DECR2

Summary

DECR2 (2,4-dienoyl-CoA reductase 2, HGNC:2754) is a protein-coding gene on chromosome 16p13.3, encoding Peroxisomal 2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing] (Q9NUI1). Auxiliary enzyme of beta-oxidation.

Enables 2,4-dienoyl-CoA reductase (NADPH) activity and trans-2-enoyl-CoA reductase (NADPH) activity. Involved in unsaturated fatty acid biosynthetic process. Predicted to be located in cytosol and peroxisomal membrane. Predicted to be active in peroxisome.

Source: NCBI Gene 26063 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 100 total
• GTEx eGene: eQTL in 50 tissues, sQTL in 37 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.73 (unconstrained)
• MANE Select transcript: NM_020664
• Interaction hub: 1,809 STRING partners (top 9% of genes corpus-wide)
• Notable: 100 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2754
Approved symbol	DECR2
Name	2,4-dienoyl-CoA reductase 2
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	PDCR, SDR17C1
Ensembl gene	ENSG00000242612
Ensembl biotype	protein_coding
OMIM	615839
Entrez	26063

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 21 nonsense_mediated_decay, 20 protein_coding, 3 retained_intron, 3 protein_coding_CDS_not_defined

MANE Select: ENST00000219481

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 6, TSL 3: 3, TSL 5: 7

ENST00000219481, ENST00000424398, ENST00000429116, ENST00000437024, ENST00000439661, ENST00000445291, ENST00000461749, ENST00000461802, ENST00000461947, ENST00000465166, ENST00000469922, ENST00000627716, ENST00000631605, ENST00000632744, ENST00000633025, ENST00000633348, ENST00000633923, ENST00000876953, ENST00000876954, ENST00000876955, ENST00000876956, ENST00000876957, ENST00000876958, ENST00000876959, ENST00000876960, ENST00000876961, ENST00000876962, ENST00000931574, ENST00000949770, ENST00000949771, ENST00000993375, ENST00000993376, ENST00000993377, ENST00000993378, ENST00000993379, ENST00000993380, ENST00000993381, ENST00000993382, ENST00000993383, ENST00000993384, ENST00000993385, ENST00001049453, ENST00001049454, ENST00001049455, ENST00001049456, ENST00001062745, ENST00001137652

RefSeq mRNA: 1 — MANE Select: NM_020664 NM_020664

CCDS: CCDS10409

Canonical transcript exons

ENST00000219481 — 9 exons

Exon	Start	End
ENSE00003496745	410691	410784
ENSE00003554540	406346	406397
ENSE00003558181	410243	410367
ENSE00003633106	404956	405024
ENSE00003640577	407425	407560
ENSE00003643647	411361	411578
ENSE00003780221	401885	402043
ENSE00003790014	410972	411076
ENSE00003846318	411890	412482

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 98.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.4641 / max 177.9587, expressed in 1754 samples.

Highest expression (Bgee): lobe of liver, liver, adrenal gland cortex, mucosa of transverse colon, adrenal gland.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DECR2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 50 tissues and its splicing (sQTL) in 37 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 87 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	1.0e-95	-1.26	16:406416:T:G
Cells Cultured fibroblasts	eqtl	4.2e-91	-0.58	16:406416:T:G
Thyroid	eqtl	4.4e-69	-0.66	16:406416:T:G
Nerve Tibial	eqtl	8.4e-67	-0.63	16:406416:T:G
Colon Transverse	sqtl	4.5e-62	-1.09	16:406416:T:G
Skin Sun Exposed Lower leg	sqtl	1.6e-59	-0.87	16:407226:G:A
Adipose Subcutaneous	eqtl	2.0e-58	-0.44	16:406416:T:G
Skin Sun Exposed Lower leg	eqtl	6.9e-58	-0.50	16:406416:T:G
Thyroid	sqtl	4.3e-57	+0.85	16:409422:A:G
Lung	eqtl	3.7e-56	-0.56	16:406416:T:G
Esophagus Mucosa	eqtl	2.1e-53	+0.52	16:409422:A:G
Skin Not Sun Exposed Suprapubic	sqtl	4.5e-52	-0.86	16:407226:G:A
Esophagus Muscularis	eqtl	2.7e-51	-0.56	16:406416:T:G
Adipose Subcutaneous	sqtl	8.4e-49	-0.83	16:406416:T:G
Skin Not Sun Exposed Suprapubic	eqtl	1.7e-46	-0.50	16:406416:T:G
Esophagus Mucosa	sqtl	2.7e-46	+0.87	16:418055:G:A
Breast Mammary Tissue	sqtl	1.7e-44	+0.90	16:418184:T:C
Nerve Tibial	sqtl	4.6e-42	-0.85	16:406416:T:G
Artery Tibial	eqtl	1.7e-41	-0.48	16:406416:T:G
Stomach	eqtl	9.8e-41	-0.56	16:406416:T:G

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
151913	5.7786	1722
151914	2.6396	1405
151916	0.0158	5
151915	0.0157	7
151917	0.0144	5

Top tissues by expression

showing 100 of 137 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.32	gold quality
liver	UBERON:0002107	96.67	gold quality
right adrenal gland cortex	UBERON:0035827	94.34	gold quality
mucosa of transverse colon	UBERON:0004991	94.31	gold quality
left adrenal gland cortex	UBERON:0035825	94.17	gold quality
right adrenal gland	UBERON:0001233	93.96	gold quality
duodenum	UBERON:0002114	93.77	gold quality
left adrenal gland	UBERON:0001234	93.60	gold quality
transverse colon	UBERON:0001157	92.17	gold quality
cortex of kidney	UBERON:0001225	92.14	gold quality
adult mammalian kidney	UBERON:0000082	92.05	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.02	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.42	gold quality
apex of heart	UBERON:0002098	91.19	gold quality
body of pancreas	UBERON:0001150	91.17	gold quality
adrenal gland	UBERON:0002369	90.90	gold quality
metanephros cortex	UBERON:0010533	90.89	gold quality
gastrocnemius	UBERON:0001388	90.83	gold quality
small intestine	UBERON:0002108	90.76	gold quality
muscle of leg	UBERON:0001383	90.33	gold quality
colon	UBERON:0001155	89.46	gold quality
kidney	UBERON:0002113	89.36	gold quality
body of stomach	UBERON:0001161	89.35	gold quality
intestine	UBERON:0000160	89.28	gold quality
fundus of stomach	UBERON:0001160	89.09	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.05	gold quality
left uterine tube	UBERON:0001303	87.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.67	gold quality
cerebellar hemisphere	UBERON:0002245	87.61	gold quality
prostate gland	UBERON:0002367	87.60	gold quality
cerebellum	UBERON:0002037	87.55	gold quality
cerebellar cortex	UBERON:0002129	87.54	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.46	gold quality
lower esophagus	UBERON:0013473	87.45	gold quality
right testis	UBERON:0004534	87.38	gold quality
skeletal muscle tissue	UBERON:0001134	87.25	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.20	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.06	gold quality
omental fat pad	UBERON:0010414	86.91	gold quality
left testis	UBERON:0004533	86.85	gold quality
stomach	UBERON:0000945	86.68	gold quality
adipose tissue	UBERON:0001013	86.67	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.61	gold quality
esophagus	UBERON:0001043	86.59	gold quality
esophagus mucosa	UBERON:0002469	86.47	gold quality
mucosa of stomach	UBERON:0001199	86.40	gold quality
minor salivary gland	UBERON:0001830	86.37	gold quality
lower esophagus mucosa	UBERON:0035834	86.37	gold quality
saliva-secreting gland	UBERON:0001044	86.28	gold quality
endocervix	UBERON:0000458	86.26	gold quality
testis	UBERON:0000473	86.05	gold quality
ectocervix	UBERON:0012249	85.95	gold quality
thoracic mammary gland	UBERON:0005200	85.94	gold quality
right ovary	UBERON:0002118	85.65	gold quality
right atrium auricular region	UBERON:0006631	85.48	gold quality
pituitary gland	UBERON:0000007	85.47	gold quality
heart left ventricle	UBERON:0002084	85.44	gold quality
cortical plate	UBERON:0005343	85.36	gold quality
skin of leg	UBERON:0001511	85.25	gold quality
putamen	UBERON:0001874	85.02	gold quality
zone of skin	UBERON:0000014	84.94	gold quality
adenohypophysis	UBERON:0002196	84.90	gold quality
skin of abdomen	UBERON:0001416	84.89	gold quality
anatomical system	UBERON:0000467	84.78	gold quality
material anatomical entity	UBERON:0000465	84.76	gold quality
multicellular organism	UBERON:0000468	84.76	gold quality
pancreas	UBERON:0001264	84.75	gold quality
muscle tissue	UBERON:0002385	84.70	gold quality
nucleus accumbens	UBERON:0001882	84.67	gold quality
left ovary	UBERON:0002119	84.63	gold quality
ascending aorta	UBERON:0001496	84.51	gold quality
body of uterus	UBERON:0009853	84.49	gold quality
stromal cell of endometrium	CL:0002255	84.48	gold quality
heart	UBERON:0000948	84.45	gold quality
thoracic aorta	UBERON:0001515	84.37	gold quality
temporal lobe	UBERON:0001871	84.21	gold quality
left coronary artery	UBERON:0001626	84.14	gold quality
myometrium	UBERON:0001296	84.12	gold quality
amygdala	UBERON:0001876	84.12	gold quality
caudate nucleus	UBERON:0001873	84.02	gold quality
right frontal lobe	UBERON:0002810	83.95	gold quality
uterine cervix	UBERON:0000002	83.80	gold quality
vagina	UBERON:0000996	83.76	gold quality
popliteal artery	UBERON:0002250	83.73	gold quality
tibial artery	UBERON:0007610	83.73	gold quality
right coronary artery	UBERON:0001625	83.69	gold quality
brain	UBERON:0000955	83.66	gold quality
ovary	UBERON:0000992	83.62	gold quality
Ammon’s horn	UBERON:0001954	83.32	gold quality
upper lobe of left lung	UBERON:0008952	83.28	gold quality
sural nerve	UBERON:0015488	83.14	gold quality
anterior cingulate cortex	UBERON:0009835	83.04	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.98	gold quality
tibial nerve	UBERON:0001323	82.95	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.87	gold quality
right lung	UBERON:0002167	82.81	gold quality
cerebral cortex	UBERON:0000956	82.54	gold quality
granulocyte	CL:0000094	82.44	gold quality
spleen	UBERON:0002106	82.36	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Corpus callosum	tissue	30.3
Liver	tissue	30.2
Frontal cortex	tissue	29.0
Spinal cord	tissue	24.6
Olfactory bulb	tissue	24.6
Ventral forebrain	tissue	24.1
Cerebral cortex	tissue	23.9
Insular cortex	tissue	23.9
Amygdala	tissue	22.8
Medulla oblongata	tissue	22.8
Basal ganglia	tissue	22.5
Midbrain	tissue	22.1
Temporal cortex	tissue	21.8
Putamen	tissue	21.1
Superior colliculi	tissue	20.9
Somatosensory cortex	tissue	20.7
Hippocampal formation	tissue	20.6
Septum	tissue	20.3
Substantia nigra	tissue	20.2
Occipital cortex	tissue	19.6
Duodenum	tissue	19.5
Retrosplenial cortex	tissue	19.5
Pons	tissue	19.2
Entorhinal cortex	tissue	19.2
Prefrontal cortex	tissue	19.1
Periaqueductal gray	tissue	18.9
Retrosplenial and cingulate cortex	tissue	18.7
Motor cortex	tissue	18.1
Thalamus	tissue	18.0
Cerebellum	tissue	18.0
Hypothalamus	tissue	17.5
Caudate putamen	tissue	15.8
Kidney	tissue	13.8
Pancreas	tissue	13.6
Small intestine	tissue	11.3
Colon	tissue	10.1
Pituitary gland	tissue	9.7
Skeletal muscle	tissue	9.6
Vagina	tissue	9.2
Adrenal gland	tissue	9.0
Salivary gland	tissue	7.7
Stomach 1	tissue	6.9
Seminal vesicle	tissue	6.7
Tongue	tissue	6.7
Adipose tissue	tissue	6.3
Heart muscle	tissue	5.7
Bone marrow	tissue	5.4
Prostate	tissue	4.3
Breast	tissue	3.6
Cervix	tissue	3.3
Skin 1	tissue	3.3
Testis	tissue	3.3
Ovary	tissue	2.9
Endometrium 1	tissue	2.8
Fallopian tube	tissue	2.8
Rectum	tissue	2.7
Hippocampus	tissue	2.4
Esophagus	tissue	2.2
Choroid plexus	tissue	2.2
Placenta	tissue	2.2

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — White matter (30.3), Dorsal spinal cord (24.6), Ventral spinal cord (23.9), Ventral hippocampus (20.6), Subiculum (19.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting DECR2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

23 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-491-3P	98.88	68.86	1224
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-6765-3P	97.83	64.59	1165
HSA-MIR-1226-3P	97.51	66.32	1063
HSA-MIR-3157-5P	97.41	67.61	998

Functional genomics

gnomAD constraint: pLI 8.6e-15, LOEUF 1.73, missense Z -1.63 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000219481 — one region, missense o/e 1.14.

Literature-anchored findings (GeneRIF, showing 1)

• Peroxisomal beta-oxidation enzyme, DECR2, regulates lipid metabolism and promotes treatment resistance in advanced prostate cancer. (PMID:38216720)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	decr2	ENSDARG00000045257
mus_musculus	Decr2	ENSMUSG00000036775
rattus_norvegicus	Decr2	ENSRNOG00000088984

Paralogs (1): DECR1 (ENSG00000104325)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1347059) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 6 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal brain morphology	1
increased heart rate variability	1
abnormal sinus arrhythmia	1
cardiovascular system phenotype	1
increased circulating creatinine level	1
increased grip strength	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Mycobacterium tuberculosis CDC1551	P9WGQ4	100.0%	Diamond
Mycobacterium tuberculosis H37Rv	P9WGQ5	100.0%	Diamond
Pongo abelii	Q5RBV3	98.6%	Diamond
Papaver bracteatum	A4UHT7	95.8%	Diamond
Papaver somniferum	Q071N0	95.8%	Diamond
[Clostridium] scindens	P19337	90.4%	Diamond
Arabidopsis thaliana	Q9SLA8	89.9%	Diamond
Caenorhabditis elegans	Q22230	86.4%	Diamond
Cavia porcellus	Q9JIF5	76.2%	Diamond
Haemophilus influenzae Rd KW20	P44432	75.3%	Diamond
Bacillus subtilis subsp. subtilis str. 168	P54616	73.7%	Diamond
Synechocystis sp. PCC 6803 substr. Kazusa	P73016	72.1%	Diamond
Nostoc sp. PCC 7120 = FACHB-418	Q05069	72.1%	Diamond
Pseudomonas aeruginosa PAO1	Q9ZFE4	69.2%	Diamond
Sinorhizobium meliloti 1021	P58380	66.2%	Diamond
Ambrosiozyma monospora	Q70FD1	55.7%	Diamond
Aspergillus niger ATCC 1015	G3YG17	53.9%	Diamond
Saccharomyces cerevisiae S288C	P32573	45.1%	Diamond
Comamonas testosteroni	P80702	43.0%	Diamond
Streptomyces sp. C5	Q53882	37.6%	Diamond
Clostridium sp. ATCC 29733	P21215	36.6%	Diamond
Aspergillus versicolor	L7WRR9	35.6%	Diamond
Klebsiella pneumoniae	P37079	35.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MRPL28	protein-coding	10573
NME4	protein-coding	4833
PGAP6	protein-coding	58986
AXIN1	protein-coding	8312
MIR5587	ncRNA	100847028
LINC00235	ncRNA	64493
CAPN15	protein-coding	6650
RAB11FIP3	protein-coding	9727
MIR3176	ncRNA	100423037

Protein

Protein identifiers

Peroxisomal 2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing] — Q9NUI1 (reviewed: Q9NUI1)

Alternative names: 2,4-dienoyl-CoA reductase 2, Short chain dehydrogenase/reductase family 17C member 1

All UniProt accessions (7): A0A0J9YWI0, A0A0J9YXZ6, A0A0J9YY83, Q9NUI1, G3V0I9, H7C078, Q4VXZ8

UniProt curated annotations — full annotation on UniProt →

Function. Auxiliary enzyme of beta-oxidation. Participates in the degradation of unsaturated fatty enoyl-CoA esters having double bonds in both even- and odd-numbered positions in peroxisome. Catalyzes the NADP-dependent reduction of 2,4-dienoyl-CoA to yield trans-3-enoyl-CoA. Has activity towards short and medium chain 2,4-dienoyl-CoAs, but also towards 2,4,7,10,13,16,19-docosaheptaenoyl-CoA, suggesting that it does not constitute a rate limiting step in the peroxisomal degradation of docosahexaenoic acid.

Subunit / interactions. Monomer, dimer and oligomer.

Subcellular location. Peroxisome.

Similarity. Belongs to the short-chain dehydrogenases/reductases (SDR) family. 2,4-dienoyl-CoA reductase subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NUI1-1	1	yes
Q9NUI1-2	2
Q9NUI1-3	3

RefSeq proteins (1): NP_065715* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002347	SDR_fam	Family
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR045017	DECR2-like	Family
IPR057326	KR_dom	Domain

Pfam: PF13561

Enzyme classification (BRENDA)

• EC 1.3.1.124 — 2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing] (BRENDA: 7 organisms, 32 substrates, 3 inhibitors, 26 Km, 1 kcat entries)
• EC 1.3.1.34 — 2,4-dienoyl-CoA reductase [(2E)-enoyl-CoA-producing] (BRENDA: 7 organisms, 19 substrates, 4 inhibitors, 17 Km, 7 kcat entries)

Substrate kinetics (BRENDA)

19 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NADPH	0.0025–0.215	8
NADPH	0.0004–0.0605	8
TRANS-TRANS-2,4-HEXADIENOYL-COA	0.0045–0.154	5
(2E,4E)-2,4-DECADIENOYL-COA	0.006–0.0154	3
(2E,4E)-2,4-HEXADIENOYL-COA	0.0265–0.059	2
2,4,7,10,13,16,19-DOCOSAHEPTAENOYL-COA	0.102–0.155	2
2-TRANS,4-TRANS-HEXADIENOYL-COA	0.0005–0.108	2
(2E,4E)-2,4-OCTADIENOYL-COA	0.0158	1
2,4-DECADIENOYL-COA	0.006	1
2-FLUORO-TRANS-TRANS-2,4-OCTADIENOYL-COA	0.0065	1
5-METHYL-TRANS-TRANS-2,4-HEXADIENOYL-COA	0.016	1
(2E,4E)-2,4-DECADIENOYL-COA	0.0127	1
(2E,4E)-2,4-HEXADIENOYL-COA	0.0716	1
2,4,7,10,13,16,19-DOCOSAHEPTAENOYL-COA	0.102	1

Catalyzed reactions (Rhea)

• (2E,4Z,7Z,10Z,13Z,16Z,19Z)-docosaheptaenoyl-CoA + NADPH + H(+) = (3E,7Z,10Z,13Z,16Z,19Z)-docosahexaenoyl-CoA + NADP(+) (RHEA:44920)
• a (2E,4E)-dienoyl-CoA + NADPH + H(+) = a 4,5-saturated-(3E)-enoyl-CoA + NADP(+) (RHEA:45912)
• a (2E,4Z)-dienoyl-CoA + NADPH + H(+) = a 4,5-saturated-(3E)-enoyl-CoA + NADP(+) (RHEA:61892)

UniProt features (53 total): helix 16, binding site 10, strand 9, modified residue 4, splice variant 4, mutagenesis site 4, turn 3, initiator methionine 1, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
4FC7	Studies on DCR shed new light on peroxisomal beta-oxidation: Crystal structure of the …	X-RAY DIFFRACTION	1.84
4FC6	Studies on DCR shed new light on peroxisomal beta-oxidation: Crystal structure of the …	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NUI1-F1	95.77	0.92

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): peroxisomes; microtubules

Antibody reliability (HPA): IF approved

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 (10)

Position	Role
182	NADP(+)
208–214	NADP(+)
219	substrate
35–40	NADP(+)
60–64	NADP(+)
60	substrate
86	NADP(+)
88	substrate
118	substrate
126–128	substrate

Post-translational modifications (4)

Type	Positions
N-acetylalanine	2
N6-acetyllysine	151, 291
Phosphoserine	287

Mutagenesis-validated functional residues (4)

Position	Phenotype
86	reduces enzyme activity by 98%.
137	reduces enzyme activity by 97%.
186	reduces enzyme activity by about 95%.
268	reduces enzyme activity by 97%.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-390247	Beta-oxidation of very long chain fatty acids	curated
R-HSA-8978868	Fatty acid metabolism	—
R-HSA-1430728	Metabolism	—
R-HSA-556833	Metabolism of lipids	—
R-HSA-390918	Peroxisomal lipid metabolism	—
R-HSA-9033241	Peroxisomal protein import	electronic
R-HSA-9609507	Protein localization	—

MSigDB gene sets: 111 (showing top): GOBP_LIPID_MODIFICATION, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOMF_GTPASE_BINDING, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_FATTY_ACID_BETA_OXIDATION_USING_ACYL_COA_OXIDASE, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, GOBP_FATTY_ACID_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS

GO Biological Process (5): fatty acid metabolic process (GO:0006631), unsaturated fatty acid biosynthetic process (GO:0006636), fatty acid beta-oxidation using acyl-CoA oxidase (GO:0033540), lipid metabolic process (GO:0006629), fatty acid catabolic process (GO:0009062)

GO Molecular Function (4): 2,4-dienoyl-CoA reductase (NADPH) activity (GO:0008670), trans-2-enoyl-CoA reductase (NADPH) activity (GO:0019166), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (3): peroxisome (GO:0005777), peroxisomal membrane (GO:0005778), cytosol (GO:0005829)

Reactome top-level categories

5 top-level categories:

Category	Pathways
Peroxisomal lipid metabolism	1
Protein localization	1
Fatty acid metabolism	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

17 GO namespaces:

Category	Terms
oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor	2
lipid metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid biosynthetic process	1
unsaturated fatty acid metabolic process	1
fatty acid beta-oxidation	1
primary metabolic process	1
fatty acid metabolic process	1
lipid catabolic process	1
monocarboxylic acid catabolic process	1
binding	1
catalytic activity	1
microbody	1
peroxisome	1
microbody membrane	1
cytoplasm	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 12 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
unsaturated fatty acid biosynthetic process	BP	direct assay
2,4-dienoyl-CoA reductase (NADPH) activity	MF	direct assay
trans-2-enoyl-CoA reductase (NADPH) activity	MF	direct assay

Protein interactions and networks

STRING

showing 16 of 1,809 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DECR2	EHHADH	Q08426	605
DECR2	ACAA1	P09110	554
DECR2	EVA1B	Q9NVM1	488
DECR2	ZNF563	Q8TA94	480
DECR2	KRTCAP3	Q53RY4	478
DECR2	ECI2	O75521	471
DECR2	PRR35	P0CG20	459
DECR2	ACOX1	Q15067	444
DECR2	RRP36	Q96EU6	424
DECR2	ECI1	P42126	419
DECR2	SPMIP7	A4D263	408
DECR2	ACOT8	O14734	405
DECR2	HSD17B4	P51659	402
DECR2	KBTBD12	Q3ZCT8	395
DECR2	KLHDC8B	Q8IXV7	394
DECR2	ACOT4	Q8N9L9	394

IntAct

Human interaction partners of DECR2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

9 partners by confidence:

Partner	Interaction type	MIscore	Records
C14orf119	physical association	0.560	3
OSGIN1	physical association	0.560	3
USP11	physical association	0.560	3
VPS26C	physical association	0.560	3
WDTC1	physical association	0.500	1
EP300	physical association	0.370	1
ATP1A3	association	0.350	1
TRIM55	physical association	0.000	1
TRIM63	physical association	0.000	1

BioGRID (76 interactions; top human partners by supporting records): PEX5 (Affinity Capture-MS; 4 records), PDZK1 (Affinity Capture-MS; 2 records), SESTD1 (Affinity Capture-MS; 2 records), ACAA1 (FRET), AGO2 (Affinity Capture-RNA), AGPS (Proximity Label-MS), APP (Reconstituted Complex), ATP1A3 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), BAG2 (Affinity Capture-MS), BSG (Affinity Capture-MS), C14orf119 (Two-hybrid), C1orf85 (Affinity Capture-MS), CAPZB (Affinity Capture-MS), CAT (Proximity Label-MS)

Disease & clinical

Genetic variants

Variant evidence for DECR2: 100 ClinVar records (0 pathogenic / likely pathogenic); 3 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	4
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 46 predictions of 1,243):

Position(s)	Effect	Δscore	Sites
16:410690	acceptor_loss	1.0000	2
16:411077–411078	donor_loss	1.0000	5
16:411359–411360	acceptor_loss	1.0000	5
16:402044–402045	donor_loss	0.9900	5
16:402059	donor_gain	0.9900
16:406344–406345	acceptor_loss	0.9900	6
16:406398–406399	donor_loss	0.9900	6
16:410241–410242	acceptor_loss	0.9900	6
16:410689–410690	acceptor_loss	0.9900	4
16:410970–410971	acceptor_loss	0.9900	6

AlphaMissense

697 missense substitutions predicted likely pathogenic (of 1,888 scored), across 194 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D86	8	0.954	0.985
D268	8	0.945	0.979
F118	8	0.943	0.996
N117	8	0.923	0.994
D137	8	0.845	0.956
R60	7	0.966	0.996
F142	7	0.934	0.986
W196	7	0.930	0.993
N112	7	0.927	0.995
F130	7	0.926	0.980
H177	7	0.908	0.974
K182	7	0.907	0.991
E195	7	0.907	0.967
N162	7	0.882	0.994
F32	7	0.824	0.985
C80	7	0.824	0.977
F104	7	0.802	0.934
H191	7	0.781	0.940
D108	7	0.748	0.924
G262	6	0.935	0.992

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:615839 | disease phenotypes:

GWAS associations

3 associations:

Study	Trait	p-value
GCST009733_194	Urinary metabolite levels in chronic kidney disease	2e-12
GCST012335_13	Hodgkin’s lymphoma	2e-12
GCST005951_22	Body mass index	5e-11

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0005116	urinary metabolite measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066268 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, decreases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Valproic Acid	decreases expression, decreases methylation	2
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
tetrahydropalmatine	increases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
aflatoxin B2	increases methylation	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
avobenzone	decreases expression	1
K 7174	decreases expression	1
nutlin 3	affects cotreatment, increases expression, increases secretion	1
bisphenol B	increases expression	1
jinfukang	affects cotreatment, increases expression	1
MT19c compound	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	increases secretion, affects cotreatment, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Ivermectin	decreases expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Methyl Methanesulfonate	increases expression	1
NADP	affects binding, increases activity	1
Phthalic Acids	increases methylation	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Smoke	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651270	Binding	Binding affinity to human DECR2 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for DECR2 across ~30M SureChEMBL compounds — explore on Sugi Predict.