Table 1 List of pathogenic mutations in LARKS identified to increase the likelihood of steric-zipper formation

From: Identifying amyloid-related diseases by mapping mutations in low-complexity protein domains to pathologies

protein

Mutation residue no.

Wild type

Mutant

Predicted LARKS

Predicted zipper

FUS

191

G

S

SGGGYG

SSGGYG

 

225

G

V

SGGGGG

SGGGVG

 

230

G

C

GGGGGY

GGGCGY

GATAD1

59

G

A

GFGAAT

AFGAAT

hnRNPA1

304

S

N

GGSGSN

GGSGNN

hnRNPA2

290

D

V

SGNYND

SGNYNV

 

290

D

V

NYNDFG

NYNVFG

KRT8

53

G

V

GLGGGY

GLGGVY

 

53

G

V

LGGGYG

LGGVYG

 

54

Y

C

YGGASG

CGGASG

 

54

Y

C

GYGGAS

GCGGAS

 

54

Y

H

GYGGAS

GHGGAS

 

55

G

A

GYGGAS

GYAGAS

 

62

G

C

MGGITA

MGCITA

 

62

G

C

SGMGGI

SGMGCI

 

62

G

C

GGITAV

GCITAV

PURA

40

G

R

GGGGSG

GRGGSG

TDP-43

290

G

A

GFGNSR

GFANSR

 

290

G

A

GNSRGG

ANSRGG

 

294

G

A

GNSRGG

GNSRAG

 

294

G

A

SRGGGA

SRAGGA

 

294

G

V

NSRGGG

NSRVGG

 

294

G

V

RGGGAG

RVGGAG

 

294

G

V

GNSRGG

GNSRVG

 

295

G

R

GGGAGL

GRGAGL

 

295

G

S

GGGAGL

GSGAGL

 

298

G

S

AGLGNN

ASLGNN

  1. Proteins like FUS, hnRNPA1, hnRNPA2, and TDP43 are known to form reversible phase separations, as well as irreversible amyloid aggregates. Numerous mutations occurring in the head domain of KRT8 were also identified, primarily associated with liver disease. Mutations in proteins GATAD1 (GATA zinc finger domain-containing 1) and PURA (transcriptional activator of Pur-alpha) were also identified by the in silico screen.
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