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Fetal anomalies

Gene: KIAA0556

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

4 reviews

Arina Puzriakova (Genomics England Curator)

I don't know

Comment on list classification: Upgrading from Red to Amber and tagging for additional GMS expert review to determine whether there is sufficient evidence to indicate that the phenotype is prenatally relevant.

The main finding that may plausibly be detected prenatally is cerebellar hypoplasia / molar tooth sign. Other possible fetal scan findings include: PMIDs 26714646 and 32164589 each reference one case with cleft lip and palate (although the latter had dual molecular findings) and PMID 40428346 had post-axial polydactyly. Although molar-tooth sign was present in a number of cases, there is no indication that prenatal abnormalities were detected in published cases.
Created: 29 Oct 2025, 11:02 a.m. | Last Modified: 29 Oct 2025, 11:02 a.m.
Panel Version: 6.115
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.
Created: 29 Oct 2025, 10:52 a.m. | Last Modified: 29 Oct 2025, 10:52 a.m.
Panel Version: 6.112

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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

Publications

Created: 29 Oct 2025, 10:52 a.m.
Last Modified: 29 Oct 2025, 10:52 a.m.
Panel version: 6.112

Eleanor Williams (Genomics England Curator)

Added new-gene-name tag, new approved HGNC gene symbol for KIAA0556 is KATNIP
Created: 20 Oct 2025, 4:19 p.m. | Last Modified: 20 Oct 2025, 4:19 p.m.
Panel Version: 6.104
Created: 20 Oct 2025, 4:19 p.m.
Last Modified: 20 Oct 2025, 4:19 p.m.
Panel version: 6.104

Achchuthan Shanmugasundram (Genomics England Curator)

This gene and phenotype were reviewed during meetings between November 2023 & July 2024. The meetings included representatives of the North Thames and Central & South R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Natalie Chandler, Alison Male and Lyn Chitty (North Thames GLH), Stephanie Allen, Natalie Bibb, Esther Kinning and Denise Williams (Central & South GLH) and Natalie Canham, Anna De Burca and Samantha Doyle R21 Clinical Oversight Group.
Created: 29 Aug 2024, 8:33 p.m. | Last Modified: 29 Aug 2024, 8:33 p.m.
Panel Version: 4.36
Created: 29 Aug 2024, 8:33 p.m.
Last Modified: 29 Aug 2024, 8:33 p.m.
Panel version: 4.36

Natalie Canham (Liverpool Women's Hospital)

Red List (low evidence)

2 papers with single families (3 affected in one, 2 in the other), plus 2 with co-occurrence of variants in this gene and another, including one - PMID:32164589 - with another Joubert gene. Red
Created: 29 Aug 2024, 8:07 p.m. | Last Modified: 29 Aug 2024, 8:07 p.m.
Panel Version: 4.35

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Joubert syndrome 26, OMIM:616784

Publications

Created: 29 Aug 2024, 8:07 p.m.
Last Modified: 29 Aug 2024, 8:07 p.m.
Panel version: 4.35

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • NHS GMS
Phenotypes
  • Joubert syndrome 26, OMIM:616784
  • Joubert syndrome 26, MONDO:0014771
Tags
new-gene-name Q3_25_promote_green Q3_25_expert_review
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: 1

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: KIAA0556 were changed from Joubert syndrome 26, OMIM:616784 to Joubert syndrome 26, OMIM:616784; Joubert syndrome 26, MONDO:0014771

29 Oct 2025, Gel status: 1

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: KIAA0556 were set to 27245168; 26714646

29 Oct 2025, Gel status: 1

Added Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_25_promote_green tag was added to gene: KIAA0556. Tag Q3_25_expert_review tag was added to gene: KIAA0556.

20 Oct 2025, Gel status: 1

Added Tag

Eleanor Williams (Genomics England Curator)

Tag new-gene-name tag was added to gene: KIAA0556.

29 Aug 2024, Gel status: 1

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

Achchuthan Shanmugasundram (Genomics England Curator)

gene: KIAA0556 was added gene: KIAA0556 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red Mode of inheritance for gene: KIAA0556 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIAA0556 were set to 27245168; 26714646 Phenotypes for gene: KIAA0556 were set to Joubert syndrome 26, OMIM:616784