Table 1.

Syndromes associated with PHEO/PGL and frequency of genetic mutations (reviewed in 51, 94, 95)

Molecular cluster	Gene	Location	Syndrome	Germline mutation frequency*	Somatic mutation frequency*
Krebs cycle (Cluster 1a)	SDHA	5p15	PGL5	<5%	0%
	SDHB	1p36.13	PGL4	10%	0%
	SDHC	1q23.3	PGL3	<5%	0%
	SDHD	11q23	PGL1	10%	0%
	SDHAF2	11q12	PGL2	<1%	0%
	FH	1q42.1		<5%	0%
	MDH2			unknown	unknown
	IDH			unknown	unknown
Pseudohypoxic (Cluster 1b)	VHL	3p25.3	Von Hippel-Lindau	10%	10%
	HIF2A	2p21	Pacak-Zhuang Syndrome	<5%	5–7%
	PHD1/EGLN2	19q13.2		unknown	unknown
	PHD2/EGLN1	1q42.2		unknown	unknown
Kinase signaling (Cluster 2)	NF1	17q11.2	Neurofibromatosis type 1	<5%	20–40%
	RET	10q11.21	MEN2	10%	10%
	TMEM127	2q11.2		<5%	0%
	MAX	14q23.3		<5%	<5%
	KIF1Bβ	1p36.22		0%	NA
	HRAS	11p15.5		0%	10%
	ATRX	Xq21.1		unknown	unknown

^*Germline mutation/somatic mutation frequency among all PHEOs/PGLs

Abbreviations: ATRX, alpha thalassemia/mental retardation syndrome X-linked; EGLN1/2, Egl-9 family hypoxia inducible factor 1/2FH, fumarate hydratase; HIF2A, hypoxia-inducible factor 2α; HRAS, Harvey rat sarcoma viral oncogene homolog; IDH, isocitrate dehydrogenase; KIF1Bβ; Inesin family member 1B; MAX, myc associated factor X; MDH2, malate dehydrogenase 2; NF1, neurofibromin 1; PHD1/2, prolyl hydroxylase domain-containing protein 1/2; RET, rearranged during transfection protooncogene; SDHA, -B, -C, -D, succinate dehydrogenase complex, subunit A, B, C, D; SDHAF2, SDH complex assembly factor 2; TMEM127, transmembrane protein 127; VHL, von Hippel-Lindau.