Mitochondrial complex 2 deficiency, nuclear type 2

Summary

Mitochondrial complex 2 deficiency, nuclear type 2 (MONDO:0030935) is a disease caused by SDHAF1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: SDHAF1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial complex 2 deficiency, nuclear type 2
Mondo ID	MONDO:0030935
OMIM	619166
UMLS	C5436933
MedGen	1742371
GARD	0016429
Is cancer (heuristic)	no

Also known as: MC2DN2 · mitochondrial complex 2 deficiency, nuclear type 2 · mitochondrial complex II deficiency, nuclear type 2

Data availability: 9 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › congenital myopathy › congenital structural myopathy › inborn mitochondrial myopathy › mitochondrial complex II deficiency, nuclear type › mitochondrial complex 2 deficiency, nuclear type 2

Related subtypes (3): mitochondrial complex 2 deficiency, nuclear type 3, mitochondrial complex 2 deficiency, nuclear type 4, mitochondrial complex II deficiency, nuclear type 1

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

9 retrieved; paginated sample, class counts are floors:

4 pathogenic, 2 likely pathogenic, 1 benign, 1 uncertain significance, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1699123	NM_001042631.3(SDHAF1):c.28C>T (p.Gln10Ter)	LOC130064279	Pathogenic	criteria provided, single submitter
1027545	NM_001042631.3(SDHAF1):c.170G>A (p.Gly57Glu)	LOC130064280	Pathogenic	no assertion criteria provided
429	NM_001042631.3(SDHAF1):c.169G>C (p.Gly57Arg)	LOC130064280	Pathogenic	criteria provided, single submitter
430	NM_001042631.3(SDHAF1):c.164G>C (p.Arg55Pro)	LOC130064280	Pathogenic	no assertion criteria provided
280451	NM_001042631.3(SDHAF1):c.156C>A (p.Tyr52Ter)	SDHAF1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2691857	NM_001042631.3(SDHAF1):c.95T>A (p.Val32Glu)	LOC130064279	Likely pathogenic	criteria provided, single submitter
426195	NM_001042631.3(SDHAF1):c.22C>T (p.Gln8Ter)	LOC130064279	Likely pathogenic	criteria provided, single submitter
2584803	NM_001042631.3(SDHAF1):c.43T>G (p.Tyr15Asp)	LOC130064279	Uncertain significance	criteria provided, single submitter
193150	NM_001042631.3(SDHAF1):c.269G>C (p.Cys90Ser)	LOC130064281	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
SDHAF1	Definitive	Autosomal recessive	mitochondrial complex 2 deficiency, nuclear type 2	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SDHAF1	Orphanet:3208	Isolated succinate-CoQ reductase deficiency

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
SDHAF1	HGNC:33867	ENSG00000205138	A6NFY7	Succinate dehydrogenase assembly factor 1, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SDHAF1	Succinate dehydrogenase assembly factor 1, mitochondrial	Plays an essential role in the assembly of succinate dehydrogenase (SDH), an enzyme complex (also referred to as respiratory complex II) that is a component of both the tricarboxylic acid (TCA) cycle and the mitochondrial electron transpor…

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SDHAF1	Other/Unknown	no		Complex1_LYR_dom, Complex1_LYR_SDHAF1_LYRM8, SDHAF1

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
olfactory bulb	1
parotid gland	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SDHAF1	277	ubiquitous	marker	type B pancreatic cell, olfactory bulb, parotid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SDHAF1	884

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SDHAF1	A6NFY7	77.46

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
Maturation of TCA enzymes and regulation of TCA cycle	1	571.0×	0.005	SDHAF1
Citric acid cycle (TCA cycle)	1	423.0×	0.005	SDHAF1
Aerobic respiration and respiratory electron transport	1	88.5×	0.015	SDHAF1
Metabolism	1	11.6×	0.086	SDHAF1

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
mitochondrial respiratory chain complex II assembly	1	4213.0×	2e-04	SDHAF1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SDHAF1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
E	Difficult family or no structure, no drug	1	SDHAF1

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)
SDHAF1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.