FOXRED2

Summary

FOXRED2 (FAD dependent oxidoreductase domain containing 2, HGNC:26264) is a protein-coding gene on chromosome 22q12.3, encoding FAD-dependent oxidoreductase domain-containing protein 2 (Q8IWF2). Probable flavoprotein which may function in endoplasmic reticulum associated degradation (ERAD).

Enables flavin adenine dinucleotide binding activity. Involved in ERAD pathway. Located in endoplasmic reticulum lumen.

Source: NCBI Gene 80020 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 123 total
• MANE Select transcript: NM_001102371

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26264
Approved symbol	FOXRED2
Name	FAD dependent oxidoreductase domain containing 2
Location	22q12.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23322, ERFAD
Ensembl gene	ENSG00000100350
Ensembl biotype	protein_coding
OMIM	613777
Entrez	80020

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 17 protein_coding, 4 retained_intron

ENST00000216187, ENST00000366463, ENST00000397223, ENST00000397224, ENST00000423980, ENST00000684868, ENST00000685224, ENST00000685344, ENST00000685612, ENST00000686024, ENST00000686867, ENST00000687273, ENST00000688825, ENST00000688870, ENST00000689211, ENST00000689781, ENST00000691242, ENST00000692693, ENST00000862038, ENST00000920372, ENST00000946934

RefSeq mRNA: 4 — MANE Select: NM_001102371 NM_001102371, NM_001363041, NM_001363042, NM_024955

CCDS: CCDS13929, CCDS93159

Canonical transcript exons

ENST00000397224 — 9 exons

Exon	Start	End
ENSE00000880061	36495967	36496208
ENSE00000880062	36497991	36498156
ENSE00000880063	36501241	36501407
ENSE00000880064	36504098	36504367
ENSE00000880065	36504515	36504766
ENSE00000880066	36505896	36506423
ENSE00001386208	36487190	36490267
ENSE00001631635	36493633	36493803
ENSE00001744718	36507009	36507040

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 91.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.9279 / max 108.5483, expressed in 1656 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193954	6.5200	1607
193955	2.5169	1227
193952	0.4039	209
193953	0.4021	252
193950	0.0491	14
193951	0.0359	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	91.14	silver quality
tendon of biceps brachii	UBERON:0008188	89.83	silver quality
ventricular zone	UBERON:0003053	87.44	gold quality
prefrontal cortex	UBERON:0000451	86.60	gold quality
ganglionic eminence	UBERON:0004023	85.28	gold quality
cingulate cortex	UBERON:0003027	83.70	gold quality
anterior cingulate cortex	UBERON:0009835	83.70	gold quality
frontal cortex	UBERON:0001870	83.64	gold quality
frontal lobe	UBERON:0016525	83.64	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.33	gold quality
neocortex	UBERON:0001950	83.32	gold quality
right frontal lobe	UBERON:0002810	83.28	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.47	gold quality
stromal cell of endometrium	CL:0002255	82.27	gold quality
amygdala	UBERON:0001876	81.75	gold quality
cerebral cortex	UBERON:0000956	81.59	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.98	gold quality
superior frontal gyrus	UBERON:0002661	80.79	gold quality
cortical plate	UBERON:0005343	80.76	gold quality
temporal lobe	UBERON:0001871	80.57	gold quality
pigmented layer of retina	UBERON:0001782	80.56	gold quality
type B pancreatic cell	CL:0000169	80.52	gold quality
telencephalon	UBERON:0001893	80.48	gold quality
olfactory bulb	UBERON:0002264	80.21	gold quality
entorhinal cortex	UBERON:0002728	80.19	gold quality
medial globus pallidus	UBERON:0002477	80.18	gold quality
cerebellar cortex	UBERON:0002129	80.09	gold quality
cerebellar hemisphere	UBERON:0002245	80.04	gold quality
right hemisphere of cerebellum	UBERON:0014890	79.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

88 targeting FOXRED2, 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-4533	100.00	69.48	2758
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4708-3P	99.51	67.99	870

Literature-anchored findings (GeneRIF, showing 2)

• ERFAD facilitates the dislocation of certain endoplasmic reticulum-associated degradation substrates to the cytosol. (PMID:19706418)
• Expression of FOXRED2 increases activity of hypoxia-targeted prodrugs. (PMID:24632291)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	foxred2	ENSDARG00000061354
mus_musculus	Foxred2	ENSMUSG00000016552
rattus_norvegicus	Foxred2	ENSRNOG00000005749
caenorhabditis_elegans		WBGENE00001476
caenorhabditis_elegans		WBGENE00001478
caenorhabditis_elegans		WBGENE00001480
caenorhabditis_elegans	C01H6.4	WBGENE00007254
caenorhabditis_elegans	C46H11.2	WBGENE00016728

Paralogs (5): FMO3 (ENSG00000007933), FMO1 (ENSG00000010932), FMO4 (ENSG00000076258), FMO2 (ENSG00000094963), FMO5 (ENSG00000131781)

Protein

Protein identifiers

FAD-dependent oxidoreductase domain-containing protein 2 — Q8IWF2 (reviewed: Q8IWF2)

Alternative names: Endoplasmic reticulum flavoprotein associated with degradation

All UniProt accessions (6): Q8IWF2, A0A8I5KTD3, A0A8I5KV30, A0A8I5KVQ6, A0A8I5KZ46, B0QYA2

UniProt curated annotations — full annotation on UniProt →

Function. Probable flavoprotein which may function in endoplasmic reticulum associated degradation (ERAD). May bind non-native proteins in the endoplasmic reticulum and target them to the ubiquitination machinery for subsequent degradation.

Subunit / interactions. Interacts with SEL1L. May interact with OS9 and DNAJC10. Interacts with TXNDC16.

Subcellular location. Endoplasmic reticulum lumen.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the FOXRED2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IWF2-1	1	yes
Q8IWF2-2	2

RefSeq proteins (4): NP_001095841, NP_001349970, NP_001349971, NP_079231 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily
IPR050982	Auxin_biosynth/cation_transpt	Family

Pfam: PF13738

UniProt features (14 total): sequence variant 5, sequence conflict 2, signal peptide 1, chain 1, region of interest 1, short sequence motif 1, compositionally biased region 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWF2-F1	87.68	0.75

Functional residue map

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

Glycosylation sites (1): 143

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 133 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_ERAD_PATHWAY, GOBP_PROTEIN_CATABOLIC_PROCESS, TCCCRNNRTGC_UNKNOWN, GOCC_ENDOPLASMIC_RETICULUM_LUMEN, GOBP_PROTEOLYSIS, RAY_TUMORIGENESIS_BY_ERBB2_CDC25A_DN, GOMF_FLAVIN_ADENINE_DINUCLEOTIDE_BINDING, GOMF_MONOOXYGENASE_ACTIVITY, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN

GO Biological Process (1): ERAD pathway (GO:0036503)

GO Molecular Function (4): monooxygenase activity (GO:0004497), flavin adenine dinucleotide binding (GO:0050660), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (2): endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
oxidoreductase activity	1
nucleotide binding	1
anion binding	1
binding	1
catalytic activity	1
endoplasmic reticulum	1
intracellular organelle lumen	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1530 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOXRED2	SEL1L	Q9UBV2	829
FOXRED2	OS9	Q13438	821
FOXRED2	DNAJC10	Q8IXB1	760
FOXRED2	TXNDC16	Q9P2K2	748
FOXRED2	UGGT2	Q9NYU1	569
FOXRED2	DNAJB11	Q9UBS4	532
FOXRED2	HYOU1	Q9Y4L1	502
FOXRED2	HMGXB4	Q9UGU5	490
FOXRED2	NDOR1	Q9UHB4	481
FOXRED2	SUMF2	Q8NBJ7	452
FOXRED2	PCYOX1	Q9UHG3	450
FOXRED2	ERLEC1	Q96DZ1	447
FOXRED2	NENF	Q9UMX5	447
FOXRED2	PPIB	P23284	425
FOXRED2	EDEM3	Q9BZQ6	425

IntAct

62 interactions, top by confidence:

A	B	Type	Score
FOXRED2	SEL1L	psi-mi:“MI:0915”(physical association)	0.780
SEL1L	FOXRED2	psi-mi:“MI:0915”(physical association)	0.780
TXNDC16	FOXRED2	psi-mi:“MI:0914”(association)	0.730
FOXRED2	TOMM40	psi-mi:“MI:0914”(association)	0.530
	PLOD2	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
FOXRED2	CLGN	psi-mi:“MI:0914”(association)	0.530
GPIHBP1	ADAM10	psi-mi:“MI:0914”(association)	0.530
FOXRED2	DNAJC10	psi-mi:“MI:0915”(physical association)	0.400
FOXRED2	OS9	psi-mi:“MI:0915”(physical association)	0.400
NDUFAF3	NDUFS8	psi-mi:“MI:0914”(association)	0.350
Cep131	WBP2	psi-mi:“MI:0914”(association)	0.350
Nfyc	BDP1	psi-mi:“MI:0914”(association)	0.350
Samm50	ZC3H18	psi-mi:“MI:0914”(association)	0.350
Ufl1	PRSS1	psi-mi:“MI:0914”(association)	0.350
PB2	ESYT2	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
FOXRED2	CASK	psi-mi:“MI:0914”(association)	0.350
TXNDC16	FLNA	psi-mi:“MI:0914”(association)	0.350
TXNDC16	ENO1	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
MFAP4	CRLF1	psi-mi:“MI:0914”(association)	0.350
CDH23	GTPBP10	psi-mi:“MI:0914”(association)	0.350

BioGRID (142): TXNDC16 (Affinity Capture-MS), VDAC1 (Affinity Capture-MS), DPY30 (Affinity Capture-MS), EMD (Affinity Capture-MS), GALK1 (Affinity Capture-MS), NIPSNAP1 (Affinity Capture-MS), CASK (Affinity Capture-MS), RPL10 (Affinity Capture-MS), ACTG2 (Affinity Capture-MS), CANX (Affinity Capture-MS), LIN7C (Affinity Capture-MS), SEL1L (Affinity Capture-MS), GANAB (Affinity Capture-MS), USH2A (Affinity Capture-MS), FOXRED2 (Affinity Capture-MS)

ESM2 similar proteins: A2WYE9, A4HVU6, B0UXS1, B3H5R0, B7F7B9, B8NHD6, D3ZKV9, F4JLK2, O04932, O04933, O22060, P0A3V2, P0A3V3, P25017, P31927, P31928, P49031, P49897, P55073, Q02527, Q04564, Q09109, Q09288, Q0JGK4, Q10470, Q197C5, Q3ED68, Q3USW5, Q41607, Q42652, Q43845, Q43876, Q5I3B1, Q5XV99, Q67WN8, Q6DN07, Q6FLD4, Q6P6G2, Q6QN11, Q6ZHZ1

Diamond homologs: B0UXS1, Q3USW5, Q8IWF2, A4YXZ8, B3QJ15, Q6N2U4, Q89HV6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 79 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	7	18.9×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	106
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2231 predictions. Top by Δscore:

Variant	Effect	Δscore
22:36490266:CT:C	acceptor_gain	1.0000
22:36493628:GTTAC:G	donor_loss	1.0000
22:36493629:TTA:T	donor_loss	1.0000
22:36493630:TAC:T	donor_loss	1.0000
22:36493631:A:AT	donor_loss	1.0000
22:36493632:C:CA	donor_loss	1.0000
22:36493799:CTGTT:C	acceptor_gain	1.0000
22:36493801:GTT:G	acceptor_gain	1.0000
22:36493802:TT:T	acceptor_gain	1.0000
22:36493804:C:CC	acceptor_gain	1.0000
22:36493805:T:G	acceptor_loss	1.0000
22:36493806:G:C	acceptor_gain	1.0000
22:36496065:T:TA	donor_gain	1.0000
22:36497982:GCTAC:G	donor_loss	1.0000
22:36497983:CTACT:C	donor_loss	1.0000
22:36497984:TAC:T	donor_loss	1.0000
22:36497985:ACT:A	donor_loss	1.0000
22:36497987:T:TG	donor_loss	1.0000
22:36497988:CACTC:C	donor_loss	1.0000
22:36497989:A:AC	donor_gain	1.0000
22:36497989:AC:A	donor_loss	1.0000
22:36497989:ACT:A	donor_gain	1.0000
22:36497989:ACTC:A	donor_gain	1.0000
22:36497990:C:CA	donor_gain	1.0000
22:36497990:CT:C	donor_gain	1.0000
22:36497990:CTC:C	donor_gain	1.0000
22:36497990:CTCC:C	donor_gain	1.0000
22:36497990:CTCCT:C	donor_gain	1.0000
22:36498153:CGCA:C	acceptor_gain	1.0000
22:36498157:C:CC	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000195269 (22:36492744 C>G), RS1000311836 (22:36487225 G>A), RS1000427 (22:36494058 G>A,C), RS1000475542 (22:36487036 AC>A), RS1000765086 (22:36501666 A>G), RS1000831994 (22:36502218 C>T), RS1000884655 (22:36507228 G>C,T), RS1001102996 (22:36507570 T>C), RS1001233508 (22:36507393 A>G), RS1001259542 (22:36502834 C>A,G,T), RS1001272672 (22:36498163 C>T), RS1001313432 (22:36502594 C>T), RS1001457627 (22:36492543 C>T), RS1001515573 (22:36496740 T>TG), RS1001628321 (22:36503592 T>A,G)

Disease associations

OMIM: gene MIM:613777 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, increases expression	4
bisphenol A	increases expression, affects expression	2
entinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation	2
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Tretinoin	decreases expression	2
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
chromium hexavalent ion	increases abundance, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Copper	affects binding, decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Folic Acid	decreases expression	1
Lead	decreases expression	1
Methotrexate	decreases expression	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Dronabinol	increases expression	1
Thiram	decreases expression	1

Clinical trials (associated diseases)

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