PLPBP

pyridoxal phosphate binding protein

Basic information

Region (hg38): 8:37762594-37779768

Previous symbols: [ "PROSC" ]

Links

ENSG00000147471 ∙ NCBI:11212 ∙ OMIM:604436 ∙ HGNC:9457 ∙ Uniprot:O94903 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pyridoxine-dependent epilepsy (Supportive), mode of inheritance: AR
• epilepsy, early-onset, vitamin B6-dependent (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, early-onset 1, vitamin B6-dependent	AR	Neurologic	The condition involves neonatal or early-onset seizures, and medical treatment (with activated vitamin B6 and/or pyridoxine) has been reported as beneficial related to seizure control	Neurologic	27912044

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLPBP gene.

• not provided (180 variants)
• Epilepsy, early-onset, vitamin B6-dependent (25 variants)
• Inborn genetic diseases (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLPBP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				39	2	41
missense	1	2	78	4	1	86
nonsense	5	1	1			7
start loss			1			1
frameshift	5		2			7
inframe indel						0
splice donor/acceptor (+/-2bp)	4					4
splice region			5	6		11
non coding			2	29	6	37
Total	15	3	84	72	9

Highest pathogenic variant AF is 0.000237

Variants in PLPBP

This is a list of pathogenic ClinVar variants found in the PLPBP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-37762660-A-G			Uncertain significance (Jul 01, 2023)
8-37762665-G-A			Pathogenic (Apr 06, 2022)
8-37762666-A-C			Likely benign (Dec 31, 2023)
8-37762667-G-A			Uncertain significance (Oct 03, 2023)
8-37762670-C-T			Uncertain significance (Sep 01, 2022)
8-37762674-C-T			Likely benign (Apr 22, 2023)
8-37762675-A-G			Uncertain significance (Jun 20, 2022)
8-37762677-C-G			Uncertain significance (May 13, 2022)
8-37762678-A-C		Epilepsy, early-onset, vitamin B6-dependent	Uncertain significance (-)
8-37762678-A-G		Epilepsy, early-onset, vitamin B6-dependent	Uncertain significance (-)
8-37762678-A-T			Uncertain significance (May 19, 2022)
8-37762691-T-TG		Inborn genetic diseases	Pathogenic (Oct 28, 2022)
8-37762692-G-T			Likely benign (Sep 05, 2023)
8-37762694-G-C			Uncertain significance (Jun 08, 2022)
8-37762695-A-G			Likely benign (Nov 18, 2023)
8-37762699-G-C		Epilepsy, early-onset, vitamin B6-dependent	Uncertain significance (Aug 13, 2022)
8-37762701-G-A			Likely benign (Nov 27, 2023)
8-37762701-GTGCGCAT-G			Pathogenic (Dec 31, 2021)
8-37762703-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 24, 2023)
8-37762705-G-A			Uncertain significance (Aug 16, 2022)
8-37762705-G-T			Likely benign (Jan 19, 2024)
8-37762708-T-C			Likely benign (Jan 11, 2024)
8-37762711-C-T		Epilepsy, early-onset, vitamin B6-dependent	Uncertain significance (Jul 25, 2018)
8-37762713-G-T			Likely benign (Nov 19, 2023)
8-37762715-C-T			Uncertain significance (Oct 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLPBP	protein_coding	protein_coding	ENST00000328195	8	17173

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0397	0.954	125693	0	55	125748	0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.981	125	160	0.782	0.00000886	1784
Missense in Polyphen		36	49.077	0.73354		536
Synonymous	-0.381	68	64.1	1.06	0.00000388	528
Loss of Function	2.41	5	15.1	0.331	8.26e-7	163

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000640	0.000640
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000213	0.000211
Middle Eastern	0.000109	0.000109
South Asian	0.000229	0.000229
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000255|HAMAP-Rule:MF_03225, ECO:0000269|PubMed:27912044}.
• Disease: DISEASE: Epilepsy, early-onset, vitamin B6-dependent (EPVB6D) [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, mental retardation and learning disability. Seizures onset is in the first days or months of life. {ECO:0000269|PubMed:27912044}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.192

Intolerance Scores

• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.91

Haploinsufficiency Scores

• pHI: 0.0737
• hipred: Y
• hipred_score: 0.543
• ghis: 0.568

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Plpbp

Gene ontology

• Biological process: biological_process
• Cellular component: cytoplasm
• Molecular function: pyridoxal phosphate binding