PLPBP

Summary

PLPBP (pyridoxal phosphate binding protein, HGNC:9457) is a protein-coding gene on chromosome 8p11.23, encoding Pyridoxal phosphate homeostasis protein (O94903). Pyridoxal 5’-phosphate (PLP)-binding protein, which may be involved in intracellular homeostatic regulation of pyridoxal 5’-phosphate (PLP), the active form of vitamin B6.

This gene encodes a pyridoxal 5’-phosphate binding protein involved in the homeostatic regulation of intracellular pyridoxal 5’-phosphate. This gene has a tumor suppressive effect on hepatocellular carcinoma and other solid tumors of epithelial origin. Naturally occurring mutations in this gene are associated with a pyridoxine-dependent epilepsy.

Source: NCBI Gene 11212 — RefSeq curated summary.

At a glance

• Gene–disease (curated): epilepsy, early-onset, vitamin B6-dependent (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 249 total — 15 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 59
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_007198

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9457
Approved symbol	PLPBP
Name	pyridoxal phosphate binding protein
Location	8p11.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000147471
Ensembl biotype	protein_coding
OMIM	604436
Entrez	11212

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000328195, ENST00000518036, ENST00000520073, ENST00000521631, ENST00000522808, ENST00000523187, ENST00000523358, ENST00000523521, ENST00000523994, ENST00000872272, ENST00000872273, ENST00000872274, ENST00000958638, ENST00000958639, ENST00000958640

RefSeq mRNA: 5 — MANE Select: NM_007198 NM_001349346, NM_001349347, NM_001349348, NM_001349349, NM_007198

CCDS: CCDS6096

Canonical transcript exons

ENST00000328195 — 8 exons

Exon	Start	End
ENSE00001316868	37772755	37772889
ENSE00001326135	37775339	37775481
ENSE00002104853	37762645	37762758
ENSE00002131856	37777973	37779768
ENSE00003503176	37775918	37776016
ENSE00003507031	37766280	37766355
ENSE00003537772	37765526	37765633
ENSE00003617004	37765711	37765746

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 96.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.4116 / max 230.8001, expressed in 1815 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88450	9.2880	1777
88451	7.1038	1733
88452	4.0199	1647

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardia of stomach	UBERON:0001162	96.88	gold quality
pericardium	UBERON:0002407	96.82	gold quality
renal medulla	UBERON:0000362	96.59	gold quality
jejunal mucosa	UBERON:0000399	96.34	gold quality
pylorus	UBERON:0001166	96.19	gold quality
colonic mucosa	UBERON:0000317	95.85	gold quality
entorhinal cortex	UBERON:0002728	95.81	gold quality
adult organism	UBERON:0007023	95.79	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.78	gold quality
postcentral gyrus	UBERON:0002581	95.64	gold quality
monocyte	CL:0000576	95.52	gold quality
secondary oocyte	CL:0000655	95.48	gold quality
parietal lobe	UBERON:0001872	95.47	gold quality
mononuclear cell	CL:0000842	95.42	gold quality
lower lobe of lung	UBERON:0008949	95.31	gold quality
leukocyte	CL:0000738	95.30	gold quality
jejunum	UBERON:0002115	95.27	gold quality
islet of Langerhans	UBERON:0000006	95.20	gold quality
nipple	UBERON:0002030	95.11	gold quality
ventral tegmental area	UBERON:0002691	95.11	gold quality
inferior vagus X ganglion	UBERON:0005363	95.06	gold quality
ileal mucosa	UBERON:0000331	95.01	gold quality
pons	UBERON:0000988	94.98	gold quality
heart right ventricle	UBERON:0002080	94.91	gold quality
duodenum	UBERON:0002114	94.91	gold quality
vena cava	UBERON:0004087	94.90	gold quality
oocyte	CL:0000023	94.77	gold quality
pigmented layer of retina	UBERON:0001782	94.76	gold quality
parietal pleura	UBERON:0002400	94.75	gold quality
palpebral conjunctiva	UBERON:0001812	94.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

74 targeting PLPBP, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-4437	99.52	65.29	1266

Literature-anchored findings (GeneRIF, showing 4)

• studies suggest that PROSC is involved in intracellular homeostatic regulation of pyridoxal 5’-phosphate, supplying this cofactor to apoenzymes while minimizing any toxic side reactions (PMID:27912044)
• We therefore confirm PROSC as a novel gene for vitamin-B6-dependent epilepsy and delineate a non-specific plasma vitamin B6 profile under pyridoxine treatment. (PMID:28391250)
• Exploiting the universality of the Synechococcus elongatus COG0325 (PiPY) functions, it has been used in site-directed mutagenesis studies to shed light on disease causation by epilepsy-associated mutations in the human COG0325 gene PROSC. (PMID:28914444)
• Maintenance of cellular vitamin B6 levels and mitochondrial oxidative function depend on pyridoxal 5’-phosphate homeostasis protein. (PMID:37451483)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	plpbp	ENSDARG00000060288
mus_musculus	Plpbp	ENSMUSG00000031485
rattus_norvegicus	Plpbp	ENSRNOG00000013751
drosophila_melanogaster	CG1983	FBGN0039751
caenorhabditis_elegans		WBGENE00017285

Protein

Protein identifiers

Pyridoxal phosphate homeostasis protein — O94903 (reviewed: O94903)

Alternative names: Proline synthase co-transcribed bacterial homolog protein, Pyridoxal phosphate-binding protein

All UniProt accessions (5): O94903, E5RFX7, E5RFZ4, E5RG77, H0YBG2

UniProt curated annotations — full annotation on UniProt →

Function. Pyridoxal 5’-phosphate (PLP)-binding protein, which may be involved in intracellular homeostatic regulation of pyridoxal 5’-phosphate (PLP), the active form of vitamin B6.

Tissue specificity. Ubiquitous.

Disease relevance. Epilepsy, early-onset, 1, vitamin B6-dependent (EPEO1) [MIM:617290] An autosomal recessive neurologic disorder characterized by seizures responsive to treatment with activated vitamin B6 and/or pyridoxine. Most patients show delayed psychomotor development, intellectual disability and learning disability. Seizures onset is in the first days or months of life. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the pyridoxal phosphate-binding protein YggS/PROSC family.

RefSeq proteins (5): NP_001336275, NP_001336276, NP_001336277, NP_001336278, NP_009129* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001608	Ala_racemase_N	Domain
IPR011078	PyrdxlP_homeostasis	Family
IPR029066	PLP-binding_barrel	Homologous_superfamily

Pfam: PF01168

UniProt features (15 total): sequence variant 6, modified residue 6, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94903-F1	89.49	0.79

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 (6): 6, 47, 69, 125, 226, 244

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 247 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, MODULE_503, MODULE_195, MORF_PRKDC, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_UP, FUJII_YBX1_TARGETS_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, MODULE_147, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, MODULE_356, AP1FJ_Q2

GO Biological Process (1): vitamin B6 metabolic process (GO:0042816)

GO Molecular Function (1): pyridoxal phosphate binding (GO:0030170)

GO Cellular Component (3): cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoplasm	2
vitamin metabolic process	1
pyridine-containing compound metabolic process	1
anion binding	1
vitamin B6 binding	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1388 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLPBP	PNPO	Q9NVS9	811
PLPBP	ALDH7A1	P49419	651
PLPBP	ERLIN2	O94905	618
PLPBP	RAB11FIP1	Q6WKZ4	613
PLPBP	DDHD2	O94830	612
PLPBP	PDXK	O00764	606
PLPBP	ZNF703	Q9H7S9	605
PLPBP	LSM1	O15116	582
PLPBP	ADGRA2	Q96PE1	546
PLPBP	C2orf76	Q3KRA6	528
PLPBP	PLPP5	Q8NEB5	514
PLPBP	BAG4	O95429	509
PLPBP	TM2D2	Q9BX73	489
PLPBP	GOT1L1	Q8NHS2	475
PLPBP	ALDH4A1	P30038	463

IntAct

61 interactions, top by confidence:

A	B	Type	Score
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
GPX7	GAK	psi-mi:“MI:0914”(association)	0.640
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
SOX2	PDLIM1	psi-mi:“MI:0914”(association)	0.530
CDK5R1	DENR	psi-mi:“MI:0914”(association)	0.530
	TK2	psi-mi:“MI:0915”(physical association)	0.400
Cdca5	ATP5MF-PTCD1	psi-mi:“MI:0914”(association)	0.350
CHORDC1	SSR3	psi-mi:“MI:0914”(association)	0.350
PARD6B	PARD3	psi-mi:“MI:0914”(association)	0.350
Sgo2a	GPA33	psi-mi:“MI:0914”(association)	0.350
RPA1	PLPBP	psi-mi:“MI:0914”(association)	0.350
ANAPC15		psi-mi:“MI:0914”(association)	0.350
Klc2	KLC1	psi-mi:“MI:0914”(association)	0.350
Sesn2	CASTOR2	psi-mi:“MI:0914”(association)	0.350
Cbx4	DNAJB6	psi-mi:“MI:0914”(association)	0.350
PCK2	PLPBP	psi-mi:“MI:0914”(association)	0.350
Tgs1	EFCAB5	psi-mi:“MI:0914”(association)	0.350
Srsf1	SRRM1	psi-mi:“MI:0914”(association)	0.350
SLC25A32	NEDD8-MDP1	psi-mi:“MI:0914”(association)	0.350
OXNAD1	DENR	psi-mi:“MI:0914”(association)	0.350
FCGR2A	PLPBP	psi-mi:“MI:0914”(association)	0.350
NDUFS3	ACOT7	psi-mi:“MI:0914”(association)	0.350
RASA1		psi-mi:“MI:0914”(association)	0.350
DOK2	MYO1C	psi-mi:“MI:0914”(association)	0.350
CAV2	SURF4	psi-mi:“MI:0914”(association)	0.350
MAP2K1	SLC16A3	psi-mi:“MI:0914”(association)	0.350
FARP1	PLPBP	psi-mi:“MI:0914”(association)	0.350
ARHGAP36	HAX1	psi-mi:“MI:0914”(association)	0.350

BioGRID (128): PROSC (Affinity Capture-MS), PROSC (Affinity Capture-MS), PROSC (Affinity Capture-MS), PROSC (Affinity Capture-MS), PROSC (Affinity Capture-MS), ADI1 (Co-fractionation), ADRBK1 (Co-fractionation), ARFIP1 (Co-fractionation), ENSA (Co-fractionation), HNRNPA1 (Co-fractionation), HNRNPA3 (Co-fractionation), MYEF2 (Co-fractionation), PAPOLA (Co-fractionation), PHPT1 (Co-fractionation), PROSC (Co-fractionation)

ESM2 similar proteins: A0MTA1, A1YES6, A1YFZ3, A2T6Y4, A2T7I6, A5WVX1, B4FAT0, O54747, O94903, P0A2X3, P0A2X4, P13051, P23196, P26882, P27695, P28339, P28340, P28352, P36776, P43138, P52431, P97283, P97931, Q08752, Q08DF7, Q0J705, Q0V9S0, Q16775, Q32LH4, Q3B7M2, Q3T0G5, Q3TIU4, Q4P1V1, Q4R5U5, Q4R6C1, Q59HJ6, Q5R4Z1, Q5XIP6, Q5ZI23, Q653S9

Diamond homologs: O25156, O31727, O66631, O94903, P24562, P38197, P44506, P52055, P52056, P52057, P67080, P67081, P67082, Q1ZXI6, Q3T0G5, Q5R4Z1, Q9CPD5, Q9KUQ4, Q9P6Q1, Q9RUL6, Q9Z2Y8, Q9ZKF2, P67084, P9WFQ6, P9WFQ7, P57614, Q89A48, Q8K929, Q9CCE2, O24748

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	4
Uncertain significance	88
Likely benign	114
Benign	6

Top pathogenic / likely-pathogenic (19)

