EBP

Summary

EBP (EBP cholestenol delta-isomerase, HGNC:3133) is a protein-coding gene on chromosome Xp11.23, encoding 3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase (Q15125). Isomerase that catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers a catalytic step in the postlanosterol biosynthesis of cholesterol.

The protein encoded by this gene is an integral membrane protein of the endoplasmic reticulum. It is a high affinity binding protein for the antiischemic phenylalkylamine Ca2+ antagonist [3H]emopamil and the photoaffinity label [3H]azidopamil. It is similar to sigma receptors and may be a member of a superfamily of high affinity drug-binding proteins in the endoplasmic reticulum of different tissues. This protein shares structural features with bacterial and eukaryontic drug transporting proteins. It has four putative transmembrane segments and contains two conserved glutamate residues which may be involved in the transport of cationic amphiphilics. Another prominent feature of this protein is its high content of aromatic amino acid residues (>23%) in its transmembrane segments. These aromatic amino acid residues have been suggested to be involved in the drug transport by the P-glycoprotein. Mutations in this gene cause Chondrodysplasia punctata 2 (CDPX2; also known as Conradi-Hunermann syndrome).

Source: NCBI Gene 10682 — RefSeq curated summary.

At a glance

• Gene–disease (curated): MEND syndrome (Definitive, ClinGen) — +2 more curated relationships
• Clinical variants (ClinVar): 260 total — 48 pathogenic, 29 likely-pathogenic
• Phenotypes (HPO): 134
• Druggable target: yes — 16 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006579

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3133
Approved symbol	EBP
Name	EBP cholestenol delta-isomerase
Location	Xp11.23
Locus type	gene with protein product
Status	Approved
Aliases	D8D7I, CPX, CPXD, CHO2
Ensembl gene	ENSG00000147155
Ensembl biotype	protein_coding
OMIM	300205
Entrez	10682

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 17 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000276096, ENST00000414061, ENST00000446158, ENST00000466461, ENST00000495186, ENST00000498425, ENST00000882073, ENST00000882074, ENST00000882075, ENST00000882076, ENST00000882077, ENST00000882078, ENST00000882079, ENST00000882080, ENST00000882081, ENST00000882082, ENST00000882083, ENST00000936557, ENST00000969122, ENST00000969123

RefSeq mRNA: 1 — MANE Select: NM_006579 NM_006579

CCDS: CCDS14300

Canonical transcript exons

ENST00000495186 — 5 exons

Exon	Start	End
ENSE00000979000	48523699	48524072
ENSE00001882651	48521808	48521907
ENSE00001938779	48528234	48528716
ENSE00003520176	48526989	48527025
ENSE00003612113	48527155	48527285

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 98.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.9999 / max 551.6838, expressed in 1818 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196251	35.7512	1816
196250	11.1998	1775
196249	0.8418	529
196253	0.2070	104

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.67	gold quality
right adrenal gland	UBERON:0001233	98.48	gold quality
right adrenal gland cortex	UBERON:0035827	98.38	gold quality
left adrenal gland	UBERON:0001234	98.17	gold quality
adrenal cortex	UBERON:0001235	98.15	gold quality
mucosa of transverse colon	UBERON:0004991	98.14	gold quality
left adrenal gland cortex	UBERON:0035825	98.11	gold quality
liver	UBERON:0002107	97.71	gold quality
tendon of biceps brachii	UBERON:0008188	97.60	gold quality
adrenal gland	UBERON:0002369	97.49	gold quality
lower esophagus mucosa	UBERON:0035834	96.72	gold quality
oocyte	CL:0000023	96.67	gold quality
adrenal tissue	UBERON:0018303	96.53	gold quality
esophagus mucosa	UBERON:0002469	96.51	gold quality
cervix squamous epithelium	UBERON:0006922	96.47	gold quality
buccal mucosa cell	CL:0002336	95.49	gold quality
gingival epithelium	UBERON:0001949	95.49	gold quality
amniotic fluid	UBERON:0000173	95.30	gold quality
rectum	UBERON:0001052	95.19	gold quality
pharyngeal mucosa	UBERON:0000355	95.15	gold quality
duodenum	UBERON:0002114	95.13	gold quality
apex of heart	UBERON:0002098	95.11	gold quality
gingiva	UBERON:0001828	95.08	gold quality
right atrium auricular region	UBERON:0006631	94.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.73	gold quality
endometrium epithelium	UBERON:0004811	94.47	gold quality
nipple	UBERON:0002030	94.44	gold quality
transverse colon	UBERON:0001157	94.37	gold quality
squamous epithelium	UBERON:0006914	94.32	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.22	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6524	no	335.09
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting EBP, 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-574-5P	100.00	66.01	989
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-643	97.35	67.91	805
HSA-MIR-10398-5P	97.12	64.94	1051

Literature-anchored findings (GeneRIF, showing 14)

