SDHAF3

Summary

SDHAF3 (succinate dehydrogenase complex assembly factor 3, HGNC:21752) is a protein-coding gene on chromosome 7q21.3, encoding Succinate dehydrogenase assembly factor 3, mitochondrial (Q9NRP4). 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….

Predicted to be involved in mitochondrial respiratory chain complex II assembly; regulation of gluconeogenesis; and succinate metabolic process. Located in mitochondrion.

Source: NCBI Gene 57001 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_020186

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21752
Approved symbol	SDHAF3
Name	succinate dehydrogenase complex assembly factor 3
Location	7q21.3
Locus type	gene with protein product
Status	Approved
Aliases	DC11, Sdh7, LYRM10
Ensembl gene	ENSG00000196636
Ensembl biotype	protein_coding
OMIM	615773
Entrez	57001

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000360382, ENST00000432641, ENST00000479853, ENST00000489852

RefSeq mRNA: 1 — MANE Select: NM_020186 NM_020186

CCDS: CCDS5648

Canonical transcript exons

ENST00000432641 — 2 exons

Exon	Start	End
ENSE00001417318	97181012	97181763
ENSE00001714317	97117698	97117897

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 90.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.8713 / max 294.0051, expressed in 1692 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79796	17.8772	1688
79797	0.5263	297
79795	0.4161	238
79794	0.0516	20

Top tissues by expression

270 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.43	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.02	gold quality
rectum	UBERON:0001052	89.82	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.08	gold quality
right adrenal gland cortex	UBERON:0035827	88.90	gold quality
right atrium auricular region	UBERON:0006631	88.87	gold quality
islet of Langerhans	UBERON:0000006	88.69	gold quality
right adrenal gland	UBERON:0001233	88.67	gold quality
mucosa of transverse colon	UBERON:0004991	88.67	gold quality
left adrenal gland	UBERON:0001234	88.59	gold quality
left adrenal gland cortex	UBERON:0035825	88.38	gold quality
right lobe of liver	UBERON:0001114	88.09	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.05	gold quality
body of pancreas	UBERON:0001150	87.25	gold quality
muscle of leg	UBERON:0001383	87.09	gold quality
oocyte	CL:0000023	86.99	gold quality
gastrocnemius	UBERON:0001388	86.99	gold quality
heart left ventricle	UBERON:0002084	86.84	gold quality
right testis	UBERON:0004534	86.82	gold quality
left testis	UBERON:0004533	86.61	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.59	gold quality
adrenal gland	UBERON:0002369	86.47	gold quality
metanephros cortex	UBERON:0010533	86.21	gold quality
pancreas	UBERON:0001264	86.16	gold quality
adrenal cortex	UBERON:0001235	86.15	gold quality
cardiac ventricle	UBERON:0002082	86.12	gold quality
cardiac atrium	UBERON:0002081	85.93	gold quality
anterior cingulate cortex	UBERON:0009835	85.92	gold quality
cingulate cortex	UBERON:0003027	85.79	gold quality
spinal cord	UBERON:0002240	85.64	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.89
E-MTAB-6524	no	176.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting SDHAF3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-4666B	99.64	68.69	1282

Literature-anchored findings (GeneRIF, showing 3)

• ACN9 is involved in the predisposition to alcohol dependence. (PMID:18163977)
• Single nucleotide polymorphism in ACN9 gene is associated with alcohol dependence. (PMID:25821040)
• SDHAF3 interacts directly with SDHB (residue 242 being key to this interaction), and that a variant in SDHAF3 (c.157 T > C [p.Phe53Leu]) may be more prevalent in individuals with familial and sporadic pheochromocytoma and paraganglioma, and is hypomorphic via impaired interaction with SDHB. (PMID:28738844)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sdhaf3	ENSDARG00000036092
mus_musculus	Sdhaf3	ENSMUSG00000042505
rattus_norvegicus	Sdhaf3	ENSRNOG00000011283
drosophila_melanogaster	Sdhaf3	FBGN0038437
caenorhabditis_elegans		WBGENE00009139

Protein

Protein identifiers

Succinate dehydrogenase assembly factor 3, mitochondrial — Q9NRP4 (reviewed: Q9NRP4)

All UniProt accessions (2): Q9NRP4, F8W9V1

UniProt curated annotations — full annotation on UniProt →

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 SDHAF1.

Subunit / interactions. Interacts with SDHB within an SDHA-SDHB subcomplex.

Subcellular location. Mitochondrion matrix.

Similarity. Belongs to the complex I LYR family. SDHAF3 subfamily.

RefSeq proteins (1): NP_064571* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008381	SDHAF3/Sdh7	Family

Pfam: PF13233

UniProt features (2 total): transit peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRP4-F1	89.29	0.76

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9854311	Maturation of TCA enzymes and regulation of TCA cycle
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism
R-HSA-71403	Citric acid cycle (TCA cycle)

MSigDB gene sets: 108 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_MONOSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_REGULATION_OF_GLUCOSE_METABOLIC_PROCESS, GOBP_GLUCOSE_METABOLIC_PROCESS, GOBP_REGULATION_OF_CARBOHYDRATE_BIOSYNTHETIC_PROCESS, AACTTT_UNKNOWN, GOBP_MONOSACCHARIDE_METABOLIC_PROCESS, TTTNNANAGCYR_UNKNOWN

GO Biological Process (2): regulation of gluconeogenesis (GO:0006111), mitochondrial respiratory chain complex II assembly (GO:0034553)

GO Molecular Function (0):

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial intermembrane space (GO:0005758), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Citric acid cycle (TCA cycle)	1
Metabolism	1
Aerobic respiration and respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	2
gluconeogenesis	1
regulation of glucose metabolic process	1
regulation of carbohydrate biosynthetic process	1
mitochondrial respiratory chain complex assembly	1
respiratory chain complex II assembly	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial envelope	1
organelle envelope lumen	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

720 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SDHAF3	SDHAF1	A6NFY7	899
SDHAF3	SDHAF4	Q5VUM1	883
SDHAF3	SDHAF2	Q9NX18	845
SDHAF3	F5H5T6	F5H5T6	797
SDHAF3	SDHA	P31040	768
SDHAF3	LYRM4	Q9HD34	715
SDHAF3	LYRM1	O43325	711
SDHAF3	SDHD	O14521	691
SDHAF3	ETFRF1	Q6IPR1	661
SDHAF3	SDHB	P21912	645
SDHAF3	LYRM2	Q9NU23	639
SDHAF3	LYRM7	Q5U5X0	634
SDHAF3	SDHC	Q99643	577
SDHAF3	NXT2	Q9NPJ8	545
SDHAF3	NFS1	Q9Y697	521

IntAct

10 interactions, top by confidence:

A	B	Type	Score
SDHA	SDHB	psi-mi:“MI:0914”(association)	0.820
SDHAF3	NDUFAB1	psi-mi:“MI:0914”(association)	0.640
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (45): C6orf57 (Affinity Capture-MS), NDUFAB1 (Affinity Capture-MS), BOLA3 (Affinity Capture-MS), PMPCA (Affinity Capture-MS), GOLPH3 (Affinity Capture-MS), NDUFAB1 (Affinity Capture-MS), ECH1 (Affinity Capture-MS), ACP6 (Affinity Capture-MS), GLRX5 (Affinity Capture-MS), SDHB (Affinity Capture-MS), C1QBP (Affinity Capture-MS), ATP5J (Affinity Capture-MS), SDHB (Affinity Capture-MS), ACN9 (Affinity Capture-MS), C6orf57 (Affinity Capture-MS)

ESM2 similar proteins: A0JPA6, A1C9A5, A1D9R4, A2R2Q4, A3LNG8, A4DA73, A5DH70, A5PLG0, A9UL63, B0YEJ3, B4F7A1, B5FZA8, B5X5U9, B5XD90, B6GWX1, B8JLQ0, B8MP27, C4Y4R9, C5DEI4, C9SBR9, O46098, P56556, P82116, Q02366, Q0CVW0, Q0MQA3, Q0MQA4, Q0MQA5, Q0P574, Q0UIG9, Q0VCG0, Q2M2S9, Q4QQY2, Q4SQJ2, Q4WHK3, Q5AX36, Q5BBH7, Q5REC3, Q5U5X0, Q5XIY4

Diamond homologs: A7S1H9, P0C146, P0CM00, P0CM01, Q04401, Q0P574, Q4IN52, Q4PCI7, Q59L89, Q5BBH7, Q5XIY4, Q6BIY6, Q6CUY0, Q6FMR7, Q6TUF2, Q751X1, Q7SF55, Q86H49, Q8BQU3, Q8SZ16, Q9NRP4, Q9P7Y2, Q4WHK3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

21 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1076 predictions. Top by Δscore:

Variant	Effect	Δscore
7:97145935:GTTTT:G	donor_gain	1.0000
7:97145936:TTTTT:T	donor_gain	1.0000
7:97181008:TTA:T	acceptor_loss	1.0000
7:97181010:A:AG	acceptor_gain	1.0000
7:97181011:G:GG	acceptor_gain	1.0000
7:97181011:GGT:G	acceptor_gain	1.0000
7:97181011:GGTGT:G	acceptor_gain	1.0000
7:97136468:GTAA:G	donor_gain	0.9900
7:97145939:T:G	donor_gain	0.9900
7:97145939:T:TG	donor_gain	0.9900
7:97181010:AGGT:A	acceptor_gain	0.9900
7:97181011:GGTG:G	acceptor_gain	0.9900
7:97117852:GACC:G	donor_gain	0.9800
7:97136472:G:GG	donor_gain	0.9800
7:97145314:T:TA	donor_gain	0.9800
7:97145315:A:AA	donor_gain	0.9800
7:97181010:AG:A	acceptor_gain	0.9800
7:97181011:GG:G	acceptor_gain	0.9800
7:97117822:G:GG	donor_gain	0.9700
7:97117894:G:GT	donor_gain	0.9700
7:97117895:G:T	donor_gain	0.9600
7:97126169:G:GT	donor_gain	0.9600
7:97145310:G:GT	donor_gain	0.9600
7:97150123:G:GT	donor_gain	0.9600
7:97150128:AG:A	donor_gain	0.9600
7:97181002:A:AG	acceptor_gain	0.9600
7:97181008:TTAGG:T	acceptor_gain	0.9600
7:97181009:TAGGT:T	acceptor_gain	0.9600
7:97117895:G:GT	donor_gain	0.9500
7:97127420:T:G	acceptor_gain	0.9500

AlphaMissense

819 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:97117838:T:C	F39L	0.987
7:97117840:T:A	F39L	0.987
7:97117840:T:G	F39L	0.987
7:97117880:T:C	F53L	0.986
7:97117882:C:A	F53L	0.986
7:97117882:C:G	F53L	0.986
7:97117892:T:A	W57R	0.976
7:97117892:T:C	W57R	0.976
7:97181139:T:C	L101S	0.976
7:97117881:T:C	F53S	0.970
7:97117894:G:C	W57C	0.970
7:97117894:G:T	W57C	0.970
7:97117839:T:C	F39S	0.960
7:97181148:T:C	L104P	0.954
7:97181159:G:C	A108P	0.951
7:97117781:C:G	H20D	0.945
7:97117815:G:A	G31D	0.940
7:97117760:T:G	Y13D	0.935
7:97117881:T:G	F53C	0.930
7:97117893:G:C	W57S	0.929
7:97117823:T:C	Y34H	0.928
7:97117831:A:C	K36N	0.917
7:97117831:A:T	K36N	0.917
7:97117839:T:G	F39C	0.916
7:97117814:G:C	G31R	0.913
7:97117815:G:T	G31V	0.911
7:97117837:A:C	E38D	0.908
7:97117837:A:T	E38D	0.908
7:97117770:T:A	V16D	0.903
7:97117783:C:A	H20Q	0.901

dbSNP variants (sampled 300 via entrez): RS1000023314 (7:97128052 C>G,T), RS1000029169 (7:97149604 G>A), RS1000075833 (7:97128277 A>G), RS1000252917 (7:97160105 C>T), RS1000271163 (7:97173355 A>C), RS1000288685 (7:97175024 T>C), RS1000346474 (7:97146116 C>G,T), RS1000347258 (7:97166551 G>A,T), RS1000376820 (7:97166800 A>G,T), RS1000438328 (7:97138392 A>C), RS1000493549 (7:97126184 A>C), RS1000496170 (7:97141991 A>G), RS1000571259 (7:97123718 G>C,T), RS1000586853 (7:97168853 A>G), RS1000625848 (7:97176467 C>T)

Disease associations

OMIM: gene MIM:615773 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002034_1	Adverse response to radiation therapy	4.000000e-06
GCST004750_19	Squamous cell lung carcinoma	4.000000e-06
GCST006979_140	Heel bone mineral density	8.000000e-20

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	6
bisphenol A	decreases expression, affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
arsenite	increases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
beta-methylcholine	affects expression	1
corosolic acid	decreases expression	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
abrine	decreases expression	1
jinfukang	increases expression, affects cotreatment	1
Temozolomide	increases expression	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Hydralazine	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Phenobarbital	affects expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Thiram	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.