MCID: HRD031
MIFTS: 46

Hereditary Paraganglioma-Pheochromocytoma Syndromes

Categories: Cancer diseases, Endocrine diseases, Genetic diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Hereditary Paraganglioma-Pheochromocytoma Syndromes

MalaCards integrated aliases for Hereditary Paraganglioma-Pheochromocytoma Syndromes:

Name: Hereditary Paraganglioma-Pheochromocytoma Syndromes 25 26 30 6
Hereditary Pheochromocytoma-Paraganglioma 54 26 60
Hereditary Paraganglioma-Pheochromocytoma 54 26
Familial Pheochromocytoma-Paraganglioma 54 60
Paragangliomas 4 26 74
Paragangliomas 2 26 74
Paragangliomas 3 26 74
Familial Paraganglioma-Pheochromocytoma Syndromes 26
Sdhx-Related Paraganglioma-Pheochromocytoma 54
Familial Paraganglioma Syndrome 26
Paragangliomas 1 26
Paraganglioma 74
Fpgl/pheo 26
Fpgl 26

Characteristics:

Orphanet epidemiological data:

60
hereditary pheochromocytoma-paraganglioma
Inheritance: Autosomal dominant; Age of onset: Childhood; Age of death: adult;

GeneReviews:

25
Penetrance Age-related penetrance. penetrance estimates vary (see table 3). penetrance was initially believed to be quite high, but larger studies with less bias from probands suggest a much lower penetrance. no reliable penetrance data are currently available for max, sdhaf2, or tmem127 pathogenic variants...

Classifications:

Orphanet: 60  
Rare endocrine diseases


Summaries for Hereditary Paraganglioma-Pheochromocytoma Syndromes

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 29072Disease definitionHereditary paraganglioma-pheochromocytomas (PGL/PCC) are rare neuroendocrine tumors represented by paragangliomas (occurring in any paraganglia from the skull base to the pelvic floor) and pheochromocytomas (adrenal medullary paragangliomas; see this term).EpidemiologyHereditary PGL/PCCs represent 30% of all PGL/PCC, for which prevalence is around 1/500,000 for PCC and 1/1,000,000 for PGL.Clinical descriptionPGL can be either hypersecreting (catecholamines) or non-secreting and PCCs usually secrete catecholamines. Secreting (sympathetic) PGLs are predominantly found in the thoracic, abdominal and pelvic areas. Hypersecretion manifests as sustained or paroxysmal elevations in blood pressure, headache, episodic profuse sweating, palpitations, pallor and apprehension or anxiety. Urinary bladder PGL may be revealed by painless hematuria and blood pressure increase after micturition. Non-secreting (parasympathetic) PGLs are predominantly located in the head and neck and present as enlarging masses that may be asymptomatic or may be associated with unilateral hearing loss, pulsatile tinnitus, cough, hoarseness of voice, pharyngeal fullness, swallowing difficulty, pain and/or problems with tongue motion. There are no validated markers of malignancy (rate around 15%); the only criterion is the presence of metastases. Gastric stromal tumors and renal cancers are rarely associated.EtiologyUp to 10% of genetically determined PCC/PGLs are due to a SDHx germline mutation. Hereditary PCC/PGLs are caused by mutations in the SDHD, SDHC, SDHB, SDHA and SDHAF2 (or SDH5) genes (11q23, 1q21, 1p36.1-p35, 5p15 and 11q31.1 respectively). Transmission is autosomal dominant but associated with maternal genomic imprinting for SDHD and SDHAF2 and expressed when the mutation is inherited from the father. Penetrance depends on the gene, age and tumor sites. Tumors in patients with SDHB mutations are more likely to become malignant than those in patients with other SDHx mutations.Diagnostic methodsDiagnosis is based on clinical examination and family history. Young age at onset, presence of bilateral, extra-adrenal or multiple tumors, or malignancy suggest an inherited disorder. Imaging studies (MRI, CT) are used to detect tumors and may include functional imaging (scintigraphy, PET). Biochemical testing includes plasma free metanephrines and/or 24 hour-urinary fractionated metanephrines. Molecular genetic testing confirms the diagnosis.Differential diagnosisDifferential diagnoses include non-hereditary PCC/PGL (although hereditary PCC/PGL tends to present at younger ages, to be multi-focal, bilateral, and recurrent, or to have multiple synchronous neoplasms), PCC/PGL associated with other hereditary conditions (neurofibromatosis type 1, von Hippel-Lindau syndrome, multiple endocrine neoplasia type 2, Carney triad and Carney-Stratakis syndrome; see these terms) and familial PCC due to TMEM127 mutation.Antenatal diagnosisPrenatal testing is not recommended. Presymptomatic testing is proposed in at-risk children from 6 years of age.Management and treatmentTreatment for secreting tumors involves blood pressure control with alpha-blockers followed by surgery by specialized teams. If the tumors have not metastasized, surgical resection can be curative. Follow-up is required due to the risk of recurrence and malignancy in particular for SDHB mutation-carriers. For head and neck PGL, external radiotherapy can be proposed. When metastases have occurred, other treatment options including chemotherapy and targeted radiotherapy should be proposed.PrognosisThe disease may be fatal, but some have lived with malignant PCC/PGL for 20 years or more.Visit the Orphanet disease page for more resources.