• Molecular analysis of EBP mutations were made. (PMID:17378690)
• Emopamil binding protein (EBP)-shRNA sequences were designed and tested for their effectiveness. (PMID:17498944)
• We found two novel (3G–>T and 419-422delTTCT) and one known mutation in the EBP gene. The strong phenotypic variability in our patients suggests that there is no clear genotype-phenotype correlation. (PMID:17949453)
• two unrelated Thai girls with chondrodysplasia punctata type 2. Mutation analysis by PCR-sequencing the entire coding region of emopamil binding protein(EBP) successfully revealed two potentially pathogenic, novel mutations, c.616G–>T and c.382delC. (PMID:18573709)
• postzygotic mosaicism on an ichthyosiform skin lesion in the mother of a girl with X-linked dominant chondrodysplasia punctata associated with a novel EBP mutation. (PMID:21931045)
• Results show a clear relationship between abnormal sterol profile and the EBP gene mutation (PMID:22121851)
• Elastin binding protein and FKBP65 modulate the kinetics of self-assembly of tropoelastin in an in vitro system. (PMID:24106871)
• With non-mosaic EBP mutations in males. (PMID:24459067)
• Report steroidomimetic aminomethyl spiroacetals as novel inhibitors of the enzyme Delta8,7-sterol isomerase in cholesterol biosynthesis. (PMID:24493593)
• This study expands the current phenotypic spectrum of males with hypomorphic EBP mutations and supports to the hypothesis that there exists an X-linked recessive entity independent of CDPX2. (PMID:24700572)
• Mutation analysis revealed a heterozygous novel missense mutation, c.204G>T (p.W68C), in exon 2. (PMID:24915996)
• EBP adopts an unreported fold involving five transmembrane-helices (TMs) that creates a membrane cavity presenting a pharmacological binding site that accommodates multiple different ligands. Mutagenesis studies on specific residues abolish the isomerase activity and decrease the multidrug binding capacity. (PMID:31165728)
• The human sterol delta(8)-Delta(7) isomerase was expressed in P. pastoris to 200mgL-1. The membrane protein enzyme could be solubilized readily in dodecyl maltoside. The solubilized protein displayed a symmetric peak on size exclusion chromatography. (PMID:31381990)
• Thermostabilization of Membrane Proteins by Consensus Mutation: A Case Study for a Fungal Delta8-7 Sterol Isomerase. (PMID:32105736)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ebp	ENSDARG00000046098
mus_musculus	Ebp	ENSMUSG00000031168
rattus_norvegicus	Ebp	ENSRNOG00000004903

Paralogs (1): EBPL (ENSG00000123179)

Protein

Protein identifiers

3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase — Q15125 (reviewed: Q15125)

Alternative names: Cholestenol Delta-isomerase, Cholesterol-5,6-epoxide hydrolase subunit EBP, Delta(8)-Delta(7) sterol isomerase, Emopamil-binding protein

All UniProt accessions (4): Q15125, A0A024QYX0, C9J719, C9JJ78

UniProt curated annotations — full annotation on UniProt →

Function. Isomerase that catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers a catalytic step in the postlanosterol biosynthesis of cholesterol. Component of the microsomal antiestrogen binding site (AEBS), a multiproteic complex at the ER membrane that consists of an association between EBP and 7-dehydrocholesterol reductase/DHCR7. This complex is responsible for cholesterol-5,6-epoxide hydrolase (ChEH) activity, which consists in the hydration of cholesterol-5,6-epoxides (5,6-EC) into cholestane-3beta,5alpha,6beta-triol (CT). The precise role of each component of this complex has not been described yet.

Subcellular location. Endoplasmic reticulum membrane. Nucleus envelope. Cytoplasmic vesicle.

Disease relevance. Chondrodysplasia punctata 2, X-linked dominant (CDPX2) [MIM:302960] A clinically and genetically heterogeneous disorder characterized by punctiform calcification of the bones. The key clinical features of CDPX2 are chondrodysplasia punctata, linear ichthyosis, cataracts and short stature. CDPX2 is a rare disorder of defective cholesterol biosynthesis, biochemically characterized by an increased amount of 8-dehydrocholesterol and cholest-8(9)-en-3-beta-ol in the plasma and tissues. The disease is caused by variants affecting the gene represented in this entry. MEND syndrome (MEND) [MIM:300960] An X-linked recessive disorder associated with a defect in sterol biosynthesis. Disease manifestations and severity are highly variable. Clinical features include intellectual disability, short stature, scoliosis, digital abnormalities, cataracts, and dermatologic abnormalities. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Cholestenol Delta-isomerase and cholesterol-5,6-epoxide hydrolase (ChEH) activities are inhibited by tamoxifen and the selective AEBS ligand (4-benzyl-phenoxy)-ethyl-N-pyrrolidine (PBPE). ChEH activity is inhibited by oleic acid.

Pathway. Steroid biosynthesis; cholesterol biosynthesis.

Miscellaneous. Binds to the phenylalkylamine calcium-ion antagonist emopamil, an anti-ischemic drug.

Similarity. Belongs to the EBP family.

RefSeq proteins (1): NP_006570* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007905	EBP	Family
IPR033118	EXPERA	Domain

Pfam: PF05241

Enzyme classification (BRENDA):

• EC 5.3.3.5 — cholestenol DELTA-isomerase (BRENDA: 9 organisms, 31 substrates, 110 inhibitors, 4 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
4ALPHA-METHYL-ERGOSTA-8,24-DIEN-3BETA-OL	0.522	1
CHOLESTA-8,24-DIEN-3BETA-OL	0.512	1
STIGMASTA-8-EN-3BETA-OL	0.116	1
ZYMOSTEROL	0.05	1

Catalyzed reactions (Rhea), 4 shown:

• 5,6alpha-epoxy-5alpha-cholestan-3beta-ol + H2O = 5alpha-cholestane-3beta,5,6beta-triol (RHEA:11964)
• 5,6beta-epoxy-5beta-cholestan-3beta-ol + H2O = 5alpha-cholestane-3beta,5,6beta-triol (RHEA:15113)
• lathosterol = 5alpha-cholest-8-en-3beta-ol (RHEA:15281)
• zymosterol = 5alpha-cholesta-7,24-dien-3beta-ol (RHEA:33999)

UniProt features (45 total): mutagenesis site 14, sequence variant 9, helix 8, transmembrane region 4, turn 3, strand 2, initiator methionine 1, chain 1, sequence conflict 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8W0R	ELECTRON MICROSCOPY	2.8
8W0S	ELECTRON MICROSCOPY	2.8
6OHT	X-RAY DIFFRACTION	3.2
6OHU	X-RAY DIFFRACTION	3.53

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15125-F1	95.83	0.93

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 (1): 2

Mutagenesis-validated functional residues (14):

Position	Phenotype
68	reduces catalytic activity to less than 35% of wild-type.
75	reduces catalytic activity to less than 35% of wild-type.
76	reduces catalytic activity to less than 10% of wild-type.
80	reduces catalytic activity to less than 10% of wild-type.
111	reduces catalytic activity to less than 2% of wild-type.
121	reduces catalytic activity to less than 35% of wild-type.
121	no effect on catalytic activity.
122	reduces catalytic activity to less than 10% of wild-type.
125	reduces catalytic activity to less than 10% of wild-type.
188	reduces catalytic activity to less than 35% of wild-type.
189	reduces catalytic activity to less than 35% of wild-type.
189	no effect on catalytic activity.
193	reduces catalytic activity to less than 10% of wild-type.
196	reduces catalytic activity to less than 10% of wild-type.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6807047	Cholesterol biosynthesis via desmosterol (Bloch pathway)
R-HSA-9969901	Cholesterol biosynthesis from zymosterol (modified Kandutsch-Russell pathway)
R-HSA-6807062	Zymostenol biosynthesis via lathosterol (Kandutsch-Russell pathway)

MSigDB gene sets: 559 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, JI_RESPONSE_TO_FSH_UP, MODULE_162, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, MORF_UBE2I, MORF_CDK2, LUCAS_HNF4A_TARGETS_UP, GGGTGGRR_PAX4_03, GOLDRATH_ANTIGEN_RESPONSE, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_BONE_DEVELOPMENT, MODULE_206, GOBP_STEROID_BIOSYNTHETIC_PROCESS

GO Biological Process (11): cholesterol biosynthetic process (GO:0006695), cholesterol metabolic process (GO:0008203), hemopoiesis (GO:0030097), obsolete cholesterol biosynthetic process via desmosterol (GO:0033489), obsolete cholesterol biosynthetic process via lathosterol (GO:0033490), ossification involved in bone maturation (GO:0043931), lipid metabolic process (GO:0006629), steroid biosynthetic process (GO:0006694), steroid metabolic process (GO:0008202), sterol metabolic process (GO:0016125), sterol biosynthetic process (GO:0016126)

GO Molecular Function (8): C-8 sterol isomerase activity (GO:0000247), steroid Delta-isomerase activity (GO:0004769), cholesterol-5,6-oxide hydrolase activity (GO:0033963), identical protein binding (GO:0042802), cholestenol delta-isomerase activity (GO:0047750), protein binding (GO:0005515), hydrolase activity (GO:0016787), isomerase activity (GO:0016853)

GO Cellular Component (7): nuclear envelope (GO:0005635), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytoplasmic vesicle (GO:0031410), nuclear membrane (GO:0031965), nucleus (GO:0005634), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cholesterol biosynthesis	3

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intramolecular oxidoreductase activity, transposing C=C bonds	3
sterol metabolic process	2
steroid metabolic process	2
catalytic activity	2
nucleus	2
endomembrane system	2
cytoplasm	2
intracellular membrane-bounded organelle	2
organelle membrane	2
cholesterol metabolic process	1
sterol biosynthetic process	1
secondary alcohol biosynthetic process	1
secondary alcohol metabolic process	1
cell development	1
ossification	1
bone maturation	1
primary metabolic process	1
lipid biosynthetic process	1
lipid metabolic process	1
steroid biosynthetic process	1
ether hydrolase activity	1
protein binding	1
binding	1
organelle envelope	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular vesicle	1
nuclear envelope	1
cellular anatomical structure	1

Protein interactions and networks

STRING

782 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EBP	DHCR7	Q9UBM7	940
EBP	SC5D	O75845	939
EBP	NSDHL	Q15738	929
EBP	KCNH6	Q9H252	901
EBP	TM7SF2	O76062	896
EBP	ARSL	P51690	833
EBP	FADS1	O60427	814
EBP	FDFT1	P37268	712
EBP	LBR	Q14739	706
EBP	DHCR24	Q15392	694
EBP	LSS	P48449	646
EBP	SIGMAR1	Q99720	635
EBP	MSMO1	Q15800	627
EBP	HMGCR	P04035	588
EBP	SQLE	Q14534	587

IntAct

616 interactions, top by confidence:

