Alternative titles; symbolsORPHAN SHORT-CHAIN DEHYDROGENASE/REDUCTASE; SDROHGNC Approved Gene Symbol: SDR9C7Cytogenetic location: 12q13.3 Genomic coordinates...
Alternative titles; symbols
HGNC Approved Gene Symbol: SDR9C7
Cytogenetic location: 12q13.3 Genomic coordinates (GRCh38): 12:56,923,132-56,934,407 (from NCBI)
▼ Cloning and Expression
Using PCR techniques, Chen et al. (2002) cloned a novel member of the short-chain dehydrogenase/reductase (SDR) family from mouse 17-day embryo cDNA. They identified a human ortholog, designated SDRO, in the human genome database and obtained a partial sequence of the rat ortholog with degenerate PCR. Human SDRO encodes a 313-amino acid protein that shares 83% sequence identity with the mouse protein. Northern blot analysis on both mouse and human tissues revealed that SDRO is highly expressed in liver, with expression in mouse liver as early as embryonic day 7. A single 1.6-kb transcript is present in human tissues, whereas 4 transcripts are present in mouse tissues.
By RT-PCR analysis of total RNA from a human skin sample, keratinocytes, and fibroblasts, Shigehara et al. (2016) demonstrated expression of SDR9C7 in skin and keratinocytes, but not fibroblasts. Indirect immunofluorescence showed that SDR9C7 is predominantly expressed in granular and cornified layers of the epidermis.
▼ Gene Structure
Chen et al. (2002) determined that the SDRO gene contains 4 exons.
By sequence analysis, Chen et al. (2002) mapped the SDRO gene to chromosome 12, where some other members of the SDR family, including RDH5 (601617) and RODH (606623), have been mapped. By radiation hybrid analysis, they mapped the mouse Sdro gene to chromosome 10 along with other members of the Sdr family, including Crad1, Crad2, and Rdh4.
▼ Gene Function
Although SDRO has homology to other SDRs that metabolize retinoids and/or steroids, Chen et al. (2002) found that SDRO does not have retinoid, 3-alpha-, 17-beta- or 11-beta-hydroxysteroid dehydrogenase activities. They suggested that SDRO may catalyze the metabolism of another class of nuclear receptor ligands, or may regulate metabolism by binding substrates or products, or by serving as a regulatory factor.
▼ Molecular Genetics
In affected members of 3 consanguineous Lebanese families with congenital ichthyosis mapping to chromosome 12q13-q14 (ARCI13; 617574), Shigehara et al. (2016) identified homozygosity for 2 different missense mutations in the SDR9C7 gene, I200T (609769.0001) and R72W (609769.0002).
In 3 sibs from a consanguineous Pakistani family with congenital ichthyosis, Karim et al. (2017) identified homozygosity for a 1-bp duplication in the SDR9C7 gene (609769.0003) that segregated with disease in the family and was not found in controls.
▼ ALLELIC VARIANTS ( 3 Selected Examples):
.0001 ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 13
SDR9C7, ILE200THR (rs770729222)
In affected members of 2 consanguineous Lebanese families with congenital ichthyosis (ARCI13; 617574), Shigehara et al. (2016) identified homozygosity for a c.599T-C transition (rs770729222) in exon 3 of the SDR9C7 gene, resulting in an ile200-to-thr (I200T) substitution at a highly conserved residue. The mutation segregated fully with disease in both families and was not found in 300 population-matched controls. The families were from the same region of Lebanon and shared an identical haplotype around SDR9C7. Functional analysis in HEK293T cells showed significantly reduced levels of the I200T mutant compared to wildtype SDR9C7.
.0002 ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 13
SDR9C7, ARG72TRP (rs530109812)
In a consanguineous Lebanese family with congenital ichthyosis (ARCI13; 617574), Shigehara et al. (2016) identified homozygosity for a c.214C-T transition (rs53019812) in exon 1 of the SDR9C7 gene, resulting in an arg72-to-trp (R72W) substitution at a highly conserved residue. The mutation segregated fully with disease in the family and was not found in 300 population-matched controls. Functional analysis in HEK293T cells showed significantly reduced levels of the R72W mutant compared to wildtype SDR9C7. Indirect immunofluorescence of patient skin showed SDR9C7 expression in the granular layer comparable to that in control skin, but only weak expression in the cornified layer, suggesting aberrant expression of the mutant protein during terminal differentiation of the epidermis.
.0003 ICHTHYOSIS, CONGENITAL, AUTOSOMAL RECESSIVE 13
SDR9C7, 1-BP DUP, 364A
In 3 sibs from a consanguineous Pakistani family with congenital ichthyosis (ARCI13; 617574), Karim et al. (2017) identified homozygosity for a 1-bp duplication (c.364dupA) in the SDR9C7 gene, causing a frameshift predicted to result in a premature termination codon (Thr122IlefsTer3). The mutation segregated with disease in the family and was not found in 100 controls or in an in-house database of 20 exomes.