Table 1.

List of genes and known functions of the top 20 genes mutated less than expected

\	Gene name	Ratio	Obs. rank	Sim. rank	Annotation	Loc	Function	Refs
1	TRAPPC9	0.07	5891	2	trafficking protein particle complex 9	PM	NF-kappa-B signaling	[19]
2	LPP	0.11	3611	11	LIM domain containing preferred translocation partner in lipoma	NU	Localized at focal adhesions and cell–cell contact sites; shuttles to the nucleus where it affects transcription	[20–25]
3	ELFN2	0.12	4446	13	extracellular leucine-rich repeat and fibronectin type III domain containing 2	UK	Unknown	–
4	ANKLE2	0.13	3107	16	ankyrin repeat and LEM domain containing 2	NU	Mitosis	[26, 27]
5	SHROOM3	0.14	4931	28	shroom family member 3	CY	Regulating cell shape in certain tissues	[28–33]
6	PGR	0.14	3798	27	progesterone receptor	NU	Regulation of gene expression and affect cellular proliferation and differentiation in target tissues	[34–37]
7	MAP1B	0.15	6400	39	microtubule-associated protein 1B	CY	Microtubule assembly	[38–44]
8	OBSL1	0.15	5649	38	obscurin-like 1	PM	Links internal cytoskeleton to cell membrane	[45–47]
9	CELSR1	0.15	6483	57	cadherin, EGF LAG seven-pass G-type receptor 1	PM	Involved in cell adhesion	[48, 49]
10	DBNL	0.16	5544	50	drebrin-like	CY	For organ development and immune response. Promote proliferation, colony formation, migration, invasion	[50–53]
11	PHF21A	0.16	3552	36	PHD finger protein 21A	NU	Repression of neuron-specific genes through repressor element-1 or neural restrictive silencer	[54–56]
12	TRPV6	0.16	5245	48	transient receptor potential cation channel, subfamily V, member 6	PM	Calcium channels required for assembly and regulation	[57–63]
13	VEGFA	0.16	4406	47	vascular endothelial growth factor A	ES	Angiogenesis, endothelial cell growth, cell migration, apoptosis	[64–84]
14	GRIP2	0.17	3298	51	glutamate receptor interacting protein 2	OM	Bind AMPA receptors and target AMPA receptors to synapses	[85, 86]
15	RALGDS	0.17	4874	61	ral guanine nucleotide dissociation stimulator	CY	effectors of Ras-related GTPases that participate in signaling	[87, 88] [89]
16	CCDC144A	0.17	4302	58	coiled-coil domain containing 144A	UK	Unknown	–
17	RAI1	0.17	3399	55	retinoic acid induced 1	CY	associated with severity and response to medication in schizophrenia patients	[90–92]
18	TBC1D2B	0.17	3106	52	TBC1 domain family, member 2B	UK	Unknown	–
19	SMG1	0.17	5523	82	smg-1 homolog phosphatidylinositol 3-kinase-related kinase	CY	Involve in tumorigenesis as a new tumor suppressor	(93–95)
20	BRWD1	0.18	4873	85	bromodomain and WD repeat domain containing 1	NU	Unknown	–

Ratio: The ratio of the observed number of mutations to the simulated number of mutations. Obs. Rank: observed rank with 1 being the most mutated in the TCGA data. Sim. Rank: simulated rank with 1 being the most mutated in simulations.

Loc.: cellular localization, PM: Plasma membrane, NU: Nuclear, UK: Unknown, CY: Cytoplasm, ES: Extracellular space