ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000022.10) (NC_000022.11)
  • Haploinsufficiency score: Gene associated with autosomal recessive phenotype
  • Strength of Evidence (disclaimer): Gene associated with autosomal recessive phenotype
  • Haploinsufficiency Phenotype: BLOOD GROUP, P1PK SYSTEM

Haploinsufficiency phenotype comments:

Homozygous or compound heterozygous null mutations in A4GALT result in the rare p phenotype of the P1PK histo-blood group system, which is associated with severe transfusion reactions and increased risk for miscarriage. Furukawa et al., 2002 (PMID: 10993874) reported a Japanese patient with a homozygous nonsense mutation and 4-alpha-galactosyltransferase activity of 0.08% of wild type. Westman et al. 2014 (PMID: 24417201) report three patients with different ethnic backgrounds with homozygous deletions (20.8-32.8 kb) including the proposed promoter, non-coding exons 1 and 2a, and potential binding sites for erythroid transcription factors that resulted in loss of transcription. See Westman et al, 2014 (PMID: 23927681) for a description of 20 null mutations resulting in the p-phenotype. See also additional case reports, PMIDs 23744321, 23225054, 24327159, 21092013, 20053607, 18067504.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity