Pheochromocytoma/paraganglioma syndrome 7

Summary

Pheochromocytoma/paraganglioma syndrome 7 (MONDO:0032771) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pheochromocytoma/paraganglioma syndrome 7
Mondo ID	MONDO:0032771
OMIM	618475
DOID	DOID:0061222
UMLS	C5193116
MedGen	1673088
GARD	0016356
Is cancer (heuristic)	no

Also known as: paragangliomas 7 · PGL7 · pheochromocytoma/paraganglioma syndrome 7

Data availability: 3 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › autonomic nervous system disorder › autonomic nervous system neoplasm › paraganglioma › pheochromocytoma/paraganglioma syndrome 7

Related subtypes (11): head and neck paraganglioma, pheochromocytoma/paraganglioma syndrome 4, pheochromocytoma/paraganglioma syndrome 1, pheochromocytoma/paraganglioma syndrome 2, pheochromocytoma/paraganglioma syndrome 3, pheochromocytoma/paraganglioma syndrome 5, sporadic pheochromocytoma/secreting paraganglioma, non-secreting paraganglioma, parasympathetic paraganglioma, sympathetic paraganglioma, pheochromocytoma/paraganglioma syndrome 6

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

3 retrieved; paginated sample, class counts are floors:

3 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2440812	NM_001933.5(DLST):c.911A>G (p.Asp304Gly)	DLST	Uncertain significance	criteria provided, multiple submitters, no conflicts
2517173	NM_001933.5(DLST):c.647G>T (p.Gly216Val)	DLST	Uncertain significance	criteria provided, multiple submitters, no conflicts
635133	NM_001933.5(DLST):c.1121G>A (p.Gly374Glu)	DLST	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
DLST	Supportive	Autosomal dominant	hereditary pheochromocytoma-paraganglioma	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DLST	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DLST	HGNC:2911	ENSG00000119689	P36957	Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DLST	Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial	Dihydrolipoamide succinyltransferase (E2) component of the 2-oxoglutarate dehydrogenase complex.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DLST	Enzyme (other)	yes	1.2.1.105	Biotin_lipoyl, 2-oxoacid_DH_actylTfrase, 2-oxoA_DH_lipoyl-BS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DLST	283	ubiquitous	marker	apex of heart, right adrenal gland cortex, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DLST	3,692

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DLST	P36957	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
OADH complex synthesizes glutaryl-CoA from 2-OA	1	3806.7×	7e-04	DLST
OGDH complex synthesizes succinyl-CoA from 2-OG	1	2855.0×	7e-04	DLST
Glycine degradation	1	1631.4×	8e-04	DLST
Protein lipoylation	1	1038.2×	1e-03	DLST

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete L-lysine catabolic process to acetyl-CoA via L-saccharopine	1	5617.3×	5e-04	DLST
2-oxoglutarate decarboxylation to succinyl-CoA	1	5617.3×	5e-04	DLST
succinyl-CoA metabolic process	1	3370.4×	6e-04	DLST
2-oxoglutarate metabolic process	1	936.2×	0.002	DLST
tricarboxylic acid cycle	1	510.7×	0.002	DLST
generation of precursor metabolites and energy	1	343.9×	0.003	DLST

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DLST	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
DLST	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DLST	1.2.1.105	2-oxoglutarate dehydrogenase system

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

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

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DLST	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.