Genes associated with “hereditary spastic paraplegia”

Diagnostic yield calculator →

120 genes foundHPO: Spastic paraplegiaOpen Targets: hereditary spastic paraplegia3 PanelApp panels

How are genes scored? (0–100 composite)

-5–15

ClinGen

0–15

HPO Freq

0–15

Open Targets

0–12

Phen2Gene

0–10

ClinVar

0–8

Constraint

0–8

Dosage

0–8

OMIM CS

0–8

PanelApp

0–5

OMIM

0–5

G2P

0–4

Breadth

Tiers:Strong Candidates (≥20)Consider (≥8)Possible (≥3)

Evidence dots:

HPOClinVarPhen2GeneOpen TargetsPanelApp

hover for details

Strong Candidates

58 genes

SPG11 →

SPG11 vesicle trafficking associated, spatacsin

score

ClinGen: DefinitivePanel: Green (3) ↑P2G #4GTR ↑

Spastic paraplegia

Frequency

P/LP Variants

OT Score

0.85

SPAST →

spastin

score

Panel: Green (3) ↑P2G #3GTR ↑

Spastic paraplegia

Frequency

P/LP Variants

OT Score

0.90

GBA2 →

glucosylceramidase beta 2

score

ClinGen: DefinitivePanel: Green (3) ↑P2G #48GTR ↑

Spastic paraplegia

Frequency

100%

n=5

P/LP Variants

OT Score

0.83

DDHD1 →

DDHD domain containing 1

score

ClinGen: DefinitivePanel: Green (3) ↑P2G #34GTR ↑

Spastic paraplegia

Frequency

33%

n=3

P/LP Variants

OT Score

0.79

NT5C2 →

5'-nucleotidase, cytosolic II

score

ClinGen: DefinitivePanel: Green (3) ↑GTR ↑

Spastic paraplegia

Frequency

100%

n=9

P/LP Variants

OT Score

0.80

FA2H →

fatty acid 2-hydroxylase

score

ClinGen: DefinitivePanel: Green (3) ↑GTR ↑

Spastic paraplegia

Frequency

P/LP Variants

OT Score

0.85

ENTPD1 →

ectonucleoside triphosphate diphosphohydrolase 1

score

ClinGen: DefinitivePanel: Green (3) ↑P2G #47GTR ↑

Spastic paraplegia

Frequency

100%

n=4

P/LP Variants

OT Score

0.77

AP5Z1 →

adaptor related protein complex 5 subunit zeta 1

score

ClinGen: DefinitivePanel: Green (3) ↑GTR ↑

Spastic paraplegia

Frequency

100%

n=2

P/LP Variants

OT Score

0.79

SPG7 →

SPG7 matrix AAA peptidase subunit, paraplegin

score

ClinGen: DefinitivePanel: Green (3) ↑P2G #5GTR ↑

Spastic paraplegia

Frequency

P/LP Variants

OT Score

0.85

Score

Gene

Evidence

Freq

P/LP

Description

52CYP2U1

DefP:G×3

Spastic paraplegia

CYP2U1DefP:G×3

0.85

Spastic paraplegia

51L1CAM

DefP:G×3#8

Spastic paraplegia

L1CAMDefP:G×3#8

40%

0.83

Spastic paraplegia

49ARL6IP1

DefP:G×3

Spastic paraplegia

ARL6IP1DefP:G×3

0.76

Spastic paraplegia

49B4GALNT1

DefP:G×3

Spastic paraplegia

B4GALNT1DefP:G×3

0.82

Spastic paraplegia

47ERLIN2

DefP:G×3

Spastic paraplegia

ERLIN2DefP:G×3

0.83

