Pheochromocytoma/paraganglioma syndrome 6

Summary

Pheochromocytoma/paraganglioma syndrome 6 (MONDO:0032767) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pheochromocytoma/paraganglioma syndrome 6
Mondo ID	MONDO:0032767
OMIM	618464
DOID	DOID:0061221
UMLS	C5193112
MedGen	1681559
GARD	0016354
Is cancer (heuristic)	no

Also known as: paragangliomas 6 · PGL6 · pheochromocytoma/paraganglioma syndrome 6

Data availability: 7 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 6

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 7

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

7 retrieved; paginated sample, class counts are floors:

5 pathogenic, 1 conflicting classifications of pathogenicity, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
635126	NM_003562.5(SLC25A11):c.715C>A (p.Pro239Thr)	SLC25A11	Pathogenic	no assertion criteria provided
635127	NM_003562.5(SLC25A11):c.439A>G (p.Met147Val)	SLC25A11	Pathogenic	no assertion criteria provided
635128	NM_003562.5(SLC25A11):c.708C>T (p.Ala236=)	SLC25A11	Pathogenic	no assertion criteria provided
635129	NM_003562.5(SLC25A11):c.421G>A (p.Glu141Lys)	SLC25A11	Pathogenic	no assertion criteria provided
635130	NM_003562.5(SLC25A11):c.107_108del (p.Thr36fs)	SLC25A11	Pathogenic	no assertion criteria provided
1319152	NM_003562.5(SLC25A11):c.828C>A (p.Phe276Leu)	SLC25A11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3892450	NM_003562.5(SLC25A11):c.454C>T (p.Arg152Trp)	SLC25A11	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
SLC25A11	Supportive	Autosomal dominant	hereditary pheochromocytoma-paraganglioma	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC25A11	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
SLC25A11	HGNC:10981	ENSG00000108528	Q02978	Mitochondrial 2-oxoglutarate/malate carrier protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC25A11	Mitochondrial 2-oxoglutarate/malate carrier protein	Catalyzes the transport of 2-oxoglutarate (alpha-oxoglutarate) across the inner mitochondrial membrane in an electroneutral exchange for malate.

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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC25A11	Transporter	yes		MCP_transmembrane, MCP_dom_sf, Mito_Metabolite_Transporter

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
hindlimb stylopod muscle	1
right atrium auricular region	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC25A11	289	ubiquitous	marker	apex of heart, hindlimb stylopod muscle, right atrium auricular region

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLC25A11	2,474

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC25A11	Q02978	87.54

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Organic anion transport by SLC5/17/25 transporters	1	1427.5×	0.003	SLC25A11
Malate-aspartate shuttle	1	1268.9×	0.003	SLC25A11
R-HSA-425393	1	129.8×	0.018	SLC25A11
Respiratory electron transport	1	95.2×	0.018	SLC25A11
Aerobic respiration and respiratory electron transport	1	88.5×	0.018	SLC25A11
SLC-mediated transmembrane transport	1	59.2×	0.023	SLC25A11
Transport of small molecules	1	25.1×	0.045	SLC25A11
Metabolism	1	11.6×	0.086	SLC25A11

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
malate-aspartate shuttle	1	1872.4×	0.002	SLC25A11
gluconeogenesis	1	324.1×	0.004	SLC25A11
lipid transport	1	263.3×	0.004	SLC25A11

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
SLC25A11	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SLC25A11	1	Binding:1

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	0
D	Druggable family + AlphaFold only, no drug	1	SLC25A11
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)
SLC25A11	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.