SDHAF1

succinate dehydrogenase complex assembly factor 1, the group of LYR motif containing|Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 19:35995188-35996312

Links

ENSG00000205138 ∙ NCBI:644096 ∙ OMIM:612848 ∙ HGNC:33867 ∙ Uniprot:A6NFY7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex II deficiency, nuclear type 1 (Strong), mode of inheritance: AR
• mitochondrial complex II deficiency (Supportive), mode of inheritance: AR
• mitochondrial complex II deficiency (Moderate), mode of inheritance: AR
• Leigh syndrome (Limited), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR
• mitochondrial complex 2 deficiency, nuclear type 2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex II deficiency, nuclear type 2	AR	Biochemical; Cardiovascular	Medical treatment (eg, riboflavin, ubiquinol) may be beneficial; Individuals may multisystemic, including cardiac, involvemen (which can include arrhythmias), and surveillance and early interventions may be beneficial	Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	12112045; 16737791; 19465911; 22995659; 23322652

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SDHAF1 gene.

• not_provided (30 variants)
• Inborn_genetic_diseases (30 variants)
• Mitochondrial_complex_II_deficiency,_nuclear_type_1 (8 variants)
• Mitochondrial_complex_2_deficiency,_nuclear_type_2 (8 variants)
• not_specified (4 variants)
• SDHAF1-related_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SDHAF1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001042631.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				15		15
missense	3	1	38	2		44
nonsense	1	2				3
start loss			1			1
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	4	3	39	17	0

Highest pathogenic variant AF is 0.0000158078

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SDHAF1	protein_coding	protein_coding	ENST00000378887	1	1131

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0870	0.577	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.379	49	57.1	0.859	0.00000286	681
Missense in Polyphen		16	19.595	0.81653		223
Synonymous	0.936	21	27.2	0.772	0.00000137	259
Loss of Function	-0.0930	1	0.905	1.11	3.87e-8	8

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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. Promotes maturation of the iron-sulfur protein subunit SDHB of the SDH catalytic dimer, protecting it from the deleterious effects of oxidants. May act together with SDHAF3. {ECO:0000269|PubMed:19465911, ECO:0000269|PubMed:24954417}.

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.272
• ghis: 0.536

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.448

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sdhaf1

Gene ontology

• Biological process: mitochondrial respiratory chain complex II assembly
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: protein binding