Variant ID	HGVS	Classification
1323499	NM_007198.4(PLPBP):c.211C>T (p.Gln71Ter)	Pathogenic
1806055	NM_007198.4(PLPBP):c.387del (p.Trp130fs)	Pathogenic
2112606	NM_007198.4(PLPBP):c.207+1G>C	Pathogenic
2136656	NM_007198.4(PLPBP):c.249_252del (p.Ser84fs)	Pathogenic
2425699	NC_000008.10:g.(?37632837)(37633554_?)del	Pathogenic
2743804	NM_007198.4(PLPBP):c.207C>A (p.Tyr69Ter)	Pathogenic
2745421	NM_007198.4(PLPBP):c.292C>T (p.Gln98Ter)	Pathogenic
2761004	NM_007198.4(PLPBP):c.316del (p.Met106fs)	Pathogenic
3215368	NM_007198.4(PLPBP):c.35dup (p.Val13fs)	Pathogenic
3245576	NC_000008.10:g.(?37620178)(37635622_?)del	Pathogenic
374852	NM_007198.4(PLPBP):c.233C>G (p.Ser78Ter)	Pathogenic
374853	NM_007198.4(PLPBP):c.524T>C (p.Leu175Pro)	Pathogenic
374854	NM_007198.4(PLPBP):c.207+1G>A	Pathogenic
374855	NM_007198.4(PLPBP):c.320-2A>G	Pathogenic
503895	NM_007198.4(PLPBP):c.370_373del (p.Asp124fs)	Pathogenic
2136657	NM_007198.4(PLPBP):c.614G>A (p.Arg205Gln)	Likely pathogenic
2444519	NM_007198.4(PLPBP):c.389G>A (p.Trp130Ter)	Likely pathogenic
2797687	NM_007198.4(PLPBP):c.319+1G>C	Likely pathogenic
4739088	NM_007198.4(PLPBP):c.122G>A (p.Arg41Gln)	Likely pathogenic

SpliceAI

992 predictions. Top by Δscore:

Variant	Effect	Δscore
8:37762764:G:GT	donor_gain	1.0000
8:37762768:G:GT	donor_gain	1.0000
8:37765523:CA:C	acceptor_loss	1.0000
8:37765524:A:AG	acceptor_gain	1.0000
8:37765524:A:C	acceptor_loss	1.0000
8:37765524:AG:A	acceptor_gain	1.0000
8:37765525:G:GA	acceptor_gain	1.0000
8:37765525:GG:G	acceptor_gain	1.0000
8:37765525:GGAT:G	acceptor_gain	1.0000
8:37765627:GAAC:G	donor_gain	1.0000
8:37765630:C:CG	donor_gain	1.0000
8:37765634:G:GG	donor_gain	1.0000
8:37765747:G:GG	donor_gain	1.0000
8:37772750:TACA:T	acceptor_loss	1.0000
8:37772752:CA:C	acceptor_loss	1.0000
8:37772753:A:AG	acceptor_gain	1.0000
8:37772753:A:AT	acceptor_loss	1.0000
8:37772754:G:GG	acceptor_gain	1.0000
8:37772754:GC:G	acceptor_gain	1.0000
8:37772754:GCT:G	acceptor_gain	1.0000
8:37772754:GCTGT:G	acceptor_gain	1.0000
8:37772850:TTAA:T	donor_gain	1.0000
8:37772885:AGAGA:A	donor_gain	1.0000
8:37772886:GAGA:G	donor_gain	1.0000
8:37772886:GAGAG:G	donor_gain	1.0000
8:37772887:AGA:A	donor_gain	1.0000
8:37772888:GA:G	donor_gain	1.0000
8:37772888:GAG:G	donor_gain	1.0000
8:37772890:G:A	donor_loss	1.0000
8:37772890:G:GG	donor_gain	1.0000

