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Fetal anomalies

Gene: GPKOW

Amber List (moderate evidence)
GPKOW (G-patch domain and KOW motifs)
EnsemblGeneIds (GRCh38): ENSG00000068394
EnsemblGeneIds (GRCh37): ENSG00000068394
OMIM: 301003, Gene2Phenotype
GPKOW is in 3 panels

3 reviews

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

To date, three GPKOW variants have been associated with male-lethal microcephaly with intrauterine growth restriction (PMID: 28612833; 40221893).

Carroll et al 2017 (PMID: 28612833) report a splicing variant (NM_015698.4: c.331+5G>A) in a multigenerational family, with four female carriers, all of those who could be measured have short stature and microcephaly. Male-lethal microcephaly with intrauterine growth restriction was seen in three males within the family and two further male fetuses were terminated after ultrasound diagnosis of intrauterine growth restriction (IUGR). Analysis of patient IV-1 (terminated fetus), showed the presence of a hemizygous NM_015698.4: c.331+5G>A, which had been inherited from his carrier mother.

Two further GPKOW variants were identified by Mok, et al 2025 (PMID: 40221893), in three individuals from two families. These frameshift variants were in the last exon of GPKOW (NM_015698.5: c.1329dupG, p.(Arg441SerfsTer30) and c.1323_1324del, p.(Ser444GlufsTer28)). The male carriers of NM_015698.5: c.1329dupG had IUGR, and other features, but not microcephaly nor lethality. The male carrier of c.1323_1324del had IUGR and microcephaly and was terminated at (33/40). The mothers of these cases had short stature, microcephaly (in one case) and other phenotypic features.

Extensive support from functional studies were also presented in PMID: 28612833; 40221893.
Created: 14 Jul 2025, 8:41 p.m. | Last Modified: 14 Jul 2025, 8:41 p.m.
Panel Version: 6.9

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
syndromic disease, MONDO:0002254

Publications

Created: 14 Jul 2025, 8:41 p.m.
Last Modified: 14 Jul 2025, 8:41 p.m.
Panel version: 6.116

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

The review for this gene will be added to PanelApp at a future date.
Created: 24 Apr 2025, 10:38 a.m. | Last Modified: 24 Apr 2025, 10:38 a.m.
Panel Version: 5.96
Created: 24 Apr 2025, 10:38 a.m.
Last Modified: 24 Apr 2025, 10:38 a.m.
Panel version: 5.96

Rebecca Foulger (Genomics England curator)

I don't know

DDG2P rating in original PAGE list: Probable.
Created: 11 Dec 2018, 9:05 a.m.
Created: 11 Dec 2018, 9:05 a.m.

Panel version: 0.9

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review Amber
  • PAGE Additional Gene List
Phenotypes
  • microcephaly with intrauterine growth restriction
Tags
Q2_25_ promote_green
OMIM
301003
Clinvar variants
Variants in GPKOW
Penetrance
None
Publications
Panels with this gene

History Filter Activity

24 Apr 2025, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: GPKOW were changed from male-lethal microcephaly with intrauterine growth restriction to microcephaly with intrauterine growth restriction

24 Apr 2025, Gel status: 2

Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q2_25_ promote_green tag was added to gene: GPKOW.

24 Apr 2025, Gel status: 2

Set mode of inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for gene: GPKOW was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

24 Apr 2025, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: GPKOW were set to 28612833

8 Nov 2018, Gel status: 2

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

Rebecca Foulger (Genomics England curator)

gene: GPKOW was added gene: GPKOW was added to Fetal anomalies. Sources: PAGE Additional Gene List,Expert Review Amber Mode of inheritance for gene: GPKOW was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: GPKOW were set to 28612833 Phenotypes for gene: GPKOW were set to male-lethal microcephaly with intrauterine growth restriction