1. Panels
  2. Fetal anomalies
  3. HMGCS1
Genes in panel
Prev Next

Fetal anomalies

Gene: HMGCS1

Amber List (moderate evidence)
HMGCS1 (3-hydroxy-3-methylglutaryl-CoA synthase 1)
EnsemblGeneIds (GRCh38): ENSG00000112972
EnsemblGeneIds (GRCh37): ENSG00000112972
OMIM: 142940, Gene2Phenotype
HMGCS1 is in 3 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

Sarah Graham (West Midlands Regional Genetics Laboratory, Birmingham Women's and Children’s NHS Foundation Trust)

I don't know

Amber on skeletal dysplasia and congenital myopathy, tagged to be promoted to green. PMID 39531736: variants in 5 patients from 4 families with rigid spine syndrome - childhood-onset myopathy characterized by slowly progressive or non-progressive scoliosis, neck and spine contractures, hypotonia and respiratory insufficiency - age of onset from birth to 4 years; patient were normal at birth except for one noted to have poor head control shortly after birth. Variants: homozygous p.S447P, compound heteozygous p.S115Wfs*12/p.Q29L, compound heterozygous p.R430K/p.G297V, compound heterozygous p.C268S/p.M70T. Functional studies in a zebrafish model demonstrate reduced function for the missense variants. Missense variants are in missense-constrained catalytic domains.Similar phenotype to SELENON, which was added to the fetal anomalies panel in 2026 due to prenatal presentation of arthrogryposis and scoliosis. Further evidence needed for prenatal presentation for HMGCS1 variants; likely that biallelic loss-of-function variants would have a severe prenatal-onset phenotype as seen in knockout zebrafish model.
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
congenital myopathy 28 with rigid spine, MONDO:0980756; Congenital myopathy 28 with rigid spine, OMIM:621433; Congenital myopathy 28 with rigid spine

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
  • congenital myopathy 28 with rigid spine, MONDO:0980756
  • Congenital myopathy 28 with rigid spine, OMIM:621433
  • Congenital myopathy 28 with rigid spine
OMIM
142940
Clinvar variants
Variants in HMGCS1
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: HMGCS1 was added gene: HMGCS1 was added to Fetal anomalies. Sources: Expert Review Amber,NHS GMS Mode of inheritance for gene: HMGCS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HMGCS1 were set to 39531736 Phenotypes for gene: HMGCS1 were set to congenital myopathy 28 with rigid spine, MONDO:0980756; Congenital myopathy 28 with rigid spine, OMIM:621433; Congenital myopathy 28 with rigid spine