PGRMC2

Summary

PGRMC2 (progesterone receptor membrane component 2, HGNC:16089) is a protein-coding gene on chromosome 4q28.2, encoding Membrane-associated progesterone receptor component 2 (O15173). Required for the maintenance of uterine histoarchitecture and normal female reproductive lifespan.

Enables heme binding activity. Involved in adipose tissue development. Located in endoplasmic reticulum and nuclear envelope.

Source: NCBI Gene 10424 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 28 total
• Druggable target: yes
• MANE Select transcript: NM_006320

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16089
Approved symbol	PGRMC2
Name	progesterone receptor membrane component 2
Location	4q28.2
Locus type	gene with protein product
Status	Approved
Aliases	PMBP, DG6
Ensembl gene	ENSG00000164040
Ensembl biotype	protein_coding
OMIM	607735
Entrez	10424

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 nonsense_mediated_decay

ENST00000296425, ENST00000394276, ENST00000503588, ENST00000503872, ENST00000509070, ENST00000512483, ENST00000520121, ENST00000613358

RefSeq mRNA: 1 — MANE Select: NM_006320 NM_006320

CCDS: CCDS3739

Canonical transcript exons

ENST00000296425 — 3 exons

Exon	Start	End
ENSE00001418898	128269242	128271413
ENSE00002296546	128287373	128287813
ENSE00003700954	128272362	128272517

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 98.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 65.3158 / max 541.6656, expressed in 1820 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53907	57.8274	1819
53906	2.8077	833
53905	2.4542	1217
53909	0.6852	389
53908	0.5973	340
53904	0.3316	129
53910	0.3135	46
53902	0.1340	59
53911	0.0906	29
53903	0.0743	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	98.49	gold quality
islet of Langerhans	UBERON:0000006	97.89	gold quality
stromal cell of endometrium	CL:0002255	97.42	gold quality
colonic epithelium	UBERON:0000397	97.19	gold quality
skin of abdomen	UBERON:0001416	97.14	gold quality
upper arm skin	UBERON:0004263	97.09	gold quality
zone of skin	UBERON:0000014	97.01	gold quality
skin of leg	UBERON:0001511	96.97	gold quality
adipose tissue	UBERON:0001013	96.96	gold quality
rectum	UBERON:0001052	96.77	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.71	gold quality
omental fat pad	UBERON:0010414	96.67	gold quality
peritoneum	UBERON:0002358	96.65	gold quality
connective tissue	UBERON:0002384	96.61	gold quality
pancreas	UBERON:0001264	96.49	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.47	gold quality
mucosa of stomach	UBERON:0001199	96.42	gold quality
thoracic mammary gland	UBERON:0005200	96.29	gold quality
body of pancreas	UBERON:0001150	96.28	gold quality
gall bladder	UBERON:0002110	96.28	gold quality
mammary gland	UBERON:0001911	96.27	gold quality
jejunum	UBERON:0002115	96.17	gold quality
upper leg skin	UBERON:0004262	96.11	gold quality
descending thoracic aorta	UBERON:0002345	96.06	gold quality
popliteal artery	UBERON:0002250	95.99	gold quality
tibial artery	UBERON:0007610	95.99	gold quality
mammalian vulva	UBERON:0000997	95.97	gold quality
duodenum	UBERON:0002114	95.93	gold quality
penis	UBERON:0000989	95.91	gold quality
synovial joint	UBERON:0002217	95.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8559	yes	433.24
E-ANND-3	yes	9.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

197 targeting PGRMC2, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-513B-5P	99.99	69.96	2150
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-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 12)

• The expression of a novel progesterone-binding protein (hmPR1/PGMRC1) was investigated. Transcripts of this protein have been detected in human sperm. (PMID:15702432)
• PGRMC2 inhibits migration of SKOV-3 ovarian cancer cells in vitro. (PMID:23064006)
• It deserves further examination as data point to a role of PGRMC2 as tumor suppressor, migration inhibitor and regulator of cytochrome P450 proteins. (PMID:23276631)
• In secretory phase endometrium from women with advanced stage endometriosis, PGRMC-2 expression is downregulated. (PMID:23793472)
• 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)
• Demonstrate a change in myometriumPGRMC1 expression and changes in PGRMC1 and PGRMC2 cell localisation in association with parturition. (PMID:25266650)
• show that progesterone receptor membrane component 2 (PGRMC2) is required for delivery of labile, or signalling haem, to the nucleus (PMID:31748741)
• Results found PGRMC2 to be targeted by miR-3687. Further data indicate that PGRMC2 mRNA expression in oesophageal squamous cell carcinoma (ESCC) may be related to cell proliferation and local progression. (PMID:31810911)
• The role of progesterone receptor membrane component (PGRMC) in the endometrium. (PMID:35526781)
• Progesterone receptor membrane component 2 is critical for human placental extravillous trophoblast invasion. (PMID:37665239)
• Deciphering the role of PGRMC2 in the human endometrium during the menstrual cycle and in vitro decidualization using an in vitro approach. (PMID:38452349)
• PGRMC2 and HLA-G regulate immune homeostasis in a microphysiological model of human maternal-fetal membrane interface. (PMID:39179795)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pgrmc2	ENSDARG00000030237
mus_musculus	Pgrmc2	ENSMUSG00000049940
rattus_norvegicus	Pgrmc2	ENSRNOG00000014051
drosophila_melanogaster	MSBP	FBGN0030703
drosophila_melanogaster	CG16957	FBGN0032519
caenorhabditis_elegans		WBGENE00006890

Paralogs (3): VMP1 (ENSG00000062716), PGRMC1 (ENSG00000101856), CYB5D2 (ENSG00000167740)

Protein

Protein identifiers

Membrane-associated progesterone receptor component 2 — O15173 (reviewed: O15173)

Alternative names: Progesterone membrane-binding protein, Steroid receptor protein DG6

All UniProt accessions (4): O15173, U3KPU8, U3KQ70, U3KQM0

UniProt curated annotations — full annotation on UniProt →

Function. Required for the maintenance of uterine histoarchitecture and normal female reproductive lifespan. May serve as a universal non-classical progesterone receptor in the uterus. Intracellular heme chaperone required for delivery of labile, or signaling heme, to the nucleus. Plays a role in adipocyte function and systemic glucose homeostasis. In brown fat, which has a high demand for heme, delivery of labile heme in the nucleus regulates the activity of heme-responsive transcriptional repressors such as NR1D1 and BACH1.

Subunit / interactions. Interacts with PGRMC1. Interacts with AAAS.

Subcellular location. Membrane. Nucleus envelope. Endoplasmic reticulum. Secreted.

Tissue specificity. Expressed by endometrial glands and stroma (at protein level). Detected in urine (at protein level).

Domain organisation. The cytochrome b5 heme-binding domain lacks the conserved iron-binding His residues at positions 137 and 161.

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?
O15173-1	1	yes
O15173-2	2

RefSeq proteins (1): NP_006311* (*=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 (14 total): modified residue 5, region of interest 2, compositionally biased region 2, chain 1, transmembrane region 1, glycosylation site 1, splice variant 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15173-F1	79.83	0.58

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 (5): 210, 211, 90, 104, 208

Glycosylation sites (1): 15

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013405	RHOD GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9707616	Heme signaling

MSigDB gene sets: 259 (showing top): RNGTGGGC_UNKNOWN, HORIUCHI_WTAP_TARGETS_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_IRON_COORDINATION_ENTITY_TRANSPORT, GOBP_TRANSITION_METAL_ION_TRANSPORT, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_IRON_ION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GTGCCTT_MIR506, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS

GO Biological Process (3): adipose tissue development (GO:0060612), heme transport (GO:0015886), nuclear receptor-mediated steroid hormone signaling pathway (GO:0030518)

GO Molecular Function (6): nuclear steroid receptor activity (GO:0003707), steroid binding (GO:0005496), heme transmembrane transporter activity (GO:0015232), heme binding (GO:0020037), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (9): extracellular region (GO:0005576), nuclear envelope (GO:0005635), nucleoplasm (GO:0005654), endoplasmic reticulum (GO:0005783), endomembrane system (GO:0012505), membrane (GO:0016020), glutamatergic synapse (GO:0098978), nucleus (GO:0005634), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RHO GTPase cycle	5
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
binding	2
endomembrane system	2
intracellular membrane-bounded organelle	2
animal organ development	1
connective tissue development	1
nitrogen compound transport	1
iron coordination entity transport	1
steroid hormone receptor signaling pathway	1
nuclear receptor-mediated signaling pathway	1
nuclear receptor activity	1
nuclear receptor-mediated steroid hormone signaling pathway	1
lipid binding	1
heme transport	1
transmembrane transporter activity	1
tetrapyrrole binding	1
nucleus	1
organelle envelope	1
nuclear lumen	1
cytoplasm	1
vacuole	1
plasma membrane	1
synapse	1
cell junction	1

Protein interactions and networks

STRING

968 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PGRMC2	PGR	P06401	872
PGRMC2	PAQR8	Q8TEZ7	839
PGRMC2	PAQR7	Q86WK9	820
PGRMC2	PAQR5	Q9NXK6	809
PGRMC2	AAAS	Q9NRG9	755
PGRMC2	PAQR6	Q6TCH4	670
PGRMC2	CYB5B	O43169	662
PGRMC2	CYB5A	P00167	656
PGRMC2	FECH	P22830	619
PGRMC2	PAQR9	Q6ZVX9	607
PGRMC2	LARP1B	Q659C4	545
PGRMC2	GPER1	Q99527	532
PGRMC2	SERBP1	Q8NC51	523
PGRMC2	PGRMC1	O00264	520
PGRMC2	A0A0J9YW77	A0A0J9YW77	505

IntAct

331 interactions, top by confidence:

A	B	Type	Score
ITPRIP	PGRMC2	psi-mi:“MI:0915”(physical association)	0.670
PGRMC2	VAPA	psi-mi:“MI:0915”(physical association)	0.670
PGRMC2	ITPRIP	psi-mi:“MI:0915”(physical association)	0.670
PGRMC1	PGRMC2	psi-mi:“MI:0915”(physical association)	0.670
GID8	PGRMC2	psi-mi:“MI:0914”(association)	0.640
PGRMC2	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.590
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
	PGRMC2	psi-mi:“MI:0915”(physical association)	0.560
RNF8	PGRMC2	psi-mi:“MI:0915”(physical association)	0.560
PEX16	PGRMC2	psi-mi:“MI:0915”(physical association)	0.560
FA2H	PGRMC2	psi-mi:“MI:0915”(physical association)	0.560
STX3	PGRMC2	psi-mi:“MI:0915”(physical association)	0.560
TMEM19	PGRMC2	psi-mi:“MI:0915”(physical association)	0.560
UBXN8	PGRMC2	psi-mi:“MI:0915”(physical association)	0.560
TMEM86B	PGRMC2	psi-mi:“MI:0915”(physical association)	0.560
PGRMC2	BAG4	psi-mi:“MI:0915”(physical association)	0.560
PGRMC2	AQP10	psi-mi:“MI:0915”(physical association)	0.560
PGRMC2	FA2H	psi-mi:“MI:0915”(physical association)	0.560
PGRMC2	SFXN1	psi-mi:“MI:0915”(physical association)	0.560
PGRMC2	STX3	psi-mi:“MI:0915”(physical association)	0.560
PGRMC2	RUSF1	psi-mi:“MI:0915”(physical association)	0.560
PGRMC2	TMEM86A	psi-mi:“MI:0915”(physical association)	0.560
PEDS1-UBE2V1	PGRMC2	psi-mi:“MI:0915”(physical association)	0.560
PGRMC2	TMEM107	psi-mi:“MI:0915”(physical association)	0.560
PGRMC2	PMP22	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (387): PGRMC2 (Affinity Capture-MS), PGRMC2 (Affinity Capture-MS), PGRMC2 (Affinity Capture-MS), PGRMC2 (Affinity Capture-MS), PGRMC2 (Affinity Capture-MS), PGRMC2 (Proximity Label-MS), PGRMC2 (Proximity Label-MS), PGRMC2 (Proximity Label-MS), PGRMC2 (Proximity Label-MS), PGRMC2 (Proximity Label-MS), PGRMC2 (Proximity Label-MS), PGRMC2 (Proximity Label-MS), PGRMC2 (Proximity Label-MS), PGRMC2 (Proximity Label-MS), PGRMC2 (Proximity Label-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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

599 predictions. Top by Δscore:

Variant	Effect	Δscore
4:128271409:TTTTT:T	acceptor_gain	1.0000
4:128271410:TTTT:T	acceptor_gain	1.0000
4:128271411:TTT:T	acceptor_gain	1.0000
4:128271412:TT:T	acceptor_gain	1.0000
4:128272357:AATAC:A	donor_loss	1.0000
4:128272358:ATAC:A	donor_loss	1.0000
4:128272359:TA:T	donor_loss	1.0000
4:128272363:TTTAA:T	donor_gain	1.0000
4:128272394:T:A	donor_gain	1.0000
4:128272513:ACCCG:A	acceptor_gain	1.0000
4:128272514:CCCG:C	acceptor_gain	1.0000
4:128272514:CCCGC:C	acceptor_gain	1.0000
4:128272515:CCG:C	acceptor_gain	1.0000
4:128272515:CCGC:C	acceptor_gain	1.0000
4:128272516:CG:C	acceptor_gain	1.0000
4:128272516:CGC:C	acceptor_gain	1.0000
4:128272517:GC:G	acceptor_loss	1.0000
4:128272518:C:CC	acceptor_gain	1.0000
4:128271411:TTTC:T	acceptor_loss	0.9900
4:128271412:TTCTG:T	acceptor_loss	0.9900
4:128271413:TCTGA:T	acceptor_loss	0.9900
4:128271414:C:A	acceptor_loss	0.9900
4:128271414:C:CC	acceptor_gain	0.9900
4:128271427:C:CT	acceptor_gain	0.9900
4:128272360:A:AC	donor_gain	0.9900
4:128272361:C:CC	donor_gain	0.9900
4:128272516:C:T	acceptor_gain	0.9900
4:128287392:G:GA	donor_gain	0.9900
4:128287415:T:A	donor_gain	0.9900
4:128288021:T:TA	donor_gain	0.9900

AlphaMissense

1438 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:128271360:A:G	Y210H	1.000
4:128271389:A:G	L200P	1.000
4:128271395:C:A	G198V	1.000
4:128271395:C:T	G198D	1.000
4:128271396:C:A	G198C	1.000
4:128271396:C:G	G198R	1.000
4:128271407:T:C	Y194C	1.000
4:128271408:A:C	Y194D	1.000
4:128271408:A:G	Y194H	1.000
4:128272366:A:C	F190L	1.000
4:128272366:A:T	F190L	1.000
4:128272367:A:C	F190C	1.000
4:128272367:A:G	F190S	1.000
4:128272368:A:G	F190L	1.000
4:128272378:C:A	W186C	1.000
4:128272378:C:G	W186C	1.000
4:128272379:C:A	W186L	1.000
4:128272379:C:G	W186S	1.000
4:128272380:A:G	W186R	1.000
4:128272380:A:T	W186R	1.000
4:128272385:C:G	R184P	1.000
4:128272388:A:T	V183D	1.000
4:128272412:A:C	L175W	1.000
4:128272412:A:G	L175S	1.000
4:128272462:A:C	F158L	1.000
4:128272462:A:T	F158L	1.000
4:128272464:A:G	F158L	1.000
4:128272464:A:T	F158I	1.000
4:128272469:G:T	A156D	1.000
4:128272470:C:G	A156P	1.000