MalaCards based summary : Hereditary Paraganglioma-Pheochromocytoma Syndromes, also known as hereditary pheochromocytoma-paraganglioma, is related to paragangliomas 1 and pheochromocytoma, and has symptoms including aphonia An important gene associated with Hereditary Paraganglioma-Pheochromocytoma Syndromes is MAX (MYC Associated Factor X), and among its related pathways/superpathways are Pathways in cancer and Glucose / Energy Metabolism. Affiliated tissues include testes, adrenal gland and kidney, and related phenotypes are extraadrenal pheochromocytoma and adrenal pheochromocytoma

Genetics Home Reference : 26 Hereditary paraganglioma-pheochromocytoma is an inherited condition characterized by the growth of noncancerous (benign) tumors in structures called paraganglia. Paraganglia are groups of cells that are found near nerve cell bunches called ganglia. A tumor involving the paraganglia is known as a paraganglioma. A type of paraganglioma known as a pheochromocytoma develops in the adrenal glands, which are located on top of each kidney and produce hormones in response to stress. Other types of paraganglioma are usually found in the head, neck, or trunk. People with hereditary paraganglioma-pheochromocytoma develop one or more paragangliomas, which may include pheochromocytomas.

GeneReviews: NBK1548

Related Diseases for Hereditary Paraganglioma-Pheochromocytoma Syndromes

Diseases related to Hereditary Paraganglioma-Pheochromocytoma Syndromes via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 39)
# Related Disease Score Top Affiliating Genes
1 paragangliomas 1 31.8 RET SDHB SDHC SDHD TIMM8B
2 pheochromocytoma 29.9 FH KIF1B MAX RET SDHA SDHAF2
3 paraganglioma 29.3 MAX RET SDHA SDHAF2 SDHB SDHC
4 paragangliomas 4 11.8
5 acromegaly 11.5
6 paragangliomas 2 11.5
7 paragangliomas 3 11.5
8 adrenal gland pheochromocytoma 10.6
9 glomus tumor 10.2 SDHB SDHD
10 bone disease 10.1
11 chondroma 10.1 SDHB SDHC SDHD
12 hereditary leiomyomatosis and renal cell cancer 10.1 FH SDHB
13 multiple endocrine neoplasia, type iia 10.1 RET SDHB SDHD
14 multiple endocrine neoplasia, type i 10.1 RET SDHB SDHD
15 autosomal genetic disease 10.0 RET SDHB SDHD
16 extra-adrenal pheochromocytoma 10.0 SDHAF2 SDHB SDHC SDHD
17 seminal vesicle tumor 10.0 SDHA SDHB
18 lymphatic system disease 10.0 SDHB SDHC SDHD TMEM127
19 fumarate hydratase deficiency 10.0 FH VHL
20 paraganglioma and gastric stromal sarcoma 10.0 SDHB SDHC SDHD TIMM8B
21 spastic quadriplegia 9.9 SDHA SDHD
22 quadriplegia 9.9 SDHA SDHD
23 renal cell carcinoma, papillary, 1 9.9 FH SDHB VHL
24 plethora of newborn 9.8 FH SDHB SDHC SDHD
25 adrenal medulla cancer 9.8 RET SDHAF2 SDHB SDHC SDHD
26 multiple endocrine neoplasia 9.8 RET SDHB SDHC VHL
27 carney triad 9.8 SDHA SDHB SDHC SDHD
28 carotid artery occlusion 9.8
29 glomus vagale tumor 9.8
30 gastrointestinal stromal tumor 9.8 SDHA SDHB SDHC SDHD
31 familial renal papillary carcinoma 9.7 FH RET
32 neural crest tumor 9.7 SDHA SDHAF2 SDHB SDHC SDHD
33 mitochondrial complex ii deficiency 9.7 SDHA SDHAF2 SDHB SDHC SDHD
34 neurofibromatosis, type iv, of riccardi 9.7 RET SDHB SDHC SDHD VHL
35 von hippel-lindau syndrome 9.7 RET SDHB SDHC SDHD VHL
36 persistent generalized lymphadenopathy 9.6 SDHA SDHAF2 SDHB SDHC SDHD TMEM127
37 lymph node disease 9.6 SDHA SDHAF2 SDHB SDHC SDHD TMEM127
38 sporadic pheochromocytoma 9.5 MAX RET SDHB SDHC SDHD VHL
39 endocrine organ benign neoplasm 9.3 RET SDHA SDHAF2 SDHB SDHC SDHD

Graphical network of the top 20 diseases related to Hereditary Paraganglioma-Pheochromocytoma Syndromes:



Diseases related to Hereditary Paraganglioma-Pheochromocytoma Syndromes

Symptoms & Phenotypes for Hereditary Paraganglioma-Pheochromocytoma Syndromes

Human phenotypes related to Hereditary Paraganglioma-Pheochromocytoma Syndromes:

60 33 (show all 41)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 extraadrenal pheochromocytoma 60 33 hallmark (90%) Very frequent (99-80%) HP:0006737
2 adrenal pheochromocytoma 60 33 hallmark (90%) Very frequent (99-80%) HP:0006748
3 dysphonia 60 33 frequent (33%) Frequent (79-30%) HP:0001618
4 proteinuria 60 33 frequent (33%) Frequent (79-30%) HP:0000093
5 fatigue 60 33 frequent (33%) Frequent (79-30%) HP:0012378
6 weight loss 60 33 frequent (33%) Frequent (79-30%) HP:0001824
7 chest pain 60 33 frequent (33%) Frequent (79-30%) HP:0100749
8 hypercalcemia 60 33 frequent (33%) Frequent (79-30%) HP:0003072
9 episodic abdominal pain 60 33 frequent (33%) Frequent (79-30%) HP:0002574
10 cerebral hemorrhage 60 33 frequent (33%) Frequent (79-30%) HP:0001342
11 nausea 60 33 frequent (33%) Frequent (79-30%) HP:0002018
12 episodic hyperhidrosis 60 33 frequent (33%) Frequent (79-30%) HP:0001069
13 sinus tachycardia 60 33 frequent (33%) Frequent (79-30%) HP:0011703
14 palpitations 60 33 frequent (33%) Frequent (79-30%) HP:0001962
15 recurrent paroxysmal headache 60 33 frequent (33%) Frequent (79-30%) HP:0002331
16 flushing 60 33 frequent (33%) Frequent (79-30%) HP:0031284
17 glomerulosclerosis 60 33 frequent (33%) Frequent (79-30%) HP:0000096
18 episodic paroxysmal anxiety 60 33 frequent (33%) Frequent (79-30%) HP:0000740
19 hypertensive retinopathy 60 33 frequent (33%) Frequent (79-30%) HP:0001095
20 paraganglioma of head and neck 60 33 frequent (33%) Frequent (79-30%) HP:0002864
21 elevated urinary norepinephrine 60 33 frequent (33%) Frequent (79-30%) HP:0003345
22 positive regitine blocking test 60 33 frequent (33%) Frequent (79-30%) HP:0003574
23 elevated urinary epinephrine 60 33 frequent (33%) Frequent (79-30%) HP:0003639
24 pulsatile tinnitus 60 33 frequent (33%) Frequent (79-30%) HP:0008629
25 paroxysmal vertigo 60 33 frequent (33%) Frequent (79-30%) HP:0010532
26 elevated urinary dopamine 60 33 frequent (33%) Frequent (79-30%) HP:0011979
27 tremor 60 33 occasional (7.5%) Occasional (29-5%) HP:0001337
28 pallor 60 33 occasional (7.5%) Occasional (29-5%) HP:0000980
29 congestive heart failure 60 33 occasional (7.5%) Occasional (29-5%) HP:0001635
30 vocal cord paralysis 60 33 occasional (7.5%) Occasional (29-5%) HP:0001605
31 hematuria 60 33 occasional (7.5%) Occasional (29-5%) HP:0000790
32 renal cell carcinoma 60 33 occasional (7.5%) Occasional (29-5%) HP:0005584
33 retinal capillary hemangioma 60 33 occasional (7.5%) Occasional (29-5%) HP:0009711
34 conductive hearing impairment 60 33 occasional (7.5%) Occasional (29-5%) HP:0000405
35 cranial nerve compression 60 33 occasional (7.5%) Occasional (29-5%) HP:0001293
36 panic attack 60 33 occasional (7.5%) Occasional (29-5%) HP:0025269
37 elevated calcitonin 60 33 occasional (7.5%) Occasional (29-5%) HP:0003528
38 arachnoid hemangiomatosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0012222
39 aniridia 60 33 very rare (1%) Very rare (<4-1%) HP:0000526
40 paraganglioma 60 Very frequent (99-80%)
41 hypertension associated with pheochromocytoma 60 Frequent (79-30%)

UMLS symptoms related to Hereditary Paraganglioma-Pheochromocytoma Syndromes:


aphonia

GenomeRNAi Phenotypes related to Hereditary Paraganglioma-Pheochromocytoma Syndromes according to GeneCards Suite gene sharing:

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-1 9.58 RET SDHD VHL
2 Decreased viability GR00221-A-2 9.58 MAX RET SDHD VHL
3 Decreased viability GR00221-A-3 9.58 MAX
4 Decreased viability GR00221-A-4 9.58 RET SDHD
5 Decreased viability GR00231-A 9.58 RET
6 Decreased viability GR00301-A 9.58 RET VHL
7 Decreased viability GR00381-A-1 9.58 SDHD
8 Decreased viability GR00402-S-2 9.58 MAX RET SDHD VHL

Drugs & Therapeutics for Hereditary Paraganglioma-Pheochromocytoma Syndromes

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Familial Investigations of Childhood Cancer Predisposition Recruiting NCT03050268

Search NIH Clinical Center for Hereditary Paraganglioma-Pheochromocytoma Syndromes

Genetic Tests for Hereditary Paraganglioma-Pheochromocytoma Syndromes

Genetic tests related to Hereditary Paraganglioma-Pheochromocytoma Syndromes:

# Genetic test Affiliating Genes
1 Hereditary Paraganglioma-Pheochromocytoma Syndromes 30 MAX

Anatomical Context for Hereditary Paraganglioma-Pheochromocytoma Syndromes

MalaCards organs/tissues related to Hereditary Paraganglioma-Pheochromocytoma Syndromes:

42
Testes, Adrenal Gland, Kidney, Tongue, Heart, Bone, Lymph Node

Publications for Hereditary Paraganglioma-Pheochromocytoma Syndromes

Articles related to Hereditary Paraganglioma-Pheochromocytoma Syndromes:

# Title Authors Year
1
The utility of SDHB and FH immunohistochemistry in patients evaluated for hereditary paraganglioma-pheochromocytoma syndromes. ( 29079178 )
2018
2
A Novel SDHB IVS2-2A>C Mutation Is Responsible for Hereditary Pheochromocytoma/Paraganglioma Syndrome. ( 29925701 )
2018
3
Von Hippel-Lindau and Hereditary Pheochromocytoma/Paraganglioma Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood. ( 28620007 )
2017
4
Hereditary paraganglioma-pheochromocytoma syndromes associated with SDHD and RET mutations. ( 24375508 )
2014
5
SDHB-Associated Paraganglioma in a Pediatric Patient and Literature Review on Hereditary Pheochromocytoma-Paraganglioma Syndromes. ( 25298897 )
2014
6
Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. ( 24893135 )
2014
7
American Society of Clinical Oncology Expert Statement: collection and use of a cancer family history for oncology providers. ( 24493721 )
2014
8
Juvenile-onset hereditary pheochromocytoma-paraganglioma syndrome. ( 23318864 )
2013
9
Canadian guideline on genetic screening for hereditary renal cell cancers. ( 24319509 )
2013
10
Renal tumors and hereditary pheochromocytoma-paraganglioma syndrome type 4. ( 21366490 )
2011

Variations for Hereditary Paraganglioma-Pheochromocytoma Syndromes

ClinVar genetic disease variations for Hereditary Paraganglioma-Pheochromocytoma Syndromes:

6 (show top 50) (show all 647)
# Gene Variation Type Significance SNP ID Assembly Location
1 SDHAF2 NM_017841.2(SDHAF2): c.232G> A (p.Gly78Arg) single nucleotide variant Pathogenic rs113560320 GRCh37 Chromosome 11, 61205292: 61205292
2 SDHAF2 NM_017841.2(SDHAF2): c.232G> A (p.Gly78Arg) single nucleotide variant Pathogenic rs113560320 GRCh38 Chromosome 11, 61437820: 61437820
3 SDHD NM_003002.3(SDHD): c.112C> T (p.Arg38Ter) single nucleotide variant Pathogenic rs80338843 GRCh37 Chromosome 11, 111958640: 111958640
4 SDHD NM_003002.3(SDHD): c.112C> T (p.Arg38Ter) single nucleotide variant Pathogenic rs80338843 GRCh38 Chromosome 11, 112087916: 112087916
5 SDHD NM_003002.3(SDHD): c.242C> T (p.Pro81Leu) single nucleotide variant Pathogenic rs80338844 GRCh37 Chromosome 11, 111959663: 111959663
6 SDHD NM_003002.3(SDHD): c.242C> T (p.Pro81Leu) single nucleotide variant Pathogenic rs80338844 GRCh38 Chromosome 11, 112088939: 112088939
7 SDHD NM_003002.3(SDHD): c.274G> T (p.Asp92Tyr) single nucleotide variant Pathogenic rs80338845 GRCh37 Chromosome 11, 111959695: 111959695
8 SDHD NM_003002.3(SDHD): c.274G> T (p.Asp92Tyr) single nucleotide variant Pathogenic rs80338845 GRCh38 Chromosome 11, 112088971: 112088971
9 SDHD NM_003002.3(SDHD): c.341A> G (p.Tyr114Cys) single nucleotide variant Pathogenic rs104894304 GRCh37 Chromosome 11, 111965555: 111965555
10 SDHD NM_003002.3(SDHD): c.341A> G (p.Tyr114Cys) single nucleotide variant Pathogenic rs104894304 GRCh38 Chromosome 11, 112094831: 112094831
11 SDHD NM_003002.3(SDHD): c.95C> A (p.Ser32Ter) single nucleotide variant Pathogenic rs104894305 GRCh37 Chromosome 11, 111958623: 111958623
12 SDHD NM_003002.3(SDHD): c.95C> A (p.Ser32Ter) single nucleotide variant Pathogenic rs104894305 GRCh38 Chromosome 11, 112087899: 112087899
13 SDHD NM_003002.3(SDHD): c.3G> C (p.Met1Ile) single nucleotide variant Pathogenic rs80338842 GRCh37 Chromosome 11, 111957634: 111957634
14 SDHD NM_003002.3(SDHD): c.3G> C (p.Met1Ile) single nucleotide variant Pathogenic rs80338842 GRCh38 Chromosome 11, 112086910: 112086910
15 SDHD NM_003002.3(SDHD): c.416T> C (p.Leu139Pro) single nucleotide variant Pathogenic rs80338847 GRCh37 Chromosome 11, 111965630: 111965630
16 SDHD NM_003002.3(SDHD): c.416T> C (p.Leu139Pro) single nucleotide variant Pathogenic rs80338847 GRCh38 Chromosome 11, 112094906: 112094906
17 SDHD NM_003002.3(SDHD): c.57delG (p.Leu20Cysfs) deletion Pathogenic rs587776649 GRCh38 Chromosome 11, 112087861: 112087861
18 SDHD NM_003002.3(SDHD): c.57delG (p.Leu20Cysfs) deletion Pathogenic rs587776649 GRCh37 Chromosome 11, 111958585: 111958585
19 SDHC NM_003001.3(SDHC): c.405+1G> A single nucleotide variant Pathogenic/Likely pathogenic rs587776653 GRCh37 Chromosome 1, 161326631: 161326631
20 SDHC NM_003001.3(SDHC): c.405+1G> A single nucleotide variant Pathogenic/Likely pathogenic rs587776653 GRCh38 Chromosome 1, 161356841: 161356841
21 SDHB NM_003000.2(SDHB): c.268C> T (p.Arg90Ter) single nucleotide variant Pathogenic rs74315366 GRCh37 Chromosome 1, 17359573: 17359573
22 SDHB NM_003000.2(SDHB): c.268C> T (p.Arg90Ter) single nucleotide variant Pathogenic rs74315366 GRCh38 Chromosome 1, 17033078: 17033078
23 SDHB NM_003000.2(SDHB): c.590C> G (p.Pro197Arg) single nucleotide variant Likely pathogenic rs74315367 GRCh37 Chromosome 1, 17350520: 17350520
24 SDHB NM_003000.2(SDHB): c.590C> G (p.Pro197Arg) single nucleotide variant Likely pathogenic rs74315367 GRCh38 Chromosome 1, 17024025: 17024025
25 SDHB NM_003000.2(SDHB): c.725G> A (p.Arg242His) single nucleotide variant Pathogenic rs74315368 GRCh37 Chromosome 1, 17349143: 17349143
26 SDHB NM_003000.2(SDHB): c.725G> A (p.Arg242His) single nucleotide variant Pathogenic rs74315368 GRCh38 Chromosome 1, 17022648: 17022648
27 SDHB NM_003000.2(SDHB): c.79C> T (p.Arg27Ter) single nucleotide variant Pathogenic rs74315369 GRCh37 Chromosome 1, 17371377: 17371377
28 SDHB NM_003000.2(SDHB): c.79C> T (p.Arg27Ter) single nucleotide variant Pathogenic rs74315369 GRCh38 Chromosome 1, 17044882: 17044882
29 SDHB NM_003000.2(SDHB): c.418G> T (p.Val140Phe) single nucleotide variant Pathogenic/Likely pathogenic rs267607032 GRCh37 Chromosome 1, 17355100: 17355100
30 SDHB NM_003000.2(SDHB): c.418G> T (p.Val140Phe) single nucleotide variant Pathogenic/Likely pathogenic rs267607032 GRCh38 Chromosome 1, 17028605: 17028605
31 SDHD NM_003002.3(SDHD): c.284T> C (p.Leu95Pro) single nucleotide variant Pathogenic rs80338846 GRCh37 Chromosome 11, 111959705: 111959705
32 SDHD NM_003002.3(SDHD): c.284T> C (p.Leu95Pro) single nucleotide variant Pathogenic rs80338846 GRCh38 Chromosome 11, 112088981: 112088981
33 MAX NM_002382.4(MAX): c.223C> T (p.Arg75Ter) single nucleotide variant Pathogenic rs387906650 GRCh37 Chromosome 14, 65544703: 65544703
34 MAX NM_002382.4(MAX): c.223C> T (p.Arg75Ter) single nucleotide variant Pathogenic rs387906650 GRCh38 Chromosome 14, 65077985: 65077985
35 MAX NM_002382.4(MAX): c.97C> T (p.Arg33Ter) single nucleotide variant Pathogenic rs387906651 GRCh37 Chromosome 14, 65560500: 65560500
36 MAX NM_002382.4(MAX): c.97C> T (p.Arg33Ter) single nucleotide variant Pathogenic rs387906651 GRCh38 Chromosome 14, 65093782: 65093782
37 SDHB NM_003000.2(SDHB): c.423+1G> A single nucleotide variant Pathogenic rs398122805 GRCh37 Chromosome 1, 17355094: 17355094
38 SDHB NM_003000.2(SDHB): c.423+1G> A single nucleotide variant Pathogenic rs398122805 GRCh38 Chromosome 1, 17028599: 17028599
39 SDHB NM_003000.2(SDHB): c.32G> A (p.Arg11His) single nucleotide variant Conflicting interpretations of pathogenicity rs111430410 GRCh37 Chromosome 1, 17380483: 17380483
40 SDHB NM_003000.2(SDHB): c.32G> A (p.Arg11His) single nucleotide variant Conflicting interpretations of pathogenicity rs111430410 GRCh38 Chromosome 1, 17053988: 17053988
41 SDHC NM_003001.3(SDHC): c.*78G> A single nucleotide variant Conflicting interpretations of pathogenicity rs182629842 GRCh37 Chromosome 1, 161332301: 161332301
42 SDHC NM_003001.3(SDHC): c.*78G> A single nucleotide variant Conflicting interpretations of pathogenicity rs182629842 GRCh38 Chromosome 1, 161362511: 161362511
43 SDHC NM_003001.3(SDHC): c.43C> T (p.Arg15Ter) single nucleotide variant Pathogenic rs201286421 GRCh37 Chromosome 1, 161293426: 161293426
44 SDHC NM_003001.3(SDHC): c.43C> T (p.Arg15Ter) single nucleotide variant Pathogenic rs201286421 GRCh38 Chromosome 1, 161323636: 161323636
45 SDHAF2 NM_017841.2(SDHAF2): c.52A> G (p.Arg18Gly) single nucleotide variant Uncertain significance rs200911550 GRCh37 Chromosome 11, 61205112: 61205112
46 SDHAF2 NM_017841.2(SDHAF2): c.52A> G (p.Arg18Gly) single nucleotide variant Uncertain significance rs200911550 GRCh38 Chromosome 11, 61437640: 61437640
47 SDHAF2 NM_017841.2(SDHAF2): c.97C> T (p.Arg33Cys) single nucleotide variant Likely benign rs144867876 GRCh37 Chromosome 11, 61205157: 61205157
48 SDHAF2 NM_017841.2(SDHAF2): c.97C> T (p.Arg33Cys) single nucleotide variant Likely benign rs144867876 GRCh38 Chromosome 11, 61437685: 61437685
49 SDHB NM_003000.2(SDHB): c.287-1G> C single nucleotide variant Pathogenic/Likely pathogenic rs397516833 GRCh37 Chromosome 1, 17355232: 17355232
50 SDHB NM_003000.2(SDHB): c.287-1G> C single nucleotide variant Pathogenic/Likely pathogenic rs397516833 GRCh38 Chromosome 1, 17028737: 17028737