A	B	Type	Score
EBP	CREB3	psi-mi:“MI:0915”(physical association)	0.560
GYPA	EBP	psi-mi:“MI:0915”(physical association)	0.560
NRM	EBP	psi-mi:“MI:0915”(physical association)	0.560
TMEM120A	EBP	psi-mi:“MI:0915”(physical association)	0.560
SFXN3	EBP	psi-mi:“MI:0915”(physical association)	0.560
SLC30A8	EBP	psi-mi:“MI:0915”(physical association)	0.560
CES1	EBP	psi-mi:“MI:0915”(physical association)	0.560
EHHADH	EBP	psi-mi:“MI:0915”(physical association)	0.560
SLC38A7	EBP	psi-mi:“MI:0915”(physical association)	0.560
SLC35A4	EBP	psi-mi:“MI:0915”(physical association)	0.560
SLC48A1	EBP	psi-mi:“MI:0915”(physical association)	0.560
EBP	ARL13B	psi-mi:“MI:0915”(physical association)	0.560
C5	EBP	psi-mi:“MI:0915”(physical association)	0.560
LRP10	EBP	psi-mi:“MI:0915”(physical association)	0.560
LTC4S	EBP	psi-mi:“MI:0915”(physical association)	0.560
HMOX2	EBP	psi-mi:“MI:0915”(physical association)	0.560
GIMAP5	EBP	psi-mi:“MI:0915”(physical association)	0.560
STX7	EBP	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (286): EBP (Affinity Capture-RNA), EBP (Affinity Capture-RNA), EBP (Affinity Capture-RNA), EBP (Affinity Capture-RNA), EBP (Affinity Capture-MS), EBP (Affinity Capture-MS), EBP (Affinity Capture-MS), EBP (Affinity Capture-MS), EBP (Proximity Label-MS), EBP (Proximity Label-MS), EBP (Affinity Capture-MS), EBP (Affinity Capture-MS), EBP (Affinity Capture-MS), EBP (Affinity Capture-MS), EBP (Affinity Capture-MS)

ESM2 similar proteins: A0A067DFU5, A0A067E3D8, A0A1Y0BRF5, A0A9Y1LNE1, A0A9Y1LQX3, A5D7E2, A7S6Y0, A9UY97, B6HV37, B6JWP7, F4HW17, F4KIB2, O48962, O59802, O64761, O94673, P0DXH1, P25338, P38312, P70245, Q06537, Q09906, Q0V982, Q10255, Q12155, Q15125, Q28GF5, Q4KLL4, Q4V7N7, Q54ZW0, Q55E32, Q5R8F1, Q5R8Y6, Q5RDY2, Q5U3Y7, Q60490, Q641M3, Q66HF2, Q6DCP8, Q8BH24

Diamond homologs: A0A067DFU5, A0A067E3D8, A0A9Y1LNE1, A0A9Y1LQX3, O48962, P0DXH1, P70245, Q15125, Q60490, Q9FTZ2, Q9JJ46, Q9BY08, Q9D0P0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 195 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
Insertion of tail-anchored proteins into the endoplasmic reticulum membrane	5	22.7×	4e-04
Sphingolipid de novo biosynthesis	6	16.3×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
vesicle fusion	8	29.4×	2e-07
obsolete vesicle docking	5	23.4×	1e-03
endoplasmic reticulum to Golgi vesicle-mediated transport	8	6.6×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	48
Likely pathogenic	29
Uncertain significance	69
Likely benign	43
Benign	14

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069093	NM_006579.3(EBP):c.387G>A (p.Trp129Ter)	Pathogenic
11483	NM_006579.3(EBP):c.87G>A (p.Trp29Ter)	Pathogenic
11484	NM_006579.3(EBP):c.187C>T (p.Arg63Ter)	Pathogenic
11486	NM_006579.3(EBP):c.338+1G>T	Pathogenic
11487	NM_006579.3(EBP):c.390del (p.Pro131fs)	Pathogenic
11488	NM_006579.3(EBP):c.586_587insA (p.Trp196Ter)	Pathogenic
11489	NM_006579.3(EBP):c.386G>A (p.Trp129Ter)	Pathogenic
11490	NM_006579.3(EBP):c.523C>T (p.Gln175Ter)	Pathogenic
11491	NM_006579.3(EBP):c.587G>A (p.Trp196Ter)	Pathogenic
11492	NM_006579.3(EBP):c.440G>A (p.Arg147His)	Pathogenic
11493	NM_006579.3(EBP):c.53T>C (p.Leu18Pro)	Pathogenic
1322814	NM_006579.3(EBP):c.301+1G>A	Pathogenic
1352397	NM_006579.3(EBP):c.36G>A (p.Trp12Ter)	Pathogenic
1453472	NM_006579.3(EBP):c.107_111del (p.Phe36fs)	Pathogenic
158530	NM_006579.3(EBP):c.141G>T (p.Trp47Cys)	Pathogenic
158532	NM_006579.3(EBP):c.182G>A (p.Trp61Ter)	Pathogenic
158536	NM_006579.3(EBP):c.292_296del (p.Ser98fs)	Pathogenic
158538	NM_006579.3(EBP):c.301+2T>A	Pathogenic
158540	NM_006579.3(EBP):c.304A>T (p.Lys102Ter)	Pathogenic
158541	NM_006579.3(EBP):c.310T>C (p.Tyr104His)	Pathogenic
158545	NM_006579.3(EBP):c.328C>T (p.Arg110Ter)	Pathogenic
158548	NM_006579.3(EBP):c.464_465del (p.Ser155fs)	Pathogenic
158549	NM_006579.3(EBP):c.480T>G (p.Tyr160Ter)	Pathogenic
1699251	NM_006579.3(EBP):c.338+1G>C	Pathogenic
1712643	NM_006579.3(EBP):c.404G>A (p.Trp135Ter)	Pathogenic
2015626	NM_006579.3(EBP):c.485del (p.Asp162fs)	Pathogenic
209038	NM_006579.3(EBP):c.33C>A (p.Tyr11Ter)	Pathogenic
209040	NM_006579.3(EBP):c.139T>C (p.Trp47Arg)	Pathogenic
210902	NM_006579.3(EBP):c.225dup (p.His76fs)	Pathogenic
210903	NM_006579.3(EBP):c.329_332dup (p.Tyr111Ter)	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1482 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:48527213:A:C	S133R	0.987
X:48527215:C:A	S133R	0.987
X:48527215:C:G	S133R	0.987
X:48526993:A:C	K102N	0.985
X:48526993:A:T	K102N	0.985
X:48527016:G:C	R110P	0.980
X:48527010:A:T	D108V	0.979
X:48523973:T:A	W68R	0.978
X:48523973:T:C	W68R	0.978
X:48524072:T:A	W101R	0.977
X:48524072:T:C	W101R	0.977
X:48526992:A:T	K102I	0.977
X:48527009:G:C	D108H	0.977
X:48527010:A:C	D108A	0.977
X:48527012:A:C	S109R	0.976
X:48527014:C:A	S109R	0.976
X:48527014:C:G	S109R	0.976
X:48527011:C:A	D108E	0.973
X:48527011:C:G	D108E	0.973
X:48528350:T:A	W196R	0.969
X:48528350:T:C	W196R	0.969
X:48527204:G:A	G130R	0.968
X:48527204:G:C	G130R	0.968
X:48526997:T:C	Y104H	0.966
X:48527182:A:C	E122D	0.965
X:48527182:A:T	E122D	0.965
X:48528234:G:A	G157D	0.962
X:48524010:A:T	E80V	0.961
X:48527006:G:A	G107R	0.961
X:48527006:G:C	G107R	0.961

