SLC6A18

• Haploinsufficiency score: Haploinsufficiency unlikely
• Strength of Evidence (disclaimer): Haploinsufficiency unlikely

Evidence for haploinsufficiency phenotype

PubMed ID	Description
32487729	Rausell et al. (2020) suggested that this gene is dosage sensitivity unlikely because it had at least one homozygous LoF variant present in >1% of the gnomAD population. Examples of homozygous LoF or likely LoF variants in this gene in gnomAD include p.Lys20SerfsTer10 (1 homozygous individual), p.Tyr319Ter (18840 homozygous individuals), and c.975-2A>T (1 homozygous individual).
22344438	MacArthur et al. (2012) suggested that this gene is dosage sensitivity unlikely because it had at least one homozygous LoF variant present at >5% of the 1000 Genomes Project database.
28406212	Saleheen et al. (2017) identified 1 adult individual in a Pakistani population with a homozygous LoF variants in this gene. The individuals were originally recruited for a study evaluating risk of myocardial infarction. Individuals within that study found to have homozygous predicted LOF variants were phenotyped for ?more than 200 biochemical and disease traits?.
25807282	Sulem et al. (2015) identified 18557 individuals in an Icelandic population with a homozygous LoF variants in this gene. This population was participating in a variety of disease projects and the researchers pulled this population to investigate how often homozygous LoF variants were found in this population.
32461654	Karczewski et al. (2020) identifies 443,769 high confidence loss of function variants in the Genome Aggregation Database (gnomAD) population including these LoF and likely LoF variants (p.Lys20SerfsTer10, p.Tyr319Ter, and c.975-2A>T). Several methods were used to identify these genes including manual curation and utilizing LOEUF scores.

Haploinsufficiency phenotype comments:

This gene was classified as dosage sensitivity unlikely on 2/2/2021 based on review of population data as described in the PMIDs above. These genes all have at least one curated homozygous loss of function variant in 1% or greater of the gnomAD population dataset and some have also been observed in additional population datasets. As of January 2021, there are no disease associations found in OMIM, and no reports suggesting a Mendelian disease association in the literature. The gnomAD pLI score is 0 and the LOEUF score is 1.47 predicting that this gene is tolerant of LoF variation.

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