Table 1.

Novel candidate HSP genes. List of novel candidate HSP genes identified through WES, divided into major functional modules (ERAD, etc.). OMIM nomenclature refers to established or new (beginning with SPG58) locus. Position refers to the Genome Browser release 19 map. Family 787 has a compound heterozygous mutation in the MARS gene. C, complicated; U, uncomplicated forms of HSP. ADP, adenosine diphosphate; IMP, inosine monophosphate; ATP, adenosine triphosphate; DDHD, Asp-Asp-His domain; GPI, glycosyl phosphatidylinositol; GTPase, guanosine triphosphatase; tRNA, transfer RNA. N/A, not applicable. Single-letter amino acid abbreviations are as follows: C, Cys; E, Glu; F, Phe; G, Gly; I, Ile; K, Lys; L, Leu; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; and X, termination.

Gene Symbol	Locus Nomenclature	Entrez Gene ID	Gene Name	Putative Biological Function	Family #	Position (hg19)	Nucleotide Change	Deduced Protein Change	Effect on Protein	Phenotype
Endoplasmic reticulum and ER-associated degradation (ERAD)
ARL6IP1	SPG61	23204	ADP-ribosylation factor- like 6 interacting protein 1	Protein transport	827	chr16:18804609 TGTTT>T	c.576_579delAAAC	p.K193Ffs36X	Frameshift	C
ERLIN1	SPG62	10613	ER lipid raft associated 1	ER-associated degradation	786 1098 1598	chr10:101914679 G>A chr10:101943559 C>A chr10:101912067 CCTGGTA>C	c.C763T c.G149T c.862_868delACCAGG	p. R255X p.G50V p.del203-204YQ	Stop codon Missense Frameshift	U U
Endosome and membrane trafficking
KIF1C	SPG58	10749	Kinesin family member 1C	Retrograde Golgi to ER transport	789 803 RBT53	chr17:4904143 G>A chr17:4925567 C>T Del	c.G183A c.C2191T -	Splice p.R731X -	N/A Stop codon Absent protein	C U C
USPS	SPG59	9101	Ubiquitin specific peptidase 8	Deubiquitinating enyzme	882	chr15:50769124 C>A	c.C928A	p.Q310K	Missense	C
WDR48	SPG60	57599	WD repeat domain 48	Regulator of deubiquitination	910	chr3:39135498 AAAG>A	c.1879_1881delAAG	p.del628E	Amino acid del	C
Nucleotide metabolism
AMPD2	SPG63	271	Adenosine monophosphate deaminase 2	Deaminates AMP to IMP in purine nucleotide metabolism	1526	chr1:110167989 CT>C	c.318delT	p.C107Afs365X	Frameshift	C
ENTPD1	SPG64	953	Ectonucleoside triphosphate diphosphohydrolase 1	Hydrolyzes ATP and other nucleotides to regulate purinergic transmission	1242 1800	chr10:97605168 G>A chr10:97604339 G>T	c.G649A c.G719T	p.G217R p.E181X	Missense Stop codon	C C
NT5C2	SPG65	22978	5′-nucleotidase, cytosolic II	Preferentially hydrolyzes IMP, in both purine/pyrimidine nucleotide metabolism	659 1290 1549 NGT2 1829	chr10:104899162 C>T chr10:104850739 CT>C chr10:104853067 C>A chr10:104934653 C>T chr10:104861028 T> A	c.175+1G>A c.1225delA c.988-1G>T c.G86A c.A445T	Splice p.S409Vfs436X Splice p.R29X p.R149X	N/A Frameshift N/A Stop codon Stop codon	U C U U C
Lipid/Myelination related
ARS	SPG66	340075	Arylsulfatase family, member I	Hydrolyze sulfate esters Hormone biosynthesis	1349	chr5:149676845 A>AT	c.1641insA	p.C548Mfs559X	Frameshift	C
DDHD2	SPG54	23259	DDHD domain-containing protein 2	Phospholipase preferentially hydrolyzes phosphatidic acid	1675 1314	chr8:38103473 C>G chr8:38103270 C>T	c.1057+5C>G c.C859T	Splice p.R287X	N/A Stop codon	C C
PGAP1	SPG67	80055	Post-GPI attachment to proteins 1	GPI biosynthesis	1241	chr2:197712670 C>A	c.1952+1G>T	Splice	N/A	C
Axon guidance/synapse related
FLRT1	SPG68	23769	Fibronectin leucine rich transmembrane protein 1	Cell adhesion and receptor signaling	709	chr11:63885762 T>C	c.T2023C	Stop-loss	Stop-loss	C
RAB3GAP2	SPG69	25782	RAB3 GTPase activating protein subunit 2	Exocytosis of neurotransmitters and hormones	738	chr1:220357421 A>C	c.T1955G	p.L252X	Stop codon	C
Other
MARS	SPG70	4141	Methionyl-tRNA synthetase	Cytosolic methionyl-tRNA synthetase	787	chr12:57881886 G>A chr12:57908741 C>T	c.G13A;c.C2104T	p.V5M;p.R702W	Missense Missense	C
ZFR	SPG71	51663	Zinc finger RNA binding protein	RNA localization?	1611	chr5:32406955 A>G	c.T956C	p.L319P	Missense	U