Table 4:

AP3B1 Pathogenic Gene Variants Associated with Hermansky-Pudlak Syndrome Type 2 (HPS-2)

#	mRNA NM_003664.4	Amino Acid NP_003655.3	Exon/Intron	Variant Type 1	Ethnic Background 2	References and Footnotes
1	c.2T>G	p.Met1Arg 3	Exon 1	Start-loss	Australian	(Cetica et al., 2015)
2	c.62delG	p.Gly21Valfs*20	Exon 1	Frameshift	-	(Jessen et al., 2013)
3	c.155_158delAGAG	p.Glu52Alafs*11	Exon 2	Indel	Caucasian, English	(Wenham et al., 2010)
4	c.177delA	p.Lys59Asnfs*5	Exon 2	Frameshift	-	(de Boer et al., 2017)
5	c.305T>C	p.Leu102Pro 4	Exon 4	Missense	-	(Jessen et al., 2013)
6	c.716G>A	p.Trp239*	Exon 7	Nonsense	Moroccan	(de Boer et al., 2017)
7	c.904A>T	p.Arg302*	Exon 8	Nonsense	-	(Enders et al., 2006)
8	c.1063_1064delCAinsTATCAATATC	p.Gln355Tyrfs*6	Exon 10	Indel	Italian	(Fontana et al., 2006)
9	c.1095+5G>A	IVS10+5G>A	Intron10	Splice site	Mexican	(Chiang et al., 2010)
10	c.1168–1G>C 6	IVS11–1G>C	Intron11	Splice site	Dutch	(Dell'Angelica et al., 1999; Gochuico et al., 2012) 5,6
11	c.1473+6T>C	IVS14+6T>C	Intron14	Splice site	-	(Clark et al., 2003)
12	c.1525C>T	p.Arg509*	Exon 15	Nonsense	Cajun, Houma Indian	(Huizing et al., 2002)
13	c.1619dupG	p.Ala541Serfs*25	Exon 15	Frameshift	-	(Clark et al., 2003)
14	g.del8168-bp 7	del exon 15	Introns14+15, Exon 15	Indel	Turkish	(Jung et al., 2006) 7
15	g.del1872-bp 7	del exon 15	Introns14+15, Exon 15	Indel	-	(Hengst et al., 2018) 7
16	del exon 16	-	Exon 16	Indel	-	(Jessen et al., 2013)
17	c.1739T>G	p.Leu580Arg	Exon 16	Missense	Dutch	(Dell'Angelica et al., 1999)
18	c.1754delT	p.Val585Glufs*6	Exon 16	Frameshift	Caucasian	(de Boer et al., 2017)
19	c.1789dupA	p.Ile597Asnfs*12	Exon 16	Frameshift	Italian	(Fontana et al., 2006)
20	c.1839_1842delTAGA	p.Asp613Glufs*38	Exon 17	Indel	-	(de Boer et al., 2017; Hengst et al., 2018; Jung et al., 2006)
21	c.1975G>T	p.Glu659*	Exon 18	Nonsense	Cajun, Houma Indian	(Huizing et al., 2002)
22	c.2041G>T	p.Glu681*	Exon 18	Nonsense	-	(Ammann et al., 2017; Jessen et al., 2013)
23	g.del624-bp 8 c.del2077_2164	p.Glu693Valfs*13	Intron18, Exon 19	Indel	Maltese	(Wenham et al., 2010)
24	c.2546T>G	p.Leu849*	Exon 22	Nonsense	-	(Hengst et al., 2018)
25	c.2702C>G 9	p.Ser901Cys	Exon 23	Missense Splice site	Caucasian	(de Boer et al., 2017) 9
26	c.2770delC	p.Leu924Phefs*3	Exon 23	Frameshift	-	(Jessen et al., 2013)
27	c.2944delC	p.Leu982Cysfs*19	Exon 25	Frameshift	-	(Hengst et al., 2018)
28	c.3222_3223delTG 10	p.Lys1076Asnfs*60	Exon 27	Indel-Stop-loss	United Arabic Emirates	(Hengst et al., 2018; Jessen et al., 2013; Kurnik et al., 2013) 10
29	inv(5)p15.1-q14.1 11	-	-	Indel-chrom. inversion	Lebanese	(Jones et al., 2013) 11

¹When deletion/insertion is 1 nucleotide it is named Frame shift, when larger it is named Indel.

²Extracted from literature reference. ‘-‘ = unreported.

³This variant likely leads to a loss of protein translation in the start codon of the longest splice variant of AP3B1 (NM_003664.4).

⁴Gray highlight: missense variant. See Supplemental Table S1 for pathogenicity predictions.

⁵At least one of the reported cases with this variant was identified by next generation sequencing.

⁶This variant was originally described as del63-bp in the patients’ cDNA (Dell'Angelica et al., 1999), but later found to be due to a gDNA splice site variant, skipping the 63-bp exon 12 (Gochuico et al., 2012).

⁷Described as g.151312_159483del8172-bp (NG_007268) (Hengst et al., 2018). It is possible that del8168-bp reported by (Jung et al., 2006) is the same deletion.

⁸This deletion was reported as: NC_00005.8:g.180242–180866del.

⁹This nucleotide change activates a cryptic donor splice and causes a deletion of 112bp within exon 23 on the mRNA level, resulting in a frame shift and a premature termination codon p.Val900Thrfs*63 (de Boer et al., 2017).

¹⁰This frameshift in the AP3B1 C-terminal coding region results in a prolonged altered protein, beyond the termination codon, with 42 additional C-terminal amino acids compared to the wild type protein (Kurnik et al., 2013).

¹¹Chromosomal inversion breakpoints occur within the AP3B1 gene (Jones et al., 2013).