DECR1

Summary

DECR1 (2,4-dienoyl-CoA reductase 1, HGNC:2753) is a protein-coding gene on chromosome 8q21.3, encoding 2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing], mitochondrial (Q16698). Auxiliary enzyme of beta-oxidation.

Enables 2,4-dienoyl-CoA reductase (NADPH) activity; NADPH binding activity; and identical protein binding activity. Involved in fatty acid beta-oxidation. Located in cytosol; mitochondrion; and nucleoplasm. Part of catalytic complex.

Source: NCBI Gene 1666 — RefSeq curated summary.

At a glance

• Gene–disease (curated): liver disorder (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 79 total
• Druggable target: yes
• MANE Select transcript: NM_001359

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2753
Approved symbol	DECR1
Name	2,4-dienoyl-CoA reductase 1
Location	8q21.3
Locus type	gene with protein product
Status	Approved
Aliases	SDR18C1
Ensembl gene	ENSG00000104325
Ensembl biotype	protein_coding
OMIM	222745
Entrez	1666

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 18 protein_coding, 6 protein_coding_CDS_not_defined, 6 nonsense_mediated_decay, 2 retained_intron

ENST00000220764, ENST00000517301, ENST00000517314, ENST00000517597, ENST00000517761, ENST00000518725, ENST00000519007, ENST00000519328, ENST00000519410, ENST00000520148, ENST00000520227, ENST00000520859, ENST00000521603, ENST00000521668, ENST00000522161, ENST00000522583, ENST00000523447, ENST00000524326, ENST00000524332, ENST00000886497, ENST00000886498, ENST00000886499, ENST00000886500, ENST00000886501, ENST00000886502, ENST00000886503, ENST00000886504, ENST00000934678, ENST00000934679, ENST00000934680, ENST00000965487, ENST00000965488

RefSeq mRNA: 2 — MANE Select: NM_001359 NM_001330575, NM_001359

CCDS: CCDS6250, CCDS87618

Canonical transcript exons

ENST00000220764 — 10 exons

Exon	Start	End
ENSE00002128622	90051838	90053633
ENSE00003514008	90019086	90019172
ENSE00003542519	90051677	90051739
ENSE00003581861	90018909	90018966
ENSE00003612288	90044849	90044995
ENSE00003628307	90042728	90042800
ENSE00003650000	90017124	90017326
ENSE00003660402	90036841	90036940
ENSE00003663078	90020909	90021056
ENSE00003845926	90001477	90001561

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 99.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 72.9229 / max 1299.6301, expressed in 1824 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89689	72.1491	1824
89688	0.7422	422
89690	0.0213	2
89691	0.0103	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	99.36	gold quality
heart right ventricle	UBERON:0002080	99.28	gold quality
right adrenal gland	UBERON:0001233	99.23	gold quality
heart left ventricle	UBERON:0002084	99.22	gold quality
cardiac ventricle	UBERON:0002082	99.21	gold quality
right adrenal gland cortex	UBERON:0035827	99.20	gold quality
right lobe of liver	UBERON:0001114	99.19	gold quality
adrenal tissue	UBERON:0018303	99.15	gold quality
apex of heart	UBERON:0002098	99.08	gold quality
left adrenal gland	UBERON:0001234	99.07	gold quality
right atrium auricular region	UBERON:0006631	98.96	gold quality
left adrenal gland cortex	UBERON:0035825	98.93	gold quality
cardiac atrium	UBERON:0002081	98.92	gold quality
adrenal cortex	UBERON:0001235	98.90	gold quality
adrenal gland	UBERON:0002369	98.89	gold quality
myocardium	UBERON:0002349	98.86	gold quality
mucosa of transverse colon	UBERON:0004991	98.83	gold quality
heart	UBERON:0000948	98.82	gold quality
rectum	UBERON:0001052	98.73	gold quality
liver	UBERON:0002107	98.66	gold quality
monocyte	CL:0000576	98.61	gold quality
adult mammalian kidney	UBERON:0000082	98.47	gold quality
mononuclear cell	CL:0000842	98.44	gold quality
leukocyte	CL:0000738	98.41	gold quality
duodenum	UBERON:0002114	98.38	gold quality
jejunal mucosa	UBERON:0000399	98.34	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.28	gold quality
right testis	UBERON:0004534	98.24	gold quality
metanephros cortex	UBERON:0010533	98.20	gold quality
transverse colon	UBERON:0001157	98.08	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	7.63
E-MTAB-9388	no	8.85
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 13)

• Structure and reactivity of human mitochondrial 2,4-dienoyl-CoA reductase (PMID:15531764)
• Sequence alignment indicates that there are five highly conserved acidic residues, one of which (E276) might act as a proton donor. (PMID:15629123)
• mutational defects cause chronic granulomatous disease in humans (PMID:18193341)
• The luminal NADPH pool is an important antiapoptotic factor in neutrophil granulocytes. (PMID:18472006)
• The TT genotype of C677T polymorphism in the MTHFR gene contributes to genetic susceptibility of acute ischemic stroke in a Singapore population. (PMID:19049547)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• Our study is the first to demonstrate the novel function of UA in NET formation and may provide insight into the management of patients with hyperuricemia. (PMID:24326071)
• 2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer. (PMID:32427840)
• Human DECR1 is an androgen-repressed survival factor that regulates PUFA oxidation to protect prostate tumor cells from ferroptosis. (PMID:32686647)
• Association of whole mtDNA, an NADPH G11914A variant, and haplogroups with high physical performance in an elite military troop. (PMID:33909855)
• NADPH Oxidases in the Central Nervous System: Regional and Cellular Localization and the Possible Link to Brain Diseases. (PMID:34293949)
• DECR1 directly activates HSL to promote lipolysis in cervical cancer cells. (PMID:34896618)
• Reduced 2,4-dienoyl-CoA reductase 1 is served as an unfavorable biomarker and is related to immune infiltration in cervical cancer. (PMID:37497824)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	decr1	ENSDARG00000003869
mus_musculus	Decr1	ENSMUSG00000028223
rattus_norvegicus	Decr1	ENSRNOG00000008236
caenorhabditis_elegans		WBGENE00009973
caenorhabditis_elegans		WBGENE00011467
caenorhabditis_elegans		WBGENE00012177

Paralogs (1): DECR2 (ENSG00000242612)

Protein

Protein identifiers

2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing], mitochondrial — Q16698 (reviewed: Q16698)

Alternative names: 2,4-dienoyl-CoA reductase [NADPH], Short chain dehydrogenase/reductase family 18C member 1

All UniProt accessions (8): E5RFV2, E5RGS6, E5RHR1, E5RID6, E5RJD2, E5RJG7, Q16698, H0YAW3

UniProt curated annotations — full annotation on UniProt →

Function. Auxiliary enzyme of beta-oxidation. It participates in the metabolism of unsaturated fatty enoyl-CoA esters having double bonds in both even- and odd-numbered positions in mitochondria. Catalyzes the NADP-dependent reduction of 2,4-dienoyl-CoA to yield trans-3-enoyl-CoA.

Subunit / interactions. Homotetramer.

Subcellular location. Mitochondrion.

Tissue specificity. Heart = liver = pancreas > kidney » skeletal muscle = lung.

Disease relevance. 2,4-dienoyl-CoA reductase deficiency (DECRD) [MIM:616034] A rare, autosomal recessive, inborn error of polyunsaturated fatty acids and lysine metabolism, resulting in mitochondrial dysfunction. Affected individuals have a severe encephalopathy with neurologic and metabolic abnormalities beginning in early infancy. Laboratory studies show increased C10:2 carnitine levels and hyperlysinemia. The protein represented in this entry is involved in disease pathogenesis. A selective decrease in mitochondrial NADP(H) levels due to NADK2 mutations causes a deficiency of NADPH-dependent mitochondrial enzymes, such as DECR1 and AASS.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q16698-1	1	yes
Q16698-2	2

RefSeq proteins (2): NP_001317504, NP_001350* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002347	SDR_fam	Family
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

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)

Substrate kinetics (BRENDA)

10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NADPH	0.0025–0.215	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

Catalyzed reactions (Rhea), 3 shown:

• (2E,4E)-hexadienoyl-CoA + NADPH + H(+) = (3E)-hexenoyl-CoA + NADP(+) (RHEA:44912)
• 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 (63 total): modified residue 15, helix 15, binding site 10, strand 8, mutagenesis site 4, sequence conflict 4, turn 2, transit peptide 1, chain 1, active site 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1W6U	X-RAY DIFFRACTION	1.75
1W73	X-RAY DIFFRACTION	2.1
1W8D	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16698-F1	89.20	0.81

Functional residue map

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

Catalytic / active sites (1): 199 (proton acceptor)

Ligand- & substrate-binding residues (10): 214; 240–243; 251; 66–71; 91; 91; 117; 119; 149; 157

Post-translational modifications (15): 42, 42, 49, 49, 69, 73, 97, 97, 230, 244, 244, 260, 260, 319, 319

Mutagenesis-validated functional residues (4):

Position	Phenotype
148	reduces enzyme activity by 97%.
199	reduces enzyme activity by 99%. strongly reduced affinity for substrate and for nadp.
210	reduces enzyme activity by over 99%.
214	reduces enzyme activity by over 99%.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-77288	mitochondrial fatty acid beta-oxidation of unsaturated fatty acids

MSigDB gene sets: 212 (showing top): GOBP_LIPID_MODIFICATION, MODULE_93, GOBP_FATTY_ACID_CATABOLIC_PROCESS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, BECKER_TAMOXIFEN_RESISTANCE_UP, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, ONKEN_UVEAL_MELANOMA_UP, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, HSIAO_LIVER_SPECIFIC_GENES, LANDIS_ERBB2_BREAST_PRENEOPLASTIC_DN, NIKOLSKY_BREAST_CANCER_8Q12_Q22_AMPLICON, GOBP_LIPID_METABOLIC_PROCESS, SCHLOSSER_SERUM_RESPONSE_DN, GOBP_ORGANIC_ACID_METABOLIC_PROCESS

GO Biological Process (4): fatty acid beta-oxidation (GO:0006635), positive regulation of cold-induced thermogenesis (GO:0120162), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (4): 2,4-dienoyl-CoA reductase (NADPH) activity (GO:0008670), identical protein binding (GO:0042802), NADPH binding (GO:0070402), oxidoreductase activity (GO:0016491)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytosol (GO:0005829), catalytic complex (GO:1902494)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Mitochondrial Fatty Acid Beta-Oxidation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
cytoplasm	2
fatty acid catabolic process	1
fatty acid ligase activity	1
fatty acid oxidation	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor	1
protein binding	1
anion binding	1
NADP binding	1
catalytic activity	1
nuclear lumen	1
mitochondrion	1
intracellular organelle lumen	1
protein-containing complex	1

Protein interactions and networks

STRING

3879 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DECR1	OSGIN2	Q9Y236	896
DECR1	CALB1	P05937	831
DECR1	CA7	P43166	768
DECR1	PDP1	Q9P0J1	721
DECR1	GAPDH	P00354	680
DECR1	CNGB3	Q9NQW8	650
DECR1	CALB2	P22676	637
DECR1	ECI1	P42126	621
DECR1	CPT2	P23786	551
DECR1	HADHB	P55084	531
DECR1	HADHA	P40939	527
DECR1	FPGS	Q05932	521
DECR1	ACAA2	P42765	512
DECR1	ECI2	O75521	511
DECR1	ENO1	P06733	510

IntAct

92 interactions, top by confidence:

A	B	Type	Score
PTTG1	ESPL1	psi-mi:“MI:0914”(association)	0.900
PSMD2	PSMD11	psi-mi:“MI:0914”(association)	0.730
RELA	NFKBIE	psi-mi:“MI:0914”(association)	0.620
BAIAP2	WASL	psi-mi:“MI:0914”(association)	0.550
CHMP2A	DECR1	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
ECSIT	NDUFS8	psi-mi:“MI:0914”(association)	0.530
CREB3	MYO9A	psi-mi:“MI:0914”(association)	0.530
PTTG1	PTTG1	psi-mi:“MI:0915”(physical association)	0.400
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
RPL10	RPS6	psi-mi:“MI:0914”(association)	0.350
Rcc1	WDR46	psi-mi:“MI:0914”(association)	0.350
MSH6	PARP2	psi-mi:“MI:0914”(association)	0.350
NOP56	C12orf43	psi-mi:“MI:0914”(association)	0.350
CCDC22	VPS26C	psi-mi:“MI:0914”(association)	0.350
GEMIN5	PFDN1	psi-mi:“MI:0914”(association)	0.350
Immt	GOSR1	psi-mi:“MI:0914”(association)	0.350
Ktn1	ESYT2	psi-mi:“MI:0914”(association)	0.350
EXOSC5	PAPD5	psi-mi:“MI:0914”(association)	0.350
LCOR		psi-mi:“MI:0914”(association)	0.350
JAK3	WDR46	psi-mi:“MI:0914”(association)	0.350
AK1	NBAS	psi-mi:“MI:0914”(association)	0.350
KIF11	MAP4	psi-mi:“MI:0914”(association)	0.350
NLRP5	BECN1	psi-mi:“MI:0914”(association)	0.350
NPM1	RPSA	psi-mi:“MI:0914”(association)	0.350
BCAR1	PSMD11	psi-mi:“MI:0914”(association)	0.350

BioGRID (108): DECR1 (Affinity Capture-RNA), DECR1 (Affinity Capture-RNA), DECR1 (Affinity Capture-MS), DECR1 (Affinity Capture-MS), DECR1 (Affinity Capture-MS), DECR1 (Affinity Capture-MS), DECR1 (Affinity Capture-MS), HSD17B4 (Co-fractionation), DECR1 (Affinity Capture-MS), DECR1 (Affinity Capture-MS), DECR1 (Affinity Capture-MS), DECR1 (Affinity Capture-MS), DECR1 (Affinity Capture-MS), DECR1 (Affinity Capture-MS), DECR1 (Affinity Capture-MS)

ESM2 similar proteins: A2VCW9, A4FUZ6, A8E657, A8XKG6, O02485, O08699, O17732, O48905, P11708, P13228, P14152, P15428, P46794, P51659, P51660, P57106, P70684, P93819, P97852, Q01373, Q08062, Q16698, Q29LW1, Q2TPA8, Q32PF2, Q3T0C2, Q3T145, Q4V8F9, Q54VM2, Q55FT1, Q59987, Q5RA68, Q66KC4, Q6DIY9, Q6P5L8, Q6PAB3, Q6PAY8, Q6YN16, Q7XDC8, Q7YRU4

Diamond homologs: A0A075TRB3, A0A0H3KNE7, A7IQF2, C8WMP0, F9XMW6, O07575, P0AEK4, P0AEK5, P0AEK6, P0AG84, P0AG85, P0DMP5, P10528, P16657, P39484, P39485, P54795, P69166, P73016, P80702, P9WES5, P9WGT0, P9WGT1, Q05069, Q16698, Q21929, Q5KTS5, Q64591, Q7SHI4, Q8P3K4, Q92506, Q9CQ62, Q9ZFE4, A0A1L5BUG8, A0A411KUU9, A1CFM1, D4YYG1, E0D7H5, E9Q3D4, G4N290

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	9
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1375 predictions. Top by Δscore:

Variant	Effect	Δscore
8:90001557:GGAGG:G	donor_gain	1.0000
8:90001558:GAGG:G	donor_gain	1.0000
8:90001558:GAGGG:G	donor_gain	1.0000
8:90001560:GG:G	donor_gain	1.0000
8:90001561:GG:G	donor_gain	1.0000
8:90001562:G:GG	donor_gain	1.0000
8:90019080:TTGCA:T	acceptor_loss	1.0000
8:90019081:TGCA:T	acceptor_loss	1.0000
8:90019082:GCA:G	acceptor_loss	1.0000
8:90019083:CA:C	acceptor_loss	1.0000
8:90019084:A:AG	acceptor_gain	1.0000
8:90019084:A:AT	acceptor_loss	1.0000
8:90019084:AG:A	acceptor_gain	1.0000
8:90019085:G:A	acceptor_loss	1.0000
8:90019085:G:GT	acceptor_gain	1.0000
8:90019085:GG:G	acceptor_gain	1.0000
8:90019085:GGTT:G	acceptor_gain	1.0000
8:90019085:GGTTC:G	acceptor_gain	1.0000
8:90019172:TG:T	donor_loss	1.0000
8:90019173:G:GG	donor_gain	1.0000
8:90019174:TAAGT:T	donor_loss	1.0000
8:90020907:A:AG	acceptor_gain	1.0000
8:90020908:G:GG	acceptor_gain	1.0000
8:90020908:GATT:G	acceptor_gain	1.0000
8:90036937:GCAA:G	donor_gain	1.0000
8:90036938:CAAGT:C	donor_loss	1.0000
8:90036939:AAGTA:A	donor_loss	1.0000
8:90036940:AGT:A	donor_loss	1.0000
8:90036941:G:GG	donor_gain	1.0000
8:90036941:GTA:G	donor_loss	1.0000

AlphaMissense

2184 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:90036903:A:C	S210R	0.997
8:90036905:T:A	S210R	0.997
8:90036905:T:G	S210R	0.997
8:90042744:T:A	W228R	0.997
8:90042744:T:C	W228R	0.997
8:90020935:T:A	N148K	0.995
8:90020935:T:G	N148K	0.995
8:90020936:T:C	F149L	0.994
8:90020938:T:A	F149L	0.994
8:90020938:T:G	F149L	0.994
8:90021003:G:A	G171D	0.994
8:90036916:A:T	K214I	0.993
8:90036917:A:C	K214N	0.993
8:90036917:A:T	K214N	0.993
8:90017251:G:A	G66E	0.992
8:90017322:A:C	S90R	0.992
8:90017324:C:A	S90R	0.992
8:90017324:C:G	S90R	0.992
8:90020972:T:A	W161R	0.992
8:90020972:T:C	W161R	0.992
8:90036913:C:A	A213D	0.992
8:90017317:T:A	I88K	0.991
8:90017250:G:T	G66W	0.990
8:90044966:A:C	S286R	0.990
8:90044968:T:A	S286R	0.990
8:90044968:T:G	S286R	0.990
8:90017254:G:A	G67E	0.989
8:90020916:T:A	I142K	0.989
8:90036912:G:C	A213P	0.989
8:90036922:G:A	G216D	0.989

dbSNP variants (sampled 300 via entrez): RS1000054890 (8:90053594 G>A), RS1000075698 (8:90037904 A>G), RS1000128249 (8:90053255 G>A,T), RS1000170335 (8:90028774 C>A,G,T), RS1000203172 (8:90028533 T>A,G), RS1000350821 (8:90025846 T>C), RS1000418327 (8:90018470 C>T), RS1000475969 (8:90042530 G>A,T), RS1000489188 (8:90010923 C>G), RS1000553081 (8:90020250 C>G), RS1000591232 (8:90005662 A>G), RS1000598971 (8:90049074 G>T), RS1000645305 (8:90005451 G>GA), RS1000778037 (8:90042922 AG>A), RS1000908522 (8:90050505 A>G)

Disease associations

OMIM: gene MIM:222745 | disease phenotypes: MIM:616034, MIM:251260

GenCC curated gene-disease

Disease	Classification	Inheritance
liver disorder	Limited	Autosomal recessive
progressive encephalopathy with leukodystrophy due to DECR deficiency	Limited	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
progressive encephalopathy with leukodystrophy due to DECR deficiency	No Known Disease Relationship	UD

Mondo (3): progressive encephalopathy with leukodystrophy due to DECR deficiency (MONDO:0014464), Nijmegen breakage syndrome (MONDO:0009623), liver disorder (MONDO:0005154)

Orphanet (2): Progressive encephalopathy with leukodystrophy due to DECR deficiency (Orphanet:431361), Nijmegen breakage syndrome (Orphanet:647)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001873_5	Red blood cell traits	9.000000e-48
GCST001873_6	Red blood cell traits	2.000000e-34
GCST001873_8	Red blood cell traits	4.000000e-22
GCST006585_2704	Blood protein levels	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004527	mean corpuscular hemoglobin

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008107	Liver Diseases	C06.552
D049932	Nijmegen Breakage Syndrome	C18.452.284.600
C565624	2,4-Dienoyl-CoA Reductase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067063 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.44	Kd	3630	nM	CHEMBL3752910
5.44	ED50	3630	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148227: Binding affinity to human DECR1 incubated for 45 mins by Kinobead based pull down assay	kd	3.6296	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, decreases methylation	6
bisphenol A	increases expression, affects cotreatment, decreases expression	3
trichostatin A	increases expression, affects cotreatment	3
Cyclosporine	decreases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Acetaminophen	decreases expression	2
Cadmium	increases abundance, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Cadmium Chloride	increases expression, decreases expression, increases abundance	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
lasiocarpine	decreases expression	1
triphenyl phosphate	affects expression	1
chlortoluron	decreases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
beta-methylcholine	affects expression	1
azoxystrobin	increases expression	1
K 7174	decreases expression	1
GW 4064	affects cotreatment, decreases expression	1
6-(4-chlorophenyl)imidazo(2,1-b)(1,3)thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases 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
CHEMBL5651269	Binding	Binding affinity to human DECR1 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

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D9D3	Ubigene HEK293 DECR1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00148031	PHASE4	COMPLETED	Improving Hepatitis C Treatment in Injection Drug Users
NCT00152607	PHASE4	TERMINATED	Orthotopic Liver Transplantation Using a Living Donor
NCT00155376	PHASE4	UNKNOWN	Intravenous-Morphine and Glucagon-Usage Enhanced MR Cholangiography
NCT00206076	PHASE4	COMPLETED	Mycophenolate Mofetil Immunosuppression Without/With Reduced Dose Calcineurin Inhibitor Long After Liver Transplantation
NCT00222664	PHASE4	COMPLETED	Qidong Hepatitis B Intervention Study
NCT00402402	PHASE4	COMPLETED	Comparison of Quantiferon-TB Gold Assay With Tuberculin Skin Testing in Patients With Chronic Liver Disease
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00564538	PHASE4	UNKNOWN	A Study of Thymoglobulin and Tacrolimus in Liver Transplant
NCT00657124	PHASE4	COMPLETED	Effect of Preoperative Supplementation in Insulin Resistance
NCT00659698	PHASE4	COMPLETED	Effect of an Artificial Pancreas in Patients Undergoing Hepatic Resection
NCT00742326	PHASE4	TERMINATED	Pioglitazone to Treat Fatty Liver in Patients With HIV and Hepatitis C Infections
NCT00799851	PHASE4	COMPLETED	A Randomized Controlled Trial Comparing Band Ligation and Cyanoacrylate Injection for Esophageal Varices
NCT00948220	PHASE4	COMPLETED	Influence of Antiviral Therapy on Bone Mineral Density and Metabolism in Patients With Chronic Hepatitis C
NCT01148706	PHASE4	COMPLETED	Effectiveness of ActiSight™ Needle Guidance System in Patients Undergoing CT-Guided Procedures
NCT01195181	PHASE4	COMPLETED	Different PEG-interferon and Ribavirin Schedules for Chronic Hepatitis C in the Real Clinical Practice.
NCT01303549	PHASE4	COMPLETED	Anidulafungin vs Amphotericin B Safety in High Risk Hepatic Transplant Recipients
NCT01337440	PHASE4	UNKNOWN	Efficacy and Safety of Ursodeoxycholic Acid (UDCA) Added to the DPP-4 Inhibitor in People With Type 2 Diabetes and Chronic Liver Diseases
NCT01429779	PHASE4	UNKNOWN	The Orange-III Trial: Optimised Recovery With Movicol® Preoperatively Within an Enhanced Recovery Programme
NCT01600105	PHASE4	COMPLETED	Detection of Liver Fibrosis With Magnetic Resonance Imaging (MRI)
NCT01650181	PHASE4	COMPLETED	Effects of Siliphos-Selenium-Methionine-Alpha Lipoic Acid in Patients With Fatty Liver and Non-alcoholic Steatohepatitis
NCT01958190	PHASE4	COMPLETED	Study Comparing in Livertransplantation Recipients With Tacrolimus Alone Versus Tacrolimus&Sirolimus
NCT01968395	PHASE4	COMPLETED	Pharmacokinetics of Caspofungin After One Dose in Patients With Liver Failure
NCT02347319	PHASE4	COMPLETED	To Evaluate the Efficacy of DDB/Garlic Oil in Patients With Elevated Transaminase Chronic Liver Disease
NCT02366845	PHASE4	COMPLETED	Prospective Validation of a Plasma Transfusion Dosing Algorithm in Patients With Chronic Liver Disease
NCT02489045	PHASE4	COMPLETED	Noninvasive Subharmonic Aided Pressure Estimation of Portal Hypertension
NCT02499185	PHASE4	TERMINATED	Study Evaluating Novel Biomarkers of AKI (Acute Kidney Injury) in Post-operative Patients
NCT02712775	PHASE4	WITHDRAWN	Minocycline Administration During Human Liver Transplantation
NCT02717949	PHASE4	TERMINATED	Oral Hepatitis C Treatment for Indolent Lymphoma (OPTImaL) Study
NCT02764671	PHASE4	UNKNOWN	Safety and Immunogenicity of Recombinant Hepatitis B Vaccines in the Neonates
NCT02938013	PHASE4	COMPLETED	deLIVER: Direct Acting Antiviral Effects on the Liver
NCT02949492	PHASE4	TERMINATED	Low-dose IL-2 for Treg Expansion and Tolerance (LITE)
NCT03063866	PHASE4	UNKNOWN	Randomised Controlled Study of Popofol Versus Midazolam as Sedation in Endoscopy With Advanced Liver Disease.
NCT03512210	PHASE4	COMPLETED	Monitoring SOF/VEL in Treatment Naïve, HCV Participants With Active Infection
NCT03522688	PHASE4	UNKNOWN	Impact of Dexmedetomidine on Acute Kidney Injury Following Living Donor Liver Transplantation
NCT03646292	PHASE4	COMPLETED	Antidiabetic Drugs for Steatotic Liver Disease
NCT03652636	PHASE4	COMPLETED	Evaluation of the Efficacy of Contrast Enhanced Ultrasound Compared to MRI for Differentiation of Hepatic Lesions
NCT03667157	PHASE4	COMPLETED	Liver Function After Intravenous Methylprednisolone Administration
NCT04073290	PHASE4	RECRUITING	Prevention of Post-TIPS Hepatic Encephalopathy by Administration of Rifaximin and Lactulose
NCT04588077	PHASE4	RECRUITING	Comparison Between 2-dose Versus 3-dose Regimens of Heplisav B in Cirrhosis
NCT04718051	PHASE4	UNKNOWN	S.P.PRO LIVER POWDER is Used to Improve Liver and Metabolic Indexes in People With Non-alcoholic Fatty Liver Disease