMC1 functions as a receptor through which P4 activates a signal cascade that prevents apoptosis. (PMID:19417032)
• PGRMC1 plays an essential role in the development and CDDP sensitivity of human ovarian tumors. (PMID:19797399)
• increases in vivo tumor growth, anchorage-independent growth, and migration (PMID:20164297)
• Reduced levels of PGRMC1 in peripheral leukocytes are associated with perturbed ovulatory function. (PMID:20537145)
• Pgrmc1 associates with epidermal growth factor receptor and regulates erlotinib sensitivity (PMID:20538600)
• we propose that PGRMC1 expression is regulated by the miRNAs let-7/miR-98 (PMID:21109987)
• PGRMC1 is lower in myometrium of women at term either not in labour (P = 0.004) or in labour (P = 0.005) compared with tissues from women in preterm non-labour. (PMID:21131300)
• roles of progesterone (P4) and Progesterone Receptor Membrane Component 1 (PGRMC1) in regulating mitosis of ovarian cancer cells, SKOV-3. P4’s actions appear to be dependent on PGRMC1’s function within the mitotic spindle. (PMID:21148105)
• Expression of PGRMC1 mRNAs was significantly lower in JEG-3 cells compared to non-syncytialized BeWo cells. (PMID:21455559)
• PGRMC1 negatively modulates the drug-metabolizing activities of P450. (PMID:21825115)
• Pgrmc1 localizes to secretory vesicles in cancer cells, and Pgrmc1 was secreted by lung cancer cells. Furthermore, Pgrmc1 was significantly elevated in the plasma of lung cancer patients compared to noncancer patients. (PMID:21918976)
• In patients with elevated PGRMC1 mRNA levels, gonadotropin-induced follicle development is attenuated, although sufficient numbers of follicles develop to allow for embryo and subsequent pregnancy. (PMID:22245528)
• miR-98 and miR-181a through their regulatory functions on PGRMC1, PGR, CYP19A1, TIMP3, and DDX3X expression may influence a wide range of endometrial cellular activities during normal menstrual cycle and transition into disease states. (PMID:22492871)
• The expression of PGRMC1 is strongly associated with the progression of breast cancer. (PMID:22588913)
• Data suggest that women with breast cells overexpressing PGRMC1 have higher risk of breast cancer when treated with progestins (as in some hormonal contraceptives). (PMID:23116217)
• ABHD5, PGRMC1 and SQS are novel markers for sebaceous carcinoma and can reliably distinguish sebaceous neoplasms from non-sebaceous tumors, specifically BCC with clear cell features. (PMID:23557589)
• PGRMC-1 expression is downregulated in the endometria from women with advanced stage endometriosis. (PMID:23793472)
• In a chorion cell line, PGRMC1 mediates the effects of progestins on matrix metalloproteinase 9 activity. (PMID:23813454)
• Reversely, in the HO-8910 cells treated with CDDP alone, levels of both PGRMC1 and PGR were increased while the level of PGRMC2 was decreased (PMID:23970345)
• PGRMC1 binds to key components of the autophagy machinery and is required for the degradative activity of autophagy (PMID:24113030)
• PGRMC1 can act as an adaptor protein for multiple classes of steroid receptors (PMID:24424068)
• PGRMC1 expression appears to be diminished in pregnant women with preterm premature rupture of the membranes. (PMID:24680695)
• coding mutations of PGRMC1 do not seem to be a common cause of the disease in Han Chinese (PMID:25246111)
• Demonstrate a change in myometriumPGRMC1 expression and changes in PGRMC1 and PGRMC2 cell localisation in association with parturition. (PMID:25266650)
• Loss of PGRMC1 expression is associated with endometrial tumor cell viability during chemotherapeutic stress. (PMID:25304370)
• PGRMC1 overexpression led to the epithelial-mesenchymal transition and chemoresistance in uterine sarcoma. (PMID:25596698)
• progesterone binds to hPGRMC1 and introduces spectral changes that manifest conformational changes to the heme. (PMID:25675345)
• results suggested that PGRMC1 and sigma2 receptors are two different molecular entities. (PMID:25843410)
• It can be suggested that women with breast epithelium highly expressing PGRMC1 and in interaction with ERalpha may have an increased risk to develop breast cancer. (PMID:26303031)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pgrmc1	ENSDARG00000054172
mus_musculus	Pgrmc1	ENSMUSG00000006373
rattus_norvegicus	Pgrmc1	ENSRNOG00000012786
drosophila_melanogaster	MSBP	FBGN0030703
drosophila_melanogaster	CG16957	FBGN0032519
caenorhabditis_elegans		WBGENE00006890

