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Fetal anomalies

Gene: UNC13A

Amber List (moderate evidence)
UNC13A (unc-13 homolog A)
EnsemblGeneIds (GRCh38): ENSG00000130477
EnsemblGeneIds (GRCh37): ENSG00000130477
OMIM: 609894, Gene2Phenotype
UNC13A is in 7 panels

2 reviews

Ida Ertmanska (Genomics England Curator)

This gene and phenotype were reviewed during meetings in July and August 2026. The meetings included representatives of the North Thames and Central and South R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Natalie Chandler & Louise Carr (North Thames GLH), Sarah Graham & Elizabeth Young (Central & South GLH), and Alice Gardham, Esther Kinning, Vicki Harrison, Anna DeBurca, Natalie Canham, Sunayna Best, Soo-Mi Park & Tessa Homfray (R21 Clinical Oversight Group).
Created: 29 Oct 2026, 4:13 p.m. | Last Modified: 29 Oct 2026, 4:13 p.m.
Panel Version: 8.26
Created: 29 Oct 2026, 4:13 p.m.
Last Modified: 29 Oct 2026, 4:13 p.m.
Panel version: 8.26

Soo-Mi Park (CUHNFT)

Green List (high evidence)

MIM 621455 (AR) and 621456 & 621457 (AD). G2P gene with mmoderate confidence for both allelic disorders. On R27. PMID: 41125872 reports type A with six patients with biallelic missense and LoF variants presenting with severe-to-profound GDD or intellectual disability, hypotonia, dysmorphic facies, limb conrdacture, hearing loss and seizures or death in early childhood caused by respiratory failure after pneumonia in one case. There was also poor feeding, respiratory failure, osteoporosis and cryporchidism. Brain MRI findings include enlargement of the subarachnoid spaces, increased T2-weighted signals in the globus pallidus and thin corpus callosum with mildly decreased myelin. They also report type B with a second group of 13 patients who harboured pathogenic, heterozygous de novo missense variants with multiple substitutions at amino acids 808, 811 and 814, presenting with variable degrees of GDD, hypotonia, seizures (severe and refractory) and ataxia, tremor or dyskinetic movements.TYpe C in a third group of patients was reported consisting of a family with at least four affected members across two generations harboring a pathogenic heterozygous missense variant (C587F) that caused learning difficulties to mildmoderate intellectual disability as well as controlled seizures. Using assays with expression of UNC13A variants in mouse hippocampal neurons the effects of the variants on synaptic neurotransmission confirmed disrupted function. PMID: 27648472 reports an individual diagnosed with fatal myasthenia and micropcehaly. She presented at birth with hypotonia, respiratory insufficiency, and poor feeding. She had dysmorphic facial features, small head circumference, high forehead, frontotemporal narrowing, broad nasal bridge, small jaw, high-arched palate, contractures, no voluntary eye movements, and abnormal EEG with nearly continuous multifocal sharp waves, without overt seizures. There was no electric response to photic or auditory stimulation. Brain MRI showed thin corpus callosum. EMG was abnormal PMID:36447687 reports an infant who is homozygous for LoF variants presenting with encephalopathy with alternating hypertonia and hypotonia,decreased consciousness, limited activity, weak suck and gag reflexes, extreme generalized muscle weakness, and irritability. Additional findings included severe kyphoscoliosis anddiaphragmatic, umbilical hernias, feeding difficulties amd small optic nerves. Brain autopsy findings include blunted frontal and temporal lobes, open Sylvian fissures, absence of sub-cortical U-fibers, axonal spheroids in the septum pellucidum, cerebellar Purkinje cell gliosis, spinal cord atrophy, and small optic nerves. Although no prenatal findings have been reported, the microcephal, joint cintractiures and brain malformations can be detected antenatally.Monoallelic amber, biallelic green.
Created: 29 Oct 2026, 3:51 p.m. | Last Modified: 29 Oct 2026, 3:51 p.m.
Panel Version: 8.25

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neurodevelopmental disorder with hypotonia, epilepsy, and absent speech, OMIM:621455; neurodevelopmental disorder with hypotonia, epilepsy, and absent speech, MONDO:0980940

Publications

Created: 29 Oct 2026, 3:51 p.m.
Last Modified: 29 Oct 2026, 3:51 p.m.
Panel version: 8.25

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Expert Review Amber
Phenotypes
  • Neurodevelopmental disorder with hypotonia, epilepsy, and absent speech, OMIM:621455
  • neurodevelopmental disorder with hypotonia, epilepsy, and absent speech, MONDO:0980940
OMIM
609894
Clinvar variants
Variants in UNC13A
Penetrance
None
Publications
Panels with this gene

History Filter Activity

29 Oct 2026, Gel status: 2

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

Ida Ertmanska (Genomics England Curator)

gene: UNC13A was added gene: UNC13A was added to Fetal anomalies. Sources: Expert Review Amber,NHS GMS Mode of inheritance for gene: UNC13A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UNC13A were set to 41125872; 36447687; 27648472 Phenotypes for gene: UNC13A were set to Neurodevelopmental disorder with hypotonia, epilepsy, and absent speech, OMIM:621455; neurodevelopmental disorder with hypotonia, epilepsy, and absent speech, MONDO:0980940