PKLR

Chr 1

pyruvate kinase L/R

Also known as: CNSHA2, PK1, PKL, PKRL, RPK

The protein encoded by this gene is a pyruvate kinase that catalyzes the transphosphorylation of phohsphoenolpyruvate into pyruvate and ATP, which is the rate-limiting step of glycolysis. Defects in this enzyme, due to gene mutations or genetic variations, are the common cause of chronic hereditary nonspherocytic hemolytic anemia (CNSHA or HNSHA). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPyruvate kinase hyperactivity
UniProtAnemia, congenital, non-spherocytic hemolytic, 2

Clinical highlights

Gene-disease validity (ClinGen)
pyruvate kinase deficiency of red cells · ARDefinitivesufficient evidence for diagnostic panels
2
Active trials
50
Pubs (1 yr)
P/LP submissions
P/LP missense
0.92
LOEUF
Multiple*
Mechanism· predicted
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GeneReview available — PKLR
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.92LOEUF
pLI 0.000
Z-score 1.84
OE 0.59 (0.390.92)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.98Z-score
OE missense 0.86 (0.780.94)
310 obs / 362.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.59 (0.390.92)
00.351.4
Missense OE?0.86 (0.780.94)
00.61.4
Synonymous OE?1.02
01.21.6
LoF obs/exp: 14 / 23.7Missense obs/exp: 310 / 362.5Syn Z: -0.23

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PKLR · protein map & ClinVar variants

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