dbSNP variants (sampled 300 via entrez): RS1000686960 (X:48524946 C>T), RS1001121101 (X:48526679 T>C), RS1002122004 (X:48529013 C>G,T), RS1002349147 (X:48519880 C>G,T), RS1002872236 (X:48520529 T>C), RS1003464509 (X:48522370 C>T), RS1003757682 (X:48521976 G>A), RS1004872996 (X:48524308 C>A), RS1005765581 (X:48526043 C>T), RS1006923083 (X:48521207 C>T), RS1007870129 (X:48523382 G>A), RS1008922515 (X:48524985 G>A), RS1009281683 (X:48525658 C>T), RS1009871552 (X:48527665 G>A,T), RS1010336123 (X:48527096 G>A)

Disease associations

OMIM: gene MIM:300205 | disease phenotypes: MIM:302960, MIM:300960

GenCC curated gene-disease

Disease	Classification	Inheritance
chondrodysplasia punctata 2, X-linked dominant	Definitive	X-linked
X-linked chondrodysplasia punctata 2	Definitive	X-linked
MEND syndrome	Strong	X-linked

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
MEND syndrome	Definitive	XL

Mondo (6): intellectual disability (MONDO:0001071), connective tissue disorder (MONDO:0003900), X-linked chondrodysplasia punctata 2 (MONDO:0020603), MEND syndrome (MONDO:0010498), cleft palate (MONDO:0016064), (MONDO:0026782)

Orphanet (4): X-linked dominant chondrodysplasia punctata (Orphanet:35173), MEND syndrome (Orphanet:401973), Cleft palate (Orphanet:2014), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

134 total (30 of 134 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000126	Hydronephrosis
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000237	Small anterior fontanelle
HP:0000238	Hydrocephalus
HP:0000260	Wide anterior fontanel
HP:0000272	Malar flattening
HP:0000308	Microretrognathia
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000324	Facial asymmetry
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000377	Abnormal pinna morphology
HP:0000396	Overfolded helix
HP:0000407	Sensorineural hearing impairment
HP:0000414	Bulbous nose
HP:0000422	Abnormal nasal bridge morphology
HP:0000426	Prominent nasal bridge
HP:0000470	Short neck
HP:0000472	Long neck
HP:0000474	Thickened nuchal skin fold
HP:0000482	Microcornea
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000506	Telecanthus
HP:0000518	Cataract

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D002972	Cleft Palate	C05.500.460.185; C05.660.207.540.460.185; C07.320.440.185; C07.465.525.185; C07.650.500.460.185; C07.650.525.185; C16.131.621.207.540.460.185; C16.131.850.500.460.185; C16.131.850.525.185
D003240	Connective Tissue Diseases	C17.300
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3885502 (PROTEIN FAMILY), CHEMBL4931 (SINGLE PROTEIN), CHEMBL612409 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

16 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 735,313 (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
CHEMBL15023	TRIFLUPERIDOL	4	2,646
CHEMBL187709	TRIPARANOL	4	2,314
CHEMBL188921	BUFLOMEDIL	4	2,488
CHEMBL422	TRIFLUOPERAZINE	4	20,044
CHEMBL54	HALOPERIDOL	4	60,883
CHEMBL626	NAFTIFINE	4	16,569
CHEMBL633	AMIODARONE	4	29,704
CHEMBL81	RALOXIFENE	4	78,049
CHEMBL83	TAMOXIFEN	4	171,635
CHEMBL53463	DOXORUBICIN	4	314,282
CHEMBL370753	OPIPRAMOL	3	4,875
CHEMBL954	ENCLOMIPHENE	3	17,907
CHEMBL167779	ZUCLOMIPHENE	2	8,853
CHEMBL187829	LEVEMOPAMIL	2	248
CHEMBL28211	NAFOXIDINE	2	4,745
CHEMBL363884	RONIPAMIL	2	71

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

ChEMBL bioactivities

94 potent at pChembl≥5 of 100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.22	Ki	0.6	nM	CHEMBL17470
9.05	Ki	0.9	nM	NAFOXIDINE
9.00	Kd	1	nM	TAMOXIFEN
9.00	Ki	1	nM	ENCLOMIPHENE
9.00	Ki	1	nM	CHEMBL62540
9.00	Ki	1	nM	CHEMBL365842
9.00	Ki	1	nM	RALOXIFENE
8.77	Ki	1.7	nM	CHEMBL2311153
8.76	Ki	1.72	nM	[11C]SA4503
8.76	Ki	1.72	nM	CHEMBL2311153
8.70	Ki	2	nM	ZUCLOMIPHENE
8.70	Ki	2	nM	RONIPAMIL
8.70	Ki	2	nM	CHEMBL365141
8.53	IC50	2.95	nM	CHEMBL5285995
8.52	Ki	3	nM	CHEMBL188476
8.40	Ki	4	nM	CHEMBL361085
8.30	Ki	5	nM	(S,R)-IFENPRODIL
8.30	Ki	5	nM	TAMOXIFEN
8.22	Ki	6	nM	CHEMBL187615
8.10	Ki	8	nM	TRIFLUOPERAZINE
8.03	IC50	9.36	nM	CHEMBL4454956
7.96	Ki	11	nM	TRIPARANOL
7.96	Ki	11	nM	CHEMBL4636197
7.92	IC50	12	nM	TAMOXIFEN
7.91	Kd	12.28	nM	CHEMBL5653589
7.91	ED50	12.28	nM	CHEMBL5653589
7.89	Ki	13	nM	OPIPRAMOL
7.83	Kd	14.79	nM	CHEMBL3752910
7.83	ED50	14.79	nM	CHEMBL3752910
7.82	Ki	15	nM	CHEMBL190883
7.75	Ki	18	nM	LEVEMOPAMIL
7.66	IC50	22	nM	3’-METHOXY-4’HYDROXYCLOMIPHENE
7.60	Ki	25	nM	AMIODARONE
7.55	EC50	28	nM	CHEMBL5549966
7.52	Ki	30	nM	FENPROPIMORPH
7.52	IC50	30	nM	CHEMBL222694
7.50	IC50	32	nM	CHEMBL292185
7.48	EC50	33	nM	CHEMBL4636197
7.41	Ki	39	nM	CHEMBL365722
7.41	EC50	39	nM	CHEMBL5557098
7.40	IC50	40	nM	CHEMBL222694
7.31	IC50	49	nM	CHEMBL5281526
7.30	IC50	50	nM	CHEMBL266892
7.29	Ki	51	nM	CHEMBL188044
7.27	Ki	54	nM	CHEMBL190631
7.25	EC50	56	nM	CHEMBL5567315
7.22	Ki	60	nM	BUFLOMEDIL
7.22	IC50	60	nM	CHEMBL222694
7.16	IC50	70	nM	CHEMBL266892
7.12	EC50	76	nM	CHEMBL5563511

PubChem BioAssay actives

111 with measured affinity, of 261 total; 50 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
(4aS,5S,6S,8aS)-2-(6,10-dimethylundecan-2-yl)-5,8a-dimethyl-1,3,4,4a,5,6,7,8-octahydroisoquinolin-6-ol	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0006	uM
1-[2-[4-(6-methoxy-2-phenyl-3,4-dihydronaphthalen-1-yl)phenoxy]ethyl]pyrrolidine	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0009	uM
1’-butylspiro[2,3-dihydro-1H-naphthalene-4,4’-piperidine]	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0010	uM
2-[4-[(E)-2-chloro-1,2-diphenylethenyl]phenoxy]-N,N-diethylethanamine	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0010	uM
(2S,6R)-2,6-dimethyl-4-tridecylmorpholine	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0010	uM
Tamoxifen	38728: Binding affinity towards antiestrogen binding site AEBS	kd	0.0010	uM
Raloxifene	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0010	uM
1-[2-(3-methoxy-4-(111C)methoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine	596229: Binding affinity to emopamil binding protein	ki	0.0017	uM
1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine	737388: Binding affinity to EBP (unknown origin)	ki	0.0017	uM
2-[4-[(Z)-2-chloro-1,2-diphenylethenyl]phenoxy]-N,N-diethylethanamine	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0020	uM
2-[3-[methyl(2-phenylethyl)amino]propyl]-2-phenyltetradecanenitrile	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0020	uM
(3S,8R,9S,10R,13S,14S)-3-[2-(diethylamino)ethoxy]-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0020	uM
N-benzyl-1-(2,4,6-trimethylphenyl)sulfonylpiperidin-4-amine	1923761: Inhibition of EBP (unknown origin)	ic50	0.0029	uM
N-[(E)-3-(3-chloro-4-cyclohexylphenyl)prop-2-enyl]-N-ethylcyclohexanamine	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0030	uM
2-chloro-N-[2-[4-[[(2-chlorophenyl)methylamino]methyl]cyclohexyl]ethyl]aniline	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0040	uM
4-[(1S,2R)-2-(4-benzylpiperidin-1-yl)-1-hydroxypropyl]phenol	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0050	uM
(2R)-5-[methyl(2-phenylethyl)amino]-2-phenyl-2-propan-2-ylpentanenitrile	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0060	uM
Trifluoperazine	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0080	uM
1-[1-(2,4,6-trimethylphenyl)sulfonylpiperidin-4-yl]azepane	1923761: Inhibition of EBP (unknown origin)	ic50	0.0094	uM
1-methyl-1’-(oxan-4-ylmethyl)-5-(trifluoromethyl)spiro[indole-2,4’-piperidine]-3-one	2081467: Binding affinity to human EBP expressed in HEK293 cell membrane assessed as inhibition constant incubated for 3 hrs in presence of [3H]-labeled radioligand by microplate scintillation counter	ki	0.0110	uM
2-(4-chlorophenyl)-1-[4-[2-(diethylamino)ethoxy]phenyl]-1-(4-methylphenyl)ethanol	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0110	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148278: Binding affinity to human EBP incubated for 45 mins by Kinobead based pull down assay	kd	0.0123	uM
2-[4-(3-benzo[b][1]benzazepin-11-ylpropyl)piperazin-1-yl]ethanol	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0130	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148278: Binding affinity to human EBP incubated for 45 mins by Kinobead based pull down assay	kd	0.0148	uM
N-[2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethyl]-N-propylpropan-1-amine	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0150	uM
(2S)-5-[methyl(2-phenylethyl)amino]-2-phenyl-2-propan-2-ylpentanenitrile	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0180	uM
4-[(Z)-2-chloro-1-[4-[2-(diethylamino)ethoxy]phenyl]-2-phenylethenyl]-2-methoxyphenol	38614: Displacement of [3H]tamoxifen from antiestrogen binding site (AEBS)	ic50	0.0220	uM
Amiodarone	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0250	uM
1-ethyl-8-(oxan-4-ylmethyl)-3-[4-(trifluoromethyl)phenyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione	2081495: Inhibition of EBP in human Mesenchymal stem cells assessed as zymostenol accumulation by GCMS analysis	ec50	0.0280	uM
2-hydroxy-N-[[[(2S,3S,4S,6R)-3-hydroxy-2-methyl-6-[[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxyacetyl)-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]oxan-4-yl]amino]methyl]-5-[(E)-2-[2-[2-[2-[4-[(E)-1-(4-hydroxyphenyl)-2-phenylbut-1-enyl]phenoxy]ethyl-methylamino]ethoxy]ethoxy]ethoxyiminomethyl]benzamide	282019: Growth inhibition of MCF7 cells expressing ER and antiestrogen binding sites	ic50	0.0300	uM
(2S,6R)-4-[3-(4-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0300	uM
4-[(E)-1-chloro-2-[4-[2-(diethylamino)ethoxy]phenyl]-2-phenylethenyl]-2-methoxyphenol	38614: Displacement of [3H]tamoxifen from antiestrogen binding site (AEBS)	ic50	0.0320	uM
2-(2-benzhydrylsulfanylethyl)-1-[2-(1H-imidazol-5-yl)ethyl]guanidine	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0390	uM
3-(4-cyclopropylphenyl)-1-ethyl-8-(oxan-4-ylmethyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione	2081495: Inhibition of EBP in human Mesenchymal stem cells assessed as zymostenol accumulation by GCMS analysis	ec50	0.0390	uM
4-methyl-1-[1-[4-(4-methylphenyl)phenyl]sulfonylpiperidin-4-yl]piperidine	1923761: Inhibition of EBP (unknown origin)	ic50	0.0490	uM
2-hydroxy-N-[[[(2S,3S,4S,6R)-3-hydroxy-2-methyl-6-[[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxyacetyl)-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]oxan-4-yl]amino]methyl]benzamide	282023: Growth inhibition of MDA-MB-435 cells containing antiestrogen binding sites	ic50	0.0500	uM
8-[4-(difluoromethoxy)phenyl]sulfonyl-N-(oxan-4-yl)-8-azabicyclo[3.2.1]octan-3-amine	2020203: Inhibition of human EBP isolated from HEK293T cells assessed as reduction in dihydrolathosterol-d5 formation using zymosterol-d5 as substrate pre incubated for 30 mins followed by substrate addition and incubated at 37 degC for 4 hrs by LC-APCI MRM MS analysis	ic50	0.0500	uM
(1S,5R)-8-[4-(difluoromethoxy)phenyl]sulfonyl-3-(4-methylpiperidin-1-yl)-8-azabicyclo[3.2.1]octane	2020203: Inhibition of human EBP isolated from HEK293T cells assessed as reduction in dihydrolathosterol-d5 formation using zymosterol-d5 as substrate pre incubated for 30 mins followed by substrate addition and incubated at 37 degC for 4 hrs by LC-APCI MRM MS analysis	ic50	0.0500	uM
8-[4-(difluoromethoxy)phenyl]sulfonyl-N-(oxan-4-ylmethyl)-8-azabicyclo[3.2.1]octan-3-amine	2020203: Inhibition of human EBP isolated from HEK293T cells assessed as reduction in dihydrolathosterol-d5 formation using zymosterol-d5 as substrate pre incubated for 30 mins followed by substrate addition and incubated at 37 degC for 4 hrs by LC-APCI MRM MS analysis	ic50	0.0500	uM
4-[[[(1S,5R)-8-[4-(difluoromethoxy)phenyl]sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]amino]methyl]oxan-4-ol	2020203: Inhibition of human EBP isolated from HEK293T cells assessed as reduction in dihydrolathosterol-d5 formation using zymosterol-d5 as substrate pre incubated for 30 mins followed by substrate addition and incubated at 37 degC for 4 hrs by LC-APCI MRM MS analysis	ic50	0.0500	uM
4-[[(1R,5S)-8-(2,5-dimethylpyrazol-3-yl)sulfonyl-8-azabicyclo[3.2.1]octan-3-yl]methyl]morpholine	2020203: Inhibition of human EBP isolated from HEK293T cells assessed as reduction in dihydrolathosterol-d5 formation using zymosterol-d5 as substrate pre incubated for 30 mins followed by substrate addition and incubated at 37 degC for 4 hrs by LC-APCI MRM MS analysis	ic50	0.0500	uM
8-[4-(difluoromethoxy)phenyl]sulfonyl-N-(1-methyl-2-oxabicyclo[2.1.1]hexan-4-yl)-8-azabicyclo[3.2.1]octan-3-amine	2020203: Inhibition of human EBP isolated from HEK293T cells assessed as reduction in dihydrolathosterol-d5 formation using zymosterol-d5 as substrate pre incubated for 30 mins followed by substrate addition and incubated at 37 degC for 4 hrs by LC-APCI MRM MS analysis	ic50	0.0500	uM
1-(diethylamino)propan-2-yl N-(2-heptoxyphenyl)carbamate	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0510	uM
2-[4-[(E)-4-[4-[2-(diethylamino)ethoxy]phenyl]hex-3-en-3-yl]phenoxy]-N,N-diethylethanamine	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0540	uM
1-ethyl-8-(oxan-4-ylmethyl)-3-[4-(trifluoromethyl)cyclohexyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione	2081495: Inhibition of EBP in human Mesenchymal stem cells assessed as zymostenol accumulation by GCMS analysis	ec50	0.0560	uM
4-pyrrolidin-1-yl-1-(2,4,6-trimethoxyphenyl)butan-1-one	239597: Affinity for human EMP expressed in ERG2 deficient strain of Saccharomyces cerevisiae using [3H]ifenprodil or (+)-[3H]pentazocine as radioligand	ki	0.0600	uM
1-cyclopropyl-8-(oxan-4-ylmethyl)-3-[4-(trifluoromethyl)phenyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione	2081495: Inhibition of EBP in human Mesenchymal stem cells assessed as zymostenol accumulation by GCMS analysis	ec50	0.0760	uM
4-methyl-1-[1-(2,4,6-trimethylphenyl)sulfonylpiperidin-4-yl]piperidine	1923761: Inhibition of EBP (unknown origin)	ic50	0.0973	uM
7-(3-cyclopropyl-1-methylpyrazol-5-yl)sulfonyl-N-(oxan-4-yl)-7-azaspiro[3.5]nonan-2-amine	2021666: Inhibition of EBP derived from HEK293T cells using zymosterol-d5 as substrate preincubated for 30 mins followed by substrate addition measured after 4 hrs by LC-APCI MRM MS analysis	ic50	0.1000	uM
4-[8-[(3-fluoro-2-methoxy-4-pyridinyl)sulfonyl]-8-azaspiro[4.5]decan-3-yl]morpholine	2021666: Inhibition of EBP derived from HEK293T cells using zymosterol-d5 as substrate preincubated for 30 mins followed by substrate addition measured after 4 hrs by LC-APCI MRM MS analysis	ic50	0.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
perfluorooctane sulfonic acid	decreases expression	4
sodium arsenite	decreases expression, increases expression	3
Estradiol	decreases expression, increases expression	3
Valproic Acid	affects expression, decreases expression	3
Cyclosporine	affects cotreatment, affects expression, decreases expression	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment	3
bisphenol A	affects expression, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression, decreases methylation	2
Fluorouracil	affects response to substance	2
Smoke	increases abundance, increases expression, decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
arsenite	increases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
periodate-oxidized adenosine	affects expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
cupric chloride	decreases expression	1
triacsin C	decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
avobenzone	increases expression	1
bicalutamide	decreases expression	1
phenethyl isothiocyanate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
yessotoxin	increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
beta-hydroxy simvastatin acid	affects expression	1