Paralogs (3): VMP1 (ENSG00000062716), PGRMC2 (ENSG00000164040), CYB5D2 (ENSG00000167740)

Protein

Protein identifiers

Membrane-associated progesterone receptor component 1 — O00264 (reviewed: O00264)

Alternative names: Dap1, IZA

All UniProt accessions (2): O00264, Q6IB11

UniProt curated annotations — full annotation on UniProt →

Function. Component of a progesterone-binding protein complex. Binds progesterone. Has many reported cellular functions (heme homeostasis, interaction with CYPs). Required for the maintenance of uterine histoarchitecture and normal female reproductive lifespan. Intracellular heme chaperone. Regulates heme synthesis via interactions with FECH and acts as a heme donor for at least some hemoproteins. Forms a ternary complex with TMEM97 receptor and low density lipid receptor/LDLR, which increases LDLR-mediated LDL lipoprotein internalization.

Subunit / interactions. Homodimer. Forms stable homodimer through hydrophobic heme-heme stacking interactions. Interacts with FECH; the interaction results in decreased FECH activity. Interacts with EGFR, CYP1A1 and CYP3A4; the interactions require PGRMC1 homodimerization. Interacts with TMEM97 and LDLR; the interaction increases LDL internalization. Forms a complex with TMEM97 and TSPO; the interaction occurs in MIA PaCa-2 cells but not in MCF7 cells.

Subcellular location. Microsome membrane. Smooth endoplasmic reticulum membrane. Mitochondrion outer membrane. Secreted.

Tissue specificity. Detected in urine (at protein level). Expressed by endometrial glands and stroma (at protein level). Widely expressed, with highest expression in liver and kidney.

Post-translational modifications. O-glycosylated; contains chondroitin sulfate attached to Ser-54. Ser-54 is in the cytoplasmic domain but the glycosylated form was detected in urine, suggesting that the membrane-bound form is cleaved, allowing for production of a secreted form which is glycosylated.

Domain organisation. The cytochrome b5 heme-binding domain lacks the conserved iron-binding His residues at positions 107 and 131.

Miscellaneous. Non-classical progesterone receptors involved in extranuclear signaling are classified in 2 groups: the class II progestin and adipoQ receptor (PAQR) family (also called mPRs) (PAQR5, PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like heme/steroid-binding protein family (also called MAPRs) (PGRMC1, PGRMC2, NENF and CYB5D2).

Similarity. Belongs to the cytochrome b5 family. MAPR subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
O00264-1	1	yes
O00264-2	2

RefSeq proteins (2): NP_001269550, NP_006658* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001199	Cyt_B5-like_heme/steroid-bd	Domain
IPR036400	Cyt_B5-like_heme/steroid_sf	Homologous_superfamily
IPR050577	MAPR/NEUFC/NENF-like	Family

Pfam: PF00173

UniProt features (26 total): helix 8, modified residue 4, strand 4, topological domain 2, region of interest 2, chain 1, splice variant 1, mutagenesis site 1, transmembrane region 1, domain 1, binding site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4X8Y	X-RAY DIFFRACTION	1.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00264-F1	84.74	0.65

Functional residue map

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

Ligand- & substrate-binding residues (1): 113 (axial binding residue)

Post-translational modifications (4): 74, 181, 54, 57

Mutagenesis-validated functional residues (1):

Position	Phenotype
113	abolishes interaction with cyp1a1 and cyp3a4.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 271 (showing top): GOBP_MEMORY, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_COGNITION, GOBP_BEHAVIOR, GOCC_SECRETORY_GRANULE, GOBP_ASSOCIATIVE_LEARNING, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_NEUROGENESIS, GOBP_TETRAPYRROLE_BIOSYNTHETIC_PROCESS, MORF_PSMC2, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION

GO Biological Process (8): heme biosynthetic process (GO:0006783), axon guidance (GO:0007411), memory (GO:0007613), associative learning (GO:0008306), modification of synaptic structure (GO:0099563), positive regulation of lipoprotein transport (GO:0140077), positive regulation of protein localization to plasma membrane (GO:1903078), negative regulation of synapse organization (GO:1905809)

