AKR1E2

protein-coding

aldo-keto reductase family 1 member E2, the group of Aldo-keto reductases

Gene summary

The protein encoded by this gene is a member of the aldo-keto reductase superfamily. Members in this family are characterized by their structure (evolutionarily highly conserved TIM barrel) and function (NAD(P)H-dependent oxido-reduction of carbonyl groups). Transcripts of this gene have been reported in specimens of human testis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

Previous symbols:

AKRDC1
AKR1CL2

MANE transcript

NM_001040177.3

Inheritance

ClinVar variants

U:77B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.95

Max pathogenic AF

—

Genomic locus

chr10:4,786,629-4,848,062

External References & Databases

Ensembl (ENSG00000165568)

Transcript & Mutation Effects

hg38 • Region Span ~61.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cataractLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005129

Submitter: PanelApp Australia

cataractLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005129

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AKR1E2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 65

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001040177.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar			1
missense			71 clinvar	2 clinvar	1 clinvar	74
nonsense						0
start loss						0
frameshift				2 clinvar		2
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	77	4	1	82

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001040177.3	RefSeq	NP_001035267.1	10	MANE Select
ENST00000298375.12	Ensembl	ENSP00000298375.7	10	MANE Select
NM_001271021.2	RefSeq	NP_001257950.1	8	Standard
NM_001271025.2	RefSeq	NP_001257954.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

oxidation-reduction process

Molecular Function

alditol:NADP+ 1-oxidoreductase activity
alcohol dehydrogenase (NADP+) activity
oxidoreductase activity
1,5-anhydro-D-fructose reductase activity

Cellular Component

nucleoplasm
Golgi apparatus
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000298375
Coding exons: 10
Length: 61434
Individuals with no LoFs: 125384
Homozygous LoFs: 2
Heterozygous LoFs: 362
Defined: 125748
p: 0.00145

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.314	188	176	1.07	0.00000940	2122
Missense (PolyPhen)		86	77.487	1.1099		935
Synonymous	1.68	48	65.3	0.735	0.00000385	574
Loss of Function	0.210	17	18.0	0.946	9.13e-7	209

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0076	0.0076	notable
Latino/Admixed American	0.00090	0.00090	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00071	0.00071	rare
Finnish	0.0014	0.0014	notable
European (Non-Finnish)	0.00044	0.00044	rare
South Asian	0.0034	0.0033	notable
Other	0.0023	0.0023	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: 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). {ECO:0000250|UniProtKB:Q9DCT1, ECO:0000269|PubMed:12604216, ECO:0000269|PubMed:15118078}.;

Recessive Scores

pRec: 0.102

Intolerance Scores

LoFtool: 0.946
RVIS EVS: 0.62
RVIS percentile EVS: 83.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.231

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium