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Intellectual disability

Gene: KIAA0556

Amber List (moderate evidence)
KIAA0556 (KIAA0556)
EnsemblGeneIds (GRCh38): ENSG00000047578
EnsemblGeneIds (GRCh37): ENSG00000047578
OMIM: 616650, Gene2Phenotype
KIAA0556 is in 7 panels

1 review

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: This gene was added to this panel following consultation with the Genomics England Clinical Team. Although the ID phenotype is less clear than some other features, there are two families with severe ID and another two where extent of ID is unclear or milder. There are also sufficient cases of hypotonia which is tested via the Hypotonic infant super panel, as well as short stature/hypopituitarism/growth hormone deficiency which are more likely to be picked up via the Paediatric disorders super panel. Inclusion on the ID panel would also ensure inclusion on these two super panels, where ID is a component panel.

Overall the evidence supports promotion of this gene to Green at the next GMS panel update.
Created: 29 Oct 2025, 10:01 a.m. | Last Modified: 29 Oct 2025, 10:01 a.m.
Panel Version: 9.155
KIAA0556 (also known as KATNIP) is now associated with Joubert syndrome 26, OMIM:616784 (AR) in OMIM (accessed 21st Oct 2025), and has a DEFINITIVE gene disease association with autosomal recessive ciliopathy-KATNIP (MONDO:0005308) in ClinGen (curation entry from 07/10/2023).

The ClinGen summary states that there are eight variants (nonsense, frameshift, splice-site) reported in 6 probands in 6 publications (PMIDs: 26714646, 27245168, 31197031, 36580738, 32164589, 30982090). There have been 2 additional reports since their review (PMIDs: 40725402, 40428346)

In total there are now 13 individuals from 8 families. In 2 of the families additional variants were found in other genes. These families are listed last in this review. Main phenotypes observed in the cases with only KIAA0556 variants:

- Brain abnormalities (including molar tooth sign) were seen in 9 individuals (5 families, 1 of these mild).
- Hypotonia was observed in 6 individuals (4 families).
- Short stature/Growth hormone deficiency/pituitary abnormalities were seen in 4 individuals (3 families)
- Developmental delay/intellectual disability was reported as severe in 4 individuals( 2 families), mild/unknown severity in an additional 3 individuals (2 families).
- An eye phenotype was observed in 4 individuals (3 families)
- A renal phenotype was only observed in 1 family (PMID: 40725402).

Evidence:

PMID:26714646 (Sanders et al 2015) - 3 children in a consanguineous Saudi Arabian family with global developmental delay and suspected Jouberts syndrome based on neuroimaging studies. Variable features between the children included recurrent infections (2), hypotonia( 2), cleft palate (1), small penis (1), short stature (1), hypopituitarism (2). No renal involvement. In patient fibroblasts there were a significant reduction in cilia compared to controls, and cilia that were present were abnormally long. Kiaa0556 knockout mice showed brain-specific defects resulting in hydrocephalus. In human cells KIAA0556 was found to locate a the ciliary base, axoneme and tip.

PMID:27245168 (Roosing et al 2016) - WES in consanguineous family from India identified a KIAA0556 homozygous single base pair deletion mutation in 2 siblings. Both showed nystagmus and oculomotor apraxia, bilaterial ptosis, hypotonia, characteristic ‘molar tooth’ sign on brain imaging and developmental delay (severity not noted). Cone dystrophy was identified, but gross visual function was not impaired. No renal or liver phenotype. A zebrafish model with kiaa0556 knocked down showed curly tails, smaller head size and perithoracic and abdominal edema which is like other ciliopathy morphants.

PMID:31197031 (Fujita et al 2019) - blood and/or hypothalamic hamartoma (HH, congenital brain malformation associated with drug-resistant epilepsy) tissue samples from 38 undiagnosed patients were analysed using WES. Germline, compound heterozygous variants in KIAA0556 were found in one 5 yo female patient (individual 12698), c.2373del (p.Asp791Glufs*206),c.4551+1G>A. Brain anomalies in this patient included agenesis of the corpus callosum, pituitary hypoplasia, the molar tooth sign, and HH. Other clinical features reported include hypotonia, oculomotor apraxia and developmental delay.

PMID:36580738 (Aksu Uzunhan et al 2023) - 2-year-old male with compound heterozygous variants KATNIP gene. He had growth hormone deficiency and central hypothyroidism, with some minor dysmorphic features. His neurodevelopment seemed normal, but cranial MRI abnormalities without a classical molar tooth sign, ectopic neurohypophysis and combined pituitary hormone deficiency. No renal, liver or eye phenotype.

PMID: 40725402 (Kulyamzin et al 2025) - 24 yo female from a non-consanguineous family of mixed Jewish origin who presented with type 2 glomerulonephritis at age 7 and underwent 2 kidney transplantations. She later developed SNHL, which was attributed to antibiotic toxicity, high intracranial pressure, and a differential diagnosis of cone rod dystrophy vs macular dystrophy with peripheral involvement. WES revealed two rare heterozygous variants in the KATNIP (KIAA0556) gene (NM_015202.4): c.49C>T; p.(Arg17*) and c.4711A>G; p.(Ser1571Gly). The proband was also heterozygous for a likely-pathogenic variant in POLG. Heterozygous variants in POLG have been linked to progressive external ophthalmoplegia (weakness of eye muscles), but the proband did not present with this.

PMID: 40428346 (Tedesco et al 2025) 5-year-old male from a consanguineous family of Roma ethnic background. Clinical features include severe developmental delay, hypotonia, and post-axial polydactyly. He had a normal cerebral MRI without the molar tooth sign, but showed severe anemia and esophageal atresia. WES identified a homozygous novel frameshift variant c.808del, p.Ser270ValfsTer28 in KATNIP. A good summary of all cases to date is provided.

Patients with variants in KIAA0556/KATNIP and another gene:

PMID:32164589 (Niceta et al 2020) - 7 year old with homozygosity for mutations in KIF7 and KIAA0556 identified by WES. The patient displayed Joubert syndrome complicated by iris and retinochoroidal coloboma, hypogonadism pituitary malformation, and growth hormone deficiency. Severe intellectual disability was reported.

PMID:30982090 (Cauley et al 2019) - Sudanese family in 3 siblings with homozygous truncating variants in both KIAA0556 and ADGRG1/GPR56 and a severe brain malformation (bilateral frontal polymicrogyra, mild molar tooth sign), severe psychomotor delay, intellectual disability and seizures.
Sources: ClinGen, Literature
Created: 29 Oct 2025, 9:52 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Joubert syndrome 26, OMIM:616784; Joubert syndrome 26, MONDO:0014771

Publications

Created: 29 Oct 2025, 9:52 a.m.

Panel version: 9.154

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
  • ClinGen
Phenotypes
  • Joubert syndrome 26, OMIM:616784
  • Joubert syndrome 26, MONDO:0014771
Tags
new-gene-name Q3_25_promote_green
OMIM
616650
Clinvar variants
Variants in KIAA0556
Penetrance
None
Publications
Panels with this gene

History Filter Activity

29 Oct 2025, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: kiaa0556 has been classified as Amber List (Moderate Evidence).

29 Oct 2025, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: KIAA0556 were set to

29 Oct 2025, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: kiaa0556 has been classified as Amber List (Moderate Evidence).

29 Oct 2025, Gel status: 1

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

Arina Puzriakova (Genomics England Curator)

gene: KIAA0556 was added gene: KIAA0556 was added to Intellectual disability. Sources: ClinGen,Literature new-gene-name, Q3_25_promote_green tags were added to gene: KIAA0556. Mode of inheritance for gene: KIAA0556 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: KIAA0556 were set to Joubert syndrome 26, OMIM:616784; Joubert syndrome 26, MONDO:0014771 Review for gene: KIAA0556 was set to GREEN