GO Molecular Function (7): amyloid-beta binding (GO:0001540), steroid binding (GO:0005496), heme binding (GO:0020037), protein homodimerization activity (GO:0042803), metal ion binding (GO:0046872), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (14): extracellular region (GO:0005576), mitochondrial outer membrane (GO:0005741), endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), endomembrane system (GO:0012505), membrane (GO:0016020), smooth endoplasmic reticulum membrane (GO:0030868), specific granule membrane (GO:0035579), neuron projection (GO:0043005), neuronal cell body (GO:0043025), cell body (GO:0044297), synapse (GO:0045202), mitochondrion (GO:0005739), endoplasmic reticulum membrane (GO:0005789)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
synapse organization	2
binding	2
cytoplasm	2
intracellular membrane-bounded organelle	2
porphyrin-containing compound biosynthetic process	1
heme metabolic process	1
pigment biosynthetic process	1
axonogenesis	1
neuron projection guidance	1
learning or memory	1
learning	1
lipoprotein transport	1
positive regulation of protein transport	1
regulation of lipoprotein transport	1
protein localization to plasma membrane	1
regulation of protein localization to plasma membrane	1
positive regulation of protein localization to cell periphery	1
positive regulation of protein localization to membrane	1
regulation of synapse organization	1
negative regulation of cellular component organization	1
peptide binding	1
lipid binding	1
tetrapyrrole binding	1
identical protein binding	1
protein dimerization activity	1
cation binding	1
mitochondrial membrane	1
organelle outer membrane	1
endomembrane system	1
membrane	1
cell periphery	1
vacuole	1
plasma membrane	1
endoplasmic reticulum membrane	1
smooth endoplasmic reticulum	1
bounding membrane of organelle	1
secretory granule membrane	1
specific granule	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

1636 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PGRMC1	TMEM97	Q5BJF2	985
PGRMC1	PGR	P06401	944
PGRMC1	INSIG1	O15503	934
PGRMC1	SERBP1	Q8NC51	901
PGRMC1	FECH	P22830	895
PGRMC1	PAQR7	Q86WK9	882
PGRMC1	PAQR8	Q8TEZ7	853
PGRMC1	CYP51A1	Q16850	784
PGRMC1	PAQR5	Q9NXK6	783
PGRMC1	EGFR	P00533	743
PGRMC1	CYB5B	O43169	718
PGRMC1	CYB5A	P00167	713
PGRMC1	PAQR6	Q6TCH4	695
PGRMC1	PAQR9	Q6ZVX9	641
PGRMC1	SIGMAR1	Q99720	627

IntAct

276 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
FECH	PGRMC1	psi-mi:“MI:0915”(physical association)	0.700
FECH	PGRMC1	psi-mi:“MI:0414”(enzymatic reaction)	0.700
B3GNT3	PGRMC1	psi-mi:“MI:0914”(association)	0.670
PGRMC1	PGRMC2	psi-mi:“MI:0915”(physical association)	0.670
BNIP1	NBAS	psi-mi:“MI:0914”(association)	0.640
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
DHCR24	PGRMC1	psi-mi:“MI:0915”(physical association)	0.560
PGRMC1		psi-mi:“MI:0915”(physical association)	0.560
PGRMC1	EVI2B	psi-mi:“MI:0915”(physical association)	0.560
PGRMC1	CCDC134	psi-mi:“MI:0915”(physical association)	0.560
PGRMC1	KASH5	psi-mi:“MI:0915”(physical association)	0.560
PGRMC1	CIAO1	psi-mi:“MI:0915”(physical association)	0.560
PGRMC1	GET3	psi-mi:“MI:0915”(physical association)	0.560
PGRMC1	CAMLG	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (564): PGRMC1 (Affinity Capture-MS), CREB3L1 (Two-hybrid), PGRMC1 (Affinity Capture-MS), PGRMC1 (Affinity Capture-MS), ATL3 (Co-fractionation), PGRMC1 (Two-hybrid), ITGB1BP1 (Affinity Capture-Luminescence), PGRMC1 (Affinity Capture-MS), PGRMC1 (Proximity Label-MS), PGRMC1 (Affinity Capture-MS), PGRMC1 (Affinity Capture-MS), PGRMC1 (Affinity Capture-MS), PGRMC1 (Affinity Capture-MS), PGRMC1 (Affinity Capture-MS), PGRMC1 (Affinity Capture-MS)

