Pheochromocytoma/paraganglioma syndrome 1

Summary

Pheochromocytoma/paraganglioma syndrome 1 (MONDO:0008192) is a disease caused by SDHD (GenCC Definitive), with 5 cohort genes.

At a glance

• Causal gene: SDHD (GenCC Definitive)
• Cohort genes: 5
• ClinVar variants: 204

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pheochromocytoma/paraganglioma syndrome 1
Mondo ID	MONDO:0008192
OMIM	168000
DOID	DOID:0061216
UMLS	C3494181
MedGen	488134
GARD	0007324
Is cancer (heuristic)	no

Also known as: carotid body tumours · glomus jugulare tumours · paraganglioma caused by mutation in SDHD · paragangliomas 1 · paragangliomas 1, with or without deafness · paragangliomas type 1 · PGL1 · pheochromocytoma/paraganglioma syndrome 1 · SDHD paraganglioma · SDHD-related tumor predisposition

Data availability: 204 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › pheochromocytoma/paraganglioma syndrome 1

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

204 retrieved; paginated sample, class counts are floors:

67 benign/likely benign, 39 pathogenic, 23 likely benign, 21 uncertain significance, 21 conflicting classifications of pathogenicity, 13 benign, 11 pathogenic/likely pathogenic, 9 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
831566	NC_000011.9:g.(?111171709)(111965694_?)del	HOATZ	Pathogenic	criteria provided, single submitter
1319258	NM_003002.4(SDHD):c.49C>T (p.Arg17Ter)	LOC126861339	Pathogenic	criteria provided, multiple submitters, no conflicts
239459	NC_000011.10:g.(?112086824)(112095801_?)del	LOC126861339	Pathogenic	criteria provided, single submitter
239460	NM_003002.4(SDHD):c.10dup (p.Leu4fs)	LOC126861339	Pathogenic	criteria provided, single submitter
3757250	NM_003002.4(SDHD):c.52+1G>T	LOC126861339	Pathogenic	criteria provided, multiple submitters, no conflicts
547769	NM_003002.4(SDHD):c.18_21del (p.Leu7fs)	LOC126861339	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
584168	NC_000011.10:g.(?112086898)(112094980_?)del	LOC126861339	Pathogenic	criteria provided, single submitter
618362	NM_003002.4(SDHD):c.13_14del (p.Trp5fs)	LOC126861339	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
6906	NM_003002.4(SDHD):c.3G>C (p.Met1Ile)	LOC126861339	Pathogenic	criteria provided, multiple submitters, no conflicts
6911	NM_003002.4(SDHD):c.1A>G (p.Met1Val)	LOC126861339	Pathogenic	criteria provided, multiple submitters, no conflicts
6915	NM_003002.4(SDHD):c.33C>A (p.Cys11Ter)	LOC126861339	Pathogenic	criteria provided, multiple submitters, no conflicts
6916	NM_003002.4(SDHD):c.14G>A (p.Trp5Ter)	LOC126861339	Pathogenic	criteria provided, multiple submitters, no conflicts
239658	NM_004168.4(SDHA):c.1754G>A (p.Arg585Gln)	SDHA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076624	NC_000011.9:g.(?111957547)(111958707_?)del	SDHD	Pathogenic	criteria provided, single submitter
2084230	NM_003002.4(SDHD):c.264C>A (p.Cys88Ter)	SDHD	Pathogenic	criteria provided, single submitter
21351	NM_003002.4(SDHD):c.284T>C (p.Leu95Pro)	SDHD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
230274	NM_003002.4(SDHD):c.320T>G (p.Leu107Arg)	SDHD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
231390	NM_003002.4(SDHD):c.147dup (p.His50fs)	SDHD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
239461	NM_003002.4(SDHD):c.173del (p.Gly58fs)	SDHD	Pathogenic	criteria provided, multiple submitters, no conflicts
239464	NM_003002.4(SDHD):c.242del (p.Pro81fs)	SDHD	Pathogenic	criteria provided, multiple submitters, no conflicts
2673996	NM_003002.4(SDHD):c.395C>G (p.Ser132Ter)	SDHD	Pathogenic	criteria provided, single submitter
2931847	NM_003002.4(SDHD):c.241_262del (p.Pro81fs)	SDHD	Pathogenic	criteria provided, multiple submitters, no conflicts
3904408	NM_003002.4(SDHD):c.282_283del (p.Leu95fs)	SDHD	Pathogenic	criteria provided, multiple submitters, no conflicts
412505	NM_003002.4(SDHD):c.394del (p.Ser132fs)	SDHD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
480806	NM_003002.4(SDHD):c.317G>T (p.Gly106Val)	SDHD	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
533799	NC_000011.10:g.(?112094799)(112094976_?)del	SDHD	Pathogenic	criteria provided, single submitter
547770	NM_003002.4(SDHD):c.336dup (p.Asp113Ter)	SDHD	Pathogenic	criteria provided, multiple submitters, no conflicts
583435	NC_000011.10:g.(?112088857)(112094980_?)del	SDHD	Pathogenic	criteria provided, single submitter
584289	NC_000011.10:g.(?112094795)(112094980_?)del	SDHD	Pathogenic	criteria provided, single submitter
598762	NC_000011.10:g.112093693_112095870del	SDHD	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 14 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SDHD	Definitive	Autosomal dominant	pheochromocytoma/paraganglioma syndrome 1	16

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SDHD	Orphanet:100093	Carcinoid syndrome
SDHD	Orphanet:201	Cowden syndrome
SDHD	Orphanet:276621	Sporadic pheochromocytoma/secreting paraganglioma
SDHD	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
SDHD	Orphanet:3208	Isolated succinate-CoQ reductase deficiency
SDHD	Orphanet:97286	Carney-Stratakis syndrome
SDHA	Orphanet:139411	Carney triad
SDHA	Orphanet:154	Familial isolated dilated cardiomyopathy
SDHA	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
SDHA	Orphanet:3208	Isolated succinate-CoQ reductase deficiency
SDHA	Orphanet:44890	Gastrointestinal stromal tumor
SDHA	Orphanet:97286	Carney-Stratakis syndrome
ALG9	Orphanet:730	Autosomal dominant polycystic kidney disease
ALG9	Orphanet:79328	ALG9-CDG

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SDHD	HGNC:10683	ENSG00000204370	O14521	Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial	gencc,clinvar
SDHA	HGNC:10680	ENSG00000073578	P31040	Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial	clinvar
ALG9	HGNC:15672	ENSG00000086848	Q9H6U8	Alpha-1,2-mannosyltransferase ALG9	clinvar
CARTPT	HGNC:24323	ENSG00000164326	Q16568	Cocaine- and amphetamine-regulated transcript protein	clinvar
HOATZ	HGNC:25061	ENSG00000183644	Q6PI97	Cilia- and flagella-associated protein HOATZ	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SDHD	Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial	Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
SDHA	Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial	Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
ALG9	Alpha-1,2-mannosyltransferase ALG9	Mannosyltransferase that operates in the biosynthetic pathway of dolichol-linked oligosaccharides, the glycan precursors employed in protein asparagine (N)-glycosylation.
CARTPT	Cocaine- and amphetamine-regulated transcript protein	Satiety factor closely associated with the actions of leptin and neuropeptide Y; this anorectic peptide inhibits both normal and starvation-induced feeding and completely blocks the feeding response induced by neuropeptide Y and regulated…
HOATZ	Cilia- and flagella-associated protein HOATZ	Required for motile ciliogenesis and flagellar genesis by mediating the maturation of the glycolytic enzyme ENO4.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 4 · Druggable fraction: 0.2

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	2.4×	0.353
Other/Unknown	4	1.4×	0.353

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SDHD	Other/Unknown	no		CybS, SQR/QFR_C/D
SDHA	Other/Unknown	no		FRD_SDH_FAD_BS, FAD-dep_OxRdtase_2_FAD-bd, Succ_DH_flav_su_fwd
ALG9	Enzyme (other)	yes	2.4.1.259	GPI_mannosylTrfase
CARTPT	Other/Unknown	no		CART, CART_C_sf
HOATZ	Other/Unknown	no		HOATZ-like

Expression context

Cohort genes with no expression data: 0.

5 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
jejunal mucosa	1
jejunum	1
rectum	1
apex of heart	1
heart left ventricle	1
mucosa of transverse colon	1
body of pancreas	1
endothelial cell	1
ganglionic eminence	1
hypothalamus	1
male germ line stem cell (sensu Vertebrata) in testis	1
middle temporal gyrus	1
bronchial epithelial cell	1
olfactory segment of nasal mucosa	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SDHD	287	ubiquitous	marker	jejunal mucosa, rectum, jejunum
SDHA	143	ubiquitous	marker	apex of heart, heart left ventricle, mucosa of transverse colon
ALG9	240	ubiquitous	marker	endothelial cell, body of pancreas, ganglionic eminence
CARTPT	156	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, hypothalamus, middle temporal gyrus
HOATZ	129	tissue_specific	marker	right uterine tube, bronchial epithelial cell, olfactory segment of nasal mucosa

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SDHA	6,141
CARTPT	3,160
SDHD	2,229
HOATZ	1,818
ALG9	1,167

