CBR4

Summary

CBR4 (carbonyl reductase 4, HGNC:25891) is a protein-coding gene on chromosome 4q32.3, encoding 3-oxoacyl-[acyl-carrier-protein] reductase (Q8N4T8). Component of the heterotetramer complex KAR (3-ketoacyl-[acyl carrier protein] reductase or 3-ketoacyl-[ACP] reductase) that forms part of the mitochondrial fatty acid synthase (mtFAS).

Enables several functions, including 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity; NADPH binding activity; and NADPH dehydrogenase (quinone) activity. Involved in fatty acid biosynthetic process; glycoside metabolic process; and protein tetramerization. Located in mitochondrial matrix. Part of oxidoreductase complex.

Source: NCBI Gene 84869 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 961 total
• MANE Select transcript: NM_032783

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25891
Approved symbol	CBR4
Name	carbonyl reductase 4
Location	4q32.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14431, SDR45C1
Ensembl gene	ENSG00000145439
Ensembl biotype	protein_coding
OMIM	619394
Entrez	84869

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000306193, ENST00000504480, ENST00000504561, ENST00000506808, ENST00000507752, ENST00000509108, ENST00000510042, ENST00000868053, ENST00000868054, ENST00000868055, ENST00000925517, ENST00000957769

RefSeq mRNA: 1 — MANE Select: NM_032783 NM_032783

CCDS: CCDS3812

Canonical transcript exons

ENST00000306193 — 5 exons

Exon	Start	End
ENSE00001226375	168987590	168990328
ENSE00003499899	169006755	169006891
ENSE00003557089	169002071	169002205
ENSE00003578114	169007636	169007756
ENSE00003850805	169009948	169010255

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 94.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.0307 / max 358.8404, expressed in 1815 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54794	15.2360	1806
54793	7.7946	1753

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	94.59	gold quality
calcaneal tendon	UBERON:0003701	91.93	gold quality
oocyte	CL:0000023	91.49	gold quality
right lobe of liver	UBERON:0001114	90.86	gold quality
liver	UBERON:0002107	90.66	gold quality
tendon	UBERON:0000043	90.38	gold quality
adrenal tissue	UBERON:0018303	90.34	gold quality
sperm	CL:0000019	90.15	silver quality
tibia	UBERON:0000979	90.15	gold quality
renal medulla	UBERON:0000362	90.08	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.75	gold quality
lateral nuclear group of thalamus	UBERON:0002736	89.70	gold quality
pigmented layer of retina	UBERON:0001782	89.49	gold quality
nipple	UBERON:0002030	89.34	gold quality
corpus epididymis	UBERON:0004359	89.34	gold quality
parotid gland	UBERON:0001831	88.74	silver quality
gingival epithelium	UBERON:0001949	88.57	silver quality
skin of hip	UBERON:0001554	88.55	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.47	gold quality
substantia nigra pars compacta	UBERON:0001965	88.39	gold quality
male germ cell	CL:0000015	88.13	silver quality
lateral globus pallidus	UBERON:0002476	88.09	gold quality
corpus callosum	UBERON:0002336	88.07	gold quality
esophagus squamous epithelium	UBERON:0006920	88.06	gold quality
upper leg skin	UBERON:0004262	87.90	gold quality
biceps brachii	UBERON:0001507	87.85	gold quality
duodenum	UBERON:0002114	87.66	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.58	gold quality
jejunal mucosa	UBERON:0000399	87.56	gold quality
jejunum	UBERON:0002115	87.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

106 targeting CBR4, 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-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-551B-5P	99.96	71.28	3493
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-3658	99.96	73.87	4379
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-548AG	99.77	69.25	1492

Literature-anchored findings (GeneRIF, showing 2)

