1. Panels
  2. Fetal anomalies
  3. SEC31A
Genes in panel
Prev Next

Fetal anomalies

Gene: SEC31A

Amber List (moderate evidence)
SEC31A (SEC31 homolog A, COPII coat complex component)
EnsemblGeneIds (GRCh38): ENSG00000138674
EnsemblGeneIds (GRCh37): ENSG00000138674
OMIM: 610257, Gene2Phenotype
SEC31A is in 4 panels

2 reviews

Vicki Harrison (Wessex Clinical Genetics Service)

Green List (high evidence)

Not on panelapp. Pair of sibs from a consanguineous family. Then two further patients from unrelated families. Congenital arthrogryposis/multiple joint contractures, Severe GDD, Spastic quadriplegia, Epilepsy, Progressive or congenital microcephaly, structural brain abnormalities (ACC, VM, HPE etc), dysmorphic facial features, skeletal abnormalities . Functional supporting evidence.
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
Halperin-Birk syndrome, OMIM:618651; neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies, MONDO:0032849

Publications

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

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

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
Comment on list classification: There are now 3 unrelated probands reported with 3 unique homozygous variants in SEC31A and a highly syndromic presentation, resulting in early lethality. Two individuals had IUGR. In addition, a neuron-specific sec31a knock-down in Drosophila recapitulated early lethality seen in the patients. Based on available evidence, this gene should be Green on Fetal anomalies.
Created: 14 Aug 2026, 9:28 a.m. | Last Modified: 14 Aug 2026, 9:28 a.m.
Panel Version: 8.3
PMID: 39725565 Almontashiri et al., 2025
Female proband; parents are first cousins. IUGR and multiple congenital anomalies were seen on the antenatal scan. She was born very small, with dysmorphic facial features. She had hypotonia with hyperreflexia, but no seizures. Head ultrasound revealed absent CC and an interhemispheric cyst. She had short bowed limbs, contractures, Wormian skull bones, shortening of the long bones, and microcephaly. She died at 15 days old due to bradycardia. Solo WES revealed a homozygous SEC31A splice variant c.1435-1G>A. Splice AI score is
Splice-Altering / strong (1) for this variant. RT-PCR showed exon skipping and overall reduction in SEC31A expression.

PMID: 40508110 AlTassan et al., 2025
Report of a 5yo male proband with global developmental delay, seizure disorder, hypotonia, spasticity, dysphagia, dysmorphic features, and bilateral hearing loss. Growth parameters indicated microcephaly, failure to thrive, and short stature. He was born to consanguineous parents. WES and WGS showed a homozygous SEC31A variant (c.1359C>G, p.Cys453Trp) - variant not in gnomAD v4.1.1. Unaffected parents confirmed het. Parents confirmed to be consanguineous, Arab ethnicity.

PMID: 30464055 Halperin et al., 2018
2 Bedouin sibs from a consanguineous family. The syndromic presenation included IUGR, marked developmental delay, spastic quadriplegia with profound contractures, pseudobulbar palsy with recurrent aspirations, epilepsy, dysmorphism, neurosensory deafness, optic nerve atrophy with no eye fixation, bilateral cataracts, microcephaly, and agenesis of CC. Focal and generalised tonic-clonic seizures were seen from birth. Both individuals died before age 4 years. Seq method: homozygosity mapping, WES. Both affected individuals were homozygous for the SEC31A: c.2776_2777dup, p.Ala927Thrfs*76 variant - not in gnomAD v4.1.1.

Functional evidence: Drosophila sec31a -/- null model showed early embryonic lethality. Knockdown of sec31a with RNAi in the eye yielded flies with severe eye phenotypes (disorganised ommatids). Brain-specific knockdown: larvae appeared to develop normally until death in the third instar larvae stage.
Sources: Literature
Created: 14 Aug 2026, 9:23 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Halperin-Birk syndrome, OMIM:618651; neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies, MONDO:0032849

Publications

Created: 14 Aug 2026, 9:23 a.m.

Panel version: 8.26

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Expert Review Amber
  • Literature
Phenotypes
  • Halperin-Birk syndrome, OMIM:618651
  • neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies, MONDO:0032849
Tags
Q3_26_promote_green
OMIM
610257
Clinvar variants
Variants in SEC31A
Penetrance
None
Publications
Panels with this gene

History Filter Activity

2 Nov 2026, Gel status: 2

Set Phenotypes

Ida Ertmanska (Genomics England Curator)

Phenotypes for gene: SEC31A were changed from ?Halperin-Birk syndrome, OMIM:618651; Halperin-Birk syndrome, OMIM:618651; neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies, MONDO:0032849 to Halperin-Birk syndrome, OMIM:618651; neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies, MONDO:0032849

29 Oct 2026, Gel status: 2

Added New Source, Set Phenotypes, Set publications

Ida Ertmanska (Genomics England Curator)

Source NHS GMS was added to SEC31A. Added phenotypes Halperin-Birk syndrome, OMIM:618651; neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies, MONDO:0032849 for gene: SEC31A Publications for gene: SEC31A were updated from 30464055; 39725565; 40508110 to 30464055; 40508110; 39725565

14 Aug 2026, Gel status: 2

Entity classified by Genomics England curator

Ida Ertmanska (Genomics England Curator)

Gene: sec31a has been classified as Amber List (Moderate Evidence).

14 Aug 2026, Gel status: 1

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

Ida Ertmanska (Genomics England Curator)

gene: SEC31A was added gene: SEC31A was added to Fetal anomalies. Sources: Literature Q3_26_promote_green tags were added to gene: SEC31A. Mode of inheritance for gene: SEC31A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SEC31A were set to 30464055; 39725565; 40508110 Phenotypes for gene: SEC31A were set to ?Halperin-Birk syndrome, OMIM:618651; neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies, MONDO:0032849 Review for gene: SEC31A was set to GREEN