dbSNP variants (sampled 300 via entrez): RS1000068824 (4:128278800 T>G), RS1000069955 (4:128281080 T>G), RS1000098126 (4:128276466 G>A), RS1000126285 (4:128276740 A>G), RS1000248085 (4:128269571 T>A), RS1000301797 (4:128279438 C>A,G), RS1000440529 (4:128271854 T>A), RS1000459383 (4:128278291 A>G), RS1000541683 (4:128270531 G>A), RS1000598470 (4:128269362 C>G), RS1000862080 (4:128289147 A>G), RS1001042618 (4:128283907 C>T), RS1001075243 (4:128284116 G>T), RS1001311710 (4:128276856 C>T), RS1001411472 (4:128284558 C>T)

Disease associations

OMIM: gene MIM:607735 | disease phenotypes: MIM:142623

GenCC curated gene-disease

Mondo (1): Hirschsprung disease, susceptibility to, 1 (MONDO:0007723)

Orphanet (1): Hirschsprung disease (Orphanet:388)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006143_10	Bone mineral density (total hip)	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007702	hip bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066333 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3733260	PGRMC2		0.00	0

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.27	Kd	5.415	nM	CHEMBL5653589
8.27	ED50	5.415	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148993: Binding affinity to human PGRMC2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0054	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	3
Valproic Acid	affects expression, decreases methylation, increases expression	3
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	increases expression, affects cotreatment, decreases expression, increases abundance	2
Air Pollutants	increases abundance, decreases expression, affects expression	2
Arsenic	increases expression, affects cotreatment, decreases expression, increases abundance	2
Cisplatin	decreases expression, affects reaction	2
Estradiol	affects expression, affects cotreatment, increases expression	2
Cyclosporine	decreases expression, decreases methylation	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
lead acetate	increases expression	1
decabromobiphenyl ether	decreases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
bleomycetin	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
resorcinol	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652035	Binding	Binding affinity to human PGRMC2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02343562	PHASE4	UNKNOWN	Probiotics for Prophylaxis of Postoperative Hirschsprungs Associated Enterocolitis
NCT07186647	PHASE4	COMPLETED	Laparoscopic-Assisted Transanal Pull-Through for Hirschsprung Disease in Pediatric:Short and Intermediate Outcomes of Two Different Techniques
NCT04904081	PHASE3	UNKNOWN	Feasibility of Use of Indocyanine Green in Pediatric Colorectal Surgery
NCT00630838	PHASE2	COMPLETED	Probiotic Prophylaxis of Hirschprung’s Disease Associated Enterocolitis (HAEC)
NCT01985646	EARLY_PHASE1	COMPLETED	A Trial on Conservative Treatment for Infants’ Hirschsprung Disease
NCT00478712	Not specified	RECRUITING	Hirschsprung Disease Genetic Study
NCT01515501	Not specified	COMPLETED	Endoscopic Mucosal Resection for the Diagnosis of a-Ganglionosis, a Controlled Prospective Trial (EDGE Trial)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01927809	Not specified	UNKNOWN	Genetic Mosaicism in Hirschsprung’s Disease
NCT02193685	Not specified	UNKNOWN	Identification Genetic, Immunologic and Microbial Markers of Hirschsprung Associated Enterocolitis in Children With Hirschsprung Disease
NCT02216994	Not specified	UNKNOWN	A New Scoring System Improves Diagnostic Accuracy of Intestinal Dysganglionosis –a Prospective Study
