Table 8:
HPS6 Pathogenic Gene Variants Associated with Hermansky-Pudlak Syndrome Type 6 (HPS-6)
No | mRNA NM_024747.5 | Amino Acid NP_079023.2 | Exon/Intron 1 | Variant Type 2 | Ethnic Background 3 | References and Footnotes |
---|---|---|---|---|---|---|
1 | c.62_63insCGGCG | p.Leu22Glyfs*33 | Exon 1 | Indel | - | (Lasseaux et al., 2018) 4 |
2 | c.60_64dupGCGGC | p.Leu22Argfs*33 | Exon 1 | Indel | Chinese, Japanese, Portuguese | (Bastida et al., 2019; Okamura et al., 2018; Wei et al., 2016; Wei et al., 2019) 4 |
3 | c.87_108dup22 | p.Ser37Leufs*146 | Exon 1 | Indel | Czech, Eastern/Northern European, German, Polish | (Radke et al., 2013; Summers & Schimmenti, 2014) 5 |
4 | c.141_143delinsG | p.Pro49Trpfs*126 | Exon 1 | Indel | - | (Lasseaux et al., 2018) 4 |
5 | c.155delT | p.Val52Glufs*6 | Exon 1 | Frameshift | Chinese | (Wei et al., 2016) 4 |
6 | c.206_210dupGGGCC | p.Trp71Glyfs*158 | Exon 1 | Indel | Chinese | (Wei et al., 2019) 4 |
7 | c.223C>T | p.Gln75* | Exon 1 | Nonsense | Italian | (Huizing et al., 2009) |
8 | c.233C>G | p.Pro78Arg 6 | Exon 1 | Missense | Japanese | (Okamura et al., 2019) 4 |
9 | c.238dupG | p.Asp80Glyfs*96 | Exon 1 | Frameshift | Dutch, German | (Huizing et al., 2009) |
10 | c.275T>A | p.Leu92Gln 7 | Exon 1 | Missense | - | (Lasseaux et al., 2018) 4,7 |
11 | c.288G>A | p.Trp96* | Exon 1 | Nonsense | Arabic | (Khan et al., 2016) 4 |
12 | c.337C>T | p.Arg113Trp | Exon 1 | Missense | - | (Lasseaux et al., 2018) 4 |
13 | c.383T>C | p.Val128Ala | Exon 1 | Missense | Caucasian | (Han et al., 2018) 4 |
14 | c.448_505dup58 | p.Glu169Glyfs*26 | Exon 1 | Indel | Caucasian | novel 4,8,9 |
15 | c.455C>G | p.Ser152* | Exon 1 | Nonsense | - | (Lasseaux et al., 2018) 4 |
16 | c.503_504delTG | p.Leu168Argfs*7 | Exon 1 | Indel | Chinese | (Wei et al., 2019) 4 |
17 | c.779G>A | p.Gly260Glu | Exon 1 | Missense | Punjabi Afghan | (Hull et al., 2016) 4 |
18 | c.815C>T | p.Thr272Ile | Exon 1 | Missense | Dutch, German | (Huizing et al., 2009) |
19 | c.823C>T | p.Pro275Ser | Exon 1 | Missense | Pakistani | (Yousaf et al., 2016) 4 |
20 | c.877C>T | p.Glu293* | Exon 1 | Nonsense | - | (Shamseldin et al., 2017) 4 |
21 | c.895C>T | p.Arg299Trp | Exon 1 | Missense | Chinese | (Wei et al., 2016) 4 |
22 | c.896G>C | p.Arg299Pro | Exon 1 | Missense | - | (Lasseaux et al., 2018) 4 |
23 | c.905G>A | p.Gly302Asp | Exon 1 | Missense | - | (Lasseaux et al., 2018) 4 |
24 | c.902dupT | p.Thr303Hisfs*64 | Exon 1 | Frameshift | Russian-Palestinian | (Hull et al., 2016) 4 |
25 | c.913C>T | p.Gln305* | Exon 1 | Nonsense | English, German, Scottish | (Huizing et al., 2009) |
26 | c.1065dupG 10 | p.Leu356Alafs*11 | Exon 1 | Frameshift | Israeli Bedouin | (Schreyer-Shafir et al., 2006) 10 |
27 | c.1083dupC | p.Gly362Argfs*5 | Exon 1 | Frameshift | Russian-Palestinian | (Hull et al., 2016) 4 |
28 | c.1114 C>T | p.Arg372* | Exon 1 | Nonsense | Irish, Native American (Cherokee), Scottish | (O'Brien et al., 2016) |
29 | c.1234C>T | p.Gln412* | Exon 1 | Nonsense | Italian | (Huizing et al., 2009) |
30 | c.1235_1239dupAGCGG | p.Arg414Serfs*15 | Exon 1 | Indel | Chinese | (Wei et al., 2019) 4 |
31 | c.1372delG | p.Glu458Serfs*8 | Exon 1 | Frameshift | Chinese | (Wei et al., 2016) 4 |
32 | c.1387C>T | p.Arg463* | Exon 1 | Nonsense | - | (Lasseaux et al., 2018) 4 |
33 | c.1513C>T | p.Gln505* | Exon 1 | Nonsense | Chinese | (Wei et al., 2016; Wei et al., 2019) 4 |
34 | c.1644delA | p.Gly550Glufs*2 | Exon 1 | Frameshift | Arabic | (Khan et al., 2016) 4 |
35 | c.1711_1712insAG | p.Cys571* | Exon 1 | Indel | Czech, Eastern/Northern European, German, Polish | (Radke et al., 2013; Summers & Schimmenti, 2014) 5 |
36 | c.1714_1717delCTGT | p.Leu572Alafs*40 | Exon 1 | Indel | Belgian | (Lasseaux et al., 2018; Zhang et al., 2003) 4 |
37 | c.1819C>T | p.Arg607* | Exon 1 | Nonsense | Chinese | (Lasseaux et al., 2018; Wei et al., 2019) 4 |
38 | c.1865_1866delTG | p.Leu622Argfs*12 | Exon 1 | Indel | German, Irish | (Huizing et al., 2009) |
39 | c.1898delC | p.Pro633Leufs*76 | Exon 1 | Frameshift | Japanese | (Miyamichi et al., 2016) 4 |
40 | c.1919_1920delTC | p.Val640Glyfs*29 | Exon 1 | Indel | German-Caucasian | (Andres et al., 2017) 4 |
41 | c.2038C>T | p.Gln680* | Exon 1 | Nonsense | Japanese | (Miyamichi et al., 2016; Okamura et al., 2018; Okamura et al., 2019) 4, 11 |
42 | c.2189dupC | p.Leu731Serfs*28 | Exon 1 | Frameshift | Caucasian | novel 4,8,9 |
43 | c.2207T>C | p.Leu736Pro | Exon 1 | Missense | - | (Lasseaux et al., 2018) 4 |
44 | del19,972-bp 12 | - | Exon 1 | Indel | English, German, Scottish | (Huizing et al., 2009) |
45 | del exon 1 12 | - | Exon 1 | Indel | - | (Lasseaux et al., 2018) 4 |
The HPS6 gene consists of 1 exon.
When deletion/insertion is 1 nucleotide it is named Frameshift, when larger it is named Indel.
Extracted from literature reference. ‘-‘ = unreported.
At least one of the reported individuals with this variant was identified by next generation sequencing.
The subject described in these references was also seen at NIH and is of Eastern/Northern European (Czech, German, Polish) descent. This subject is compound heterozygous for c.87_108dup22-bp and c.1711_1712insAG.
Gray highlight: missense variant. See text and Supplemental Tables for pathogenicity description.
This variant is listed as a variant of uncertain significance with a high MAF in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/).
novel = previously unreported variant and/or ethnicity, detected in the NIH HPS cohort.
This HPS6 variant was identified by exome sequencing in one unreported subject of Caucasian descent in the NIH HPS cohort. This subject is compound heterozygous for c.448_505dup58-bp and c.2189dupC.
This frameshift variant was previously described as c.1066_1067insG (p.Leu356Argfs*11) (Schreyer-Shafir et al., 2006).
This HPS6 variant c.2038C>T (p.Gln680*) appears to be a Japanese variant, as it occurs in 5 Japanese subjects and is not reported in dbSNP/ExAc databases.
The nomenclature of these HPS6 variants are included in this Table as reported, see reference for each specific variant for more details.