• CBR4 is a mitochondrial NADPH-dependent reductase for o- and p-quinones. (PMID:19000905)
• Hs17beta-HSD8 and HsCBR4 show a strong genetic interaction in vivo in yeast, where, only if they are expressed together, they rescue the respiratory deficiency and restore the lipoic acid content of oar1Delta cells. (PMID:19571038)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cbr4	ENSDARG00000009074
mus_musculus	Cbr4	ENSMUSG00000031641
rattus_norvegicus	Cbr4	ENSRNOG00000024411
drosophila_melanogaster	Adhr	FBGN0000056

Protein

Protein identifiers

3-oxoacyl-[acyl-carrier-protein] reductase — Q8N4T8 (reviewed: Q8N4T8)

Alternative names: 3-ketoacyl-[acyl-carrier-protein] reductase beta subunit, Carbonyl reductase family member 4, Quinone reductase CBR4, Short chain dehydrogenase/reductase family 45C member 1

All UniProt accessions (5): Q8N4T8, D6RAV8, D6RGF2, D6RJF4, H0Y962

UniProt curated annotations — full annotation on UniProt →

Function. Component of the heterotetramer complex KAR (3-ketoacyl-[acyl carrier protein] reductase or 3-ketoacyl-[ACP] reductase) that forms part of the mitochondrial fatty acid synthase (mtFAS). Beta-subunit of the KAR heterotetramer complex, responsible for the 3-ketoacyl-ACP reductase activity of the mtFAS, reduces 3-oxoacyl-[ACP] to (3R)-hydroxyacyl-[ACP] in a NADPH-dependent manner with no chain length preference, thereby participating in mitochondrial fatty acid biosynthesis. The homotetramer has NADPH-dependent quinone reductase activity (in vitro), hence could play a role in protection against cytotoxicity of exogenous quinones. As a heterotetramer, it can also reduce 9,10-phenanthrenequinone, 1,4-benzoquinone and various other o-quinones and p-quinones (in vitro).

Subunit / interactions. Homotetramer (in vitro). Heterotetramer with HSD17B8; contains two molecules each of HSD17B8 and CBR4. Does not form homotetramers when HSD17B8 is coexpressed, only heterotetramers (in vitro).

Subcellular location. Mitochondrion matrix.

Tissue specificity. Detected in liver and kidney (at protein level). Displays the highest expression in neuronal and muscle tissues.

Pathway. Lipid metabolism; fatty acid biosynthesis.

Similarity. Belongs to the short-chain dehydrogenases/reductases (SDR) family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N4T8-1	1	yes
Q8N4T8-2	2

RefSeq proteins (1): NP_116172* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002347	SDR_fam	Family
IPR020904	Sc_DH/Rdtase_CS	Conserved_site
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR057326	KR_dom	Domain

Pfam: PF13561

Catalyzed reactions (Rhea), 2 shown:

• a (3R)-hydroxyacyl-[ACP] + NADP(+) = a 3-oxoacyl-[ACP] + NADPH + H(+) (RHEA:17397)
• a quinone + NADPH + H(+) = a quinol + NADP(+) (RHEA:46164)

UniProt features (47 total): helix 11, mutagenesis site 8, binding site 8, strand 7, modified residue 4, turn 4, chain 1, active site 1, site 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4CQM	X-RAY DIFFRACTION	2.34
4CQL	X-RAY DIFFRACTION	2.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N4T8-F1	96.69	0.98

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 (2): 148 (proton acceptor); 169 (important for interaction with acyl carrier protein (acp))

Ligand- & substrate-binding residues (8): 11–14; 34–35; 56; 83–85; 135; 148; 152; 181–183

Post-translational modifications (4): 1, 40, 96, 195

Mutagenesis-validated functional residues (8):

Position	Phenotype
9	unable to restore growth of an oar1-deficient yeast mutant.
12	strongly reduced ability to restore growth of an oar1-deficient yeast mutant.
34	strongly reduced ability to restore growth of an oar1-deficient yeast mutant. strongly reduces nadph-dependent reductase
135	unable to restore growth of an oar1-deficient yeast mutant.
148	unable to restore growth of an oar1-deficient yeast mutant.
152	unable to restore growth of an oar1-deficient yeast mutant. abolishes nadph-dependent reductase activity with acetoacety
168	strongly reduced ability to restore growth of an oar1-deficient yeast mutant. increases nadph-dependent reductase activi
169	unable to restore growth of an oar1-deficient yeast mutant. increases nadph-dependent reductase activity with acetoacety

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-75105	Fatty acyl-CoA biosynthesis
R-HSA-1430728	Metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 163 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, chr4q32, GOBP_PROTEIN_HOMOTETRAMERIZATION, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_KETONE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_FATTY_ACYL_COA_METABOLIC_PROCESS, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS

GO Biological Process (8): fatty acid biosynthetic process (GO:0006633), daunorubicin metabolic process (GO:0044597), doxorubicin metabolic process (GO:0044598), fatty-acyl-CoA biosynthetic process (GO:0046949), protein homotetramerization (GO:0051289), protein heterotetramerization (GO:0051290), lipid metabolic process (GO:0006629), fatty acid metabolic process (GO:0006631)

GO Molecular Function (8): NAD(P)H dehydrogenase (quinone) activity (GO:0003955), 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity (GO:0004316), NADPH dehydrogenase (quinone) activity (GO:0008753), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616), quinone binding (GO:0048038), NADPH binding (GO:0070402), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), oxidoreductase complex (GO:1990204)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Fatty acid metabolism	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycoside metabolic process	2
polyketide metabolic process	2
ketone metabolic process	2
protein tetramerization	2
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
primary alcohol metabolic process	1
tertiary alcohol metabolic process	1
fatty-acyl-CoA metabolic process	1
acyl-CoA biosynthetic process	1
fatty acid derivative biosynthetic process	1
protein homooligomerization	1
protein heterooligomerization	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor	1
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	1
NAD(P)H dehydrogenase (quinone) activity	1
NADPH dehydrogenase activity	1
oxidoreductase activity, acting on CH-OH group of donors	1
small molecule binding	1
anion binding	1
NADP binding	1
binding	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1
catalytic complex	1

Protein interactions and networks

STRING

3439 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CBR4	CBR3	O75828	596
CBR4	OXSM	Q9NWU1	576
CBR4	C19orf25	Q9UFG5	556
CBR4	CBR1	P16152	546
CBR4	MCAT	Q8IVS2	499
CBR4	DHRS4	Q9BTZ2	497
CBR4	MRPL16	Q9NX20	459
CBR4	VWA8	A3KMH1	451
CBR4	HEPH	Q9BQS7	446
CBR4	AKR7A2	O43488	385
CBR4	SRD5A1	P18405	385
CBR4	POPDC2	Q9HBU9	353
CBR4	MRPS6	P82932	353
CBR4	MCEE	Q96PE7	350
CBR4	TMEM41A	Q96HV5	347

IntAct

30 interactions, top by confidence:

A	B	Type	Score
SEPTIN3	SEPTIN6	psi-mi:“MI:0914”(association)	0.800
HSD17B8	CBR4	psi-mi:“MI:0915”(physical association)	0.670
ZXDC	CBR4	psi-mi:“MI:0915”(physical association)	0.560
HSD17B8	MTIF2	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
UQCRFS1	NDUFAB1	psi-mi:“MI:0914”(association)	0.530
CFTR	CBR4	psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
SEPTIN3	SEPTIN4	psi-mi:“MI:0914”(association)	0.350
	AP3B1	psi-mi:“MI:0914”(association)	0.350
PSMB10	DDX46	psi-mi:“MI:0914”(association)	0.350
CBR4	DUSP14	psi-mi:“MI:0914”(association)	0.350
CLEC4E	ESYT2	psi-mi:“MI:0914”(association)	0.350
NIPSNAP3A	NUDT19	psi-mi:“MI:0914”(association)	0.350
PDGFRA	QSOX1	psi-mi:“MI:0914”(association)	0.350
HSD17B8	TPP1	psi-mi:“MI:0914”(association)	0.350
TAFAZZIN	BCKDK	psi-mi:“MI:0914”(association)	0.350
CBR4	BCKDK	psi-mi:“MI:0914”(association)	0.350
MTG2	BCKDK	psi-mi:“MI:0914”(association)	0.350
RAMP3	MGST3	psi-mi:“MI:0914”(association)	0.350
SLC2A2	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC39A12	ESYT2	psi-mi:“MI:0914”(association)	0.350
CLPP	NDUFA4	psi-mi:“MI:2364”(proximity)	0.270
CBR4	ZXDC	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (50): CBR4 (Affinity Capture-MS), CBR4 (Affinity Capture-MS), CBR4 (Affinity Capture-MS), CBR4 (Affinity Capture-MS), CBR4 (Affinity Capture-MS), CBR4 (Affinity Capture-RNA), CBR4 (Two-hybrid), CBR4 (Affinity Capture-MS), CBR4 (Affinity Capture-MS), CBR4 (Proximity Label-MS), CBR4 (Affinity Capture-RNA), CBR4 (Affinity Capture-MS), NDUFAF5 (Affinity Capture-MS), CBWD2 (Affinity Capture-MS), LRRC15 (Affinity Capture-MS)

ESM2 similar proteins: A4IFA7, C1DMX5, O54438, P06234, P0A2C9, P0A2D0, P0A2D1, P0A2D2, P0A5Y5, P0AEK2, P0AEK3, P14697, P17611, P33368, P37440, P38004, P42317, P43713, P45375, P50204, P50205, P50941, P55336, P70720, P72332, P73826, P9WGT2, P9WGT3, Q1NEJ0, Q1RKB7, Q21929, Q2UEK6, Q4UK62, Q56840, Q68ER2, Q68VY7, Q6NUE2, Q6P0H7, Q7TS56, Q8GAV9

Diamond homologs: A0A084R1K1, A0A097ZPC9, A0A0F7U1Z1, A0A0U5GHD4, A0A1E1FFP5, A0A1Y0BRF8, A0A2I1BSW8, A0A384JQF5, A0A3G9HAL8, A0A455R5K2, A0A6S6QNE4, A0A8D5M6H6, A0QYC2, A6SSW9, B6HV34, C1C4R8, C8WGQ3, D4A1J4, G0RNA2, G4N1P8, H1VN83, L7I518, O32184, O34308, O70351, P06235, P0A2D1, P0A2D2, P0DX40, P14802, P16542, P21215, P28486, P37079, P37440, P37694, P41177, P50160, P70684, P76633

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	625
Likely benign	271
Benign	25

Top pathogenic / likely-pathogenic (0)

SpliceAI

2995 predictions. Top by Δscore:

Variant	Effect	Δscore
4:168876907:GA:G	donor_gain	1.0000
4:168876909:G:GG	donor_gain	1.0000
4:168890913:A:AG	acceptor_gain	1.0000
4:168890914:T:G	acceptor_gain	1.0000
4:168890917:TGCA:T	acceptor_loss	1.0000
4:168890920:A:AG	acceptor_gain	1.0000
4:168890920:AGAG:A	acceptor_gain	1.0000
4:168890921:G:GC	acceptor_gain	1.0000
4:168890921:GA:G	acceptor_gain	1.0000
4:168890921:GAGG:G	acceptor_gain	1.0000
4:168890921:GAGGA:G	acceptor_gain	1.0000
4:168891031:G:GT	donor_gain	1.0000
4:168891053:AGCCG:A	donor_loss	1.0000
4:168891054:GCCG:G	donor_gain	1.0000
4:168891055:CCGGT:C	donor_loss	1.0000
4:168891056:CG:C	donor_loss	1.0000
4:168891057:GG:G	donor_loss	1.0000
4:168891058:GTACT:G	donor_loss	1.0000
4:168891059:T:A	donor_loss	1.0000
4:168894569:C:G	acceptor_gain	1.0000
4:168896601:T:G	donor_gain	1.0000
4:168903749:A:AG	acceptor_gain	1.0000
4:168903750:T:G	acceptor_gain	1.0000
4:168903754:C:G	acceptor_gain	1.0000
4:168903754:CA:C	acceptor_loss	1.0000
4:168903755:A:AG	acceptor_gain	1.0000
4:168903755:AGATC:A	acceptor_loss	1.0000
4:168903756:G:GG	acceptor_gain	1.0000
4:168903756:GA:G	acceptor_gain	1.0000
4:168903756:GAT:G	acceptor_gain	1.0000

AlphaMissense

1533 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:169002151:T:A	K152I	0.996
4:169002084:A:C	N174K	0.995
4:169002084:A:T	N174K	0.995
4:169006763:A:T	V131D	0.995
4:169002079:A:T	V176D	0.994
4:169002150:T:A	K152N	0.993
4:169002150:T:G	K152N	0.993
4:169002153:A:C	S151R	0.992
4:169002153:A:T	S151R	0.992
4:169002155:T:G	S151R	0.992
4:169002201:G:C	S135R	0.992
4:169002201:G:T	S135R	0.992
4:169002203:T:G	S135R	0.992
4:169007653:A:C	N82K	0.991
4:169007653:A:T	N82K	0.991
4:169006759:A:C	N132K	0.990
4:169006759:A:T	N132K	0.990
4:169002157:G:T	A150D	0.988
4:169002164:A:G	Y148H	0.988
4:169010046:C:T	G15D	0.988
4:169010064:C:T	G9E	0.988
4:168990173:C:A	G231W	0.987
4:168990194:C:A	G224W	0.987
4:169002118:G:T	A163D	0.987
4:169006812:A:G	C115R	0.987
4:169002159:A:C	S149R	0.986
4:169002159:A:T	S149R	0.986
4:169002161:T:G	S149R	0.986
4:169006832:A:G	L108P	0.986
4:169010073:G:T	A6D	0.984

dbSNP variants (sampled 300 via entrez): RS1000000872 (4:168944929 T>A), RS1000029680 (4:168945025 A>C), RS10000553 (4:168982458 T>C), RS1000088796 (4:168952047 C>T), RS1000129077 (4:168908231 T>C), RS1000173119 (4:168997478 T>C), RS1000239760 (4:168964560 A>G), RS1000290813 (4:168951773 T>C), RS1000295682 (4:168958561 A>G), RS1000297150 (4:168911532 T>C), RS1000385291 (4:169000157 T>C), RS1000389104 (4:168897096 G>A), RS1000402742 (4:168958273 A>G), RS10004161 (4:168983963 T>A,C), RS1000421771 (4:168987786 T>C)

Disease associations

OMIM: gene MIM:619394 | disease phenotypes: MIM:606856

GenCC curated gene-disease

Mondo (3): pancreatic adenocarcinoma (MONDO:0006047), hereditary neoplastic syndrome (MONDO:0015356), pancreatic cancer, susceptibility to, 1 (MONDO:0011739)

Orphanet (2): Inherited cancer-predisposing syndrome (Orphanet:140162), Familial pancreatic carcinoma (Orphanet:1333)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003992_44	Photic sneeze reflex	9.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic	decreases expression, increases abundance, affects methylation	3
Valproic Acid	affects expression, increases expression	3
Cyclosporine	decreases expression	3
methylmercuric chloride	decreases expression, increases expression	2
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
sodium arsenite	increases abundance, decreases expression	2
cobaltous chloride	decreases expression	2
Acetaminophen	decreases expression	2
Cisplatin	affects cotreatment, increases expression, affects expression	2
Tobacco Smoke Pollution	decreases expression	2
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression, increases abundance	1
trichostatin A	increases expression	1
perfluorooctanoic acid	increases expression	1
tobacco tar	decreases expression	1
potassium chromate(VI)	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	decreases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	increases methylation, decreases methylation, affects cotreatment	1
Air Pollutants	affects expression, increases abundance	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1T6	HAP1 CBR4 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00854477	PHASE4	COMPLETED	Pharmacokinetic Study of Adjuvant Capecitabine After Resection of Pancreatic Adenocarcinoma
NCT01401387	PHASE4	WITHDRAWN	Pancreatic Enzyme Suppletion in Pancreatic Cancer
NCT02812992	PHASE4	COMPLETED	Geriatric Assessment Directed Trial to Evaluate Gemcitabine +/- Nab-paclitaxel in Elderly Pancreatic Cancer Patients
NCT03401827	PHASE4	UNKNOWN	The Effect of Gemcitabine Plus Nab-paclitaxel as Secondary Chemotherapy in Advanced Pancreatic Cancer
NCT07262957	PHASE4	RECRUITING	Preventing Postoperative Complications in Patients Undergoing High-risk Pancreatoduodenectomy With a Bundle Approach Including Hydrocortisone, Octreotide, and the Teres Ligament Patch (PANENCA)
NCT00088894	PHASE3	COMPLETED	Gemcitabine With or Without Bevacizumab in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
NCT01013649	PHASE3	COMPLETED	Gemcitabine Hydrochloride With or Without Erlotinib Hydrochloride Followed by the Same Chemotherapy Regimen With or Without Radiation Therapy and Capecitabine or Fluorouracil in Treating Patients With Pancreatic Cancer That Has Been Removed by Surgery
NCT01231347	PHASE3	COMPLETED	QUILT-2.014: Gemcitabine and AMG 479 in Metastatic Adenocarcinoma of the Pancreas
NCT01360853	PHASE3	COMPLETED	Gemcitabine and ON 01910.Na in Previously Untreated Metastatic Pancreatic Cancer
NCT01419002	PHASE3	TERMINATED	Study to Evaluate if Neoadjuvant Radiotherapy Improves Recurrence Free Survival in Pancreatic Head Cancer
NCT01526135	PHASE3	COMPLETED	Trial Comparing Adjuvant Chemotherapy With Gemcitabine Versus mFolfirinox to Treat Resected Pancreatic Adenocarcinoma
NCT01954992	PHASE3	RECRUITING	Glufosfamide Versus 5-FU in Second Line Metastatic Pancreatic Cancer
NCT02184195	PHASE3	COMPLETED	Olaparib in gBRCA Mutated Pancreatic Cancer Whose Disease Has Not Progressed on First Line Platinum-Based Chemotherapy
NCT02436668	PHASE3	COMPLETED	Study of Ibrutinib vs Placebo, in Combination With Nab-paclitaxel and Gemcitabine, in the First Line Treatment of Patients With Metastatic Pancreatic Adenocarcinoma (RESOLVE)
NCT03126435	PHASE3	COMPLETED	EndoTAG-1+GEM vs GEM in Patients With Locally Advanced/Metastatic Pancreatic Adenocarcinoma Failed on FOLFIRINOX
NCT03377491	PHASE3	COMPLETED	Effect of Tumor Treating Fields (TTFields, 150 kHz) as Front-Line Treatment of Locally-advanced Pancreatic Adenocarcinoma Concomitant With Gemcitabine and Nab-paclitaxel (PANOVA-3)
NCT03536182	PHASE3	WITHDRAWN	Trial of Carbon Ion Versus Photon Radiotherapy for Locally Advanced, Unresectable Pancreatic Cancer
NCT03649035	PHASE3	WITHDRAWN	Eus-guided Cryothermal Ablation in Stage III Pancreatic Adenocarcinoma
NCT03665441	PHASE3	COMPLETED	Study of Eryaspase in Combination With Chemotherapy Versus Chemotherapy Alone as 2nd-Line Treatment in PAC
NCT03943667	PHASE3	COMPLETED	Gemcitabine and Paclitaxel vs Gemcitabine Alone After FOLFIRINOX Failure in Metastatic Pancreatic Ductal Adenocarcinoma
NCT04083235	PHASE3	COMPLETED	A Study to Assess the Effectiveness and Safety of Irinotecan Liposome Injection, 5-fluorouracil/Leucovorin Plus Oxaliplatin in Patients Not Previously Treated for Metastatic Pancreatic Cancer, Compared to Nab-paclitaxel+Gemcitabine Treatment
NCT04167007	PHASE3	UNKNOWN	FOLFOX vs Gemcitabine in Patients With Metastatic Pancreatic Cancer Non-fit to FOLFIRINOX
NCT04229004	PHASE3	COMPLETED	A Multi-center Trial to Evaluate Multiple Regimens in Metastatic Pancreatic Cancer
NCT04617821	PHASE3	UNKNOWN	AG vs mFOLFIRINOX as Neoadjuvant Therapy for Borderline Reseactable and Locally Advanced Pancreatic Cancer
NCT04835064	PHASE3	UNKNOWN	Pancreatic Cancer With Elevated Serum CA125 Were Compared With Those Who Did Not Receive Neoadjuvant Chemotherapy.
NCT05482516	PHASE3	RECRUITING	Evaluating Novel Therapies in ctDNA Positive GI Cancers
NCT06018883	PHASE3	ACTIVE_NOT_RECRUITING	Vitamin C to Chemotherapy Related Anemia in Pancreatic Cancer
NCT06250972	PHASE3	RECRUITING	Radiotherapy to Patients With CA19-9-elevated Advanced Pancreatic Cancer
NCT06714604	PHASE3	RECRUITING	Standard or Prolonged Neoadjuvant Chemotherapy Before Surgery for BR/LAPC
NCT06861088	PHASE3	RECRUITING	The Effect of Kinisoquin™ on Thromboembolic Events in Patients With Metastatic or Locally Advanced Pancreatic Cancer
NCT06998940	PHASE3	RECRUITING	Studying Chemotherapy With or Without Panitumumab for Unresectable, Locally Advanced, or Metastatic Pancreatic Cancer Without KRAS Mutations
NCT07081360	PHASE3	RECRUITING	Neoadjuvant vs Upfront Surgery for Resectable Pancreatic Cancer and Periampullary Cancer
NCT07409272	PHASE3	RECRUITING	A Study to Evaluate the Effectiveness and Safety of Setidegrasib, Given With Either mFOLFIRINOX or NALIRIFOX Chemotherapies, in People With Pancreatic Cancer
NCT07491445	PHASE3	RECRUITING	Study of Daraxonrasib and Daraxonrasib + GnP as First-line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma
NCT07562152	PHASE3	RECRUITING	Atebimetinib + GnP as a First Line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma
NCT00020345	PHASE2	COMPLETED	Combination Chemotherapy and Radiation Therapy Plus Surgery in Treating Patients With Advanced Cancer of the Pancreas
NCT00026104	PHASE2	COMPLETED	Combination Chemotherapy Plus Radiation Therapy With or Without Tipifarnib in Treating Patients With Locally Advanced Pancreatic Cancer
NCT00028834	PHASE2	COMPLETED	Bevacizumab and Gemcitabine in Treating Patients With Advanced Pancreatic Cancer
NCT00075647	PHASE2	COMPLETED	CCI-779 in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
NCT00091026	PHASE2	COMPLETED	Bevacizumab and Gemcitabine Combined With Either Cetuximab or Erlotinib in Treating Patients With Advanced Pancreatic Cancer