Spastic paraplegia

47WASHC5

ModP:G×3

Spastic paraplegia

WASHC5ModP:G×3

100%

0.80

Spastic paraplegia

46KIF1A

DefP:G×3

Spastic paraplegia

KIF1ADefP:G×3

0.85

Spastic paraplegia

46MAG

DefP:G×3

myelin associated glycoprotein

MAGDefP:G×3

0.80

myelin associated glycoprotein

46PLP1

DefP:G×3#10

Spastic paraplegia

PLP1DefP:G×3#10

100%

0.83

Spastic paraplegia

45ATL1

DefP:G×3

Spastic paraplegia

ATL1DefP:G×3

0.85

Spastic paraplegia

44KIF5A

DefP:G×3

Spastic paraplegia

KIF5ADefP:G×3

0.82

Spastic paraplegia

43TECPR2

P:G×3

Spastic paraplegia

TECPR2P:G×3

0.80

Spastic paraplegia

42DDHD2

P:G×3

Spastic paraplegia

DDHD2P:G×3

100%

0.83

Spastic paraplegia

40ERLIN1

DefP:G×3

ER lipid raft associated 1

ERLIN1DefP:G×3

0.76

ER lipid raft associated 1

40REEP1

P:G×3

Spastic paraplegia

REEP1P:G×3

0.81

Spastic paraplegia

40PNPLA6

DefP:G×3

Spastic paraplegia

PNPLA6DefP:G×3

17%

0.82

Spastic paraplegia

39CYP7B1

DefP:G×3

Spastic paraplegia

CYP7B1DefP:G×3

0.84

Spastic paraplegia

39UCHL1

DefP:G×2

Spastic paraplegia

UCHL1DefP:G×2

0.84

Spastic paraplegia

39ZFYVE26

P:G×3

Spastic paraplegia

ZFYVE26P:G×3

120

0.80

Spastic paraplegia

38KIDINS220

DefP:G×3

Spastic paraplegia

KIDINS220DefP:G×3

100%

0.79

Spastic paraplegia

38FARS2

DefP:G×3

Spastic paraplegia

FARS2DefP:G×3

100%

0.75

Spastic paraplegia

36AP4E1

DefP:G×3

Spastic paraplegia

AP4E1DefP:G×3

0.78

Spastic paraplegia

36CPT1C

LimP:G×2

Spastic paraplegia

CPT1CLimP:G×2

100%

0.74

Spastic paraplegia

34GJC2

DefP:A×3

Spastic paraplegia

GJC2DefP:A×3

100%

0.77

Spastic paraplegia

34ALS2

DefP:G×3#11

Spastic paraplegia

ALS2DefP:G×3#11

100%

Spastic paraplegia

34BSCL2

DefP:G×3

Spastic paraplegia

BSCL2DefP:G×3

100%

0.77

Spastic paraplegia

33ATP13A2

DefP:G×3

Spastic paraplegia

ATP13A2DefP:G×3

0.81

Spastic paraplegia

33ALDH18A1

DefP:G×3

Spastic paraplegia

ALDH18A1DefP:G×3

100%

0.83

Spastic paraplegia

31NIPA1

P:G×3

Spastic paraplegia

NIPA1P:G×3

0.76

Spastic paraplegia

30SPART

DefP:G×3

Spastic paraplegia

SPARTDefP:G×3

100%

0.80

Spastic paraplegia

29HSPD1

P:G×3

Spastic paraplegia

HSPD1P:G×3

100%

0.75

Spastic paraplegia

29UBAP1

P:G×3

Spastic paraplegia

UBAP1P:G×3

0.78

Spastic paraplegia

29CAPN1

P:G×3

Spastic paraplegia

CAPN1P:G×3

88%

0.78

Spastic paraplegia

29AP4B1

DefP:G×3

Spastic paraplegia

AP4B1DefP:G×3

Spastic paraplegia

27ABCD1

DefP:G×3#1

Spastic paraplegia

ABCD1DefP:G×3#1

Spastic paraplegia

