RFESD

Summary

RFESD (Rieske Fe-S domain containing, HGNC:29587) is a protein-coding gene on chromosome 5q15, encoding Rieske domain-containing protein (Q8TAC1).

Predicted to enable 2 iron, 2 sulfur cluster binding activity.

Source: NCBI Gene 317671 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_001131066

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29587
Approved symbol	RFESD
Name	Rieske Fe-S domain containing
Location	5q15
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000175449
Ensembl biotype	protein_coding
Entrez	317671

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000311364, ENST00000380005, ENST00000458310, ENST00000504893, ENST00000506212, ENST00000508206, ENST00000511684, ENST00000513950, ENST00000912998, ENST00000912999

RefSeq mRNA: 4 — MANE Select: NM_001131066 NM_001131065, NM_001131066, NM_001375394, NM_173362

CCDS: CCDS4075, CCDS47248

Canonical transcript exons

ENST00000380005 — 6 exons

Exon	Start	End
ENSE00001206598	95654333	95654367
ENSE00001483334	95646777	95646817
ENSE00001951500	95656046	95658082
ENSE00002316554	95653117	95653214
ENSE00003486229	95652137	95652331
ENSE00003655981	95654061	95654236

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 93.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.1498 / max 528.9109, expressed in 1315 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57626	2.5076	1157
57627	0.8331	228
57628	0.8091	86

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	93.86	gold quality
oocyte	CL:0000023	93.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.37	gold quality
trabecular bone tissue	UBERON:0002483	87.60	gold quality
bone marrow	UBERON:0002371	85.81	gold quality
right testis	UBERON:0004534	82.56	gold quality
left testis	UBERON:0004533	82.48	gold quality
testis	UBERON:0000473	81.78	gold quality
bone marrow cell	CL:0002092	81.45	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.38	gold quality
tibialis anterior	UBERON:0001385	78.02	silver quality
islet of Langerhans	UBERON:0000006	77.87	gold quality
adrenal tissue	UBERON:0018303	76.23	gold quality
muscle of leg	UBERON:0001383	75.88	gold quality
gastrocnemius	UBERON:0001388	75.84	gold quality
deltoid	UBERON:0001476	75.31	silver quality
body of pancreas	UBERON:0001150	74.30	gold quality
skin of abdomen	UBERON:0001416	74.23	gold quality
apex of heart	UBERON:0002098	74.18	gold quality
pancreas	UBERON:0001264	73.82	gold quality
stromal cell of endometrium	CL:0002255	73.66	gold quality
skin of leg	UBERON:0001511	72.82	gold quality
leukocyte	CL:0000738	72.61	gold quality
right atrium auricular region	UBERON:0006631	72.49	gold quality
monocyte	CL:0000576	72.42	gold quality
cardiac atrium	UBERON:0002081	71.90	gold quality
zone of skin	UBERON:0000014	71.48	gold quality
skin of hip	UBERON:0001554	71.47	gold quality
right adrenal gland	UBERON:0001233	71.03	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-7407	yes	324.90
E-CURD-112	yes	54.51
E-MTAB-10042	yes	48.13
E-ANND-3	yes	8.31
E-HCAD-9	yes	7.32
E-MTAB-9067	yes	4.88
E-HCAD-10	yes	3.75
E-MTAB-9467	no	0.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

52 targeting RFESD, 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-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	RFESD	ENSDARG00000042159
danio_rerio	rfesd	ENSDARG00000058725
mus_musculus	Rfesd	ENSMUSG00000043190
rattus_norvegicus	Rfesd	ENSRNOG00000012810

Protein

Protein identifiers

Rieske domain-containing protein — Q8TAC1 (reviewed: Q8TAC1)

All UniProt accessions (3): D6RBY0, D6RJG8, Q8TAC1

UniProt curated annotations — full annotation on UniProt →

Cofactor. Binds 1 [2Fe-2S] cluster per subunit.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TAC1-1	1	yes
Q8TAC1-2	2

RefSeq proteins (4): NP_001124537, NP_001124538, NP_001362323, NP_775498 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017941	Rieske_2Fe-2S	Domain
IPR036922	Rieske_2Fe-2S_sf	Homologous_superfamily
IPR054716	Sol_Rieske_ferrdox_dom	Domain

Pfam: PF22543

UniProt features (10 total): binding site 4, domain 2, modified residue 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TAC1-F1	91.09	0.82

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 57; 59; 80; 83

Post-translational modifications (2): 1, 6

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 73 (showing top): IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GATA6_01, chr5q15, SCGGAAGY_ELK1_02, GOMF_METAL_CLUSTER_BINDING, GOMF_2_IRON_2_SULFUR_CLUSTER_BINDING, PASTURAL_RIZ1_TARGETS_UP, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, MARTENS_TRETINOIN_RESPONSE_DN, CHYLA_CBFA2T3_TARGETS_DN, RATTENBACHER_BOUND_BY_CELF1, GATA1_05, DACH1_TARGET_GENES, E2F2_TARGET_GENES, EMX1_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (4): metal ion binding (GO:0046872), 2 iron, 2 sulfur cluster binding (GO:0051537), protein binding (GO:0005515), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cation binding	1
iron-sulfur cluster binding	1
binding	1
metal cluster binding	1

Protein interactions and networks

STRING

194 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RFESD	SPATA9	Q9BWV2	417
RFESD	REP15	Q6BDI9	417
RFESD	GFOD1	Q9NXC2	358
RFESD	MBD3L4	A6NDZ8	351
RFESD	SFTA2	Q6UW10	349
RFESD	EXO5	Q9H790	348
RFESD	ELAC1	Q9H777	327
RFESD	ZBTB40	Q9NUA8	325
RFESD	ASB6	Q9NWX5	322
RFESD	ELP5	Q8TE02	315
RFESD	KLHL22	Q53GT1	305
RFESD	CHRNE	Q04844	301
RFESD	MIOX	Q9UGB7	290
RFESD	CDIP1	Q9H305	286
RFESD	HELQ	Q8TDG4	275

IntAct

12 interactions, top by confidence:

A	B	Type	Score
HBQ1	RFESD	psi-mi:“MI:0915”(physical association)	0.780
RFESD	CIAO1	psi-mi:“MI:0915”(physical association)	0.400
RFESD	PRKAG1	psi-mi:“MI:0914”(association)	0.350
RFESD	HBQ1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): RFESD (Two-hybrid), RFESD (Synthetic Lethality), RFESD (Two-hybrid), PRKAA1 (Affinity Capture-MS), PRKAB1 (Affinity Capture-MS), MAD2L1BP (Affinity Capture-MS), GPIHBP1 (Affinity Capture-MS), PRKAG1 (Affinity Capture-MS), CIAO1 (Affinity Capture-MS), RFESD (Co-fractionation), RFESD (Co-fractionation)

ESM2 similar proteins: A3KMX7, E9Q401, F1LNJ2, F1QR43, G4LTX4, O18756, O35099, O75643, O94923, P27612, P30957, P54319, Q0VEJ0, Q28C34, Q2TBU5, Q5BJI9, Q5HZ68, Q5I0G3, Q5IH13, Q5IH14, Q5RCP7, Q5TFE4, Q5VV42, Q6NRD0, Q6NS26, Q6YXW6, Q71N41, Q7ZYD9, Q8BFR6, Q8C5P5, Q8CCT7, Q8K2P6, Q8TAC1, Q8TAP6, Q8TCF1, Q8W3M6, Q91WE6, Q92736, Q94E75, Q95JP6

Diamond homologs: Q8K2P6, Q8TAC1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1414 predictions. Top by Δscore:

Variant	Effect	Δscore
5:95652289:G:GT	donor_gain	1.0000
5:95653399:A:G	donor_gain	1.0000
5:95654049:A:AG	acceptor_gain	1.0000
5:95654049:AT:A	acceptor_gain	1.0000
5:95654050:T:G	acceptor_gain	1.0000
5:95654050:T:TA	acceptor_gain	1.0000
5:95654055:A:AG	acceptor_gain	1.0000
5:95654056:A:AG	acceptor_gain	1.0000
5:95654058:TAGCA:T	acceptor_loss	1.0000
5:95654059:A:AG	acceptor_gain	1.0000
5:95654059:A:T	acceptor_loss	1.0000
5:95654059:AGCAT:A	acceptor_gain	1.0000
5:95654060:G:GC	acceptor_gain	1.0000
5:95654060:GC:G	acceptor_gain	1.0000
5:95654060:GCA:G	acceptor_gain	1.0000
5:95654060:GCAT:G	acceptor_gain	1.0000
5:95654060:GCATG:G	acceptor_gain	1.0000
5:95654203:G:GT	donor_gain	1.0000
5:95654232:TTACC:T	donor_gain	1.0000
5:95654235:CC:C	donor_gain	1.0000
5:95654235:CCGT:C	donor_loss	1.0000
5:95654236:CGT:C	donor_loss	1.0000
5:95654237:G:GA	donor_loss	1.0000
5:95654237:G:GG	donor_gain	1.0000
5:95654238:T:A	donor_loss	1.0000
5:95663947:ACTT:A	donor_loss	1.0000
5:95663948:CTT:C	donor_loss	1.0000
5:95663949:TTA:T	donor_loss	1.0000
5:95663950:TACCA:T	donor_loss	1.0000
5:95663951:A:AC	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000009269 (5:95645378 C>T), RS1000510938 (5:95655104 C>G), RS1000616537 (5:95653531 T>C), RS1000920590 (5:95649376 C>G,T), RS1001157923 (5:95646668 T>C,G), RS1001434181 (5:95646077 C>G), RS1001677094 (5:95653856 C>T), RS1001803634 (5:95647975 A>T), RS1002027663 (5:95657845 A>G), RS1002191578 (5:95650216 A>G), RS1002420276 (5:95655655 G>C), RS1002614956 (5:95656729 C>A,G), RS1002635162 (5:95644834 A>C), RS1002831438 (5:95648932 C>A,G), RS1003097421 (5:95645209 G>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002887_4	Pharmacokinetics of antiepileptic drugs in severe mental disorder (concentration drug ratio)	2.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007635	concentration dose ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression	3
bisphenol F	increases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
clothianidin	decreases expression	1
(+)-JQ1 compound	increases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Vorinostat	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects expression	1
Dexamethasone	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Vanadates	increases expression	1
1-Methyl-3-isobutylxanthine	increases expression, affects cotreatment	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

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