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Intellectual disability

Gene: COPB1

Amber List (moderate evidence)
COPB1 (coatomer protein complex subunit beta 1)
EnsemblGeneIds (GRCh38): ENSG00000129083
EnsemblGeneIds (GRCh37): ENSG00000129083
OMIM: 600959, Gene2Phenotype
COPB1 is in 4 panels

4 reviews

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

Comment on list classification: As reviewed by Luke Stuart, there are now 8 individuals from 3 unrelated families reported in literature with biallelic COPB1 variants and Baralle-Macken syndrome, presenting with severe intellectual disability. There is also a Xenopus model, supportive of the gene-disease association. Hence, this gene should be promoted to Green at the next update.
Created: 13 Aug 2026, 9:28 a.m. | Last Modified: 13 Aug 2026, 9:28 a.m.
Panel Version: 11.1
Created: 13 Aug 2026, 9:28 a.m.
Last Modified: 13 Aug 2026, 9:28 a.m.
Panel version: 11.1

Luke Stuart (Genomics England Curator)

Green List (high evidence)

Macken et al., 2021 (PMID 33632302): six affected females from two families are reported, identified via whole exome or genome sequencing; homozygous COPB1 c.957+1G>T in two probands from a Polish kindred (with aberrant splicing and loss of function confirmed via functional assay), and COPB1 c.1651T>G p.(Phe551Val) homozygous in four probands from a Saudi family. Five of six subjects had microcephaly (− 2 SD); 3/6 had severe microcephaly (> 3SD) (two from family 1, one from family 2). All six patients had severe intellectual disability. In a Xenopus model, CRISPR disruption of copb1 partially recapitulated the human phenotype, causing microcephaly and cataracts. In vitro transfection studies showed abnormal Beta-COP localisation resulting from the p.(Phe551Val) variant with retention within the Golgi and defective Golgi-to-ER recycling, plus mildly reduced protein stability.

Khalid et al., 2025 (PMID 40396222) report an additional two paediatric siblings from a consanguineous Pakistani family with a homozygous missense COPB1 variant, c.2693G>T (p.Arg898Leu) and consistent phenotype, identified via WES. In addition to severe intellectual disability, both patients presented with severe microcephaly and cataracts.

A green rating is recommended based on at least three unrelated affected families with three distinct homozygous pathogenic loss of function variants segregating with disease, with supporting functional evidence and consistent phenotype comprising severe intellectual disability with variable microcephaly and cataracts.
Created: 7 Aug 2026, 4:57 p.m. | Last Modified: 7 Aug 2026, 4:57 p.m.
Panel Version: 10.95

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Baralle-Macken syndrome (OMIM #619255), accessed 08/2026

Publications

Created: 7 Aug 2026, 4:57 p.m.
Last Modified: 7 Aug 2026, 4:57 p.m.
Panel version: 10.95

Arina Puzriakova (Genomics England Curator)

Comment on list classification: New gene added by Zornitza Stark. PMID:33632302 reports on six individuals from two unrelated families with different homozygous variants in this gene. All affected patients had severe ID. Rating Amber, awaiting further cases.
Created: 30 Apr 2021, 8:49 a.m. | Last Modified: 30 Apr 2021, 8:49 a.m.
Panel Version: 3.1044
Created: 30 Apr 2021, 8:49 a.m.
Last Modified: 30 Apr 2021, 8:49 a.m.
Panel version: 3.1044

Zornitza Stark (Australian Genomics)

I don't know

Two unrelated families, some supportive functional data.
Sources: Literature
Created: 15 Apr 2021, 10:55 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Baralle-Macken syndrome, MIM# 619255; Severe intellectual disability; variable microcephaly; cataracts

Publications

Created: 15 Apr 2021, 10:55 a.m.

Panel version: 3.1015

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Baralle-Macken syndrome, OMIM:619255
  • Severe intellectual disability
  • Cataracts
  • Variable microcephaly
Tags
Q3_26_promote_green
OMIM
600959
Clinvar variants
Variants in COPB1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

13 Aug 2026, Gel status: 2

Set publications

Ida Ertmanska (Genomics England Curator)

Publications for gene: COPB1 were set to 33632302

13 Aug 2026, Gel status: 2

Removed Tag, Added Tag

Ida Ertmanska (Genomics England Curator)

Tag watchlist was removed from gene: COPB1. Tag Q3_26_promote_green tag was added to gene: COPB1.

30 Apr 2021, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist tag was added to gene: COPB1.

30 Apr 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: copb1 has been classified as Amber List (Moderate Evidence).

30 Apr 2021, Gel status: 0

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: COPB1 were changed from Baralle-Macken syndrome, MIM# 619255; Severe intellectual disability; variable microcephaly; cataracts to Baralle-Macken syndrome, OMIM:619255; Severe intellectual disability; Cataracts; Variable microcephaly

15 Apr 2021, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: COPB1 was added gene: COPB1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: COPB1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COPB1 were set to 33632302 Phenotypes for gene: COPB1 were set to Baralle-Macken syndrome, MIM# 619255; Severe intellectual disability; variable microcephaly; cataracts Review for gene: COPB1 was set to AMBER