Proteinuric renal disease

Gene: STS

I don't know

Comment on list classification: There are more than 3 unrelated individuals reported with renal disease (CAKUT, nephrotic syndrome, proteinuria) and deletions that encompass the STS gene. However, these structural variants would not be detected in the current NGS analysis pipeline. SNVs have been reported in this gene (about 10% of cases), but the individuals did not have renal disease. Hence, STS should remain Amber for Proteinuric renal disease. Instead, the ISCA-37417-Loss (Xp22.31 recurrent region (includes STS) Loss) has been suggested for promotion to Green on this panel.

Created: 7 Jul 2026, 4:43 p.m. | Last Modified: 7 Jul 2026, 4:55 p.m.

Panel Version: 6.8

PMID: 17468528 Krishnamurthy, Kapoor, and Yadav, 2007
Reported a 4yo proband with ichthyosis and a steroid-resistant nephrotic syndrome. Generalised edema and proteinuria of 4.25g/day were noted. Many male family members also had ichthyosis. Renal biopsy showed no segmental sclerosis, tubular atrophy, fibrosis, or deposits; diagnosed with minimal change disease. STS deletion detected by multiplex PCR (targeted STS gene specifically).

PMID: 22419362 Mishra et al., 2012
Report of a 4yo boy with steroid-resistant nephrotic syndrome (SRNS) with an underlying ichthyotic skin present since birth. Genetic analysis showed full deletion of the STS gene.

PMID: 23939749 Song et al., 2013
12yo male patient with X-linked ichthyosis (XLI) in association with glomerular sclerosis. Complete deletion of STS and flanking regions was detected. Renal features: renal failure, anemia, hypocalcemia, mild proteinuria (0.4g/day). Uncles also affected by ichthyosis and short stature. Authors highlight that it is unknown whether STS or the flanking regions were causal in the renal presentation.

PMID: 29672931 Diociaiuti et al., 2019
Cohort of 35 Italian male patients with X-linked ichthyosis. 27 patients showed complete STS deletion - 1 de novo, others maternally inherited. 7 patients had microdeletions of 1.3-1.6Mb, and 2 patients had large deletions of 8.2 and 9.7Mb - resulting in contiguous gene syndrome. Lastly, 7 individuals from 4 unrelated families had 4 different missense mutations in STS. Seq method: MLPA + ichthyosis NGS panel. Apart from cutaneous changes, other findings included cryptorchidism, neuropsychiatric findings, motor disabilities. No mention of renal disease. Authors note that only 10% of patients have point mutations in STS, with majority of cases harbouring STS deletions.

PMID: 35115028 Schierz et al., 2022
Male newborn with CAKUT with kidney failure and progressive vomiting. "Comparative whole-genome hybridization detected a maternal inherited interstitial deletion of 1.56 Mb on Xp22.31(6,552,712_8,115,153) × 0 involving the STS gene, but not the KAL1 gene." Other affected genes: VCX, PUDP, PNPLA4, as well as microRNAs MIR4767 and MIR651.

Created: 7 Jul 2026, 4:17 p.m. | Last Modified: 7 Jul 2026, 4:36 p.m.

Panel Version: 6.5

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Ichthyosis, X-linked, OMIM:308100

Publications

• 17468528
• 22419362
• 23939749
• 29672931
• 35115028

Green List (high evidence)

Good evidence this is a proteinuric gene. Cases of whole gene deletion of STS in Genomics England with phenotypes.
Sources: Expert list

Created: 22 May 2026, 11:49 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Proteinuria; ichthyosis

Publications

• 22419362
• 17468528