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SDR9C7
short chain dehydrogenase/reductase family 9C member 7
SDR9C7 is located on the long (q) arm of chromosome 12, at band 12q13.3. Arm ratio per GRCh38 - banding schematic.
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Overview
SDR9C7 (short chain dehydrogenase/reductase family 9C member 7) is located on chromosome 12 and encodes an enzyme belonging to the evolutionarily conserved short-chain dehydrogenase/reductase superfamily. Members of this enzyme family catalyse oxidation and reduction reactions involving small lipophilic molecules, playing diverse roles in cellular metabolism. The SDR9C7 protein is expressed in skin tissue, where it contributes to lipid-processing pathways critical for the formation and maintenance of the epidermal barrier.
Pathogenic variants in SDR9C7 follow an autosomal recessive inheritance pattern, meaning that individuals must inherit altered copies from both parents to develop associated skin conditions. These variants can disrupt normal enzyme activity, impairing lipid homeostasis in keratinocytes and leading to defects in skin barrier integrity.
What the gene does
The SDR9C7 protein functions as a dehydrogenase enzyme, catalysing redox reactions that modify lipid substrates within keratinocytes, the predominant cell type in the outermost layer of skin. Enzymes in the short-chain dehydrogenase/reductase family typically use cofactors such as NAD(+) or NADP(+) to facilitate the transfer of electrons during substrate conversion. Although the precise endogenous substrates for SDR9C7 have not been fully characterised, evidence suggests the enzyme participates in pathways that regulate the production or modification of lipids essential for stratum corneum structure.
The stratum corneum, the outermost epidermal layer, relies on a complex mixture of ceramides, cholesterol and free fatty acids to form an effective barrier against water loss and environmental insults. Proper processing of lipid precursors is critical for assembling this barrier. Research suggests that SDR9C7 contributes to these metabolic pathways, with loss of enzyme function resulting in abnormal lipid composition and impaired barrier formation. The resulting defects manifest clinically as scaling, thickening and inflammation of the skin.
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Chromosome location
SDR9C7 is located on the long arm of chromosome 12 at cytogenetic band 12q13.3. This chromosomal region contains multiple genes involved in metabolic and structural functions. The gene spans a modest genomic interval and encodes a transcript that is translated into a protein of 313 amino acids. Structural details regarding exon count and alternative splicing patterns for SDR9C7 have not been extensively documented in public databases.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein. As a member of the short-chain dehydrogenase/reductase superfamily, the SDR9C7 protein is expected to share core structural motifs typical of this enzyme class, including a conserved nucleotide-binding fold and a catalytic triad of amino acid residues. These features enable cofactor binding and catalytic activity. However, specific domain boundaries and functional modules unique to SDR9C7 remain to be mapped through structural studies.
Key variants
Pathogenic variants in SDR9C7 are rare and typically involve changes that abolish or severely reduce enzyme activity. Reported variants include missense substitutions that alter catalytically important residues, as well as frameshift and nonsense mutations that truncate the protein. Because SDR9C7-related conditions follow autosomal recessive inheritance, affected individuals carry biallelic pathogenic variants. Carrier status, with one altered copy, generally does not produce clinical manifestations.
Sample of pathogenic variants
5 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.355G>A | p.Glu119Lys | Pathogenic/Likely pathogenic | ★★☆☆ | Lamellar ichthyosis |
c.364dup | p.Thr122fs | Pathogenic | ★★☆☆ | Lamellar ichthyosis |
c.658C>T | p.Arg220Ter | Pathogenic | ★★☆☆ | Ichthyosis, congenital, autosomal recessive 13 |
c.826C>T | p.Arg276Cys | Pathogenic/Likely pathogenic | ★★☆☆ | Lamellar ichthyosis |
c.560+1G>A | - | Pathogenic | ★☆☆☆ | not provided |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Biallelic pathogenic variants in SDR9C7 have been associated with autosomal recessive congenital ichthyosis, a group of inherited disorders characterised by abnormal skin scaling and barrier dysfunction from birth or early infancy. Affected individuals may present with generalised dry, scaly skin that can range in severity. The underlying pathophysiology involves disrupted lipid metabolism in keratinocytes, leading to defective assembly of the stratum corneum lipid matrix. Clinical features and disease severity can vary depending on the specific variants inherited and the degree of residual enzyme function.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic SDR9C7 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
SDR9C7 appears on multiple NHS Genomic Medicine Service gene panels relevant to inherited skin disorders. The gene holds green (diagnostic-grade evidence) status on the Autosomal recessive congenital ichthyosis panel, the Ichthyosis and erythrokeratoderma panel (R165), and the Palmoplantar keratodermas panel (R166). SDR9C7 is also listed on the Fetal anomalies panel (R21) with green classification, reflecting its role in conditions that may be identified prenatally or in early life. Inclusion on these panels indicates that SDR9C7 variants are considered clinically actionable findings in the context of ichthyosis diagnosis within the NHS.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the SDR9C7 gene do?
SDR9C7 encodes an enzyme that catalyses lipid-processing reactions in skin cells. This enzyme helps maintain the lipid barrier in the outermost layer of skin, which is essential for preventing water loss and protecting against environmental damage.
How are SDR9C7 variants inherited?
SDR9C7-related conditions follow an autosomal recessive pattern. This means an individual must inherit a pathogenic variant from both parents to be affected. Carriers, with one altered copy, typically do not show symptoms.
What conditions are linked to SDR9C7 variants?
Biallelic pathogenic variants in SDR9C7 are associated with autosomal recessive congenital ichthyosis, a group of inherited skin disorders characterised by scaling and barrier dysfunction. The severity and specific features can vary depending on the variants involved.