PDXK

protein-coding

pyridoxal kinase

Gene summary

The protein encoded by this gene phosphorylates vitamin B6, a step required for the conversion of vitamin B6 to pyridoxal-5-phosphate, an important cofactor in intermediary metabolism. The encoded protein is cytoplasmic and probably acts as a homodimer. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

Previous symbols:

C21orf97
C21orf124

MANE transcript

NM_003681.5

Inheritance

ClinVar variants

P:4U:38B:13

Top phenotype

Hereditary motor and sensory neuropathy, type VIC, with optic atrophy (Charcot-Marie-Tooth disease, type 6C)

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr21:43,719,094-43,762,307

External References & Databases

Ensembl (ENSG00000160209)

Transcript & Mutation Effects

hg38 • Region Span ~43.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neuropathy, hereditary motor and sensory, type VIc, with optic atrophySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032792

Submitter: Labcorp Genetics (formerly Invitae)

neuropathy, hereditary motor and sensory, type VIc, with optic atrophySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032792

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Hereditary motor and sensory neuropathy, type VIC, with optic atrophy (Charcot-Marie-Tooth disease, type 6C)AR

Manifestation: Neurologic; Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 31187503

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PDXK variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 43

not providedTotal: 23

PDXK-related disorderTotal: 13

Neuropathy, hereditary motor and sensory, type VIc, with optic atrophyTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003681.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	9 clinvar	2 clinvar	12
missense	2 clinvar	1 clinvar	33 clinvar	2 clinvar		38
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)	1 clinvar		4 clinvar			5
Total	3	1	38	11	2	55

Highest pathogenic variant AF is 0.000029125431

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003681.5	RefSeq	NP_003672.1	11	MANE Select
ENST00000291565.9	Ensembl	ENSP00000291565.4	11	MANE Select
NM_001331030.2	RefSeq	NP_001317959.1	10	Standard
ENST00000327574.4	Ensembl	ENSP00000333624.4	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vitamin B6 metabolism - Homo sapiens (human)
Hypophosphatasia
Vitamin B6 Metabolism
Neutrophil degranulation
Innate Immune System

Biological Process

cell population proliferation
pyridoxal 5'-phosphate salvage
phosphorylation
vitamin B6 metabolic process
pyridoxal phosphate biosynthetic process

Molecular Function

magnesium ion binding
ATP binding
zinc ion binding
pyridoxal kinase activity
pyridoxal phosphate binding

Cellular Component

extracellular region
nucleus
nucleoplasm
cytosol
secretory granule lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000291565
Coding exons: 11
Length: 43214
Individuals with no LoFs: 125667
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125672
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.87	118	191	0.619	0.0000116	2043
Missense (PolyPhen)		20	55.608	0.35966		694
Synonymous	0.813	72	81.3	0.885	0.00000563	586
Loss of Function	3.24	3	17.7	0.169	7.53e-7	211

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for synthesis of pyridoxal-5-phosphate from vitamin B6.;

Recessive Scores

pRec: 0.173

Intolerance Scores

LoFtool: 0.300
RVIS EVS: -0.31
RVIS percentile EVS: 31.93

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.996

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium