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PLPBP

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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): 256 total — 15 pathogenic, 5 likely-pathogenic
  • GTEx eGene: eQTL in 23 tissues, sQTL in 7 (q < 0.05)
  • Phenotypes (HPO): 59
  • ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
  • Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.05 (unconstrained)
  • MANE Select transcript: NM_007198

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:9457
Approved symbolPLPBP
Namepyridoxal phosphate binding protein
Location8p11.23
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000147471
Ensembl biotypeprotein_coding
OMIM604436
Entrez11212

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 16 protein_coding, 7 nonsense_mediated_decay, 4 retained_intron

MANE Select: ENST00000328195

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 3, TSL 3: 4, TSL 4: 1

ENST00000328195, ENST00000518036, ENST00000520073, ENST00000521631, ENST00000522808, ENST00000523187, ENST00000523358, ENST00000523521, ENST00000523994, ENST00000872272, ENST00000872273, ENST00000872274, ENST00000958638, ENST00000958639, ENST00000958640, ENST00000979521, ENST00000979522, ENST00001013772, ENST00001062617, ENST00001107029, ENST00001113854, ENST00001120324, ENST00001120325, ENST00001127256, ENST00001127257, ENST00001130058, ENST00001136649

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

ExonStartEnd
ENSE000013168683777275537772889
ENSE000013261353777533937775481
ENSE000021048533776264537762758
ENSE000021318563777797337779768
ENSE000035031763777591837776016
ENSE000035070313776628037766355
ENSE000035377723776552637765633
ENSE000036170043776571137765746

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.

Highest expression (Bgee): cardia of stomach, pericardium, renal medulla, jejunal mucosa, pylorus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PLPBP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 23 tissues and its splicing (sQTL) in 7 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 30 significant tissue × QTL associations:

TissueQTLq-valueSlopeLead variant
Whole Bloodeqtl4.4e-29+0.248:37778131:A:G
Brain Nucleus accumbens basal gangliaeqtl3.2e-08+0.318:37778131:A:G
Pancreaseqtl1.0e-07+0.248:37778131:A:G
Cells EBV-transformed lymphocyteseqtl8.1e-07+0.338:37778131:A:G
Skin Sun Exposed Lower legeqtl5.5e-05+0.148:37778131:A:G
Stomachsqtl9.5e-05+1.358:37775854:T:A
Skin Not Sun Exposed Suprapubiceqtl1.6e-04+0.168:37778131:A:G
Brain Hypothalamuseqtl2.0e-04+0.308:37778131:A:G
Stomacheqtl7.8e-04+0.228:37778131:A:G
Nerve Tibialeqtl1.7e-03+0.118:37778131:A:G
Cells EBV-transformed lymphocytessqtl2.1e-03+0.748:37767936:GC:G
Spleeneqtl3.2e-03+0.228:37778131:A:G
Artery Tibialeqtl3.9e-03+0.128:37778131:A:G
Artery Tibialsqtl6.3e-03+0.868:37767939:A:T
Thyroideqtl7.4e-03+0.108:37778131:A:G
Colon Sigmoideqtl9.4e-03-0.538:37219162:A:T
Brain Caudate basal gangliasqtl9.5e-03+2.148:37754189:C:G
Colon Transverseeqtl9.7e-03+0.128:37778131:A:G
Pituitaryeqtl1.0e-02+0.198:37778131:A:G
Brain Cerebellar Hemisphereeqtl1.2e-02+0.198:37778131:A:G

FANTOM5 promoters

3 alternative TSS:

Promoter IDTPM avgSamples expressed
884509.28801777
884517.10381733
884524.01991647

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
cardia of stomachUBERON:000116296.88gold quality
pericardiumUBERON:000240796.82gold quality
renal medullaUBERON:000036296.59gold quality
jejunal mucosaUBERON:000039996.34gold quality
pylorusUBERON:000116696.19gold quality
colonic mucosaUBERON:000031795.85gold quality
entorhinal cortexUBERON:000272895.81gold quality
adult organismUBERON:000702395.79gold quality
mucosa of sigmoid colonUBERON:000499395.78gold quality
postcentral gyrusUBERON:000258195.64gold quality
monocyteCL:000057695.52gold quality
secondary oocyteCL:000065595.48gold quality
parietal lobeUBERON:000187295.47gold quality
mononuclear cellCL:000084295.42gold quality
lower lobe of lungUBERON:000894995.31gold quality
leukocyteCL:000073895.30gold quality
jejunumUBERON:000211595.27gold quality
islet of LangerhansUBERON:000000695.20gold quality
nippleUBERON:000203095.11gold quality
ventral tegmental areaUBERON:000269195.11gold quality
inferior vagus X ganglionUBERON:000536395.06gold quality
ileal mucosaUBERON:000033195.01gold quality
ponsUBERON:000098894.98gold quality
heart right ventricleUBERON:000208094.91gold quality
duodenumUBERON:000211494.91gold quality
vena cavaUBERON:000408794.90gold quality
oocyteCL:000002394.77gold quality
pigmented layer of retinaUBERON:000178294.76gold quality
parietal pleuraUBERON:000240094.75gold quality
palpebral conjunctivaUBERON:000181294.61gold quality
nephron tubuleUBERON:000123194.47gold quality
blood vessel layerUBERON:000479794.45gold quality
parotid glandUBERON:000183194.44gold quality
myocardiumUBERON:000234994.40gold quality
superior frontal gyrusUBERON:000266194.37gold quality
pancreasUBERON:000126494.29gold quality
superior vestibular nucleusUBERON:000722794.27gold quality
trabecular bone tissueUBERON:000248394.26gold quality
rectumUBERON:000105294.25gold quality
adult mammalian kidneyUBERON:000008294.24gold quality
pleuraUBERON:000097794.17gold quality
body of pancreasUBERON:000115094.16gold quality
visceral pleuraUBERON:000240194.12gold quality
substantia nigra pars compactaUBERON:000196594.04gold quality
liverUBERON:000210794.04gold quality
urethraUBERON:000005794.02gold quality
skeletal muscle tissue of rectus abdominisUBERON:000451193.97gold quality
Brodmann (1909) area 46UBERON:000648393.93gold quality
seminal vesicleUBERON:000099893.90gold quality
substantia nigra pars reticulataUBERON:000196693.82gold quality
middle temporal gyrusUBERON:000277193.81gold quality
kidneyUBERON:000211393.80gold quality
popliteal arteryUBERON:000225093.76gold quality
tibial arteryUBERON:000761093.76gold quality
right coronary arteryUBERON:000162593.75gold quality
superior surface of tongueUBERON:000737193.75gold quality
body of tongueUBERON:001187693.64gold quality
dorsal root ganglionUBERON:000004493.63gold quality
trigeminal ganglionUBERON:000167593.61gold quality
calcaneal tendonUBERON:000370193.56gold quality
descending thoracic aortaUBERON:000234593.53gold quality
kidney epitheliumUBERON:000481993.53gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450293.50gold quality
lateral globus pallidusUBERON:000247693.48gold quality
mucosa of transverse colonUBERON:000499193.38gold quality
aortaUBERON:000094793.36gold quality
mammalian vulvaUBERON:000099793.30gold quality
synovial jointUBERON:000221793.26gold quality
subthalamic nucleusUBERON:000190693.20gold quality
choroid plexus epitheliumUBERON:000391193.18gold quality
coronary arteryUBERON:000162193.08gold quality
medulla oblongataUBERON:000189693.02gold quality
hindlimb stylopod muscleUBERON:000425293.01gold quality
germinal epithelium of ovaryUBERON:000130492.97gold quality
temporal lobeUBERON:000187192.96gold quality
tongueUBERON:000172392.95gold quality
gastrocnemiusUBERON:000138892.92gold quality
muscle of legUBERON:000138392.86gold quality
left coronary arteryUBERON:000162692.85gold quality
cardiac muscle of right atriumUBERON:000337992.83gold quality
biceps brachiiUBERON:000150792.79gold quality
thoracic aortaUBERON:000151592.79gold quality
muscle organUBERON:000163092.73gold quality
heartUBERON:000094892.72gold quality
ascending aortaUBERON:000149692.71gold quality
skeletal muscle tissueUBERON:000113492.69gold quality
pharyngeal mucosaUBERON:000035592.68gold quality
cartilage tissueUBERON:000241892.64gold quality
cardiac atriumUBERON:000208192.63gold quality
cardiac ventricleUBERON:000208292.63gold quality
deltoidUBERON:000147692.62gold quality
prefrontal cortexUBERON:000045192.58gold quality
muscle tissueUBERON:000238592.58gold quality
cortex of kidneyUBERON:000122592.56gold quality
heart left ventricleUBERON:000208492.54gold quality
mucosa of paranasal sinusUBERON:000503092.54gold quality
lateral nuclear group of thalamusUBERON:000273692.50gold quality
right atrium auricular regionUBERON:000663192.48gold quality
vastus lateralisUBERON:000137992.42gold quality
left ventricle myocardiumUBERON:000656692.30gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes11.42

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cellAxisnTPMProtein (IHC)
Livertissue73.0medium
Kidneytissue54.5high
Colontissue44.2high
Skeletal muscletissue43.5medium
Choroid plexustissue40.9
Frontal cortextissue39.4
Tonguetissue39.3
Pancreastissue38.0medium
Heart muscletissue36.7medium
Caudate putamentissue36.0
Rectumtissue35.5high
Parathyroid glandtissue35.1high
Small intestinetissue35.1high
Nucleus accumbenstissue34.9
Locus coeruleustissue34.6
Hippocampustissue32.8high
Duodenumtissue32.4high
Adipose tissuetissue32.1low
Postcentral gyrustissue31.7
Stomach 1tissue31.6high
Thyroid glandtissue29.7high
Cerebral cortextissue29.0high
Somatosensory cortextissue29.0
Occipital cortextissue27.8
Hippocampal formationtissue27.7
Motor cortextissue27.1
Tonsiltissue27.1medium
Prefrontal cortextissue26.8
Salivary glandtissue26.7medium
Substantia nigratissue26.7
Thalamustissue26.5
Superior colliculitissue26.4
Seminal vesicletissue26.2medium
Fallopian tubetissue25.9medium
Thymustissue25.6
Ponstissue25.4
Entorhinal cortextissue25.3
Temporal cortextissue25.1
Retrosplenial and cingulate cortextissue24.7
Smooth muscletissue24.2medium
Lungtissue24.2medium
Spleentissue23.5high
Lymph nodetissue23.4medium
Putamentissue23.3
Retrosplenial cortextissue23.2
Insular cortextissue23.2
Midbraintissue22.6
Cerebellumtissue22.6high
Basal gangliatissue22.5low
Epididymistissue22.0medium
Septumtissue21.9
Breasttissue21.8high
Adrenal glandtissue21.8high
Urinary bladdertissue21.4medium
Ventral forebraintissue20.9
Cervixtissue20.8medium
Ovarytissue20.7low
Amygdalatissue20.2
Hypothalamustissue20.0
Appendixtissue20.0medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Corpus callosum, genu (white matter) (43.4), Area parastriata, superior (40.5), Blood vessel (39.2), Corpus callosum, splenium (white matter) (38.8), Supraoptic nucleus (37.9).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PLPBP by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 74 miRNAs:

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3613-3P100.0076.367965
HSA-MIR-4283100.0066.422097
HSA-MIR-150-5P99.9966.691976
HSA-MIR-34A-5P99.9971.211784
HSA-MIR-449A99.9971.051776
HSA-MIR-477599.9875.006394
HSA-MIR-34C-5P99.9770.451577
HSA-MIR-449B-5P99.9770.261580
HSA-MIR-365899.9673.874379
HSA-MIR-96-5P99.9572.802140
HSA-MIR-1213399.9271.822006
HSA-MIR-1271-5P99.9171.991972
HSA-MIR-153-5P99.8973.866317
HSA-MIR-4671-3P99.8872.461045
HSA-MIR-76599.8468.242442
HSA-MIR-5010-3P99.8370.602357
HSA-MIR-6515-3P99.8268.191933
HSA-MIR-205299.7969.372031
HSA-MIR-202-5P99.7867.65991
HSA-MIR-129999.7771.242389
HSA-MIR-11181-3P99.7566.382205
HSA-MIR-33A-3P99.7070.273362
HSA-MIR-6892-3P99.6866.401178
HSA-MIR-3158-5P99.6567.511763
HSA-MIR-130399.6569.771662
HSA-MIR-875-3P99.6369.472548
HSA-MIR-548AV-5P99.6070.842107
HSA-MIR-548K99.6070.842107
HSA-MIR-1252-3P99.5567.712862
HSA-MIR-443799.5265.291266

Functional genomics

gnomAD constraint: pLI 5.32e-06, LOEUF 1.05, missense Z 0.913 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000328195 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)Missense obs / expo/eConstrained
8:37,762,660–37,765,623120 / 95.11.26no
8:37,765,624–37,778,101188 / 259.30.73no

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

OrganismSymbolGene ID
danio_rerioplpbpENSDARG00000060288
mus_musculusPlpbpENSMUSG00000031485
rattus_norvegicusPlpbpENSRNOG00000013751
drosophila_melanogasterCG1983FBGN0039751
caenorhabditis_elegansWBGENE00017285

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1891207) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)Records
preweaning lethality, incomplete penetrance1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

OrganismUniProtIdentityMethod
Escherichia coli K-12P67080100.0%Diamond
Escherichia coli CFT073P67081100.0%Diamond
Escherichia coli O157:H7P67082100.0%Diamond
Mycobacterium tuberculosis variant bovis AF2122/97P67084100.0%Diamond
Mycobacterium tuberculosis CDC1551P9WFQ6100.0%Diamond
Mycobacterium tuberculosis H37RvP9WFQ7100.0%Diamond
Pongo abeliiQ5R4Z196.7%Diamond
Helicobacter pylori 26695O2515695.9%Diamond
Helicobacter pylori J99Q9ZKF295.9%Diamond
Bos taurusQ3T0G588.4%Diamond
Haemophilus influenzae Rd KW20P4450678.0%Diamond
Pasteurella multocida subsp. multocida str. Pm70Q9CPD578.0%Diamond
Vibrio alginolyticusP5205575.5%Diamond
Vibrio cholerae O1 biovar El Tor str. N16961Q9KUQ475.5%Diamond
Mycobacterium leprae TNQ9CCE273.6%Diamond
Buchnera aphidicola str. APS (Acyrthosiphon pisum)P5761459.3%Diamond
Buchnera aphidicola str. Sg (Schizaphis graminum)Q8K92959.3%Diamond
Pseudomonas aeruginosa PAO1P2456257.8%Diamond
Buchnera aphidicola str. Bp (Baizongia pistaciae)Q89A4849.1%Diamond
Dictyostelium discoideumQ1ZXI647.6%Diamond
Saccharomyces cerevisiae S288CP3819746.3%Diamond
Schizosaccharomyces pombe 972h-Q9P6Q145.4%Diamond
Aquifex aeolicus VF5O6663142.4%Diamond
Synechocystis sp. PCC 6803 substr. KazusaP5205641.8%Diamond
Bacillus subtilis subsp. subtilis str. 168O3172741.6%Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

SymbolTypeEntrez
ERLIN2protein-coding11160
ZNF703protein-coding80139
ADGRA2protein-coding25960
BRF2protein-coding55290
RAB11FIP1protein-coding80223

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): E5RFX7, E5RFZ4, E5RG77, O94903, 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)

IDNameType
IPR001608Ala_racemase_NDomain
IPR011078PyrdxlP_homeostasisFamily
IPR029066PLP-binding_barrelHomologous_superfamily

Pfam: PF01168

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

Structure

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-O94903-F189.490.79

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes, Human disease related genes, Epilepsy

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH approved · IF enhanced

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)

TypePositions
Phosphoserine6, 226, 244
N6-(pyridoxal phosphate)lysine47
Phosphotyrosine69
N6-succinyllysine125

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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

8 GO namespaces:

CategoryTerms
cellular anatomical structure2
cytoplasm2
vitamin metabolic process1
pyridine-containing compound metabolic process1
anion binding1
vitamin B6 binding1
intracellular anatomical structure1
intracellular membrane-bounded organelle1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 5 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO termNSEvidence
cytosolCCdirect assay
mitochondrionCChigh-throughput

Protein interactions and networks

STRING

showing 15 of 1,038 interactions by confidence (×1000):

Protein AProtein BPartner UniProtScore
PLPBPPNPOQ9NVS9836
PLPBPALDH7A1P49419689
PLPBPLSM1O15116630
PLPBPDDHD2O94830625
PLPBPPDXKO00764620
PLPBPERLIN2O94905571
PLPBPZNF703Q9H7S9555
PLPBPRAB11FIP1Q6WKZ4548
PLPBPBAG4O95429506
PLPBPPDXPQ96GD0497
PLPBPALDH4A1P30038487
PLPBPGOT1L1Q8NHS2486
PLPBPPLPP5Q8NEB5486
PLPBPRASSF4Q9H2L5471
PLPBPASH2LQ9UBL3464

IntAct

Human interaction partners of PLPBP in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

PartnerInteraction typeMIscoreRecords
FARP1association0.3501
FCGR2Aassociation0.3501
FMNL2association0.3501
HPS1association0.3501
KDM5Bassociation0.3501
NUDT13association0.3501
PCK2association0.3501
RPA1association0.3501
SATB1association0.3501
TMEM101association0.3501

Disease & clinical

Genetic variants

Variant evidence for PLPBP: 256 ClinVar records (20 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

ClassificationCount (floor)
Pathogenic15
Likely pathogenic5
Uncertain significance89
Likely benign114
Benign4

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 20 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant IDHGVSClassificationReviewSubmitters
503895NM_007198.4(PLPBP):c.370_373del (p.Asp124fs)Pathogeniccriteria provided, multiple submitters, no conflicts5
374855NM_007198.4(PLPBP):c.320-2A>GPathogeniccriteria provided, multiple submitters, no conflicts3
2136656NM_007198.4(PLPBP):c.249_252del (p.Ser84fs)Pathogeniccriteria provided, multiple submitters, no conflicts2
374852NM_007198.4(PLPBP):c.233C>G (p.Ser78Ter)Pathogeniccriteria provided, single submitter2
374854NM_007198.4(PLPBP):c.207+1G>APathogeniccriteria provided, single submitter2
1323499NM_007198.4(PLPBP):c.211C>T (p.Gln71Ter)Pathogeniccriteria provided, single submitter1
1806055NM_007198.4(PLPBP):c.387del (p.Trp130fs)Pathogeniccriteria provided, single submitter1
2112606NM_007198.4(PLPBP):c.207+1G>CPathogeniccriteria provided, single submitter1
2743804NM_007198.4(PLPBP):c.207C>A (p.Tyr69Ter)Pathogeniccriteria provided, single submitter1
2745421NM_007198.4(PLPBP):c.292C>T (p.Gln98Ter)Pathogeniccriteria provided, single submitter1
2761004NM_007198.4(PLPBP):c.316del (p.Met106fs)Pathogeniccriteria provided, single submitter1
3215368NM_007198.4(PLPBP):c.35dup (p.Val13fs)Pathogeniccriteria provided, single submitter1
2136657NM_007198.4(PLPBP):c.614G>A (p.Arg205Gln)Likely pathogeniccriteria provided, single submitter1
2444519NM_007198.4(PLPBP):c.389G>A (p.Trp130Ter)Likely pathogeniccriteria provided, single submitter1
2797687NM_007198.4(PLPBP):c.319+1G>CLikely pathogeniccriteria provided, single submitter1

Per-variant reference — Sugi Variant

Explore PLPBP’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 496):

Position(s)EffectΔscoreSites
8:37765524–37765525acceptor_loss1.00006
8:37772753–37772754acceptor_loss1.00004
8:37772890–37772891donor_loss1.00005
8:37775334acceptor_gain1.0000
8:37775337–37775338acceptor_loss1.00004
8:37775482–37775483donor_loss1.00005
8:37775912acceptor_gain1.0000
8:37776017–37776018donor_loss1.00005
8:37777971–37777972acceptor_loss1.00006
8:37762765donor_gain0.9900

AlphaMissense

662 missense substitutions predicted likely pathogenic (of 1,802 scored), across 163 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

ResidueLikely-pathogenic substitutionsMean am_pathogenicityMax am_pathogenicity
M22590.9600.992
M18190.9540.995
M22390.8670.969
F24780.9720.996
D22880.9690.986
N6880.9540.996
F19880.9420.994
S22280.9400.997
F6580.9340.994
H9280.9300.985
D19780.8730.930
W9170.9890.999
E6770.9770.995
K4770.9730.999
F22970.9480.983
K7670.9310.986
F9370.9290.984
C8670.9250.975
E7270.9050.969
C17270.9030.980

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

CancerPrognosticp-value
Kidney Renal Clear Cell Carcinoma (TCGA)favorable1.69e-07
Kidney Renal Clear Cell Carcinoma (validation)favorable0.000204

Disease associations

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

GenCC curated gene-disease

2 curated gene-disease records:

DiseaseClassificationInheritanceRecords
epilepsy, early-onset, vitamin B6-dependentStrongAutosomal recessive3
pyridoxine-dependent epilepsySupportiveAutosomal recessive

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (8 panels, 8 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

8 panels:

PanelRating
DDG2Pgreen
Early onset or syndromic epilepsygreen
Fetal anomaliesgreen
Hypotonic infantgreen
Intellectual disabilitygreen
Leukodystrophy, childhood onsetgreen
Paediatric disordersgreen
Unexplained death in infancy and sudden unexplained death in childhoodgreen

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

HPO phenotypes

59 phenotypes (HPO-id order):

HPOTerm
HP:0000007Autosomal recessive inheritance
HP:0000219Thin upper lip vermilion
HP:0000273Facial grimacing
HP:0000343Long philtrum
HP:0000496Abnormality of eye movement
HP:0000582Upslanted palpebral fissure
HP:0000629Periorbital fullness
HP:0000711Restlessness
HP:0000737Irritability
HP:0000750Delayed speech and language development
HP:0001249Intellectual disability
HP:0001250Seizure
HP:0001252Hypotonia
HP:0001263Global developmental delay
HP:0001270Motor delay
HP:0001276Hypertonia
HP:0001336Myoclonus
HP:0001557Prenatal movement abnormality
HP:0001942Metabolic acidosis
HP:0001943Hypoglycemia
HP:0002069Bilateral tonic-clonic seizure
HP:0002079Hypoplasia of the corpus callosum
HP:0002093Respiratory insufficiency
HP:0002104Apnea
HP:0002119Ventriculomegaly
HP:0002133Status epilepticus
HP:0002151Increased circulating lactate concentration
HP:0002188Delayed CNS myelination
HP:0002280Enlarged cisterna magna
HP:0002465Poor speech
HP:0002521Hypsarrhythmia
HP:0002643Neonatal respiratory distress
HP:0003128Lactic acidosis
HP:0003593Infantile onset
HP:0003623Neonatal onset
HP:0005484Secondary microcephaly
HP:0007359Focal-onset seizure
HP:0010819Atonic seizure
HP:0010841Multifocal epileptiform discharges
HP:0010845EEG with generalized slow activity
HP:0010851EEG with burst suppression
HP:0011097Epileptic spasm
HP:0011152Early onset absence seizures
HP:0011166Focal myoclonic seizure
HP:0011198EEG with generalized epileptiform discharges
HP:0011199EEG with generalized sharp slow waves
HP:0011968Feeding difficulties
HP:0012420Meconium stained amniotic fluid
HP:0012444Brain atrophy
HP:0012704Widened subarachnoid space
HP:0012758Neurodevelopmental delay
HP:0012768Neonatal asphyxia
HP:0020045Esodeviation
HP:0020217Focal aware motor seizure
HP:0020221Clonic seizure
HP:0025116Fetal distress
HP:0030917Low APGAR score
HP:0032792Tonic seizure
HP:0032794Myoclonic seizure

