Paediatric disorders - additional genes

Gene: SLC20A1

Green List (high evidence)

Comment on list classification: There are now 3 unrelated individuals reported with heterozygous SLC20A1 missense variants and urogenital malformations consistent with a bladder exstrophy-epispadias-cloacal exstrophy complex. This association is supported by functional studies in zebrafish and expression studies in a human embryo. There is also one individual reported with a homozygous frameshift variant, with multiple congenital anomalies. Hence, this gene can be promoted to Green on Paediatric disorders - additional genes, with MOI set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted', until more evidence emerges for the biallelic association.

Created: 5 Nov 2026, 11:26 a.m. | Last Modified: 5 Nov 2026, 11:26 a.m.

Panel Version: 8.30

PMID: 41906789 Koumakis et al., 2026
Report of a child patient with a homozygous SLC20A1 variant c.674_675delAA; p.K225TfsX34, with multiple congenital anomalies including tetralogy of Fallot, right renal agenesis, postaxial polydactyly, growth impairment, and developmental delay. Parents are healthy adults that are first cousins of Ashkenazi Jewish descent. Seq method: exome sequencing.

PMID: 32850778 Rieke et al., 2020
Sequencing of 690 individuals with bladder exstrophy-epispadias complex identified two additional monoallelic variants in SLC20A1. A het de novo variant c.893T > C (p.Val298Ala) was identified in a female proband with classic bladder exstrophy, and one additional SLC20A1 variant was detected in an affected mother who transmitted variant c.1321A>C (p.Lys441Gln) to her affected son with classic bladder exstrophy (maternal phenotype: fusion defect of pelvic bone, mild phenotype).
Functional evidence: Morpholino oligonucleotide knockdown of the zebrafish ortholog slc20a1a caused kidney cysts and malformations of the cloaca. Authors also performed immunohistochemistry of an unaffected 6-week-old human embryo and detected SLC20A1 in the urinary tract and the abdominal midline.

PMID: 27013921 Reutter et al., 2016
Bladder-Exstrophy-Epispadias Complex (BEEC) cohort. WES detected a de novo het variant c.709G>A, (p.Gly237Arg) in a female proband (Patient 407) with omphalocele, anal atresia, tethered cord, lipoma, atrial septal defect, duplex kidney (right), sacrum dysgenesis.

SLC20A1 is not yet associated with a disease entity in OMIM, G2P, or ClinGen (accessed 5th Nov 2026).
Sources: Literature

Created: 5 Nov 2026, 11:21 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
bladder exstrophy-epispadias-cloacal exstrophy complex, MONDO:0700039

Publications

• 27013921
• 32850778
• 41906789