ChEMBL screening assays

57 unique, capped per target: 34 binding, 23 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2344569	Binding	Inhibition of Delta(8)-Delta(7) sterol isomerase/Delta(24)-sterol reductase-mediated cholesterol biosynthesis in human HL60 cells assessed as increase in zymostenol and zymosterol accumulation	Stereoselective synthesis of a new class of potent and selective inhibitors of human Δ8,7-sterol isomerase. — Bioorg Med Chem
CHEMBL646778	Functional	Relative binding affinity(RBA) against AEBS (Antiestrogen binding site) using EL-4 cells	Synthesis of 2-(p-chlorobenzyl)-3-aryl-6-methoxybenzofurans as selective ligands for antiestrogen-binding sites. Effects on cell proliferation and cholesterol synthesis. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT02422056	PHASE4	COMPLETED	Acid Tranexamic Effectiveness in Reducing the Intraoperative Bleeding in Palatoplasty
NCT02915042	PHASE4	WITHDRAWN	Dexmedetomidine vs Placebo for Pediatric Cleft Palate Repair
NCT02953145	PHASE4	WITHDRAWN	The Use of Fibrin Sealant to Reduce Post Operative Pain in Cleft Palate Surgery
NCT03632044	PHASE4	ACTIVE_NOT_RECRUITING	Evaluation of Trigeminal Nerve Blockade
NCT06962306	PHASE4	RECRUITING	Optimizing Perioperative Analgesia to Lower Pain Following Cleft Palate Surgery
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00864201	PHASE3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	PHASE3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	PHASE3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT04084678	PHASE3	TERMINATED	A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH
NCT06716606	PHASE3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT00098319	PHASE3	COMPLETED	Oral Cleft Prevention Trial in Brazil
NCT00397917	PHASE3	COMPLETED	Oral Cleft Prevention Program
NCT04928352	PHASE3	RECRUITING	Nebulized Bupivacaine Analgesia for Cleft Palate Repair
NCT04928391	PHASE3	COMPLETED	A Single Bolus of Dexmedetomidine Versus Normal Saline in Postoperative Agitation
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00004357	PHASE2	COMPLETED	Absorption of Corticosteroids in Children With Juvenile Dermatomyositis
NCT00005675	PHASE2	COMPLETED	Oral Type I Collagen for Relieving Scleroderma
NCT01808196	PHASE2	COMPLETED	Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD
NCT02682511	PHASE2	ACTIVE_NOT_RECRUITING	Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension
NCT04993885	PHASE2	RECRUITING	Avatrombopag in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies