PANK2

Chr 20AR

pantothenate kinase 2

NCBI Gene: 80025ENSG00000125779UniProt: Q9BZ23

Mitochondrial isoform that catalyzes the phosphorylation of pantothenate to generate 4'-phosphopantothenate in the first and rate-determining step of coenzyme A (CoA) synthesis (PubMed:15659606, PubMed:16272150, PubMed:17242360, PubMed:17825826). Required for angiogenic activity of umbilical vein of endothelial cells (HUVEC) (PubMed:30221726)

Primary Disease Associations & Inheritance

Neurodegeneration with brain iron accumulation 1MIM #234200
AR
859
ClinVar variants
72
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PANK2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
72 Pathogenic / Likely Pathogenic· 145 VUS of 859 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.97LOEUF
pLI 0.000
Z-score 1.68
OE 0.61 (0.40–0.97)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.18Z-score
OE missense 0.97 (0.88–1.07)
298 obs / 306.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.61 (0.40–0.97)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.88–1.07)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.26
0≤1.21.6
LoF obs/exp: 13 / 21.4Missense obs/exp: 298 / 306.8Syn Z: -2.36

ClinVar Variant Classifications

859 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic26
VUS145
Likely Benign231
Benign22
Conflicting16
46
Pathogenic
26
Likely Pathogenic
145
VUS
231
Likely Benign
22
Benign
16
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
15
6
25
0
46
Likely Pathogenic
11
14
1
0
26
VUS
2
126
17
0
145
Likely Benign
0
4
72
155
231
Benign
0
0
22
0
22
Conflicting
—16
Total28150137155486

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PANK2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

PANK2-related HARP syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodegeneration with brain iron accumulation 1

MIM #234200

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Neurodegeneration with brain iron accumulation.
Hayflick SJ et al.·Handb Clin Neurol
2018Review
Pantothenate kinase-associated neurodegeneration.
Hartig MB et al.·Curr Drug Targets
2012Review
Axonal dystrophies.
Nardocci N et al.·Handb Clin Neurol
2013Review
Atypical pantothenate kinase-associated neurodegeneration with PANK2 mutations : clinical description and a review of the literature.
Pan S et al.·Neurocase
2020Review
Novel PANK2 mutation in a Chinese boy with PANK2-associated neurodegeneration: A case report and review of Chinese cases.
Zhang Y et al.·Medicine (Baltimore)
2019Review
A therapeutic approach to pantothenate kinase associated neurodegeneration: a pilot study.
Pereira A et al.·Orphanet J Rare Dis
2024
PKAN neurodegeneration and residual PANK2 activities in patient erythrocytes.
Werning M et al.·Ann Clin Transl Neurol
2020
Neurodegeneration with brain iron accumulation.
Gregory A et al.·Folia Neuropathol
2005Review
Mitochondrial and autophagic dysfunctions of skin fibroblasts derived from pantothenate kinase-associated neurodegeneration patients carrying PANK2 mutations and the rescuing effects of allantoin.
Zhu J et al.·Parkinsonism Relat Disord
2025Cohort
Concurrent PANK2 and OCA2 variants in a patient with retinal dystrophy, hypopigmented irides and neurodegeneration.
Wong EWN et al.·Ophthalmic Genet
2023Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Pharmacokinetic and Pharmacodynamic Evaluation of PZ-2891, an Anti-Alzheimer's Disease Agonist of PANK2.
Chen Y et al.·Pharmaceuticals (Basel)
2025🔓 Open Access
Distinct Neurodegenerative Pathways in Two NBIA Subtypes: Inflammatory Activation in C19orf12 but Not in PANK2 Mutation Carriers.
Skowrońska M et al.·Cells
2025🔓 Open Access
Rare PANK2 variants and pantothenate-kinase-associated neurodegeneration in the Dominican Republic.
Vardarajan BN et al.·Brain Commun
2025🔓 Open Access
Multi-level evidence reveals PANK2 as a potential target of PFOA/PFOS-induced bone metabolism disruption: From network toxicology to in vitro validation.
Shao Y et al.·Ecotoxicol Environ Saf
2025
Characterization of the Pank2-/- mouse retinal phenotype as a pre-clinical model for pantothenate kinase-associated neurodegeneration.
Su GL et al.·PLoS One
2025🔓 Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools