PANK2

Chr 20AR

pantothenate kinase 2

Also known as: C20orf48, HARP, HSS, NBIA1, PKAN

The protein catalyzes the first committed step in coenzyme A biosynthesis within mitochondria and is subject to feedback inhibition by acyl CoA species. Mutations cause pantothenate kinase-associated neurodegeneration (PKAN), also known as neurodegeneration with brain iron accumulation 1, which is inherited in an autosomal recessive pattern. The pathogenesis involves disrupted coenzyme A metabolism leading to mitochondrial dysfunction and characteristic brain iron accumulation.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.971 OMIM phenotype
Clinical SummaryPANK2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.97LOEUF
pLI 0.000
Z-score 1.68
OE 0.61 (0.400.97)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.18Z-score
OE missense 0.97 (0.881.07)
298 obs / 306.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.61 (0.400.97)
00.351.4
Missense OE0.97 (0.881.07)
00.61.4
Synonymous OE1.26
01.21.6
LoF obs/exp: 13 / 21.4Missense obs/exp: 298 / 306.8Syn Z: -2.36
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePANK2-related HARP syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6744th %ile
GOF
0.5071th %ile
LOF
0.4431th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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