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Table 2 List of interactors and binding domains, number of missense mutations, comparison observed/expected frequency, and pathway affected

From: Characterization of VHL missense mutations in sporadic clear cell renal cell carcinoma: hotspots, affected binding domains, functional impact on pVHL and therapeutic relevance

Name of the interactor

pVHL AA involved

Missense mutations count N (%)

Frequency of observed missense mutations compared to expected

p-value

Pathway of the interactor

CK2

S33, S38, S43

0 (0)

lower

ns

Protein amino acid phosphorylation

GSK3

S68

1 (1.1)

1.8X higher

ns

Wnt signaling pathway

CK1

S72

1 (1.1)

1.8X higher

ns

Wnt signaling pathway

NEDD8

K159

1 (1.1)

1.8X higher

ns

Ubl conjugation pathway

KIFAP3

1–54

0 (0)

lower

ns

Microtubule-based movement

HIF1αN

1–155

68 (77.3)

1.2X higher

**

HIF1α pathway

VDU1/USP33

54–83

22 (25)

1.3X higher

ns

Ubl conjugation pathway

VDU2/USP20

54–83

22 (25)

1.3X higher

ns

Ubl conjugation pathway

RPB7

54–113

39 (44.3)

1.2X higher

ns

Regulatory RNA pathways

VHLAK

54–213

88 (100)

equal

not applicable

Apoptosis

BCL2L11

55–143

62 (70.5)

1.3X higher

**

Apoptosis

HIF1α

67–117

45 (51.1)

1.6X higher

***

Hif1_tf pathway

EPAS1 (HIF2α)

67–117

45 (51.1)

1.6X higher

***

Vegfr1_2 pathway

RPB1

60–120

53 (60.2)

1.6X higher

***

Regulatory RNA pathways

PRKCZ

87–122

30 (34.1)

1.5X higher

**

Antiapoptosis, intracellular Signaling

CARD9

92–121

22 (25)

1.3X higher

ns

NFKB and MAPK signalling

TUBA4A

95–123

20 (22.7)

1.3X higher

ns

MT stabilization and dynamic cell polarity

KIF3A

95–123

20 (22.7)

1.3X higher

ns

Hedgehog_gli pathway

SP1

96–122

20 (22.7)

1.3X higher

ns

TGF-beta signaling pathway

JADE1

96–122

20 (22.7)

1.3X higher

ns

Apoptosis

PRKCD

113–122, 130–154

26 (29.5)

1.4X higher

ns

Regulation of receptor activity, senescence

aPKC-λ/ι

114–122

16 (18.2)

3.2X higher

***

Signalling by NGF

EEF1α1

114–138

23 (26.1)

1.7X higher

**

Protein biosynthesis

CCT-ζ-2

116–119, 148–155

13 (14.8)

2X higher

**

Chaperone-mediated protein complex assembly

TBP1

136–154

7 (8)

1.5X lower

ns

Signaling by Wnt, DNA Replication, Apoptosis

p53

154–163

8 (9.1)

1.5X higher

ns

Apoptosis

Nur77

155–213

20 (22.7)

1.6X lower

**

MAPK and NGF signaling pathways

EloC

157–171

11 (12.5)

1.3X higher

ns

Ubl conjugation pathway

HuR (RNA binding protein)

157–184

19 (21.6)

1.2X higher

ns

mRNA stabilization

EloB

170–174

1 (1.1)

2.8X lower

ns

Ubl conjugation pathway

Cullin2

181–184

6 (6.8)

2.7X higher

**

Ubl conjugation pathway

VBP1

187–213

1 (1.1)

14.9X lower

***

Morphogenesis

  1. 14 splice site mutations and a frameshift mutation for which the position of the affected amino acid cannot be determined and the missense mutation c.642 A > C/ p.X214Cys are excluded from this table. p-value summary: P-value: * < 0.05, ** < 0.01, *** < 0.001, ns “not significant”