Carney triad

Summary

Carney triad (MONDO:0011424) is a disease with 3 cohort genes and 1 clinical trial. The dominant Reactome pathway is Maturation of TCA enzymes and regulation of TCA cycle (3 cohort genes).

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 3
• ClinVar variants: 6
• Phenotypes (HPO): 21
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		150	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

21 HPO clinical features (Orphanet curated; top 21 by frequency):

HPO ID	Term	Frequency
HP:0002014	Diarrhea	Very frequent (80-99%)
HP:0002017	Nausea and vomiting	Very frequent (80-99%)
HP:0002027	Abdominal pain	Very frequent (80-99%)
HP:0002239	Gastrointestinal hemorrhage	Very frequent (80-99%)
HP:0002666	Pheochromocytoma	Very frequent (80-99%)
HP:0012378	Fatigue	Very frequent (80-99%)
HP:0100243	Leiomyosarcoma	Very frequent (80-99%)
HP:0100723	Gastrointestinal stroma tumor	Very frequent (80-99%)
HP:0001541	Ascites	Frequent (30-79%)
HP:0001649	Tachycardia	Frequent (30-79%)
HP:0002113	Pulmonary infiltrates	Frequent (30-79%)
HP:0002668	Paraganglioma	Frequent (30-79%)
HP:0002717	Adrenal overactivity	Frequent (30-79%)
HP:0008256	Adrenocortical adenoma	Frequent (30-79%)
HP:0100721	Mediastinal lymphadenopathy	Frequent (30-79%)
HP:0000822	Hypertension	Occasional (5-29%)
HP:0001903	Anemia	Occasional (5-29%)
HP:0002039	Anorexia	Occasional (5-29%)
HP:0002315	Headache	Occasional (5-29%)
HP:0002716	Lymphadenopathy	Occasional (5-29%)
HP:0011675	Arrhythmia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Carney triad
Mondo ID	MONDO:0011424
MeSH	C565803
OMIM	604287
Orphanet	139411
ICD-11	1771169701
NCIT	C94833
SNOMED CT	733492003
UMLS	C1858592
MedGen	388099
GARD	0010924
Is cancer (heuristic)	no

Also known as: Carney triad

Data availability: 6 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › endocrine system disorder › polyendocrinopathy › multiple polyglandular tumor › Carney triad

Related subtypes (2): Carney-Stratakis syndrome, multiple endocrine neoplasia

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

6 retrieved; paginated sample, class counts are floors:

2 pathogenic/likely pathogenic, 2 pathogenic, 1 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
183814	NM_003000.3(SDHB):c.380T>G (p.Ile127Ser)	SDHB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
189840	NM_003001.5(SDHC):c.6del (p.Ala3fs)	SDHC	Pathogenic	criteria provided, single submitter
189841	NM_003001.5(SDHC):c.224G>A (p.Gly75Asp)	SDHC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
7244	NM_003001.5(SDHC):c.405+1G>A	SDHC	Pathogenic	criteria provided, multiple submitters, no conflicts
189839	NM_004168.4(SDHA):c.295C>T (p.His99Tyr)	SDHA	Likely pathogenic	no assertion criteria provided
142601	NM_004168.4(SDHA):c.91C>T (p.Arg31Ter)	SDHA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 18 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
SDHB	Orphanet:139411	Carney triad
SDHB	Orphanet:201	Cowden syndrome
SDHB	Orphanet:276621	Sporadic pheochromocytoma/secreting paraganglioma
SDHB	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
SDHB	Orphanet:3208	Isolated succinate-CoQ reductase deficiency
SDHB	Orphanet:44890	Gastrointestinal stromal tumor
SDHB	Orphanet:97286	Carney-Stratakis syndrome
SDHC	Orphanet:139411	Carney triad
SDHC	Orphanet:201	Cowden syndrome
SDHC	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
SDHC	Orphanet:44890	Gastrointestinal stromal tumor
SDHC	Orphanet:97286	Carney-Stratakis syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SDHA	HGNC:10680	ENSG00000073578	P31040	Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial	clinvar
SDHB	HGNC:10681	ENSG00000117118	P21912	Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial	clinvar
SDHC	HGNC:10682	ENSG00000143252	Q99643	Succinate dehydrogenase cytochrome b560 subunit, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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).
SDHB	Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial	Iron-sulfur protein (IP) subunit of the succinate dehydrogenase complex (mitochondrial respiratory chain complex II), responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
SDHC	Succinate dehydrogenase cytochrome b560 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).

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

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)	2	8.0×	0.039
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SDHA	Other/Unknown	no		FRD_SDH_FAD_BS, FAD-dep_OxRdtase_2_FAD-bd, Succ_DH_flav_su_fwd
SDHB	Enzyme (other)	yes	1.3.5.1	2Fe-2S_ferredoxin-type, Succ_DH/fum_Rdtase_Fe-S, 2Fe2S_fd_BS
SDHC	Enzyme (other)	yes	1.3.5.1	SuccDH_FuR_B_TM-su, Succ_DH_cytb556, Succ_DH_cyt_bsu_CS

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	2
heart left ventricle	2
mucosa of transverse colon	1
cardiac ventricle	1
islet of Langerhans	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SDHA	143	ubiquitous	marker	apex of heart, heart left ventricle, mucosa of transverse colon
SDHB	293	ubiquitous	marker	heart left ventricle, cardiac ventricle, apex of heart
SDHC	134	ubiquitous	marker	islet of Langerhans, right adrenal gland cortex, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SDHA	6,141
SDHB	5,471
SDHC	5,278

Intra-cohort edges

A	B	Sources
SDHA	SDHB	biogrid_interaction, intact, string_interaction
SDHA	SDHC	biogrid_interaction, string_interaction
SDHB	SDHC	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SDHB	P21912	6
SDHA	P31040	5
SDHC	Q99643	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 3 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	3	571.0×	2e-08	SDHA, SDHB, SDHC
Citric acid cycle (TCA cycle)	3	423.0×	3e-08	SDHA, SDHB, SDHC
Respiratory electron transport	3	95.2×	2e-06	SDHA, SDHB, SDHC
Aerobic respiration and respiratory electron transport	3	88.5×	2e-06	SDHA, SDHB, SDHC
Metabolism	3	11.6×	6e-04	SDHA, SDHB, SDHC

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mitochondrial electron transport, succinate to ubiquinone	3	3370.4×	9e-11	SDHA, SDHB, SDHC
tricarboxylic acid cycle	3	510.7×	2e-08	SDHA, SDHB, SDHC
proton motive force-driven mitochondrial ATP synthesis	3	263.3×	1e-07	SDHA, SDHB, SDHC
succinate metabolic process	2	2246.9×	4e-07	SDHA, SDHB
respiratory electron transport chain	2	561.7×	6e-06	SDHA, SDHB
aerobic respiration	2	165.2×	6e-05	SDHB, SDHC
nervous system development	1	15.3×	0.064	SDHA

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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
SDHB	0	0
SDHC	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): 2.

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

Symbol	Assays	Type breakdown
SDHB	4	Binding:4
SDHA	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SDHB	1.3.5.1	succinate dehydrogenase
SDHC	1.3.5.1	succinate dehydrogenase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	2	SDHB, SDHC
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SDHB	4	SDHA
SDHC	0	SDHA

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06523582	Not specified	RECRUITING	Genetic Bases of Neuroendocrine Neoplasms in Mexican Patients