NCT02296008	Not specified	COMPLETED	3D High Resolution Anorectal Manometry in Children After Surgery for Anorectal Disorders
NCT02776176	Not specified	UNKNOWN	Enhanced Recovery After Surgery In Hirschsprung Disease
NCT02857205	Not specified	COMPLETED	MICROPRUNG : Intestinal Microbiota Analysis in Patients With or Without Hirschsprung’s Associated EnteroColitis
NCT03269812	Not specified	UNKNOWN	Laparoscopic Assisted Pull-through Versus Other Surgical Procedures for Treatment of Hirschsprung Disease
NCT03666767	Not specified	COMPLETED	Management and Outcomes of Congenital Anomalies in Low-, Middle- and High-Income Countries
NCT04020939	Not specified	COMPLETED	The Role of Indocyanine Green Angiography Fluorescence on Intestinal Resections in Pediatric Surgery.
NCT04106947	Not specified	UNKNOWN	Transition of Care for Patients With Hirschsprung Disease and Anorectal Malformations
NCT04149093	Not specified	UNKNOWN	The Association Between Calretinin and the Function of Ganglion Cells in Hirschsprung Disease
NCT04150120	Not specified	COMPLETED	eHealth as an Aid for Facilitating and Supporting Self-management in Families With Long-term Childhood Illness
NCT04213976	Not specified	UNKNOWN	Ostomy in Continuity or Conventional Ileostomy: a Retrospective Multicentric Analysis
NCT04476225	Not specified	COMPLETED	Induced Pluripotent Stem Cells for Disease Research
NCT04598841	Not specified	COMPLETED	Nutrition Support for Hirschsprung Disease
NCT04622410	Not specified	RECRUITING	Registry for Hirschsprung Disease of the BELAPS
NCT04624334	Not specified	TERMINATED	Non-invasive Assessment of Colonic Motility
NCT04730128	Not specified	COMPLETED	Translation and Validation of a Disease-specific Questionnaire for Hirschsprung’s Disease in Danish Patients
NCT04837963	Not specified	COMPLETED	Does Hirschsprung Disease Increase the Risk of Febrile Urinary Tract Infection in Children
NCT04957667	Not specified	COMPLETED	Scintigraphic Defecography for Evaluation of Functional Outcome in an Adult Hirschsprung Population
NCT05038345	Not specified	TERMINATED	Hirschsprung Disease Trends in the United States: Analysis of the National Inpatient Sample
NCT05044741	Not specified	COMPLETED	Risk Factors of Perforated HSCR in Neonates
NCT05293353	Not specified	UNKNOWN	Neokare Safety and Tolerability Assessment in Neonates With GI Problems
NCT05307419	Not specified	UNKNOWN	Full Thickness vs. Rectal Suction Biopsy in the Diagnosis of Hirschsprungs Disease
NCT05450991	Not specified	RECRUITING	Long-term Qualitative and Quantitative Outcomes of Children With Hirschsprung’s Disease and Anorectal Malformations
NCT05655845	Not specified	UNKNOWN	Risk Factors for Bowel Dysfunction at Preschool and Early Childhood Age in Children With Hirschsprung Disease
NCT06072976	Not specified	RECRUITING	The Influence of Feeding Source on the Gut Microbiome and Time to Full Feeds in Neonates With Congenital Gastrointestinal Pathologies
NCT06197061	Not specified	UNKNOWN	Comparison of Robot-assisted With Laparoscopic-assisted Modified Soave Procedure for Classical Hirschsprung Disease
NCT06573723	Not specified	RECRUITING	Institutional Registry of Rare Diseases
NCT06590142	Not specified	RECRUITING	Hirschsprung’s Advances; Working Towards Autologous tIssue therapIes
NCT06592534	Not specified	NOT_YET_RECRUITING	Babies With Enterocolitis - A Study of Faecal Calprotectin in Hirschsprung Disease (The BEACH Study)
NCT06650683	Not specified	RECRUITING	Impact of Providing Nursing Support on Parental Stress Related to Preoperative Care of a Newborn with Hirschsprung’s Disease