KDSR

Chr 18AR

3-ketodihydrosphingosine reductase

Also known as: DHSR, EKVP4, FVT1, SDR35C1

NCBI Gene: 2531 ENSG00000119537 UniProt: Q06136 OMIM: 136440

This enzyme catalyzes the reduction of 3-ketodihydrosphingosine to dihydrosphingosine in the second step of de novo sphingolipid biosynthesis at the endoplasmic reticulum membrane. Mutations cause erythrokeratodermia variabilis et progressiva 4, a skin disorder characterized by hyperkeratosis and erythematous patches, with autosomal recessive inheritance. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.578).

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene catalyzes the reduction of 3-ketodihydrosphingosine to dihydrosphingosine. The putative active site residues of the encoded protein are found on the cytosolic side of the endoplasmic reticulum membrane. A chromosomal rearrangement involving this gene is a cause of follicular lymphoma, also known as type II chronic lymphatic leukemia. The mutation of a conserved residue in the bovine ortholog causes spinal muscular atrophy. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Erythrokeratodermia variabilis et progressiva 4MIM #617526

Clinical highlights

Gene-disease validity (ClinGen)

erythrokeratodermia variabilis et progressiva 4 · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.58

LOEUF

Mechanism· predicted