SDHAF4
protein-codingsuccinate dehydrogenase complex assembly factor 4, the group of Mitochondrial respiratory chain complex assembly factors
Gene summary
Predicted to enable enzyme activator activity. Involved in cellular respiration and mitochondrial respiratory chain complex II assembly. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]
- C6orf57
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SDHAF4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_145267.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 21 | 21 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 23 | 0 | 0 | 23 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_660310.2 | 3 | MANE Select | |
| Ensembl | ENSP00000359505.3 | 3 | MANE Select | |
| Ensembl | ENSP00000695335.1 | 2 | Standard | |
| Ensembl | ENSP00000763915.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- neural retina development
- mitochondrial respiratory chain complex II assembly
- innate immune response
- cellular respiration
Molecular Function
- molecular_function
- succinate dehydrogenase (ubiquinone) activity
Cellular Component
- cellular_component
- mitochondrial respiratory chain complex II, succinate dehydrogenase complex (ubiquinone)
- mitochondrial matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000370474
- Coding exons
- 3
- Length
- 22653
- Individuals with no LoFs
- 124989
- Homozygous LoFs
- 4
- Heterozygous LoFs
- 724
- Defined
- 125717
- p
- 0.00290
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.249 | 52 | 57.3 | 0.908 | 0.00000301 | 671 |
| Missense (PolyPhen) | 17 | 24.118 | 0.70488 | 276 | ||
| Synonymous | -0.932 | 25 | 19.7 | 1.27 | 9.32e-7 | 209 |
| Loss of Function | 1.20 | 2 | 4.84 | 0.413 | 2.88e-7 | 61 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.015 | 0.015 | notable |
| Latino/Admixed American | 0.0022 | 0.0021 | notable |
| Ashkenazi Jewish | 0.00060 | 0.00060 | rare |
| East Asian | 0.0092 | 0.0092 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00053 | 0.00053 | rare |
| South Asian | 0.0054 | 0.0054 | notable |
| Other | 0.0035 | 0.0034 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: 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 transport chain, and which couples the oxidation of succinate to fumarate with the reduction of ubiquinone (coenzyme Q) to ubiquinol (PubMed:24954416). Binds to the flavoprotein subunit SDHA in its FAD-bound form, blocking the generation of excess reactive oxigen species (ROS) and facilitating its assembly with the iron-sulfur protein subunit SDHB into the SDH catalytic dimer (By similarity). {ECO:0000250|UniProtKB:P38345, ECO:0000269|PubMed:24954416}.;
Recessive Scores
- pRec
- 0.0930
Intolerance Scores
- RVIS EVS
- 0.57
- RVIS percentile EVS
- 81.89
Essentials
- Essential (gene trap)
- E