MutSig results for LUSC

Number of individuals: 135

Summary of findings

Significantly mutated genes (q≤0.1) 278
Mutations seen in COSMIC 0
Significantly mutated genes on COSMIC territory 0
Genes with clustered mutations (≤3 aa apart) 1
Significantly mutated genesets 89
. . . . . . . . . (excluding sig.mutated genes) 1

Mutation preprocessing

Read 150 MAFs of type "Broad"
Total number of mutations in input MAFs:	49189
After removing 5553 noncoding mutations:	43636
After collapsing adjacent/redundant mutations:	43634

Please see MutSigPreprocess "stdout.txt" for full details.

Mutation filtering

Number of mutations before filtering:		43634
After removing 46 mutations outside patient set:	43588
After removing 87 mutations outside gene set:	43501
After removing 12445 mutations outside category set:	31056
After removing 21260 "impossible" mutations in
gene-patient-category bins of zero coverage:	9796

Please see MutSigRun "stdout.txt" for full details.

Final mutation list

Final set of mutations used in analysis

Mutation breakdown by type

type count
De_novo_Start_InFrame 2
De_novo_Start_OutOfFrame 21
Missense_Mutation 6814
Nonsense_Mutation 482
Read-through 8
Splice_Site_DNP 17
Splice_Site_SNP 184
Synonymous 2268
Total 9796

type	count
De_novo_Start_InFrame	2
De_novo_Start_OutOfFrame	21
Missense_Mutation	6814
Nonsense_Mutation	482
Read-through	8
Splice_Site_DNP	17
Splice_Site_SNP	184
Synonymous	2268
Total	9796

Nonsilent mutations: categories and mutation rates

category n N rate rate_per_mb relative_rate
A->T 1783 49,414,217 0.000036 36.1 0.51
*Np(A/C/T)->nonflip 3900 83,231,156 0.000047 46.9 0.67
*NpG->nonflip 548 23,965,121 0.000023 22.9 0.33
C->G 583 57,782,060 0.000010 10.1 0.14
indel+null 714 107,196,277 6.66e-06 6.66 0.095
Total 7528 107,196,277 0.000070 70.2 1.00

category	n	N	rate	rate_per_mb	relative_rate
A->T	1783	49,414,217	0.000036	36.1	0.51
*Np(A/C/T)->nonflip	3900	83,231,156	0.000047	46.9	0.67
*NpG->nonflip	548	23,965,121	0.000023	22.9	0.33
C->G	583	57,782,060	0.000010	10.1	0.14
indel+null	714	107,196,277	6.66e-06	6.66	0.095
Total	7528	107,196,277	0.000070	70.2	1.00

Target coverage for each individual

(click for higher-resolution version)

Mutation counts, total coverage, and mutation rates for each individual

(click for higher-resolution version)
(click for tabular version)

Significantly mutated genes

rank gene description N n npat nsite nsil n1 n2 n3 n4 n5 p q
1 USH2A Usher syndrome 2A (autosomal recessive, mild) 133 13 13 13 3 9 0 0 0 4 <1.00e-11 <7.86e-09
2 ADAMTS12 ADAM metallopeptidase with thrombospondin type 1 motif, 12 1350 20 20 19 5 7 9 3 1 0 <1.00e-11 <7.86e-09
3 SLIT3 slit homolog 3 (Drosophila) 540 8 6 8 3 1 4 1 1 1 <1.00e-11 <7.86e-09
4 ADAM22 ADAM metallopeptidase domain 22 670 8 8 8 1 3 3 1 1 0 <1.00e-11 <7.86e-09
5 CNBD1 cyclic nucleotide binding domain containing 1 659 6 6 6 0 2 2 0 0 2 <1.00e-11 <7.86e-09
6 VWF von Willebrand factor 1517 12 12 12 1 4 5 0 1 2 <1.00e-11 <7.86e-09
7 LRP1B low density lipoprotein-related protein 1B (deleted in tumors) 16534 52 39 52 11 16 26 1 3 6 <1.00e-11 <7.86e-09
8 COL22A1 collagen, type XXII, alpha 1 5772 16 15 16 4 3 7 0 0 6 <1.00e-11 <7.86e-09
9 SVEP1 sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 4185 10 8 10 3 4 4 1 0 1 <1.00e-11 <7.86e-09
10 SPAG17 sperm associated antigen 17 8370 17 13 17 1 3 9 2 0 3 <1.00e-11 <7.86e-09
11 CSMD1 CUB and Sushi multiple domains 1 13866 28 25 28 7 8 16 0 2 2 <1.00e-11 <7.86e-09
12 PAPPA2 pappalysin 2 11978 24 20 23 10 8 14 1 0 1 <1.00e-11 <7.86e-09
13 CSMD3 CUB and Sushi multiple domains 3 28648 52 43 52 10 15 23 3 4 7 <1.00e-11 <7.86e-09
14 MYH13 myosin, heavy chain 13, skeletal muscle 6075 11 9 11 2 2 5 3 0 1 <1.00e-11 <7.86e-09
15 C6 complement component 6 6615 11 11 11 1 2 3 2 0 4 <1.00e-11 <7.86e-09
16 RYR3 ryanodine receptor 3 16065 24 23 24 8 11 10 1 0 2 <1.00e-11 <7.86e-09
17 LRP2 low density lipoprotein-related protein 2 17623 22 19 22 8 7 11 1 2 1 <1.00e-11 <7.86e-09
18 SCN1A sodium channel, voltage-gated, type I, alpha subunit 17275 18 13 18 3 8 8 0 0 2 <1.00e-11 <7.86e-09
19 PCDH15 protocadherin 15 26729 22 19 22 6 4 14 0 1 3 <1.00e-11 <7.86e-09
20 RYR2 ryanodine receptor 2 (cardiac) 75777 60 38 59 14 11 33 7 2 7 <1.00e-11 <7.86e-09
21 SPHKAP SPHK1 interactor, AKAP domain containing 36302 21 17 21 3 6 12 1 0 2 <1.00e-11 <7.86e-09
22 HEATR7B2 35164 20 16 20 2 6 8 1 0 5 <1.00e-11 <7.86e-09
23 TTN titin 336559 173 79 172 46 37 93 16 15 12 <1.00e-11 <7.86e-09
24 MUC16 mucin 16, cell surface associated 174250 68 41 68 30 17 37 5 7 2 <1.00e-11 <7.86e-09
25 AMPH amphiphysin 5805 10 10 10 3 4 4 0 0 2 2.84e-11 2.15e-08
26 GPR112 G protein-coupled receptor 112 9578 11 11 11 0 5 2 0 1 3 3.74e-11 2.71e-08
27 SMG1 1350 6 6 6 2 0 4 2 0 0 7.58e-11 5.30e-08
28 SELP selectin P (granule membrane protein 140kDa, antigen CD62) 945 6 6 6 1 1 3 0 0 2 1.14e-10 7.70e-08
29 PPFIA2 protein tyrosine phosphatase, receptor type, f polypeptide (PTPRF), interacting protein (liprin), alpha 2 132 4 4 4 0 2 0 1 0 1 1.28e-10 8.31e-08
30 DNAH11 dynein, axonemal, heavy chain 11 23377 16 16 16 4 3 9 0 1 3 1.55e-10 9.72e-08

(click for full table with 18865 genes)

rank	gene	description	N	n	npat	nsite	nsil	n1	n2	n3	n4	n5	p	q
1	USH2A	Usher syndrome 2A (autosomal recessive, mild)	133	13	13	13	3	9	0	0	0	4	<1.00e-11	<7.86e-09
2	ADAMTS12	ADAM metallopeptidase with thrombospondin type 1 motif, 12	1350	20	20	19	5	7	9	3	1	0	<1.00e-11	<7.86e-09
3	SLIT3	slit homolog 3 (Drosophila)	540	8	6	8	3	1	4	1	1	1	<1.00e-11	<7.86e-09
4	ADAM22	ADAM metallopeptidase domain 22	670	8	8	8	1	3	3	1	1	0	<1.00e-11	<7.86e-09
5	CNBD1	cyclic nucleotide binding domain containing 1	659	6	6	6	0	2	2	0	0	2	<1.00e-11	<7.86e-09
6	VWF	von Willebrand factor	1517	12	12	12	1	4	5	0	1	2	<1.00e-11	<7.86e-09
7	LRP1B	low density lipoprotein-related protein 1B (deleted in tumors)	16534	52	39	52	11	16	26	1	3	6	<1.00e-11	<7.86e-09
8	COL22A1	collagen, type XXII, alpha 1	5772	16	15	16	4	3	7	0	0	6	<1.00e-11	<7.86e-09
9	SVEP1	sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1	4185	10	8	10	3	4	4	1	0	1	<1.00e-11	<7.86e-09
10	SPAG17	sperm associated antigen 17	8370	17	13	17	1	3	9	2	0	3	<1.00e-11	<7.86e-09
11	CSMD1	CUB and Sushi multiple domains 1	13866	28	25	28	7	8	16	0	2	2	<1.00e-11	<7.86e-09
12	PAPPA2	pappalysin 2	11978	24	20	23	10	8	14	1	0	1	<1.00e-11	<7.86e-09
13	CSMD3	CUB and Sushi multiple domains 3	28648	52	43	52	10	15	23	3	4	7	<1.00e-11	<7.86e-09
14	MYH13	myosin, heavy chain 13, skeletal muscle	6075	11	9	11	2	2	5	3	0	1	<1.00e-11	<7.86e-09
15	C6	complement component 6	6615	11	11	11	1	2	3	2	0	4	<1.00e-11	<7.86e-09
16	RYR3	ryanodine receptor 3	16065	24	23	24	8	11	10	1	0	2	<1.00e-11	<7.86e-09
17	LRP2	low density lipoprotein-related protein 2	17623	22	19	22	8	7	11	1	2	1	<1.00e-11	<7.86e-09
18	SCN1A	sodium channel, voltage-gated, type I, alpha subunit	17275	18	13	18	3	8	8	0	0	2	<1.00e-11	<7.86e-09
19	PCDH15	protocadherin 15	26729	22	19	22	6	4	14	0	1	3	<1.00e-11	<7.86e-09
20	RYR2	ryanodine receptor 2 (cardiac)	75777	60	38	59	14	11	33	7	2	7	<1.00e-11	<7.86e-09
21	SPHKAP	SPHK1 interactor, AKAP domain containing	36302	21	17	21	3	6	12	1	0	2	<1.00e-11	<7.86e-09
22	HEATR7B2		35164	20	16	20	2	6	8	1	0	5	<1.00e-11	<7.86e-09
23	TTN	titin	336559	173	79	172	46	37	93	16	15	12	<1.00e-11	<7.86e-09
24	MUC16	mucin 16, cell surface associated	174250	68	41	68	30	17	37	5	7	2	<1.00e-11	<7.86e-09
25	AMPH	amphiphysin	5805	10	10	10	3	4	4	0	0	2	2.84e-11	2.15e-08
26	GPR112	G protein-coupled receptor 112	9578	11	11	11	0	5	2	0	1	3	3.74e-11	2.71e-08
27	SMG1		1350	6	6	6	2	0	4	2	0	0	7.58e-11	5.30e-08
28	SELP	selectin P (granule membrane protein 140kDa, antigen CD62)	945	6	6	6	1	1	3	0	0	2	1.14e-10	7.70e-08
29	PPFIA2	protein tyrosine phosphatase, receptor type, f polypeptide (PTPRF), interacting protein (liprin), alpha 2	132	4	4	4	0	2	0	1	0	1	1.28e-10	8.31e-08
30	DNAH11	dynein, axonemal, heavy chain 11	23377	16	16	16	4	3	9	0	1	3	1.55e-10	9.72e-08

Notes
N = number of sequenced bases in this gene across the individual set
n = number of (nonsilent) mutations in this gene across the individual set
npat = number of patients (individuals) with at least one nonsilent mutation
nsite = number of unique sites having a nonsilent mutation
nsil = number of silent mutations in this gene across the individual set
n1 = number of nonsilent mutations of type "A->T"
n2 = number of nonsilent mutations of type "*Np(A/C/T)->nonflip"
n3 = number of nonsilent mutations of type "*NpG->nonflip"
n4 = number of nonsilent mutations of type "C->G"
n5 = number of nonsilent mutations of type "indel+null"
null = mutation category that includes nonsense, frameshift, splice-site mutations
p_classic = p-value for the observed amount of nonsilent mutations being elevated in this gene
p_ns_s = p-value for the observed nonsilent/silent ratio being elevated in this gene
p = p-value (overall)
q = q-value, False Discovery Rate (Benjamini-Hochberg procedure)

COSMIC analyses

Two distinct analyses are reported using the COSMIC database:
(COS1) COSMIC used as a filter to increase power by restricting the territory of each gene
(COS2) COSMIC used as a prior for the importance of a gene

(COS1) Significantly mutated genes (COSMIC territory only)

rank gene description n cos n_cos N_cos cos_ev p q

(click for full table with 4550 genes)

Notes
n = number of mutations in this gene in the individual set
cos = number of unique mutated sites in this gene in COSMIC
n_cos = overlap between n and cos
N_cos = number of individuals × cos
cos_ev = total evidence: number of reports in COSMIC for mutations seen in this gene
p = p-value for seeing the observed amount of overlap in this gene
q = q-value, False Discovery Rate (Benjamini-Hochberg procedure)

(COS2) Genes mutated at sites that are highly reported in COSMIC

rank gene description n cos n_cos cos_ev

(click for full table with 4550 genes)

Notes
n = number of mutations in this gene in the individual set
cos = number of unique mutated sites in this gene in COSMIC
n_cos = overlap between n and cos
cos_ev = total evidence: number of reports in COSMIC for mutations seen in this gene

Mutations reported in COSMIC

gene patient chr start end type n_cos

(click for full table with 0 mutations)

Genes with clustered mutations

rank gene desc n mindist npairs3 npairs12
1 C20orf26 chromosome 20 open reading frame 26 10 0 1 1
2 DNAH8 dynein, axonemal, heavy chain 8 26 3 0 1
3 ABCA13 ATP-binding cassette, sub-family A (ABC1), member 13 16 8 0 1
4 SCN5A sodium channel, voltage-gated, type V, alpha subunit 6 19 0 0
5 GBF1 golgi-specific brefeldin A resistance factor 1 4 21 0 0
6 CUBN cubilin (intrinsic factor-cobalamin receptor) 18 30 0 0
7 PKHD1L1 polycystic kidney and hepatic disease 1 (autosomal recessive)-like 1 29 84 0 0
8 CELSR3 cadherin, EGF LAG seven-pass G-type receptor 3 (flamingo homolog, Drosophila) 6 161 0 0
9 MXRA5 matrix-remodelling associated 5 10 686 0 0
10 GPR98 G protein-coupled receptor 98 23 850 0 0
11 SYNE1 spectrin repeat containing, nuclear envelope 1 27 851 0 0
12 A2ML1 alpha-2-macroglobulin-like 1 4 Inf 0 0
13 AACS acetoacetyl-CoA synthetase 2 Inf 0 0
14 AAK1 AP2 associated kinase 1 4 Inf 0 0
15 AARS2 alanyl-tRNA synthetase 2, mitochondrial (putative) 4 Inf 0 0
16 ABCA10 ATP-binding cassette, sub-family A (ABC1), member 10 4 Inf 0 0
17 ABCA4 ATP-binding cassette, sub-family A (ABC1), member 4 8 Inf 0 0
18 ABCA6 ATP-binding cassette, sub-family A (ABC1), member 6 5 Inf 0 0
19 ABCB1 ATP-binding cassette, sub-family B (MDR/TAP), member 1 9 Inf 0 0
20 ABCB5 ATP-binding cassette, sub-family B (MDR/TAP), member 5 4 Inf 0 0
21 ABCC1 ATP-binding cassette, sub-family C (CFTR/MRP), member 1 4 Inf 0 0
22 ABCC12 ATP-binding cassette, sub-family C (CFTR/MRP), member 12 9 Inf 0 0
23 ABCC2 ATP-binding cassette, sub-family C (CFTR/MRP), member 2 2 Inf 0 0
24 ABCC8 ATP-binding cassette, sub-family C (CFTR/MRP), member 8 6 Inf 0 0
25 ABCC9 ATP-binding cassette, sub-family C (CFTR/MRP), member 9 5 Inf 0 0
26 ABCF2 ATP-binding cassette, sub-family F (GCN20), member 2 2 Inf 0 0
27 ABCF3 ATP-binding cassette, sub-family F (GCN20), member 3 2 Inf 0 0
28 ABCG8 ATP-binding cassette, sub-family G (WHITE), member 8 (sterolin 2) 5 Inf 0 0
29 ABLIM1 actin binding LIM protein 1 2 Inf 0 0
30 ABLIM3 actin binding LIM protein family, member 3 2 Inf 0 0

(click for full table with 2620 genes)

rank	gene	desc	n	mindist	npairs3	npairs12
1	C20orf26	chromosome 20 open reading frame 26	10	0	1	1
2	DNAH8	dynein, axonemal, heavy chain 8	26	3	0	1
3	ABCA13	ATP-binding cassette, sub-family A (ABC1), member 13	16	8	0	1
4	SCN5A	sodium channel, voltage-gated, type V, alpha subunit	6	19	0	0
5	GBF1	golgi-specific brefeldin A resistance factor 1	4	21	0	0
6	CUBN	cubilin (intrinsic factor-cobalamin receptor)	18	30	0	0
7	PKHD1L1	polycystic kidney and hepatic disease 1 (autosomal recessive)-like 1	29	84	0	0
8	CELSR3	cadherin, EGF LAG seven-pass G-type receptor 3 (flamingo homolog, Drosophila)	6	161	0	0
9	MXRA5	matrix-remodelling associated 5	10	686	0	0
10	GPR98	G protein-coupled receptor 98	23	850	0	0
11	SYNE1	spectrin repeat containing, nuclear envelope 1	27	851	0	0
12	A2ML1	alpha-2-macroglobulin-like 1	4	Inf	0	0
13	AACS	acetoacetyl-CoA synthetase	2	Inf	0	0
14	AAK1	AP2 associated kinase 1	4	Inf	0	0
15	AARS2	alanyl-tRNA synthetase 2, mitochondrial (putative)	4	Inf	0	0
16	ABCA10	ATP-binding cassette, sub-family A (ABC1), member 10	4	Inf	0	0
17	ABCA4	ATP-binding cassette, sub-family A (ABC1), member 4	8	Inf	0	0
18	ABCA6	ATP-binding cassette, sub-family A (ABC1), member 6	5	Inf	0	0
19	ABCB1	ATP-binding cassette, sub-family B (MDR/TAP), member 1	9	Inf	0	0
20	ABCB5	ATP-binding cassette, sub-family B (MDR/TAP), member 5	4	Inf	0	0
21	ABCC1	ATP-binding cassette, sub-family C (CFTR/MRP), member 1	4	Inf	0	0
22	ABCC12	ATP-binding cassette, sub-family C (CFTR/MRP), member 12	9	Inf	0	0
23	ABCC2	ATP-binding cassette, sub-family C (CFTR/MRP), member 2	2	Inf	0	0
24	ABCC8	ATP-binding cassette, sub-family C (CFTR/MRP), member 8	6	Inf	0	0
25	ABCC9	ATP-binding cassette, sub-family C (CFTR/MRP), member 9	5	Inf	0	0
26	ABCF2	ATP-binding cassette, sub-family F (GCN20), member 2	2	Inf	0	0
27	ABCF3	ATP-binding cassette, sub-family F (GCN20), member 3	2	Inf	0	0
28	ABCG8	ATP-binding cassette, sub-family G (WHITE), member 8 (sterolin 2)	5	Inf	0	0
29	ABLIM1	actin binding LIM protein 1	2	Inf	0	0
30	ABLIM3	actin binding LIM protein family, member 3	2	Inf	0	0

