PANK4

Chr 1AD

pantothenate kinase 4 (inactive)

Also known as: CTRCT49

NCBI Gene: 55229 ENSG00000157881 OMIM: 606162

This gene encodes a phosphatase that preferentially hydrolyzes 4'-phosphopantetheine and its oxidatively damaged forms, helping to prevent damage in the coenzyme A biosynthesis pathway and regulate intracellular CoA levels. Mutations cause autosomal dominant cataract 49. The gene is highly constrained against loss-of-function mutations (pLI 0.98), suggesting that heterozygous variants causing disease may be particularly significant.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein belonging to the pantothenate kinase family. 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 CoA. This family member is most abundant in muscle but is expressed in all tissues. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

ADLOEUF 0.301 OMIM phenotype

Clinical Summary— PANK4

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 97 VUS of 124 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.983

Z-score 4.89

OE 0.15 (0.08–0.30)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.42Z-score

OE missense 0.70 (0.64–0.76)

362 obs / 516.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.15 (0.08–0.30)

0≤0.351.4

Missense OE?0.70 (0.64–0.76)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 6 / 38.9Missense obs/exp: 362 / 516.6Syn Z: -2.13

ClinVar Variant Classifications

124 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS97

Likely Benign8

Benign2

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	1
Likely Pathogenic	0	0	0	0
VUS	97	0	0	97
Likely Benign	3	0	5	8
Benign	1	0	1	2
Total	101	1	6	108

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

View in ClinVar →

123 pathogenic / likely-pathogenic (of 142) ClinVar copy-number / structural variants overlap PANK4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →