PAFAH1B1

  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
PAFAH1B1 (HGNC:8574) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
platelet activating factor acetylhydrolase 1b regulatory subunit 1
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
MDCR, MDS
Alias symbols
LIS1, PAFAH, NudF
%HI
2.21(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.11(Read more about gnomAD LOEUF score)
Cytoband
17p13.3
Genomic Coordinates
GRCh37/hg19: chr17:2496948-2588909 NCBI Ensembl UCSC
GRCh38/hg38: chr17:2593183-2685615 NCBI Ensembl UCSC
MANE Select Transcript
NM_000430.4 ENST00000397195.10 (Read more about MANE Select)
Function
Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)), an enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and participates in PAF inactivation. Regulates the PAF-AH (I) activity in a catalytic dimer composition- dependent manner (By similarity). Required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons and postmigr... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-25827
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
10/13/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 11754098
    Cardoso et al. (2002) provide a variant update on PAFAH1B1 (LIS1), including intragenic variants from 41 patients with lissencephaly (4 from the current report and others from previous publications). Thirty-six of the 41 variants "result in a truncated or internally deleted protein." Six de novo nonsense variants are included in this publication.
  • PUBMED: 19667223
    Saillour et al. (2009) describe 31 heterozygous PAFAH1B1 variants and 8 small intragenic deletions in individuals with lissencephaly. Of the 31 point variants, 12 were nonsense, 8 were frameshift, and 5 were splicing defect variants. The 8 intragenic deletions ranged from 1 exon to almost the entire gene (exons 2-11).
HI Evidence Comments:
Loss of PAFAH1B1 (previously known as LIS1) is associated with lissencephaly. Larger deletions involving PAFAH1B1 and other genes at the 17p13.3 locus are associated with Miller-Dieker syndrome, which includes lissencephaly (often more severe than observed with PAFAH1B1 point variation) and other features, such as facial dysmorphisms. For a full description of the evidence supporting the 17p13.3 region, see ISCA-37430. See GeneReviews for additional information on PAFAH1B1-related lissencephaly. Of note, Bruno et al. (2010) further characterize genotype and phenotype correlations within the 17p13.3 microdeletion and microduplication region (PMID:20452996).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
PAFAH1B1 is located within the 17p13.3 duplication syndrome with developmental delay and other features (PMID:19520700 Roos et al. 2009). PMID:19136950 Bi et al. (2009) reported on 7 patients with duplications in 17p13. Four patients have duplications including YWHAE, two patients have gains including PAFAH1B1, and one patient has a gain that includes both genes. Subjects 5 and 6 have gains of PAFAH1B1 (and not YWHAE), but there are also 6 additional genes in these imbalances. Based on phenotype comparisons of patients with YWHAE duplications versus PAFAH1B1 duplications, the authors suggest that gain of PAFAH1B1 causes subtle brain abnormalities, developmental delay, and relative microcephaly. For a full description of evidence related to the 17p13.3 region, see ISCA-37430.

Genomic View

Select assembly: (NC_000017.10) (NC_000017.11)