AlphaMissense

1802 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:37765566:A:T	K47I	0.999
8:37766307:T:A	W91R	0.999
8:37766307:T:C	W91R	0.999
8:37765567:A:C	K47N	0.998
8:37765567:A:T	K47N	0.998
8:37765562:A:C	S46R	0.997
8:37765564:C:A	S46R	0.997
8:37765564:C:G	S46R	0.997
8:37775984:A:C	S222R	0.997
8:37775986:C:A	S222R	0.997
8:37775986:C:G	S222R	0.997
8:37777995:T:A	V240D	0.997
8:37765565:A:G	K47E	0.996
8:37765630:C:A	N68K	0.996
8:37765630:C:G	N68K	0.996
8:37766309:G:C	W91C	0.996
8:37766309:G:T	W91C	0.996
8:37766320:G:A	G95D	0.996
8:37775343:A:C	K153N	0.996
8:37775343:A:T	K153N	0.996
8:37775420:G:A	G179E	0.996
8:37778004:G:A	G243E	0.996
8:37778015:T:C	F247L	0.996
8:37778017:T:A	F247L	0.996
8:37778017:T:G	F247L	0.996
8:37765565:A:C	K47Q	0.995
8:37765566:A:C	K47T	0.995
8:37765626:A:T	E67V	0.995
8:37765721:T:C	L73P	0.995
8:37775348:G:A	G155D	0.995

dbSNP variants (sampled 300 via entrez): RS1000363244 (8:37777258 T>C), RS1000377090 (8:37763417 A>G), RS1000431946 (8:37770139 G>A,T), RS1000499558 (8:37764225 C>A,T), RS1000556923 (8:37764601 G>A,T), RS1000607277 (8:37774458 A>T), RS1000621468 (8:37769853 A>G), RS1000736028 (8:37770918 A>G), RS1000769785 (8:37768676 T>C), RS1001115880 (8:37762440 C>A), RS1001226424 (8:37771089 T>C), RS1001229041 (8:37777129 T>G), RS1001279969 (8:37777415 C>A,T), RS1001364080 (8:37764723 C>A), RS1001375442 (8:37765042 T>C)

Disease associations

OMIM: gene MIM:604436 | disease phenotypes: MIM:617290

GenCC curated gene-disease

Disease	Classification	Inheritance
epilepsy, early-onset, vitamin B6-dependent	Strong	Autosomal recessive
pyridoxine-dependent epilepsy	Supportive	Autosomal recessive

Mondo (2): epilepsy, early-onset, vitamin B6-dependent (MONDO:0015005), pyridoxine-dependent epilepsy (MONDO:0009945)

Orphanet (0):

HPO phenotypes

59 total (30 of 59 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000219	Thin upper lip vermilion
HP:0000273	Facial grimacing
HP:0000343	Long philtrum
HP:0000496	Abnormality of eye movement
HP:0000582	Upslanted palpebral fissure
HP:0000629	Periorbital fullness
HP:0000711	Restlessness
HP:0000737	Irritability
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001276	Hypertonia
HP:0001336	Myoclonus
HP:0001557	Prenatal movement abnormality
HP:0001942	Metabolic acidosis
HP:0001943	Hypoglycemia
HP:0002069	Bilateral tonic-clonic seizure
HP:0002079	Hypoplasia of the corpus callosum
HP:0002093	Respiratory insufficiency
HP:0002104	Apnea
HP:0002119	Ventriculomegaly
HP:0002133	Status epilepticus
HP:0002151	Increased circulating lactate concentration
HP:0002188	Delayed CNS myelination
HP:0002280	Enlarged cisterna magna
HP:0002465	Poor speech

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002115_11	Axial length	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005318	axial length measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536254	Pyridoxine-dependent epilepsy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725171 (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: 1,538 (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
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178582: Inhibition of PROSC (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases expression, increases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression, decreases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
quinoline	increases expression	1
beta-methylcholine	affects 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	increases expression, affects cotreatment	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Cannabidiol	affects cotreatment, decreases expression	1
Copper	affects binding, decreases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Dactinomycin	increases secretion, affects cotreatment	1
Disulfiram	affects binding, decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Haloperidol	increases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Mitoxantrone	affects response to substance	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	increases expression	1
Zinc	increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697312	Binding	Inhibition of PROSC (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT06054347	Not specified	COMPLETED	Evaluation by a Vineland II Scale of Long-term Development of Children With Pyridoxine Dependent Epilepsy