26C19ORF12

DefP:G×3

Spastic paraplegia

C19ORF12DefP:G×3

0.73

Spastic paraplegia

26HPDL

ModP:G

Spastic paraplegia

HPDLModP:G

100%

0.77

Spastic paraplegia

26SLC16A2

DefP:G×3#2

Spastic paraplegia

SLC16A2DefP:G×3#2

Spastic paraplegia

25AP4M1

DefP:G×3

AP4M1DefP:G×3

24SPG21

P:G×3

Spastic paraplegia

SPG21P:G×3

0.76

Spastic paraplegia

24KIF1C

P:G×3

kinesin family member 1C

KIF1CP:G×3

0.78

kinesin family member 1C

24RTN2

P:G×3

Spastic paraplegia

RTN2P:G×3

0.73

Spastic paraplegia

23GPT2

DefP:G

glutamic--pyruvic transaminase 2

GPT2DefP:G

0.77

glutamic--pyruvic transaminase 2

23HACE1

P:G×3

HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1

HACE1P:G×3

0.78

HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1

23IBA57

DefP:A×3

Spastic paraplegia

IBA57DefP:A×3

Spastic paraplegia

22SERAC1

DefP:G×3

SERAC1DefP:G×3

22AMPD2

P:A×3

Spastic paraplegia

AMPD2P:A×3

Spastic paraplegia

21PCYT2

P:G×3

phosphate cytidylyltransferase 2, ethanolamine

PCYT2P:G×3

0.80

phosphate cytidylyltransferase 2, ethanolamine

20DSTYK

ModP:A×3

Spastic paraplegia

DSTYKModP:A×3

100%

Spastic paraplegia

Consider

32 genes

Score

Gene

Evidence

Freq

P/LP

Description

19RNASEH2B

DefP:G×2

Spastic paraplegia

RNASEH2BDefP:G×2

Spastic paraplegia

18SPTAN1

DefP:G×2

Spastic paraplegia

SPTAN1DefP:G×2

75%

Spastic paraplegia

18AP4S1

DefP:G×3

Spastic paraplegia

AP4S1DefP:G×3

Spastic paraplegia

17PI4KA

P:A

Spastic paraplegia

PI4KAP:A

100%

Spastic paraplegia

17SLC2A1

DefP:G×2#13

Spastic paraplegia

SLC2A1DefP:G×2#13

Spastic paraplegia

17KDM5C

DefP:G×3

Progressive spastic paraplegia

KDM5CDefP:G×3

Progressive spastic paraplegia

17SLC25A15

DefP:G×2

Spastic paraplegia

SLC25A15DefP:G×2

100%

Spastic paraplegia

16GBE1

DefP:G

Spastic paraplegia

GBE1DefP:G

100%

Spastic paraplegia

16TUBB4A

DefP:G×3

TUBB4ADefP:G×3

16WDR45B

P:G×3

Spastic paraplegia

WDR45BP:G×3

100%

Spastic paraplegia

16VPS37A

LimP:A×3

Spastic paraplegia

VPS37ALimP:A×3

Spastic paraplegia

13HSNSP

NEUROPATHY, HEREDITARY SENSORY, WITH SPASTIC PARAPLEGIA, AUTOSOMAL RECESSIVE; HSNSP

HSNSP

NEUROPATHY, HEREDITARY SENSORY, WITH SPASTIC PARAPLEGIA, AUTOSOMAL RECESSIVE; HSNSP

13SPEMR

SPASTIC PARAPLEGIA, EPILEPSY, AND IMPAIRED INTELLECTUAL DEVELOPMENT; SPEMR

SPEMR

SPASTIC PARAPLEGIA, EPILEPSY, AND IMPAIRED INTELLECTUAL DEVELOPMENT; SPEMR

13SPG15

SPASTIC PARAPLEGIA 15, AUTOSOMAL RECESSIVE; SPG15

SPG15

SPASTIC PARAPLEGIA 15, AUTOSOMAL RECESSIVE; SPG15

13SPG16

Spastic paraplegia 16, X-linked, complicated

SPG16

Spastic paraplegia 16, X-linked, complicated

13SPG17

SPASTIC PARAPLEGIA 17, AUTOSOMAL DOMINANT; SPG17

SPG17

SPASTIC PARAPLEGIA 17, AUTOSOMAL DOMINANT; SPG17

13SPG20

SPASTIC PARAPLEGIA 20, AUTOSOMAL RECESSIVE; SPG20

SPG20

SPASTIC PARAPLEGIA 20, AUTOSOMAL RECESSIVE; SPG20

13SPG23

SPASTIC PARAPLEGIA 23, AUTOSOMAL RECESSIVE; SPG23

SPG23

SPASTIC PARAPLEGIA 23, AUTOSOMAL RECESSIVE; SPG23

13SPG3A

SPASTIC PARAPLEGIA 3, AUTOSOMAL DOMINANT; SPG3A

SPG3A

SPASTIC PARAPLEGIA 3, AUTOSOMAL DOMINANT; SPG3A

13SPG4

SPASTIC PARAPLEGIA 4, AUTOSOMAL DOMINANT; SPG4

SPG4

SPASTIC PARAPLEGIA 4, AUTOSOMAL DOMINANT; SPG4

13SPG5A

SPASTIC PARAPLEGIA 5A, AUTOSOMAL RECESSIVE; SPG5A

SPG5A

SPASTIC PARAPLEGIA 5A, AUTOSOMAL RECESSIVE; SPG5A

12REEP2

P:G×3

Spastic paraplegia

REEP2P:G×3

Spastic paraplegia

12CCT5

P:R×3

Spastic paraplegia

CCT5P:R×3

Spastic paraplegia

12SLC33A1

P:A×3#14

Spastic paraplegia

SLC33A1P:A×3#14

Spastic paraplegia

11ABHD16A

P:G×2

Spastic paraplegia

ABHD16AP:G×2

100%

Spastic paraplegia

11PAX3

Def#9

Spastic paraplegia

PAX3Def#9

Spastic paraplegia

11VAMP1

P:A×3

Spastic paraplegia

VAMP1P:A×3

Spastic paraplegia

11GAN

Def#6

Spastic paraplegia

GANDef#6

Spastic paraplegia

11FLVCR1

DefP:G

Spastic paraplegia

FLVCR1DefP:G

100%

Spastic paraplegia

11PDHX

Def#7

Spastic paraplegia

PDHXDef#7

Spastic paraplegia

9NFU1

DefP:A

Spastic paraplegia

NFU1DefP:A

100%

Spastic paraplegia

8ELOVL1

P:G

Spastic paraplegia

ELOVL1P:G

100%

Spastic paraplegia

Possible

24 genes — click to expand

Score

Gene

Evidence

Freq

P/LP

Description

8STXBP1

Def

Spastic paraplegia

STXBP1Def

Spastic paraplegia

7MECP2

Def

Spastic paraplegia

MECP2Def

100%

Spastic paraplegia

7PEX3

Def

Spastic paraplegia

PEX3Def

100%

Spastic paraplegia

7CNNM2

Def

CNNM2Def

7RPS6KC1

P:A

Spastic paraplegia

RPS6KC1P:A

45%

Spastic paraplegia

P:G

Spastic paraplegia

RNF170P:G

Spastic paraplegia

5MTRFR

Def

Spastic paraplegia

MTRFRDef

100%

Spastic paraplegia

5KLC2

P:R

Spastic paraplegia

KLC2P:R

Spastic paraplegia

5RNF220

Spastic paraplegia

RNF220

100%

Spastic paraplegia

5SPG10

SPASTIC PARAPLEGIA 10, AUTOSOMAL DOMINANT; SPG10

SPG10

SPASTIC PARAPLEGIA 10, AUTOSOMAL DOMINANT; SPG10

5SPG6

SPASTIC PARAPLEGIA 6, AUTOSOMAL DOMINANT; SPG6

SPG6

SPASTIC PARAPLEGIA 6, AUTOSOMAL DOMINANT; SPG6

5LAMB1

Mod

Spastic paraplegia

LAMB1Mod

Spastic paraplegia