Intra-cohort edges

A	B	Sources
SDHA	SDHD	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SDHA	P31040	5
SDHD	O14521	2
ALG9	Q9H6U8	2
CARTPT	Q16568	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HOATZ	Q6PI97	74.34

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 5 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Maturation of TCA enzymes and regulation of TCA cycle	2	380.7×	1e-04	SDHD, SDHA
Citric acid cycle (TCA cycle)	2	282.0×	1e-04	SDHD, SDHA
Defective ALG9 causes CDG-1l	1	3806.7×	0.001	ALG9
Respiratory electron transport	2	63.4×	0.001	SDHD, SDHA
Diseases associated with N-glycosylation of proteins	1	211.5×	0.013	ALG9
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1	69.2×	0.034	ALG9
Diseases of glycosylation	1	43.8×	0.045	ALG9
Aerobic respiration and respiratory electron transport	1	29.5×	0.057	SDHA
Diseases of metabolism	1	26.8×	0.057	ALG9
Asparagine N-linked glycosylation	1	20.0×	0.069	ALG9
Post-translational protein modification	1	6.4×	0.189	ALG9
Disease	1	4.4×	0.237	ALG9
Metabolism of proteins	1	4.1×	0.237	ALG9
Metabolism	1	3.9×	0.237	SDHA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mitochondrial electron transport, succinate to ubiquinone	2	1348.2×	5e-05	SDHD, SDHA
tricarboxylic acid cycle	2	204.3×	0.001	SDHD, SDHA
regulation of systemic arterial blood pressure by neurotransmitter	1	3370.4×	0.003	CARTPT
positive regulation of epinephrine secretion	1	3370.4×	0.003	CARTPT
response to corticotropin-releasing hormone	1	3370.4×	0.003	CARTPT
regulation of catecholamine secretion	1	3370.4×	0.003	SDHD
proton motive force-driven mitochondrial ATP synthesis	2	105.3×	0.003	SDHD, SDHA
regulation of circadian sleep/wake cycle, wakefulness	1	1685.2×	0.003	CARTPT
negative regulation of locomotion	1	1685.2×	0.003	CARTPT
regulation of circadian sleep/wake cycle, REM sleep	1	1685.2×	0.003	CARTPT
somatostatin secretion	1	1685.2×	0.003	CARTPT
regulation of locomotion involved in locomotory behavior	1	1685.2×	0.003	CARTPT
negative regulation of relaxation of smooth muscle	1	1685.2×	0.003	CARTPT
regulation of heart rate by chemical signal	1	1123.5×	0.004	CARTPT
regulation of circadian sleep/wake cycle, non-REM sleep	1	1123.5×	0.004	CARTPT
negative regulation of glucagon secretion	1	1123.5×	0.004	CARTPT
detection of chemical stimulus involved in sensory perception of pain	1	842.6×	0.004	CARTPT
regulation of lipid catabolic process	1	842.6×	0.004	CARTPT
succinate metabolic process	1	674.1×	0.005	SDHA
positive regulation of type B pancreatic cell proliferation	1	674.1×	0.005	CARTPT
regulation of lipid biosynthetic process	1	561.7×	0.005	CARTPT
negative regulation of eating behavior	1	561.7×	0.005	CARTPT
operant conditioning	1	481.5×	0.006	CARTPT
positive regulation of transmission of nerve impulse	1	481.5×	0.006	CARTPT
negative regulation of type B pancreatic cell apoptotic process	1	421.3×	0.006	CARTPT
adult feeding behavior	1	337.0×	0.007	CARTPT
conditioned place preference	1	337.0×	0.007	CARTPT
negative regulation of appetite	1	306.4×	0.008	CARTPT
cAMP biosynthetic process	1	280.9×	0.008	CARTPT
negative regulation of cytosolic calcium ion concentration	1	259.3×	0.008	CARTPT

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 4

Druggability breadth: 1 of 5 evidence-associated genes (20%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
SDHA	LINEZOLID

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SDHA	1	4
SDHD	0	0
ALG9	0	0
CARTPT	0	0
HOATZ	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LINEZOLID	4	SDHA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
SDHA	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ALG9	2.4.1.259, 2.4.1.261	dolichyl-P-Man:Man6GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase, dolichyl-P-Man:Man8GlcNAc2-PP-dolichol alpha-1,2-mannosyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
LINEZOLID	4	SDHA

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SDHA
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	ALG9
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	SDHD, CARTPT, HOATZ

Undrugged target profiles

4 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SDHD	0	SDHA
ALG9	0	—
CARTPT	0	—
HOATZ	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.