Paediatric disorders - additional genes

Gene: TSHZ3

I don't know

PMID: 39420202 Kesdiren et al., 2025
Report of two male siblings (F004-II.02 and F004-II.03), children of non-consanguineous German parents, with multicystic dysplastic kidneys (MCDK). WES yielded a rare variant in TSHZ3: c.172A>G p.(Ser58Gly), inherited from the unaffected father. Sibling F004-II.02 also had cryptorchidism and phimosis. Variant p.Ser58Gly has MAF = 0.004081 in gnomAD v4 (European population), and 5 homozygotes reported.
In addition, another 10 CAKUT patients from 8 families carried heterozygous TSHZ3 missense variants. These variants are also present in gnomAD with some homozygotes reported. Developmental delay / ID was also noted in 3 unrelated probands. Variants were confirmed to be inherited from a parent in 6/8 families (1 affected, 1 unaffected, and 4 of unknown status). Authors highlight that "variable expressivity, and incomplete penetrance are common in CAKUT".

PMID: 36553458 Feichtinger et al., 2022
Exome sequencing identified a heterozygous frameshift variant c.119_120dup p.Pro41SerfsTer79 in TSHZ3 in a 7-year-old girl with intellectual disability, behavioural issues, pyelocaliceal dilatation, and mild urethral stenosis. Variant was on the paternal allele, but father's DNA was unavailable for testing. Variant is not present in gnomAD v4.1.2.

PMID: 34919690 Sanchez-Martin et al., 2022
Functional mouse model - haploinsufficiency of the mouse Tshz3 gene leads to kidney defects. Tshz3+/lacZ adult mouse kidney had an average of 29% fewer glomeruli than wild-type, and reduced thickness of the glomerular basement membrane. Tshz3+/lacZ mice also had lower blood urea, phosphates, magnesium and potassium at 2 months of age.

PMID: 35292625 Caubit et al., 2022
Functional evidence: Conditional loss of the ASD-related gene Tshz3 in mouse cortical projection neurons (CPNs) and striatal cholinergic interneurons (SCINs) does not affect the numbers of these neurons, but induces changes in their electrophysiological and synaptic properties, paralleled by specific ASD-like behavioral defects.

PMID: 27668656 Caubit et al., 2016
Study identified seven new patients from six unrelated families with 19q12q13.11 deletions. The minimal region of overlap of 0.83 Mb encompasses a unique protein-coding gene, TSHZ3. Patients 3a,b, 6 and 7 have small deletions, which overlap only TSHZ3.
3/7 individuals had renal features: vesicoureteral reflux, nephrolithiasis, and pyelocalyceal dilatation. 2 probands had ID, and 2 had cognitive impairment. 6 individuals had autistic features/ behavioral disorder.
Functional evidence. In Tshz3-null mice, differentially expressed genes include layer-specific markers of cerebral cortical projection neurons (CPNs) - the human ortholog genes are strongly associated with ASD. Mice heterozygous for Tshz3 show functional changes at synapses and exhibit ASD-like behavioral abnormalities.

TSHZ3 is not yet associated with a phenotype in OMIM, ClinGen, or G2P (accessed 5th Nov 2026).
Sources: Literature

Created: 5 Nov 2026, 12:03 p.m. | Last Modified: 5 Nov 2026, 2:56 p.m.

Panel Version: 8.31

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
congenital anomaly of kidney and urinary tract, MONDO:0019719

Publications

• 27668656
• 35292625
• 36553458
• 39420202