Paediatric disorders - additional genes

Gene: NR6A1

Green List (high evidence)

Comment on phenotypes: OMIM phenotype checked 10th Apr 2026.

Created: 10 Apr 2026, 11:19 a.m. | Last Modified: 10 Apr 2026, 11:19 a.m.

Panel Version: 7.45

Comment on list classification: There are numerous individuals reported with heterozygous variants in NR6A1 and oculo-vertebral-renal syndrome, presenting with eye structural anomalies, abnormal kidney morphology (often renal agenesis), uterine anomalies, and missing vertebrae. Similar congenital skeletal and kidney malformations were seen in a knockout zebrafish model, supportive of this gene-disease association. Hence, this gene should be promoted to Green on Paediatric disorders - additional genes.

Created: 10 Apr 2026, 11:18 a.m. | Last Modified: 10 Apr 2026, 11:18 a.m.

Panel Version: 7.43

PMID: 40610405 Neelathi et al., 2025
Report of six unrelated families with heterozygous rare variants in NR6A1 gene presenting with an autosomal dominant oculo-vertebral-renal (OVR) syndrome characterised by colobomatous microphthalmia, missing vertebrae and congenital kidney abnormalities. Spina bifida and scoliosis were also present in some individuals. The variants showed incomplete penetrance and variable expressivity.
Functional evidence from in silico, cellular, and zebrafish experiments showed that reported variants were either pathogenic or likely pathogenic for OVR syndrome.

PMID: 40774958 Rasouly et al., 2025
Large cohort with CAKUT - NR6A1 confirmed as a CAKUT gene - described 13 total cases with predicted pathogenic heterozygous NR6A1 variants identified through exome seq.
Of 13 cases, 4 had both CAKUT and eye structural anomalies (e.g. coloboma), and 1 case had eye anomalies without CAKUT. Mix of LoF and missense variants. No spine anomalies reported in this cohort.

PMID: 41733738 Jacquinet et al., 2026
5 affected individuals from 3 families with phenotypes including bilateral or unilateral renal agenesis/hypoplasia, along with variable congenital uterine anomalies (3/4 female individuals) and costovertebral defects associated with heterozygous deleterious variants in NR6A1: two inherited missense (c.1175T>G;p.(Met392Arg) and c.196C>T;p.(Arg66Cys)) as well as de novo loss of function c.439C>T, p.Gln147*. No ocular malformations reported in this cohort. Seq method: Trio WES / WES.
Functional evidence: loss of nr6a1 orthologs (a & b) in zebrafish causes skeletal anomalies (missing vertebrae) and abnormal kidney morphology.
Sources: Literature

Created: 10 Apr 2026, 11:15 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Oculovertebral syndrome, OMIM:621277

Publications

• 40610405
• 40774958
• 41733738