Skeletal ciliopathies

Gene: KIAA0753

Green List (high evidence)

KIAA0753 (KIAA0753)
EnsemblGeneIds (GRCh38): ENSG00000198920
EnsemblGeneIds (GRCh37): ENSG00000198920
OMIM: 617112, Gene2Phenotype
KIAA0753 is in 8 panels

3 reviews

Eleanor Williams (Genomics England Curator)

Comment on list classification: 5 unrelated cases with homozygous or compound heterozygous variants in this gene and a ciliopathy-related phenotype.
Created: 19 Jun 2019, 4:24 p.m.
Provisionally associated with ?Orofaciodigital syndrome XV (617127) in OMIM

PMID: 26643951 - Chevrier et al 2016 - 1 case of a newborn female presenting with an oral-facial-digital (OFD) VI syndrome in which they identified two causal heterozygous mutations in the KIAA0753 gene. Both KIAA0753 mutations, one nonsense variant (c.1891A>T; p.Lys631*) and one substitution in Intron 8 (c.1546-3C>A), were confirmed by Sanger sequencing, as well as the maternal heterozygous status for the non-sense variant. The sporadic occurrence of the c.1546-3C>A variant was confirmed by samples concordance. cDNA analysis indicates the intronic variant results in skipping of Exon 8 that caused a frameshift, changed the amino acids sequence and led to the occurrence of a premature stop codon. Because both mutations appeared truncating and probably compound heterozygous, they were considered as potentially causal.

PMID: 28220259 - Stephen et al 2017 - 2 siblings with Joubert syndrome associated with growth hormone deficiency but no oral or digital anomalies. Whole exome sequencing of the family identified compound heterozygous mutations in KIAA0753, i.e., a missense mutation (p.Arg257Gly) and an intronic mutation (c.2359-1G>C). Brain MRI of the younger sibling revealed the “molar tooth sign”, and she had global developmental delay. The older sibling was diagnosed after the younger sibling, and brain MRI showed an ectopic posterior pituitary gland in addition to the molar tooth sign. Hypotonia and global developmental delay were noted at 10 months. The parents were each heterozygous for one of the variants. Cilia formation in primary fibroblasts from patients was signficantly lower than in controls.

PMID: 29138412 - Hammarsjö et al 2017 - report biallelic pathogenic variants in KIAA0753 in four patients from 3 families with short-rib type skeletal dysplasia - ranging from prenatal lethality in one fetus to viability with moderate skeletal dysplasia in three children. 2 families had the same homozygous nonsense variant but are not thought to be related. In the 3rd family the index patient was compound heterogyzous. KIAA0753 is expressed in normal fetal human growth plate and they show that the affected fetus, with a compound heterozygous frameshift and a nonsense mutation in KIAA0753, has an abnormal proliferative zone and a broad hypertrophic zone. The importance of KIAA0753 for normal skeletal development is further confirmed by findings that zebrafish embryos homozygous for a nonsense mutation in kiaa0753 display altered cartilage patterning. In family 1, they also identified an additional homozygous missense variant, c.425 C > T (p.Thr142Met) in SLC13A5 and conclude that the seizures and teeth hypoplasia in P1 and P2 are due to the homozygous SLC13A5 variant.
Created: 19 Jun 2019, 4:12 p.m. | Last Modified: 15 Nov 2019, 12:58 p.m.
Panel Version: 0.19

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Please note additional 4 patients and functional data reported in this publication.
Created: 7 Aug 2018, 4:07 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Short-rib skeletal dysplasia


Variants in this GENE are reported as part of current diagnostic practice

Alice Gardham (Genomics England)

Red List (low evidence)

Only one patient identified
Created: 25 Jan 2017, 3:50 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Orofaciodigital syndrome XV 617127



Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
  • Expert Review Green
  • Literature
  • Expert Review Green
  • ?Orofaciodigital syndrome XV 617127
  • Joubert syndrome
  • Short-rib skeletal dysplasia
Clinvar variants
Variants in KIAA0753
Panels with this gene

History Filter Activity

10 Jul 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Eleanor Williams (Genomics England Curator)

gene: KIAA0753 was added gene: KIAA0753 was added to Skeletal ciliopathies. Sources: Literature,Expert Review Green Mode of inheritance for gene: KIAA0753 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIAA0753 were set to 29138412; 28220259; 26643951 Phenotypes for gene: KIAA0753 were set to ?Orofaciodigital syndrome XV 617127; Joubert syndrome; Short-rib skeletal dysplasia