SDR42E2

Chr 16

short chain dehydrogenase/reductase family 42E, member 2

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.

ResearchSummary from RefSeq
DNmechanismLOEUF 1.62
Clinical SummarySDR42E2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
71 unique Pathogenic / Likely Pathogenic· 46 VUS of 133 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.62LOEUF
pLI 0.000
Z-score -0.04
OE 1.01 (0.651.62)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.19Z-score
OE missense 0.69 (0.580.83)
84 obs / 121.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.01 (0.651.62)
00.351.4
Missense OE0.69 (0.580.83)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 12 / 11.9Missense obs/exp: 84 / 121.0Syn Z: 0.31
DN
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

133 submitted variants in ClinVar

Classification Summary

Pathogenic55
Likely Pathogenic16
VUS46
Likely Benign8
Benign1
Conflicting4
55
Pathogenic
16
Likely Pathogenic
46
VUS
8
Likely Benign
1
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
55
Likely Pathogenic
16
VUS
46
Likely Benign
8
Benign
1
Conflicting
4
Total130

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SDR42E2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found