ESM2 similar proteins: A1ZAX1, A2CES0, A6IPG1, B0W0S3, B3MIF1, B3NML0, B4GIB1, B4HMY3, B4J789, B4KN00, B4LNA1, B4P562, B5ME19, O00264, O13995, O15173, O55022, O70251, O96005, P11035, P16081, P24534, P27967, P27969, P29412, P34826, P70580, Q0ZB76, Q17Q06, Q17QC0, Q1JQA5, Q28Z41, Q2NL17, Q3SYW6, Q5E983, Q5RAT8, Q5RED0, Q5XIU9, Q5ZKN2, Q6DET9

Diamond homologs: A2CES0, O00264, O13995, O15173, O55022, P70580, Q12091, Q17QC0, Q1JQA5, Q28FI8, Q29HF1, Q2HIW2, Q5RED0, Q5SSH8, Q5XIU9, Q5ZKN2, Q60YT6, Q6AY62, Q6IUR5, Q80UU9, Q8WUJ1, Q95250, Q9CQ45, Q9FVZ7, Q9FVZ9, Q9M2Z4, Q9SK39, Q9UMX5, Q9W376, Q9XFM6, Q9XXA7, Q7YZW5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 145 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
PD-L1(CD274) glycosylation and translocation to plasma membrane	7	36.3×	2e-07
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	7	23.5×	3e-06
Maturation of spike protein	7	18.6×	1e-05
Maturation of DENV proteins	7	14.8×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
tail-anchored membrane protein insertion into ER membrane	5	36.0×	1e-04
obsolete protein N-linked glycosylation via asparagine	6	31.1×	3e-05
protein N-linked glycosylation	7	14.2×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	34
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
988887	NC_000023.10:g.118373226_118500408del	Pathogenic
1256016	NM_006667.5(PGRMC1):c.418G>C (p.Asp140His)	Likely pathogenic
1256018	NM_006667.5(PGRMC1):c.272T>C (p.Met91Thr)	Likely pathogenic

SpliceAI

362 predictions. Top by Δscore:

Variant	Effect	Δscore
X:119236687:GCCCG:G	donor_gain	1.0000
X:119236690:CGG:C	donor_loss	1.0000
X:119236691:GGTAC:G	donor_loss	1.0000
X:119236692:G:C	donor_loss	1.0000
X:119236692:G:GG	donor_gain	1.0000
X:119236693:T:A	donor_loss	1.0000
X:119240304:T:A	acceptor_gain	1.0000
X:119240304:TGAA:T	acceptor_loss	1.0000
X:119240305:GAA:G	acceptor_loss	1.0000
X:119240306:AAGA:A	acceptor_loss	1.0000
X:119240307:A:AG	acceptor_gain	1.0000
X:119240307:A:AT	acceptor_loss	1.0000
X:119240307:AGAG:A	acceptor_gain	1.0000
X:119240307:AGAGG:A	acceptor_gain	1.0000
X:119240308:G:GC	acceptor_gain	1.0000
X:119240308:GA:G	acceptor_gain	1.0000
X:119240308:GAGG:G	acceptor_gain	1.0000
X:119240308:GAGGG:G	acceptor_gain	1.0000
X:119240389:GA:G	donor_gain	1.0000
X:119240448:G:GT	donor_gain	1.0000
X:119240448:G:T	donor_gain	1.0000
X:119240462:CTT:C	donor_gain	1.0000
X:119240463:TT:T	donor_gain	1.0000
X:119240465:G:GG	donor_gain	1.0000
X:119243143:A:AG	acceptor_gain	1.0000
X:119243144:C:G	acceptor_gain	1.0000
X:119243146:TCCA:T	acceptor_loss	1.0000
X:119243147:CCAG:C	acceptor_loss	1.0000
X:119243148:CA:C	acceptor_loss	1.0000
X:119243149:A:AG	acceptor_gain	1.0000

AlphaMissense

1277 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:119236596:T:C	L78P	1.000
X:119236632:T:C	L90P	1.000
X:119236637:G:C	A92P	1.000
X:119236655:T:C	F98L	1.000
X:119236656:T:C	F98S	1.000
X:119236657:C:A	F98L	1.000
X:119236657:C:G	F98L	1.000
X:119236665:C:T	T101I	1.000
X:119236679:T:C	F106L	1.000
X:119236681:C:A	F106L	1.000
X:119236681:C:G	F106L	1.000
X:119240317:T:C	Y113H	1.000
X:119240327:T:C	F116S	1.000
X:119240330:C:A	A117D	1.000
X:119240333:G:A	G118E	1.000
X:119240333:G:T	G118V	1.000
X:119240342:C:A	A121E	1.000
X:119240345:C:A	S122Y	1.000
X:119240345:C:T	S122F	1.000
X:119240348:G:C	R123T	1.000
X:119240348:G:T	R123M	1.000
X:119240349:G:C	R123S	1.000
X:119240349:G:T	R123S	1.000
X:119240354:T:A	L125H	1.000
X:119240354:T:C	L125P	1.000
X:119240356:G:C	A126P	1.000
X:119240357:C:A	A126D	1.000
X:119240362:T:C	F128L	1.000
X:119240364:T:A	F128L	1.000
X:119240364:T:G	F128L	1.000

dbSNP variants (sampled 300 via entrez): RS1000130913 (X:119244690 A>G), RS1001402611 (X:119236565 C>T), RS1001656160 (X:119242011 T>C), RS1001706050 (X:119241313 C>G), RS1002008841 (X:119234295 T>A), RS1002260483 (X:119244583 A>G), RS1003198259 (X:119235507 A>C,G), RS1003230891 (X:119235122 GGAGT>G), RS1003459126 (X:119239130 A>G), RS1003529615 (X:119239710 A>G), RS1004184238 (X:119235647 C>T), RS1004227575 (X:119243908 A>G), RS1004464198 (X:119236895 C>T), RS1004515669 (X:119237279 G>T), RS1005501712 (X:119235034 C>A)

Disease associations

OMIM: gene MIM:300435 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
cataract	Moderate	X-linked
primary ovarian failure	Limited	Autosomal dominant

Mondo (3): congenital portosystemic shunt (MONDO:0018811), cataract (MONDO:0005129), primary ovarian failure (MONDO:0005387)

Orphanet (2): Rare genetic premature ovarian failure (Orphanet:485382), Congenital portosystemic shunt (Orphanet:480531)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012335_9	Hodgkin’s lymphoma	9.000000e-12

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D002386	Cataract	C11.510.245
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105706 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 4,624 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL3301612	ENCORAFENIB	4	4,624