GWAS associations

1 associations:

StudyTraitp-value
GCST002115_11Axial length3e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO IDTrait name
EFO:0005318axial length measurement

MeSH disease descriptors

1 disease descriptors:

DescriptorNameTree numbers
C536254Pyridoxine-dependent epilepsy *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725171 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,601 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

MoleculeNamePhasePatents
CHEMBL1232461MOLIBRESIB21,601

PharmGKB: 1 entry (CPIC guideline: no)

ChEMBL bioactivities

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

pChemblTypeValueUnitMolecule
5.00IC501e+04nMMOLIBRESIB

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.

CompoundAssayTypeValueUnit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide2178582: Inhibition of PROSC (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysisic5010.0000uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
Tretinoinincreases expression, decreases expression3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxidedecreases expression, increases expression2
aristolochic acid Iincreases expression1
triphenyl phosphateaffects expression1
bisphenol Aincreases expression1
quinolineincreases expression1
beta-methylcholineaffects expression1
di-n-butylphosphoric acidaffects expression1
CGP 52608affects binding, increases reaction1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, increases expression1
nutlin 3affects cotreatment, increases secretion1
bisphenol Sincreases expression1
LDN 193189affects cotreatment, increases expression1
bisphenol AFincreases expression1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic aciddecreases expression1
Resveratrolaffects cotreatment, increases expression1
Cannabidiolaffects cotreatment, decreases expression1
Copperaffects binding, decreases expression1
Cuprizoneaffects cotreatment, decreases expression1
Dactinomycinaffects cotreatment, increases secretion1
Disulfiramaffects binding, decreases expression1
Enzyme Inhibitorsdecreases activity, increases O-linked glycosylation1
Haloperidolincreases expression1
Hydrogen Peroxideaffects expression1
Ivermectindecreases expression1
Leaddecreases expression1
Mitoxantroneaffects response to substance1
Plant Extractsaffects cotreatment, increases expression1
Quercetinincreases expression1
Zincincreases expression1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL5697312BindingInhibition of PROSC (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysisInhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — *Nature*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

3 trials:

NCTPhaseStatusTitle
NCT03655223Not specifiedACTIVE_NOT_RECRUITINGEarly Check: Expanded Screening in Newborns
NCT05687474Not specifiedCOMPLETEDBaby Detect : Genomic Newborn Screening
NCT06054347Not specifiedCOMPLETEDEvaluation by a Vineland II Scale of Long-term Development of Children With Pyridoxine Dependent Epilepsy

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PLPBP across ~30M SureChEMBL compounds — explore on Sugi Predict.

About this page

Built deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source. Provided for research and reference, not medical advice or a diagnosis. Data may be incomplete, especially for rare conditions. Consult a qualified clinician.

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Sources 96

This page pulls from 96 datasets indexed by BioBTree:

alliance_phenotypealphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruscellphonedbchembl_activitychembl_assaychembl_documentchembl_mechanismchembl_moleculechembl_targetciviccivic_assertioncivic_evidencecivic_variantclingen_dosageclingen_gene_validityclingen_variantclinical_trialsclinvarcollectricorumctd_gene_interactiondepmapdepmap_dependencydiamond_similarityefoensemblentrezexonfantom5_genefantom5_promotergenccgenerifgnomad_constraintgnomad_rmcgogoparentgtex_egenegtopdbgwasgwas_studyhgnchpahpa_expressionhpa_pathologyhpointactinterprointogenjasparmeshmgimimmirdbmondomsigdbneighborentrezorphanetorthologorthologentrezpanelapp_geneparalogpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_var_annotationpharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontaxonomytranscriptufeatureuniprot