Intellectual disability
Gene: KIF26A

KIF26A (kinesin family member 26A)
EnsemblGeneIds (GRCh38): ENSG00000066735
EnsemblGeneIds (GRCh37): ENSG00000066735
OMIM: 613231, Gene2Phenotype
KIF26A is in 5 panels

1 review

Ida Ertmanska (Genomics England Curator)

I don't know

Comment on list classification: At least 13 patients from 10 families have been described in literature with biallelic variants in KIF26A and KIF26A‐related disorder (PMIDs: 36228617; 36564622; 39305096). 6/8 individuals assessed presented with developmental delay and/or intellectual disability: 3 cases with mild cognitive impairment, 2 with moderate ID, 1 with 'growth retardation and developmental delay' - severity not specified. As only 2 cases meet the panel criteria of moderate/severe impairment, this gene should be rated Amber for Intellectual disability until more evidence emerges.
Created: 3 Nov 2025, 5:41 p.m. | Last Modified: 3 Nov 2025, 5:41 p.m.

Panel Version: 9.161

At least 13 patients from 10 families have been described in literature with biallelic variants in KIF26A and KIF26A‐related disorder (PMIDs: 36228617; 36564622; 39305096).

The heterogenous syndromic presentation may include developmental delay / intellectual disability (6/8, mild to moderate), cardiac defects (6/7), neurological features e.g. hypotonia (2), spasticity (2), paediatric intestinal pseudo‐obstruction (PIPO) (3/13). While only 3/13 patients were diagnosed with PIPO, 8/13 patients had gastrointestinal issues, including megacolon, ischemic small bowels, severe ascites, abdominal distension, vomiting, and intestinal obstruction. Note: several individuals died before certain clinical features could be assessed.

Brain MRI showed Ventriculomegaly/Hydrocephalus in 12/12 patients and corpus callosum agenesis / hypoplasia in 7/12 cases; unavailable in 1 case. Other malformations noted on MRI: Hypogenesis of septum pellucidum, Brainstem patterning disorder, Long midbrain, Small pons, Brain atrophy, Reduced white matter, Bilateral schizencephaly, Absent hippocampal commissure.

PMID: 39305096 Nosrati et al., 2025
Seq method: Trio exome.
Case #1 - 8yo Italian male; at birth: axial hypotonia, poor suction, failed to pass meconium, leading to surgery for Hirschsprung's disease. Compound het c.4378C > T, p.(Arg1460Trp); c.5238C > G, p.(Phe1746Leu).
Case #2 - 6mo Syrian female; presented with abdominal distension and intestinal obstruction symptoms; imaging revealed dilated bowels without mechanical obstruction; biopsies of small and large intestine showed hypoganglionosis. Homozygous for c.4085dup, p.(Ala1363Glyfs*47).
Case #3 - female born to consanguineous parents (Palestinian / Jordanian) - very different presentation: severe spastic quadriplegic cerebral palsy (CP) with epilepsy, hearing problems and cognitive impairments. Homozygous for c.3996C > A, p.(Cys1332*).

PMID: 36564622 Almannai et al., 2023
Seq method: clinical WES.
Report of 2 families with KIF26A‐related disorder.
Family 1: 4 affected individuals, homozygous for c.792dupC, p.(Val265Argfs*5), all presented with persistent abdominal distension and vomiting after birth. 3 individuals died between 2-11 months, 1 patient alive at 3.5 years.
Family 2: proband presented at 3 months with symptoms indicating intestinal obstruction and marked abdominal distension. Symptoms persist at 7yo. Homozygous for c.3330delC, p.(Ser1111Alafs*137).

36228617 Qian et al., 2022
Seq method: WES.
5 unrelated subjects with congenital brain malformations who had inherited biallelic mutations in KIF26A
A01 - consanguineous Turkish family, microcephaly (−3.45SD) and an MRI suggesting a component of cerebral atrophy, as well as dysmorphic features and ileus with megacolon. Homozygous for c.3440dupC, p.Ala1148Cysfs*20.
B01 - diagnosed prenatally with bilateral schizencephaly at 21 weeks; pregnancy terminated; compound heterozygous c.2161C>T, p.Arg721Cys, and c.4676C>T, p.Ala1559Val
C01 - male, non-consanguineous parents, presented with mild developmental delay and learning disability. Brain MRI at 18 years demonstrated agenesis of the corpus callosum; compound het KIF26A: c.4676C>T, p.Arg1624Cys, and c.4870C>T, p.Ala1559Val
D01 - was diagnosed with polymicrogyria and hydrocephalus, with inherited compound heterozygous variants in KIF26A: c.2845C>T, p.Pro949Ser, and c.4676C>T, p.Ala1559Val
E01 - male born to consanguineous parents with growth retardation and developmental delay. Brain MRI performed at 18 months revealed a thin CC, ventriculomegaly and polymicrogyria; homozygous for c.4804C>T; p.Arg1602Trp.

KIF26A is associated with Cortical dysplasia, complex, with other brain malformations 11, 620156 in OMIM (accessed 31st Oct 2025).
The association of KIF26A and 'complex cortical dysplasia with other brain malformations' is classified as Strong in ClinGen (March 2024).
Sources: Other
Created: 3 Nov 2025, 5:34 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cortical dysplasia, complex, with other brain malformations 11, OMIM:620156; cortical dysplasia, complex, with other brain malformations 11 MONDO:0859332

Publications

Created: 3 Nov 2025, 5:34 p.m.

Panel version: 9.160

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Amber
Other

Phenotypes

Cortical dysplasia, complex, with other brain malformations 11, OMIM:620156
cortical dysplasia, complex, with other brain malformations 11 MONDO:0859332

OMIM

613231

Clinvar variants

Variants in KIF26A

Penetrance

None

Publications

Panels with this gene

History Filter Activity

3 Nov 2025, Gel status: 2

Entity classified by Genomics England curator

Ida Ertmanska (Genomics England Curator)

Gene: kif26a has been classified as Amber List (Moderate Evidence).

3 Nov 2025, Gel status: 1

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

Ida Ertmanska (Genomics England Curator)

gene: KIF26A was added gene: KIF26A was added to Intellectual disability. Sources: Other Mode of inheritance for gene: KIF26A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIF26A were set to 36228617; 36564622; 39305096 Phenotypes for gene: KIF26A were set to Cortical dysplasia, complex, with other brain malformations 11, OMIM:620156; cortical dysplasia, complex, with other brain malformations 11 MONDO:0859332 Review for gene: KIF26A was set to AMBER

Intellectual disability Gene: KIF26A