Table 6:
HPS4 Pathogenic Gene Variants Associated with Hermansky-Pudlak Syndrome Type 4 (HPS-4)
| No | mRNA NM_022081.5 | Amino Acid NP_071364.4 | Exon/Intron | Variant Type 1 | Ethnic Background 2 | References and Footnotes |
|---|---|---|---|---|---|---|
| 1 | c.45G>A | p.Trp15* | Exon 3 | Nonsense | Uruguayan, Japanese | (Carmona-Rivera, Golas, et al., 2011; Okamura et al., 2018) 3 |
| 2 | c.47delA | p.Asn16Ilefs*11 | Exon 3 | Frameshift | Uruguayan | (Carmona-Rivera, Golas, et al., 2011) |
| 3 | c.57delT | p.Leu20Phefs*7 | Exon 3 | Frameshift | French, German, Irish, Northern European | (Suzuki et al., 2002) 4 |
| 4 | c.123T>A | p.Tyr41* | Exon 4 | Nonsense | Japanese | (Okamura et al., 2018) 3 |
| 5 | c.148C>T | p.Gln50* | Exon 4 | Nonsense | Chinese | (Wei et al., 2019) 3 |
| 6 | c.272T>C | p.Leu91Pro 5 | Exon 4 | Missense | Turkish | (Bastida et al., 2019) 3 |
| 7 | c.276+5G>A | IVS4+5G>A | Intron 4 | Splice site | Pakistani | (Yousaf et al., 2016) 3 |
| 8 | c.357C>G | p.Tyr119* | Exon 5 | Nonsense | Dutch, English, Irish, Polish, Slovak | novel 6,7 |
| 9 | c.412G>T | p.Glu138* | Exon 6 | Nonsense | Indian | (Anderson et al., 2003) |
| 10 | c.416G>A | p.Trp139* | Exon 6 | Nonsense | Chinese | (Power et al., 2019) |
| 11 | c.430G>T | p.Glu144* | Exon 6 | Nonsense | Indian | (Arcot Sadagopan et al., 2017) 3 |
| 12 | c.461A>G | p.His154Arg | Exon 6 | Missense | Caucasian, Japanese | (Anderson et al., 2003; Saito et al., 2013) 8,9 |
| 13 | c.541C>T | p.Gln181* | Exon 7 | Nonsense | Southern Italian | (Suzuki et al., 2002) |
| 14 | c.554G>A | p.Arg185His | Exon 7 | Missense | Indian | (Arcot Sadagopan et al., 2017) 3 |
| 15 | c.596+1G>A | IVS7+1G>A | Intron 7 | Splice site | Japanese | (Okamura et al., 2019) 3 |
| 16 | c.597–2A>T | IVS7–2A>T | Intron 7 | Splice site | - | (Jones et al., 2012) 3 |
| 17 | c.630dupC | p.Ala211Argfs*47 | Exon 8 | Frameshift | Chinese | (Wu et al., 2019) |
| 18 | c.649C>T | p.Arg217* | Exon 8 | Nonsense | Ashkenazi Jewish, English, Polish | (Anderson et al., 2003; Lozynska et al., 2018) |
| 19 | c.664G>T | p.Glu222* | Exon 8 | Nonsense | Indian | (Anderson et al., 2003) |
| 20 | c.706+1G>A | IVS9+1G>A | Intron 9 | Splice site | Dutch, English, Irish, Polish, Slovak | novel 6,7 |
| 21 | c.730C>T | p.Gln244* | Exon 10 | Nonsense | Japanese | (Araki et al., 2014) |
| 22 | c.803G>A 10 | p.Arg268Lys | Exon 10 | Missense-Splice Site | - | (Lasseaux et al., 2018) 3,10 |
| 23 | c.949_972dup24 | p.Ala317_Glu324dup | Exon 11 | Indel | Dutch | (Suzuki et al., 2002) |
| 24 | c.1132C>T | p.Gln378* | Exon 11 | Nonsense | - | novel 11 |
| 25 | c.1318C>T | p.Gln440* | Exon 11 | Nonsense | Turkish | (Sandrock-Lang et al., 2018) |
| 26 | c.1546C>T | p.Gln516* | Exon 11 | Nonsense | Caucasian | novel 6,8 |
| 27 | c.1547_1548delAG | p.Gln516Argfs*42 | Exon 11 | Indel | Indian | (Arcot Sadagopan et al., 2017) 3 |
| 28 | c.1713+5G>C | IVS11+5G>C | Intron 11 | Splicing | Chinese | (Wei et al., 2019) 3 |
| 29 | c.1856C>T | p.Pro619Leu | Exon 13 | Missense | - | (Lasseaux et al., 2018) 3 |
| 30 | c.1858C>T | p.Gln620* | Exon 13 | Nonsense | - | (Sakata et al., 2013) |
| 31 | c.1891C>T | p.Gln631* | Exon 13 | Nonsense | German South Tirol | (Suzuki et al., 2002) |
| 32 | c.1897_1898dupCG | p.Ser634Alafs*3 | Exon 13 | Indel | Japanese | (Okamura et al., 2019) 3 |
| 33 | c.2054delC | p.Pro685Leufs*17 | Exon 14 | Frameshift | Sri Lankan, Spanish | (Bachli et al., 2004; Bastida et al., 2019) 3 |
| 34 | c.2089_2093dupAAGCA | p.Lys699Serfs*5 | Exon 14 | Indel | Austrian, Czech, English, German, Hungaran, Irish, Scandinavian, Swiss | (Anderson et al., 2003; Suzuki et al., 2002) |
When deletion/insertion is 1 nucleotide it is named Frame shift, when larger it is named Indel.
Extracted from literature reference. ‘-‘ = unreported.
At least one of the reported cases with this variant was identified by next generation sequencing.
This HPS4 variant was identified in heterozygous state in one unreported subject of French-German-Irish descent in the NIH HPS cohort.
Gray highlight: missense variant. See Supplemental Table S1 for pathogenicity description.
novel = previously unreported variant detected in the NIH HPS cohort.
This HPS4 variant was identified in one unreported subject of Dutch-English-Irish-Polish-Slovak descent in the NIH HPS cohort. This subject is compound heterozygous for c.357C>G and c.706+1G>A.
This HPS4 variant was identified in one unreported subject of Caucasian descent in the NIH HPS cohort. This individual is compound heterozygous for c.461A>G and c.1546C>T.
This variant was found homozygous in two Japanese siblings with HPS and mental disorder (schizophrenia and major depression). It was suggested that HPS4 gene variants are associated with susceptibility to schizophrenia (Saito et al., 2013) and/or cognitive function (Kuratomi et al., 2013).
This (missense) HPS4 variant c.803G>A; p.Arg268Lys (Lasseaux et al., 2018) occurs at the exon10/intron 11 splice site junction and is predicted to affect splicing (Supplemental Table S2).
This nonsense variant c.1132C>T (p.Gln378*) was found homozygous in one unreported female subject in the NIH cohort (referred by Dr. Everman, Greenwood Genetics Center, Greenville, SC).