SDR42E2

Chr 16

short chain dehydrogenase/reductase family 42E, member 2

NCBI Gene: 100288072 ENSG00000183921 UniProt: A6NKP2

The protein is predicted to function as an oxidoreductase in steroid biosynthesis, using NAD or NADP as cofactors. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, typically presenting in early infancy with seizures and severe developmental delays. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected individuals.

GeneReviews ResearchSummary from RefSeq

Predicted to enable oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor. Predicted to be involved in steroid biosynthetic process. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews ResearchGenerating clinical summary…

DNmechanismLOEUF 1.62

Clinical Summary— SDR42E2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

4 total variants — no pathogenic classifications of 4 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SDR42E2

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.62LOEUF

pLI 0.000

Z-score -0.04

OE 1.01 (0.65–1.62)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.19Z-score

OE missense 0.69 (0.58–0.83)

84 obs / 121.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.01 (0.65–1.62)

0≤0.351.4

Missense OE?0.69 (0.58–0.83)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 12 / 11.9Missense obs/exp: 84 / 121.0Syn Z: 0.31

This gene — mechanism propensity

0.7230th %ile

GOF

0.5856th %ile

LOF

0.3259th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

4 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Benign4

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	0	0	0	0
Likely Benign	1	1	2	4
Benign	0	0	0	0
Total	1	1	2	4

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

View in ClinVar →

71 pathogenic / likely-pathogenic (of 130) ClinVar copy-number / structural variants overlap SDR42E2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →