PXK

protein-coding

PX domain containing serine/threonine kinase like

Gene summary

This gene encodes a phox (PX) domain-containing protein which may be involved in synaptic transmission and the ligand-induced internalization and degradation of epidermal growth factors. Variations in this gene may be associated with susceptibility to systemic lupus erythematosus (SLE). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

MANE transcript

NM_017771.5

Inheritance

—

ClinVar variants

U:78B:6

Top phenotype

systemic lupus erythematosus

gnomAD constraint

pLI —, LoF o/e 0.29

Max pathogenic AF

—

Genomic locus

chr3:58,332,880-58,426,127

External References & Databases

Ensembl (ENSG00000168297)

Transcript & Mutation Effects

hg38 • Region Span ~93.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

systemic lupus erythematosusSUPPORTIVE

Inheritance Pattern: Unknown

Disease ID:MONDO:0007915

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PXK variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 69

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017771.5. 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			2 clinvar	2 clinvar	1 clinvar	5
missense			69 clinvar	2 clinvar	1 clinvar	72
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	78	4	2	84

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 123 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017771.5	RefSeq	NP_060241.2	18	MANE Select
ENST00000356151.7	Ensembl	ENSP00000348472.2	18	MANE Select
NM_001289095.2	RefSeq	NP_001276024.1	18	Standard
NM_001289096.2	RefSeq	NP_001276025.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein phosphorylation
inflammatory response
negative regulation of ATPase activity
regulation of membrane potential
negative regulation of ion transport

Molecular Function

nucleotide binding
actin binding
protein kinase activity
ATP binding
phosphatidylinositol binding

Cellular Component

cytoplasm
microtubule organizing center
cytosol
plasma membrane
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000356151
Coding exons: 18
Length: 93142
Individuals with no LoFs: 125727
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 125748
p: 0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.09	246	299	0.822	0.0000160	3740
Missense (PolyPhen)		51	76.478	0.66685		960
Synonymous	0.569	108	116	0.933	0.00000675	1093
Loss of Function	4.06	11	38.0	0.290	0.00000229	445

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.00017	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to and modulates brain Na,K-ATPase subunits ATP1B1 and ATP1B3 and may thereby participate in the regulation of electrical excitability and synaptic transmission. May not display kinase activity. {ECO:0000250|UniProtKB:Q8BX57, ECO:0000303|PubMed:16142408}.;

Recessive Scores

pRec: 0.0984

Intolerance Scores

LoFtool: 0.559
RVIS EVS: 0.27
RVIS percentile EVS: 70.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.988

Gene Damage Prediction

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