AKR1E2

Chr 10

aldo-keto reductase family 1 member E2

ENSG00000165568 UniProt: Q96JD6 OMIM: 617451

The protein is an aldo-keto reductase that catalyzes the NADPH-dependent reduction of 1,5-anhydro-D-fructose to 1,5-anhydro-D-glucitol and has low reductase activity towards other substrates. This gene is not highly constrained against loss-of-function variants and is not currently associated with any established Mendelian disease phenotypes in major clinical databases.

OMIM ResearchSummary from RefSeq, UniProt

Catalyzes the NADPH-dependent reduction of 1,5-anhydro-D-fructose (AF) to 1,5-anhydro-D-glucitol (By similarity). Has low NADPH-dependent reductase activity towards 9,10-phenanthrenequinone (in vitro) (PubMed:12604216, PubMed:15118078)

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.42

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.42LOEUF

pLI 0.000

Z-score 0.21

OE 0.95 (0.65–1.42)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.31Z-score

OE missense 1.07 (0.95–1.20)

188 obs / 176.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.95 (0.65–1.42)

0≤0.351.4

Missense OE?1.07 (0.95–1.20)

0≤0.61.4

Synonymous OE?0.74

0≤1.21.6

LoF obs/exp: 17 / 18.0Missense obs/exp: 188 / 176.3Syn Z: 1.68

Background carrier burden — how many people carry a rare variant somewhere in AKR1E2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

470 rare PASS variants

Rare truncating (LoF)

1 in 490

99 rare PASS variants

Rare synonymous (reference)

1 in 540

122 rare PASS variants

Rare missense and truncating variants are carried at similar rates in AKR1E2; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 160	1 in 910
South Asian	~43k	1 in 82	1 in 680
Remaining (unassigned)	~30k	1 in 88	1 in 350
European (Finnish)	~27k	1 in 410	none seen
Admixed American	~22k	1 in 110	1 in 330
African / African American	~21k	1 in 82	1 in 930
East Asian	~20k	1 in 130	1 in 440
Ashkenazi Jewish	~13k	1 in 350	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 76	1 in 290

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 10 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 10.? see exons ↓