Notes
n = number of mutations in this gene in the individual set
mindist = distance (in aa) between closest pair of mutations in this gene
npairs3 = how many pairs of mutations are within 3 aa of each other
npairs12 = how many pairs of mutations are within 12 aa of each other

Significantly mutated genesets

rank geneset description N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 p q
1 GPCRDB_CLASS_B_SECRETIN_ LIKE 20 CALCR(2), CRHR1(3), CRHR2(1), ELTD1(9), EMR1(5), EMR2(3), GLP2R(2), GPR64(3) 70035 28 22 28 7 6 13 1 4 4 <1.00e-11 <7.70e-10
2 STRIATED_MUSCLE_ CONTRACTION 37 ACTN3(2), DMD(10), MYBPC3(1), MYH6(8), MYH7(6), MYH8(14), MYOM1(2), NEB(9), TNNT3(1), TTN(173) 823331 226 91 225 69 52 114 20 19 21 <1.00e-11 <7.70e-10
3 NO1PATHWAY Shear stress in endothelial cells increases cytoplasmic calcium, which activates nitric oxide synthase III to release NO, which in turn regulates cardiac contractions. 28 CHRM1(1), CHRNA1(2), FLT4(1), NOS3(1), RYR2(60), SLC7A1(2) 268724 67 41 66 20 12 38 7 3 7 <1.00e-11 <7.70e-10
4 HSA04720_LONG_TERM_ POTENTIATION Genes involved in long-term potentiation 67 ADCY8(8), ARAF(1), BRAF(4), CACNA1C(14), CAMK2A(2), CAMK2D(1), CAMK4(1), CREBBP(10), EP300(4), GRIA1(5), GRIN2B(11), GRM1(8), ITPR1(1), ITPR2(5), ITPR3(3), KRAS(2), MAPK1(1), MAPK3(1), PLCB1(6), PLCB4(3), PPP3CC(1), PRKCA(3), RAF1(1), RPS6KA2(2) 461187 98 57 98 27 29 39 4 10 16 <1.00e-11 <7.70e-10
5 HSA04730_LONG_TERM_ DEPRESSION Genes involved in long-term depression 74 ARAF(1), BRAF(4), CACNA1A(6), CRHR1(3), GNAS(2), GRIA1(5), GRM1(8), GUCY2C(3), GUCY2D(1), ITPR1(1), ITPR2(5), ITPR3(3), KRAS(2), LYN(1), MAPK1(1), MAPK3(1), NOS3(1), PLA2G4A(4), PLCB1(6), PLCB4(3), PPP2R2A(1), PRKCA(3), RAF1(1), RYR1(23) 551618 89 53 89 25 15 50 3 10 11 <1.00e-11 <7.70e-10
6 HSA04020_CALCIUM_ SIGNALING_PATHWAY Genes involved in calcium signaling pathway 169 ADCY2(11), ADCY3(3), ADCY4(3), ADCY8(8), ATP2A3(2), ATP2B1(4), ATP2B2(4), ATP2B4(1), CACNA1A(6), CACNA1C(14), CACNA1D(1), CACNA1E(14), CACNA1F(3), CACNA1G(4), CACNA1H(1), CACNA1I(7), CAMK2A(2), CAMK2D(1), CAMK4(1), CHRM1(1), EGFR(2), ERBB3(2), GNAL(1), GNAS(2), GRM1(8), ITPR1(1), ITPR2(5), ITPR3(3), MYLK(1), NOS3(1), P2RX4(1), PDE1A(2), PDGFRB(5), PHKG1(1), PHKG2(1), PLCB1(6), PLCB4(3), PLCE1(6), PPP3CC(1), PRKCA(3), RYR1(23), RYR2(60), RYR3(24), SLC8A3(5), TBXA2R(1) 1662500 259 92 258 73 60 141 15 18 25 <1.00e-11 <7.70e-10
7 SMOOTH_MUSCLE_CONTRACTION 138 ADCY2(11), ADCY3(3), ADCY4(3), ADCY5(2), ADCY8(8), ATP2A3(2), CAMK2A(2), CAMK2D(1), CREB3(1), CRHR1(3), GRK4(1), IL1B(1), ITPR1(1), ITPR2(5), ITPR3(3), NOS3(1), PRKCA(3), PRKCE(2), PRKCZ(1), RGS6(3), RYR1(23), RYR2(60), RYR3(24), TNXB(12), USP5(1) 1159895 177 77 176 52 51 89 11 11 15 <1.00e-11 <7.70e-10
8 CALCIUM_REGULATION_ IN_CARDIAC_CELLS 139 ADCY2(11), ADCY3(3), ADCY4(3), ADCY5(2), ADCY8(8), ATP1B2(1), ATP2A3(2), ATP2B1(4), ATP2B2(4), CACNA1A(6), CACNA1C(14), CACNA1D(1), CACNA1E(14), CAMK2A(2), CAMK2D(1), CAMK4(1), CHRM1(1), GJB1(1), GRK4(1), ITPR1(1), ITPR2(5), ITPR3(3), PEA15(1), PRKCA(3), PRKCE(2), PRKCZ(1), RGS6(3), RYR1(23), RYR2(60), RYR3(24), SLC8A3(5), USP5(1) 1466343 212 88 211 58 59 109 11 13 20 <1.00e-11 <7.70e-10
9 HSA04512_ECM_RECEPTOR_ INTERACTION Genes involved in ECM-receptor interaction 87 AGRN(1), CD36(1), CHAD(1), COL11A2(6), COL1A1(4), COL4A1(6), COL4A4(6), COL4A6(2), COL5A3(7), FNDC3A(1), GP1BA(3), GP5(3), HSPG2(4), ITGA1(1), ITGA2(5), ITGA5(1), ITGA7(2), ITGA8(8), ITGB4(2), ITGB6(1), LAMA1(7), LAMA2(10), LAMA3(6), LAMA5(5), LAMB1(5), LAMB2(3), LAMB4(3), RELN(27), TNC(5), TNXB(12), VWF(12) 1365132 160 78 160 51 48 77 5 12 18 1.60e-10 1.10e-08
10 LAIRPATHWAY The local acute inflammatory response is mediated by activated macrophages and mast cells or by complement activation. 16 C3(1), C6(11), C7(4), ITGAL(2), SELP(6) 74494 24 23 24 8 5 10 3 0 6 6.75e-10 4.16e-08

(click for full table with 616 genesets)

rank	geneset	description	N_genes	mut_tally	N	n	npat	nsite	nsil	n1	n2	n3	n4	n5	p	q
1	GPCRDB_CLASS_B_SECRETIN_ LIKE		20	CALCR(2), CRHR1(3), CRHR2(1), ELTD1(9), EMR1(5), EMR2(3), GLP2R(2), GPR64(3)	70035	28	22	28	7	6	13	1	4	4	<1.00e-11	<7.70e-10
2	STRIATED_MUSCLE_ CONTRACTION		37	ACTN3(2), DMD(10), MYBPC3(1), MYH6(8), MYH7(6), MYH8(14), MYOM1(2), NEB(9), TNNT3(1), TTN(173)	823331	226	91	225	69	52	114	20	19	21	<1.00e-11	<7.70e-10
3	NO1PATHWAY	Shear stress in endothelial cells increases cytoplasmic calcium, which activates nitric oxide synthase III to release NO, which in turn regulates cardiac contractions.	28	CHRM1(1), CHRNA1(2), FLT4(1), NOS3(1), RYR2(60), SLC7A1(2)	268724	67	41	66	20	12	38	7	3	7	<1.00e-11	<7.70e-10
4	HSA04720_LONG_TERM_ POTENTIATION	Genes involved in long-term potentiation	67	ADCY8(8), ARAF(1), BRAF(4), CACNA1C(14), CAMK2A(2), CAMK2D(1), CAMK4(1), CREBBP(10), EP300(4), GRIA1(5), GRIN2B(11), GRM1(8), ITPR1(1), ITPR2(5), ITPR3(3), KRAS(2), MAPK1(1), MAPK3(1), PLCB1(6), PLCB4(3), PPP3CC(1), PRKCA(3), RAF1(1), RPS6KA2(2)	461187	98	57	98	27	29	39	4	10	16	<1.00e-11	<7.70e-10
5	HSA04730_LONG_TERM_ DEPRESSION	Genes involved in long-term depression	74	ARAF(1), BRAF(4), CACNA1A(6), CRHR1(3), GNAS(2), GRIA1(5), GRM1(8), GUCY2C(3), GUCY2D(1), ITPR1(1), ITPR2(5), ITPR3(3), KRAS(2), LYN(1), MAPK1(1), MAPK3(1), NOS3(1), PLA2G4A(4), PLCB1(6), PLCB4(3), PPP2R2A(1), PRKCA(3), RAF1(1), RYR1(23)	551618	89	53	89	25	15	50	3	10	11	<1.00e-11	<7.70e-10
6	HSA04020_CALCIUM_ SIGNALING_PATHWAY	Genes involved in calcium signaling pathway	169	ADCY2(11), ADCY3(3), ADCY4(3), ADCY8(8), ATP2A3(2), ATP2B1(4), ATP2B2(4), ATP2B4(1), CACNA1A(6), CACNA1C(14), CACNA1D(1), CACNA1E(14), CACNA1F(3), CACNA1G(4), CACNA1H(1), CACNA1I(7), CAMK2A(2), CAMK2D(1), CAMK4(1), CHRM1(1), EGFR(2), ERBB3(2), GNAL(1), GNAS(2), GRM1(8), ITPR1(1), ITPR2(5), ITPR3(3), MYLK(1), NOS3(1), P2RX4(1), PDE1A(2), PDGFRB(5), PHKG1(1), PHKG2(1), PLCB1(6), PLCB4(3), PLCE1(6), PPP3CC(1), PRKCA(3), RYR1(23), RYR2(60), RYR3(24), SLC8A3(5), TBXA2R(1)	1662500	259	92	258	73	60	141	15	18	25	<1.00e-11	<7.70e-10
7	SMOOTH_MUSCLE_CONTRACTION		138	ADCY2(11), ADCY3(3), ADCY4(3), ADCY5(2), ADCY8(8), ATP2A3(2), CAMK2A(2), CAMK2D(1), CREB3(1), CRHR1(3), GRK4(1), IL1B(1), ITPR1(1), ITPR2(5), ITPR3(3), NOS3(1), PRKCA(3), PRKCE(2), PRKCZ(1), RGS6(3), RYR1(23), RYR2(60), RYR3(24), TNXB(12), USP5(1)	1159895	177	77	176	52	51	89	11	11	15	<1.00e-11	<7.70e-10
8	CALCIUM_REGULATION_ IN_CARDIAC_CELLS		139	ADCY2(11), ADCY3(3), ADCY4(3), ADCY5(2), ADCY8(8), ATP1B2(1), ATP2A3(2), ATP2B1(4), ATP2B2(4), CACNA1A(6), CACNA1C(14), CACNA1D(1), CACNA1E(14), CAMK2A(2), CAMK2D(1), CAMK4(1), CHRM1(1), GJB1(1), GRK4(1), ITPR1(1), ITPR2(5), ITPR3(3), PEA15(1), PRKCA(3), PRKCE(2), PRKCZ(1), RGS6(3), RYR1(23), RYR2(60), RYR3(24), SLC8A3(5), USP5(1)	1466343	212	88	211	58	59	109	11	13	20	<1.00e-11	<7.70e-10
9	HSA04512_ECM_RECEPTOR_ INTERACTION	Genes involved in ECM-receptor interaction	87	AGRN(1), CD36(1), CHAD(1), COL11A2(6), COL1A1(4), COL4A1(6), COL4A4(6), COL4A6(2), COL5A3(7), FNDC3A(1), GP1BA(3), GP5(3), HSPG2(4), ITGA1(1), ITGA2(5), ITGA5(1), ITGA7(2), ITGA8(8), ITGB4(2), ITGB6(1), LAMA1(7), LAMA2(10), LAMA3(6), LAMA5(5), LAMB1(5), LAMB2(3), LAMB4(3), RELN(27), TNC(5), TNXB(12), VWF(12)	1365132	160	78	160	51	48	77	5	12	18	1.60e-10	1.10e-08
10	LAIRPATHWAY	The local acute inflammatory response is mediated by activated macrophages and mast cells or by complement activation.	16	C3(1), C6(11), C7(4), ITGAL(2), SELP(6)	74494	24	23	24	8	5	10	3	0	6	6.75e-10	4.16e-08

Notes: (Please see notes under significantly mutated gene table)

Significantly mutated genesets (excluding significantly mutated genes)

rank geneset description N_genes mut_tally N n npat nsite nsil n1 n2 n3 n4 n5 p q
1 GPCRDB_CLASS_B_SECRETIN_ LIKE 19 CALCR(2), CRHR1(3), CRHR2(1), EMR1(5), EMR2(3), GLP2R(2), GPR64(3) 63050 19 17 19 7 5 10 1 2 1 2.17e-06 0.0013
2 GPCRDB_CLASS_C_METABOTROPIC_ GLUTAMATE_PHEROMONE 12 CASR(5), GRM2(3) 19889 8 8 8 3 2 5 0 1 0 0.00037 0.11
3 ST_MYOCYTE_AD_PATHWAY Cardiac myocytes have a variety of adrenergic receptors that induce subtype-specific signaling effects. 22 APC(7), EPHB2(3), ITPR1(1), ITPR2(5), ITPR3(3), KCNJ9(3), MAPK1(1), RHO(1) 145209 24 22 24 3 5 11 2 2 4 0.00069 0.12
4 HSA04664_FC_EPSILON_ RI_SIGNALING_PATHWAY Genes involved in Fc epsilon RI signaling pathway 72 BTK(2), IL4(1), INPP5D(4), LYN(1), MAP2K6(2), MAPK1(1), MAPK3(1), MS4A2(1), PIK3R5(4), PLA2G4A(4), PRKCA(3), PRKCE(2), RAF1(1), SOS1(3) 207363 30 25 30 7 6 17 0 3 4 0.00079 0.12
5 HSA00950_ALKALOID_ BIOSYNTHESIS_I Genes involved in alkaloid biosynthesis I 5 DDC(3), TAT(3) 13232 6 6 6 1 2 4 0 0 0 0.0011 0.14
6 IL12PATHWAY IL12 and Stat4 Dependent Signaling Pathway in Th1 Development 20 CD3E(1), CXCR3(1), IL12RB2(2), JAK2(3), MAP2K6(2) 40623 9 8 9 2 1 4 0 1 3 0.0015 0.15
7 TRKAPATHWAY Nerve growth factor (NGF) promotes neuronal survival and proliferation by binding its receptor TrkA, which activates PI3K/AKT, Ras, and the MAP kinase pathway. 12 NTRK1(5), PRKCA(3), SOS1(3) 61862 11 11 11 1 0 7 0 2 2 0.0020 0.18
8 GLYCOLYSISPATHWAY Glycolysis is an evolutionarily conserved pathway by which one glucose molecule is converted to two pyruvate molecules for a gain of 2 ATP. 9 GPI(3), HK1(3), PGK1(2) 37507 8 7 8 0 5 2 0 0 1 0.0023 0.18
9 TPOPATHWAY Thrombopoietin binds to its receptor and activates cell growth through the Erk and JNK MAP kinase pathways, protein kinase C, and JAK/STAT activation. 22 JAK2(3), MAPK3(1), PRKCA(3), RAF1(1), RASA1(2), SOS1(3), STAT1(1), STAT5B(1) 108948 15 15 15 1 1 8 0 2 4 0.0030 0.21
10 ST_INTERLEUKIN_4_ PATHWAY Like IL-13, IL-4 is produced by Th2 cells on activation of the T cell antigen receptor, and by mast and basophil cells on activation of the IgE receptor. 26 IL4(1), INPP5D(4), JAK2(3), SOS1(3) 56800 11 11 11 0 1 7 0 2 1 0.0042 0.25

(click for full table with 616 genesets)

rank	geneset	description	N_genes	mut_tally	N	n	npat	nsite	nsil	n1	n2	n3	n4	n5	p	q
1	GPCRDB_CLASS_B_SECRETIN_ LIKE		19	CALCR(2), CRHR1(3), CRHR2(1), EMR1(5), EMR2(3), GLP2R(2), GPR64(3)	63050	19	17	19	7	5	10	1	2	1	2.17e-06	0.0013
2	GPCRDB_CLASS_C_METABOTROPIC_ GLUTAMATE_PHEROMONE		12	CASR(5), GRM2(3)	19889	8	8	8	3	2	5	0	1	0	0.00037	0.11
3	ST_MYOCYTE_AD_PATHWAY	Cardiac myocytes have a variety of adrenergic receptors that induce subtype-specific signaling effects.	22	APC(7), EPHB2(3), ITPR1(1), ITPR2(5), ITPR3(3), KCNJ9(3), MAPK1(1), RHO(1)	145209	24	22	24	3	5	11	2	2	4	0.00069	0.12
4	HSA04664_FC_EPSILON_ RI_SIGNALING_PATHWAY	Genes involved in Fc epsilon RI signaling pathway	72	BTK(2), IL4(1), INPP5D(4), LYN(1), MAP2K6(2), MAPK1(1), MAPK3(1), MS4A2(1), PIK3R5(4), PLA2G4A(4), PRKCA(3), PRKCE(2), RAF1(1), SOS1(3)	207363	30	25	30	7	6	17	0	3	4	0.00079	0.12
5	HSA00950_ALKALOID_ BIOSYNTHESIS_I	Genes involved in alkaloid biosynthesis I	5	DDC(3), TAT(3)	13232	6	6	6	1	2	4	0	0	0	0.0011	0.14
6	IL12PATHWAY	IL12 and Stat4 Dependent Signaling Pathway in Th1 Development	20	CD3E(1), CXCR3(1), IL12RB2(2), JAK2(3), MAP2K6(2)	40623	9	8	9	2	1	4	0	1	3	0.0015	0.15
7	TRKAPATHWAY	Nerve growth factor (NGF) promotes neuronal survival and proliferation by binding its receptor TrkA, which activates PI3K/AKT, Ras, and the MAP kinase pathway.	12	NTRK1(5), PRKCA(3), SOS1(3)	61862	11	11	11	1	0	7	0	2	2	0.0020	0.18
8	GLYCOLYSISPATHWAY	Glycolysis is an evolutionarily conserved pathway by which one glucose molecule is converted to two pyruvate molecules for a gain of 2 ATP.	9	GPI(3), HK1(3), PGK1(2)	37507	8	7	8	0	5	2	0	0	1	0.0023	0.18
9	TPOPATHWAY	Thrombopoietin binds to its receptor and activates cell growth through the Erk and JNK MAP kinase pathways, protein kinase C, and JAK/STAT activation.	22	JAK2(3), MAPK3(1), PRKCA(3), RAF1(1), RASA1(2), SOS1(3), STAT1(1), STAT5B(1)	108948	15	15	15	1	1	8	0	2	4	0.0030	0.21
10	ST_INTERLEUKIN_4_ PATHWAY	Like IL-13, IL-4 is produced by Th2 cells on activation of the T cell antigen receptor, and by mast and basophil cells on activation of the IgE receptor.	26	IL4(1), INPP5D(4), JAK2(3), SOS1(3)	56800	11	11	11	0	1	7	0	2	1	0.0042	0.25

Notes: (Please see notes under significantly mutated gene table)

Significantly mutated genes (q≤0.1)	278
Mutations seen in COSMIC	0
Significantly mutated genes on COSMIC territory	0
Genes with clustered mutations (≤3 aa apart)	1
Significantly mutated genesets	89
. . . . . . . . . (excluding sig.mutated genes)	1