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  3. CUL1
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Severe microcephaly

Gene: CUL1

Amber List (moderate evidence)
CUL1 (cullin 1)
EnsemblGeneIds (GRCh38): ENSG00000055130
EnsemblGeneIds (GRCh37): ENSG00000055130
OMIM: 603134, Gene2Phenotype
CUL1 is in 2 panels

1 review

Ida Ertmanska (Genomics England Curator)

I don't know

Comment on list classification: There are now 4 unrelated individuals with heterozygous variants in CUL1 and a neurodevelopmental disorder, including microcephaly. However, these cases do not meet the threshold for severe microcephaly (OFC more than -3 SD below mean, or <0.4 pct). Hence, CUL1 can only be rated Amber on Severe microcephaly.
Created: 27 Oct 2026, 12:30 p.m. | Last Modified: 28 Oct 2026, 4:50 p.m.
Panel Version: 9.52
PMID: 41189326 Xu et al., 2025
Study identified heterozygous de novo and inherited variants in the CUL1 gene in four unrelated families with severe microcephaly, ID and developmental delays (severe in 3 probands). OFC was <1st percentile in 3 families and <3rd percentile in the fourth family. Infantile spasms were reported in 2 probands.
Variants identifier: p.Gln607*, p.Met450Leu, p.(Arg273∗), and c.483+1G>A. Method: Trio exome seq.
Functional evidence: developed a zebrafish model with knockdown of cul1a&b, which exhibited significant reductions in central nervous system size and behavioral defects, mirroring the clinical phenotypes observed in patients.

CUL1 is not yet associated with a disease entity in OMIM (accessed 27th Oct 2026).
Sources: Literature
Created: 27 Oct 2026, 12:23 p.m. | Last Modified: 27 Oct 2026, 12:34 p.m.
Panel Version: 9.51

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

Created: 27 Oct 2026, 12:23 p.m.
Last Modified: 28 Oct 2026, 4:50 p.m.
Panel version: 9.52

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • neurodevelopmental disorder, MONDO:0700092
  • microcephaly, MONDO:0001149
OMIM
603134
Clinvar variants
Variants in CUL1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

28 Oct 2026, Gel status: 2

Removed Tag

Ida Ertmanska (Genomics England Curator)

Tag Q4_26_promote_green was removed from gene: CUL1.

27 Oct 2026, Gel status: 2

Set Phenotypes

Ida Ertmanska (Genomics England Curator)

Phenotypes for gene: CUL1 were changed from neurodevelopmental disorder, MONDO:0700092 to neurodevelopmental disorder, MONDO:0700092; microcephaly, MONDO:0001149

27 Oct 2026, Gel status: 2

Entity classified by Genomics England curator

Ida Ertmanska (Genomics England Curator)

Gene: cul1 has been classified as Amber List (Moderate Evidence).

27 Oct 2026, Gel status: 1

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

Ida Ertmanska (Genomics England Curator)

gene: CUL1 was added gene: CUL1 was added to Severe microcephaly. Sources: Literature Q4_26_promote_green tags were added to gene: CUL1. Mode of inheritance for gene: CUL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CUL1 were set to 41189326 Phenotypes for gene: CUL1 were set to neurodevelopmental disorder, MONDO:0700092 Review for gene: CUL1 was set to GREEN