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 5 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.69	Kd	204	nM	ENCORAFENIB
6.19	Kd	651.4	nM	CHEMBL3752910
6.19	ED50	651.4	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 183 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
Encorafenib	1425109: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.2040	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148992: Binding affinity to human PGRMC1 incubated for 45 mins by Kinobead based pull down assay	kd	0.6514	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	5
bisphenol A	affects expression, decreases expression	3
Air Pollutants	decreases expression, increases abundance	2
Doxorubicin	decreases expression, affects response to substance	2
Valproic Acid	affects expression, decreases methylation	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
testosterone enanthate	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
titanium dioxide	increases expression	1
arsenite	affects binding, increases reaction	1
afimoxifene	increases expression	1
cobaltous chloride	increases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
cetrorelix	affects cotreatment, decreases expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
picoxystrobin	increases expression	1
bisphenol AF	increases expression	1
Gefitinib	decreases response to substance	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Arsenic	increases abundance, increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991822	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1PR	Abcam K-562 PGRMC1 KO	Cancer cell line	Female
CVCL_D2LC	Abcam Raji PGRMC1 KO	Cancer cell line	Male
CVCL_WQ27	Abcam Jurkat PGRMC1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00273221	PHASE4	UNKNOWN	Combined Phacotube vs Phacotrabeculectomy:A Randomized Controlled Trial
NCT00312299	PHASE4	COMPLETED	Posterior Capsule Opacification Study
NCT00345046	PHASE4	COMPLETED	A Comparison of Three Different Formulations of Prednisolone Acetate 1%
NCT00347243	PHASE4	COMPLETED	Wavefront Analisys and Contrast Sensitivity of Spherical and Aspherical Intraocular Lenses
NCT00347503	PHASE4	COMPLETED	Aqueous Concentrations and PGE2 Inhibition of Ketorolac 0.4% vs. Bromfenac 0.09% in Cataract Patients
NCT00348244	PHASE4	COMPLETED	Ketorolac vs. Steroid in the Prevention of CME
NCT00348270	PHASE4	COMPLETED	Comparison of the Quality of Vision Provided by AMO Tecnis Z9000 and Alcon Laboratories MA60 Acrysof Posterior Chamber Intraocular Lenses
NCT00348582	PHASE4	COMPLETED	Acular LS vs. Nevanac in Post op Inflammation Following Cataract Surgery
NCT00348621	PHASE4	COMPLETED	A Study of Interventions to Reduce Disability From Visual Loss in Nursing Home Residents
NCT00349583	PHASE4	COMPLETED	Efficacy of Topical Cyclosporine Versus Tears for Improving Visual Outcomes Following Multifocal IOL Implantation
NCT00355446	PHASE4	COMPLETED	Bioavailability of Bimatoprost Ophthalmic Solution in Human Aqueous.
NCT00386438	PHASE4	COMPLETED	Efficacy of Honan Balloon in Intraocular Pressure Reduction Before Phacoemulsification
NCT00392275	PHASE4	COMPLETED	Penetrance of Third Generation Fluoroquinolones in Eyes With Functioning Filtering Blebs
NCT00428363	PHASE4	COMPLETED	Effect of Optic Edge Design in a Silicone Intraocular Lens on Posterior Capsule Opacification
NCT00449267	PHASE4	COMPLETED	Aurolab Hydrophobic Foldable Intraocular Lens Study
NCT00459303	PHASE4	COMPLETED	Comparison of Functional Vision Provided by AMO Tecnis Z9000 and Alcon SA60AT Acrysof
NCT00469690	PHASE4	COMPLETED	Aqueous Concentrations and PGE2 Inhibition of Ketorolac 0.4% vs. Bromfenac 0.09% in Cataract Patients: Trough Drug Effects
NCT00576485	PHASE4	COMPLETED	Spherical Aberration and Contrast Sensitivity in IOLs
NCT00612729	PHASE4	COMPLETED	Light Filters in Intraocular Lenses (IOLs) and Its Influence on Colour and Contrast Vision.
NCT00612781	PHASE4	COMPLETED	Yellow Versus White Study
NCT00630019	PHASE4	COMPLETED	Ocular Tissue Levels of 1.5% Levofloxacin Ophthalmic Solution Compared to an Active Comparator
NCT00673803	PHASE4	COMPLETED	Influence of Two Different Preloaded Intraocular Lens (IOLs) on Posterior Capsule Opacification
NCT00684138	PHASE4	COMPLETED	ACRYSOF® ReSTOR® Aspheric +3.0 D Add Power Intraocular Lens (IOL)
NCT00698724	PHASE4	COMPLETED	Comparing Optical Coherence Tomography (OCT) and Visual Acuity Outcomes in Subjects Undergoing Cataract Surgery, Who Receive Xibrom Ophthalmic Solution and Standard Presurgical Care vs. Xibrom Ophthalmic Solution Plus Prednisolone Acetate 1% and Standard Presurgical Care
NCT00710905	PHASE4	TERMINATED	Visual Function With Contralateral AcrySof® ReSTOR® Aspheric SN6AD1 and SN6AD3
NCT00710931	PHASE4	COMPLETED	Visual Function With Bilateral AcrySof® ReSTOR® Aspheric SN6AD1
NCT00711347	PHASE4	COMPLETED	Intraoperative Floppy Iris Syndrome
NCT00712244	PHASE4	COMPLETED	DisCoVisc Versus DuoVisc, Healon5 and AmVisc Plus
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00719732	PHASE4	COMPLETED	Visual Function After Implantation of Bilateral AcrySof ReSTOR Aspheric +3
NCT00721253	PHASE4	COMPLETED	Visual Outcomes of Subjects Bilaterally Implanted With ReSTOR Aspheric +4 vs. Tecnis or Acri.LISA
NCT00731640	PHASE4	COMPLETED	Contralateral ReSTOR / Monofocal or Phakic Eye
NCT00732030	PHASE4	COMPLETED	Low Cylinder Toric
NCT00758199	PHASE4	COMPLETED	Determination of Optimum Duration of Treatment With Bromfenac (Xibrom) Eyedrops Following Cataract Surgery
NCT00760058	PHASE4	WITHDRAWN	Visual Outcome and Visual Quality After Bilateral Implantation of the AcrySof® IQ IOL Compared to MI60® and Tecnis® IOL
NCT00760487	PHASE4	COMPLETED	Visual Function After Implantation of Bilateral AcrySof® Toric Natural Intraocular Lens
NCT00761488	PHASE4	WITHDRAWN	Recommendations for Monitoring Clinical Experience Following Implantation of the AcrySof® Toric
NCT00763360	PHASE4	COMPLETED	To Compare the Ability of DiscoVisc® OVD to Protect the Corneal Endothelium and Maintain Anterior Chamber Space With Healon® and Amvisc® PLUS During Cataract Surgery.
NCT00786370	PHASE4	COMPLETED	Dexmedetomidine vs. Propofol for Cataract Surgery
NCT00786565	PHASE4	COMPLETED	Clinical Evaluation of a New Aspheric Intraocular Lens.