Cosmic variations for Hereditary Paraganglioma-Pheochromocytoma Syndromes:

9 (show top 50) (show all 58)
# Cosmic Mut ID Gene Symbol COSMIC Disease Classification
(Primary site, Site subtype, Primary histology, Histology subtype)
Mutation CDS Mutation AA GRCh38 Location Conf
1 COSM14283 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.491A>G p.Q164R 3:10149814-10149814 0
2 COSM17662 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.492G>T p.Q164H 3:10149815-10149815 0
3 COSM18097 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.482G>A p.R161Q 3:10149805-10149805 0
4 COSM144972 VHL adrenal gland,NS,pheochromocytoma,benign c.245G>T p.R82L 3:10142092-10142092 0
5 COSM14321 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.227T>A p.F76Y 3:10142074-10142074 0
6 COSM144971 VHL adrenal gland,NS,pheochromocytoma,benign c.244C>G p.R82G 3:10142091-10142091 0
7 COSM6444479 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.260T>C p.V87A 3:10142107-10142107 0
8 COSM144975 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.475A>G p.K159E 3:10149798-10149798 0
9 COSM100047 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.389T>G p.V130G 3:10146562-10146562 0
10 COSM14311 VHL adrenal gland,NS,pheochromocytoma,benign c.499C>T p.R167W 3:10149822-10149822 0
11 COSM17982 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.496G>T p.V166F 3:10149819-10149819 0
12 COSM236660 VHL adrenal gland,adrenal gland,pheochromocytoma,benign c.250G>C p.V84L 3:10142097-10142097 0
13 COSM17988 VHL adrenal gland,NS,pheochromocytoma,benign c.341-1G>T p.? 3:10146513-10146513 0
14 COSM43931 TP53 adrenal gland,adrenal gland,adrenal cortical carcinoma,functioning c.523C>A p.R175S 17:7675089-7675089 0
15 COSM11286 TP53 adrenal gland,adrenal gland,adrenal cortical carcinoma,functioning c.1015G>T p.E339* 17:7670694-7670694 0
16 COSM10801 TP53 adrenal gland,adrenal gland,adrenal cortical carcinoma,functioning c.404G>A p.C135Y 17:7675208-7675208 0
17 COSM10659 TP53 adrenal gland,adrenal gland,adrenal cortical carcinoma,functioning c.817C>T p.R273C 17:7673803-7673803 0
18 COSM11071 TP53 adrenal gland,adrenal gland,adrenal cortical carcinoma,functioning c.1009C>T p.R337C 17:7670700-7670700 0
19 COSM44175 TP53 adrenal gland,adrenal gland,adrenal cortical carcinoma,functioning c.644G>C p.S215T 17:7674887-7674887 0
20 COSM966 RET adrenal gland,adrenal gland,pheochromocytoma,benign c.1900T>C p.C634R 10:43114500-43114500 0
21 COSM965 RET adrenal gland,adrenal gland,pheochromocytoma,benign c.2753T>C p.M918T 10:43121968-43121968 0
22 COSM220089 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.1885G>A p.Q616fs*4 17:31225134-31225134 0
23 COSM329092 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.1721+3A>T p.A548fs*13 17:31221932-31221932 0
24 COSM30670 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.7646C>G p.S2549* 17:31356490-31356490 0
25 COSM329090 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.226G>T p.E76* 17:31159031-31159031 0
26 COSM5885098 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.5665G>T p.E1889* 17:31330351-31330351 0
27 COSM329093 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.1722-1G>A p.? 17:31223443-31223443 0
28 COSM330587 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.205-1G>C p.R69Xfs*7 17:31159009-31159009 0
29 COSM327926 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.3158C>A p.S1053* 17:31230886-31230886 0
30 COSM327927 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.7582C>T p.Q2528* 17:31352381-31352381 0
31 COSM33676 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.6855C>A p.Y2285* 17:31338739-31338739 0
32 COSM3402726 NF1 adrenal gland,NS,pheochromocytoma,benign c.1307C>A p.S436* 17:31206286-31206286 0
33 COSM1710108 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.7300C>T p.Q2434* 17:31349230-31349230 0
34 COSM330588 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.2409+1G>A p.A776_Q803del 17:31227607-31227607 0
35 COSM329089 NF1 adrenal gland,adrenal gland,pheochromocytoma,benign c.1466A>G p.Y489C 17:31214524-31214524 0
36 COSM707 MET adrenal gland,adrenal gland,pheochromocytoma,benign c.3029C>T p.T1010I 7:116771936-116771936 0
37 COSM5967149 MET adrenal gland,adrenal gland,pheochromocytoma,benign c.607T>A p.S203T 7:116699691-116699691 0
38 COSM5946188 MET adrenal gland,adrenal gland,pheochromocytoma,benign c.352A>T p.M118L 7:116699436-116699436 0
39 COSM4445248 MEN1 adrenal gland,adrenal gland,adrenal cortical carcinoma,functioning c.1132G>T p.E378* 11:64805688-64805688 0
40 COSM4445249 MEN1 adrenal gland,adrenal gland,adrenal cortical carcinoma,functioning c.808C>A p.L270M 11:64807195-64807195 0
41 COSM4445247 MEN1 adrenal gland,adrenal gland,adrenal cortical carcinoma,functioning c.812G>C p.G271A 11:64807191-64807191 0
42 COSM4445246 MED12 adrenal gland,adrenal gland,adrenal cortical carcinoma,functioning c.4857G>T p.K1619N 23:71134842-71134842 0
43 COSM499 HRAS adrenal gland,adrenal gland,pheochromocytoma,benign c.182A>G p.Q61R 11:533874-533874 0
44 COSM496 HRAS adrenal gland,adrenal gland,pheochromocytoma,benign c.181C>A p.Q61K 11:533875-533875 0
45 COSM486 HRAS adrenal gland,adrenal gland,pheochromocytoma,benign c.37G>C p.G13R 11:534286-534286 0
46 COSM1732355 H3F3A adrenal gland,adrenal gland,pheochromocytoma,benign c.103G>T p.G35W 1:226064454-226064454 0
47 COSM19176 FGFR1 adrenal gland,adrenal gland,pheochromocytoma,benign c.1638C>A p.N546K 8:38417331-38417331 0
48 COSM6188660 EPAS1 adrenal gland,adrenal gland,pheochromocytoma,benign c.1592C>T p.P531L 2:46380264-46380264 0
49 COSM6476262 EPAS1 adrenal gland,NS,pheochromocytoma,benign c.1601C>T p.P534L 2:46380273-46380273 0
50 COSM6196613 EPAS1 adrenal gland,adrenal gland,pheochromocytoma,benign c.1589C>A p.A530E 2:46380261-46380261 0

