PANK2

protein-coding

pantothenate kinase 2, the group of Pantothenate kinase family|MicroRNA protein coding host genes

Gene summary

This gene encodes a protein belonging to the pantothenate kinase family and is the only member of that family to be expressed in mitochondria. Pantothenate kinase is a key regulatory enzyme in the biosynthesis of coenzyme A (CoA) in bacteria and mammalian cells. It catalyzes the first committed step in the universal biosynthetic pathway leading to CoA and is itself subject to regulation through feedback inhibition by acyl CoA species. Mutations in this gene are associated with HARP syndrome and pantothenate kinase-associated neurodegeneration (PKAN), formerly Hallervorden-Spatz syndrome. Alternative splicing, involving the use of alternate first exons, results in multiple transcripts encoding different isoforms. [provided by RefSeq, Jul 2008]

Previous symbols:

C20orf48
NBIA1

MANE transcript

NM_001386393.1

Inheritance

AR, AD

ClinVar variants

P:155U:189B:187

Top phenotype

Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration; Neurodegeneration with brain iron accumulation 1

gnomAD constraint

pLI —, LoF o/e 0.61

Max pathogenic AF

—

Genomic locus

chr20:3,888,839-3,929,887

External References & Databases

Ensembl (ENSG00000125779)

Transcript & Mutation Effects

hg38 • Region Span ~41.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pantothenate kinase-associated neurodegenerationSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009319

Submitter: Genomics England PanelApp

pantothenate kinase-associated neurodegenerationSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009319

Submitter: Labcorp Genetics (formerly Invitae)

pantothenate kinase-associated neurodegenerationDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009319

Submitter: G2P

Clinical Genomic Database (CGD)

Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration; Neurodegeneration with brain iron accumulation 1AD/AR

Manifestation: Gastrointestinal; Hematologic; 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: 477009; 7158329; 3969211; 1447570; 1734303; 7885538; 7898702; 8944032; 11479594; 12058097; 12510040; 14638969; 15911822; 15642932; 16240131; 16437574; 16687521; 18981035; 20301663; 21286947

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PANK2 variants in ClinVar

15 Conditions Cataloged

Pigmentary pallidal degenerationTotal: 532

not providedTotal: 152

not specifiedTotal: 74

Inborn genetic diseasesTotal: 64

PANK2-related disorderTotal: 26

Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degenerationTotal: 14

Retinitis pigmentosaTotal: 3

Dystonic disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001386393.1. 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			3 clinvar	180 clinvar		183
missense	20 clinvar	49 clinvar	181 clinvar	7 clinvar		257
nonsense	15 clinvar	2 clinvar	2 clinvar			19
start loss		2 clinvar				2
frameshift	32 clinvar	19 clinvar				51
splice donor/acceptor (+/-2bp)	7 clinvar	9 clinvar	3 clinvar			19
Total	74	81	189	187	0	531

Highest pathogenic variant AF is 0.000244726

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001386393.1	RefSeq	NP_001373322.1	7	MANE Select
ENST00000610179.7	Ensembl	ENSP00000477429.2	7	MANE Select
NM_001324191.2	RefSeq	NP_001311120.1	6	Standard
NM_001324192.1	RefSeq	NP_001311121.1	2	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
pank2	Danio rerio	Structure: nucleate erythrocyte Quality: spatial pattern abnormal

Gene / Model

Organism

Observed Phenotype

pank2

Danio rerio

Structure: nucleate erythrocyte

Quality: spatial pattern

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pantothenate and CoA biosynthesis - Homo sapiens (human)
Coenzyme A biosynthesis
Vitamin B5 - CoA biosynthesis from pantothenate
Metabolism
Vitamin B5 (pantothenate) metabolism

Biological Process

spermatid development
aerobic respiration
coenzyme biosynthetic process
coenzyme A biosynthetic process
pantothenate metabolic process

Molecular Function

pantothenate kinase activity
ATP binding

Cellular Component

nucleus
mitochondrion
mitochondrial intermembrane space
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000316562
Coding exons: 7
Length: 38120
Individuals with no LoFs: 125698
Homozygous LoFs: 0
Heterozygous LoFs: 50
Defined: 125748
p: 0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.179	298	307	0.971	0.0000165	3576
Missense (PolyPhen)		50	88.235	0.56667		1021
Synonymous	-2.36	163	129	1.26	0.00000696	1224
Loss of Function	1.68	13	21.4	0.608	0.00000111	261

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00025	0.00025	rare
South Asian	0.00016	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be the master regulator of the CoA biosynthesis. {ECO:0000250}.;
Disease: DISEASE: Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration (HARP) [MIM:607236]: Rare syndrome with many clinical similarities to PKAN. {ECO:0000269|PubMed:12058097}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.192

Intolerance Scores

LoFtool: 0.132
RVIS EVS: -0.23
RVIS percentile EVS: 37.11

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.994

Gene Damage Prediction

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