Expression for Hereditary Paraganglioma-Pheochromocytoma Syndromes

Search GEO for disease gene expression data for Hereditary Paraganglioma-Pheochromocytoma Syndromes.

Pathways for Hereditary Paraganglioma-Pheochromocytoma Syndromes

GO Terms for Hereditary Paraganglioma-Pheochromocytoma Syndromes

Cellular components related to Hereditary Paraganglioma-Pheochromocytoma Syndromes according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial inner membrane GO:0005743 9.65 SDHA SDHB SDHC SDHD TIMM8B
2 mitochondrion GO:0005739 9.65 FH KIF1B MDH2 SDHA SDHAF2 SDHB
3 respiratory chain complex II GO:0045273 9.16 SDHB SDHC
4 mitochondrial respiratory chain complex II, succinate dehydrogenase complex (ubiquinone) GO:0005749 8.92 SDHA SDHB SDHC SDHD

Biological processes related to Hereditary Paraganglioma-Pheochromocytoma Syndromes according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.83 MDH2 SDHA SDHB SDHC SDHD
2 electron transport chain GO:0022900 9.54 SDHA SDHB SDHC
3 respiratory electron transport chain GO:0022904 9.4 SDHA SDHB
4 aerobic respiration GO:0009060 9.33 MDH2 SDHB SDHC
5 succinate metabolic process GO:0006105 9.32 SDHA SDHB
6 malate metabolic process GO:0006108 9.26 FH MDH2
7 mitochondrial electron transport, succinate to ubiquinone GO:0006121 9.26 SDHA SDHAF2 SDHC SDHD
8 tricarboxylic acid cycle GO:0006099 9.17 FH MDH2 SDHA SDHAF2 SDHB SDHC

Molecular functions related to Hereditary Paraganglioma-Pheochromocytoma Syndromes according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 electron transfer activity GO:0009055 9.46 SDHA SDHB SDHC SDHD
2 oxidoreductase activity, acting on the CH-CH group of donors GO:0016627 9.32 SDHA SDHC
3 succinate dehydrogenase activity GO:0000104 9.26 SDHA SDHD
4 ubiquinone binding GO:0048039 8.96 SDHB SDHD
5 succinate dehydrogenase (ubiquinone) activity GO:0008177 8.92 SDHA SDHB SDHC SDHD

Sources for Hereditary Paraganglioma-Pheochromocytoma Syndromes

3 CDC
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10 dbSNP
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17 EFO
18 ExPASy
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29 GO
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