DDIT3

Summary

DDIT3 (DNA damage inducible transcript 3, HGNC:2726) is a protein-coding gene on chromosome 12q13.3, encoding DDIT3 upstream open reading frame protein (P0DPQ6). Product of the upstream open reading frame (uORF) of DDIT3/CHOP that is specifically produced in absence of stress, thereby preventing translation of downstream stress effector DDIT3/CHOP.

This gene encodes a member of the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors. The protein functions as a dominant-negative inhibitor by forming heterodimers with other C/EBP members, such as C/EBP and LAP (liver activator protein), and preventing their DNA binding activity. The protein is implicated in adipogenesis and erythropoiesis, is activated by endoplasmic reticulum stress, and promotes apoptosis. Fusion of this gene and FUS on chromosome 16 or EWSR1 on chromosome 22 induced by translocation generates chimeric proteins in myxoid liposarcomas or Ewing sarcoma. Multiple alternatively spliced transcript variants encoding two isoforms with different length have been identified.

Source: NCBI Gene 1649 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 32 total
• Phenotypes (HPO): 3
• Transcription factor: yes — 104 downstream targets (CollecTRI)
• MANE Select transcript: NM_004083

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2726
Approved symbol	DDIT3
Name	DNA damage inducible transcript 3
Location	12q13.3
Locus type	gene with protein product
Status	Approved
Aliases	CHOP10, GADD153, CHOP
Ensembl gene	ENSG00000175197
Ensembl biotype	protein_coding
OMIM	126337
Entrez	1649

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000346473, ENST00000547303, ENST00000547526, ENST00000551116, ENST00000552740, ENST00000623876

RefSeq mRNA: 8 — MANE Select: NM_004083 NM_001195053, NM_001195054, NM_001195055, NM_001195056, NM_001195057, NM_001413641, NM_001413642, NM_004083

CCDS: CCDS55838, CCDS8943

Canonical transcript exons

ENST00000346473 — 4 exons

Exon	Start	End
ENSE00001179644	57517706	57517753
ENSE00001268595	57517269	57517438
ENSE00002378057	57516593	57517180
ENSE00003917401	57520418	57520514

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 54.2863 / max 2350.5358, expressed in 1816 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131706	54.2863	1816

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	97.26	gold quality
pituitary gland	UBERON:0000007	96.67	gold quality
left lobe of thyroid gland	UBERON:0001120	96.44	gold quality
thyroid gland	UBERON:0002046	96.35	gold quality
substantia nigra	UBERON:0002038	95.79	gold quality
mucosa of stomach	UBERON:0001199	95.77	gold quality
right lobe of thyroid gland	UBERON:0001119	95.76	gold quality
hypothalamus	UBERON:0001898	95.76	gold quality
putamen	UBERON:0001874	95.72	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.60	gold quality
caudate nucleus	UBERON:0001873	95.53	gold quality
right lobe of liver	UBERON:0001114	95.44	gold quality
cortex of kidney	UBERON:0001225	95.40	gold quality
nucleus accumbens	UBERON:0001882	95.40	gold quality
popliteal artery	UBERON:0002250	95.00	gold quality
tibial artery	UBERON:0007610	94.98	gold quality
thoracic mammary gland	UBERON:0005200	94.71	gold quality
omental fat pad	UBERON:0010414	94.71	gold quality
adult mammalian kidney	UBERON:0000082	94.60	gold quality
Ammon’s horn	UBERON:0001954	94.53	gold quality
adipose tissue	UBERON:0001013	94.42	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.34	gold quality
anterior cingulate cortex	UBERON:0009835	94.29	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.26	gold quality
amygdala	UBERON:0001876	94.03	gold quality
brain	UBERON:0000955	94.02	gold quality
metanephros cortex	UBERON:0010533	93.95	gold quality
temporal lobe	UBERON:0001871	93.94	gold quality
left adrenal gland cortex	UBERON:0035825	93.92	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.89	gold quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-MTAB-7052	yes	3128.43
E-GEOD-98556	yes	1540.16
E-HCAD-31	yes	1227.11
E-MTAB-9154	yes	1153.20
E-MTAB-10485	yes	1052.62
E-GEOD-81608	yes	1008.34
E-MTAB-11121	yes	913.03
E-MTAB-10018	yes	910.37
E-MTAB-8530	yes	810.01
E-GEOD-76312	yes	638.63
E-MTAB-8559	yes	638.16
E-GEOD-75140	yes	388.72
E-HCAD-5	yes	31.81
E-HCAD-4	yes	19.81
E-GEOD-135922	yes	13.11

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

104 targets.

Target	Regulation
ADH1C
ADIPOQ	Repression
ANKRD1	Repression
AP1	Activation
ASNS	Repression
ATF2	Repression
ATF4
ATF5	Repression
ATG5	Activation
BAK1	Activation
BBC3	Activation
BCL2	Repression
BCL2L11	Activation
BDKRB2	Unknown
BGLAP	Repression
CA6
CALCA
CASP3
CASP4
CASP9
CAT
CCL2	Activation
CCL5	Repression
CDK2	Unknown
CDK9
CDKN1A	Activation
CEBPA	Repression
CEBPB	Repression
CEBPD
CRP	Unknown

Upstream regulators (CollecTRI, top): AP1, ATF2, ATF3, ATF4, ATF5, ATF6, BRCA1, CEBPB, CEBPD, CEBPG, DDIT3, E2F1, EIF2AK3, EIF2AK4, ESR1, ETS1, FLCN, FLI1, FOS, FOXO3, FUS, JDP2, JUN, MAFA, MAFG, MAX, MYC, NCK1, NFE2L2, NFKB1, NFYA, PIGBOS1, PPARA, PPARG, PPP1R15A, RB1, RELA, SLC7A5, SP1, STAT3

miRNA regulators (miRDB)

20 targeting DDIT3, 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-96-5P	99.95	72.80	2140
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-299-3P	97.73	66.67	773
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-663B	97.40	62.91	664
HSA-MIR-4654	95.86	65.72	751
HSA-MIR-4769-5P	95.37	66.09	570
HSA-MIR-769-5P	94.45	64.56	603

Literature-anchored findings (GeneRIF, showing 40)

• Nitric oxide-induced apoptosis in RAW 264.7 macrophages is mediated by endoplasmic reticulum stress pathway involving ATF6 and CHOP (PMID:11805088)
• Activation of peroxisome proliferator-activated receptor-gamma stimulates the growth arrest and DNA-damage inducible 153 gene in non-small cell lung carcinoma cells (PMID:11948400)
• expression mediated by AP-1 and C-EBP is involved in deoxycholic acid-induced apoptosis (PMID:12069855)
• HRG stimulation of mammary epithelial cells induces the expression of GADD153 mRNA and protein and transcription of GADD153 promoter. (PMID:12082616)
• Genomic sequences necessary for transcriptional activation by amino acid deprivation of mammalian cells. chop expression is associated with cell stress and apoptosis. (PMID:12097650)
• These results suggest that GADD153 overexpression induced by N-(4-hydroxyphenyl)retinamide(4HPR) may contribute to the anticancer effects (induction of apoptosis and growth arrest) of 4HPR on cancer cells. (PMID:12138118)
• GADD 153 may play an important role in melanoma progression (PMID:12168790)
• This nuclear transcription factor triggers down-regulation of TFF expression in human stomach neoplasm cells cultivated in vitro. (PMID:12297725)
• CHOP (C/EBPzeta)is constitutively multiubiquitinated & degraded by the proteasome. Ubiquitination and degradation are suppressed by forming dimers through the leucine zipper domains. (PMID:12618752)
• CHOP up-regulates IL-6 transcription by trapping negative regulating NF-IL6 isoform. (PMID:12706815)
• CK2-mediated phosphorylation of CHOP inhibits its transcriptional activity (PMID:12876286)
• Transferrin and other target genes identified may play a functional role in the downstream pathway of GADD153. (PMID:12939601)
• CHOP expression induction by amino acid limitation requires both ATF4 expression and ATF2 phosphorylation (PMID:14630918)
• These findings suggest that phenethylisothiocyanate creates an oxidative cellular environment that induces DNA damage and GADD153, 34 and 45 gene activation, which in turn helps trigger apoptosis (PMID:14635187)
• Oil A induces apoptosis of pancreatic cancer cells via activating caspase cascade, modifying cell cycle progress and changing cell cycle-regulating proteins and GADD expression. (PMID:14669326)
• One of the components of the Endoplasmic reticulum stress-mediated apoptosis pathway is C/EBP homologous protein (CHOP), also known as growth arrest- and DNA damage-inducible gene 153 (GADD153). (PMID:14685163)
• AP1 and CHOP are induced by MEKK3 and have roles in TRAF7-related apoptosis (PMID:15001576)
• Depriving cells of iron increased mRNA expression of GADD153 at the level of transcription rather than mRNA stability; neither reactive oxygen species nor DNA damage was involved in triggering GADD153 gene activation (PMID:15053923)
• GADD153 protein was detected before the appearance of apoptotic features in colon cancer cells, which raises the possibility that GADD153 protein might be important for curcumin-induced apoptosis. (PMID:15271854)
• CRP induced an increase of GADD153 mRNA expression. CRP regulation of GADD153 in VSMCs occurs at the posttranscriptional level by mRNA stabilization. GADD153 colocalized to apoptotic VSMCs in coronary lesions, supporting a role in CRP-induced cell death. (PMID:15277326)
• data suggest that different FUS/CHOP variants cause transformation of mesenchymal cells via the same pathways with comparable efficacy (PMID:15286712)
• Retinoic acid signaling in granulocytic differentiation involves regulated expression of CHOP and C/EBPepsilon in a coordinated fashion. (PMID:15308577)
• deoxycholate-induced upregulation of GADD153 mRNA expression occurred at the level of transcription without involving reactive oxygen species and MAPK signaling (PMID:15316935)
• Results indicate that PKC, especially PKCdelta, plays an important role in the induction of GADD153 mRNA following oxidative stress. (PMID:15327748)
• Prostaglandin E2 induces interleukin-8 gene transcription by activating C/EBP homologous protein in human T lymphocytes (PMID:15659384)
• Effect of FUS-DDIT3 fusion on IL6 expression is C/EBP beta dependent in myxoid lipoxarcoma. (PMID:15688424)
• oncogenic Ras-mediated cellular transformation also involves downmodulation of important molecules such as Gadd153 that negatively regulate cell growth and survival (PMID:15870698)
• data provide the first evidence that the posttranscriptional expression of the Gadd153 gene can be regulated by ROS produced by All-trans-N-(4-hydroxyphenyl)retinamide (PMID:15917187)
• insufficient dosage of C/EBPzeta might be involved in the development of leukemia (PMID:16005964)
• CHOP participates in adaptive responses of the epidermis following UVB/UVA exposure in vivo (PMID:16098044)
• Data show that C/EBP zeta was down-regulated in CML patients, which might play a role in the leukemogenesis. (PMID:16331558)
• Upregulation of GADD153 is a key requirement for cancer prevention in combination with EGCG. (PMID:16463383)
• The fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype when expressed in a primitive sarcoma cell line. (PMID:16651630)
• hypoglycaemia-induced necrotic cell death of neuroblastoma cells is an active process mediated via the induction of the transcription factor CHOP (PMID:16942595)
• Findings suggest that a regulatory thiol redox-sensitive signaling cascade exists in the molecular pathway leading to induction of GADD153 expression by curcumin. (PMID:17171638)
• DR5/TRAIL-R2 expression is upregulated by fenretinide via the induction of the transcription factor CHOP (PMID:17273769)
• results suggest that the presence of MELAS and NARP mtDNA mutations elicits upregulation of CHOP and ASNS genes through the elevation of ATF4 expression and its binding to the amino acid regulatory element and nutrient-sensing response element-1 (PMID:17276738)
• FUS-DDIT3 is a chimeric oncogene generated by the most common chromosomal translocation t(12;16)(q13;p11) associated to liposarcomas. (PMID:17468515)
• A switch between C/enhancer-binding protein (CEBP) zeta and CEBP beta operates at the CEBP site on the C-reactive protein (CRP)promoter to regulate CRP transcription. (PMID:17513780)
• GADD153 (CHOP) and Bcl-2-binding component 3 (PUMA) and apoptosis are induced by 4-hydroxybenzylretinone in a process that is caspase- dependent and independent of the retinoic acid receptor (PMID:17616685)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ddit3	ENSDARG00000059836
mus_musculus	Ddit3	ENSMUSG00000025408
rattus_norvegicus	Ddit3	ENSRNOG00000006789

Protein

Protein identifiers

DDIT3 upstream open reading frame protein — P0DPQ6 (reviewed: P0DPQ6, P35638)

Alternative names: Alternative DDIT3 protein

All UniProt accessions (3): F8W133, P35638, Q53YD1

UniProt curated annotations — full annotation on UniProt →

Function. Product of the upstream open reading frame (uORF) of DDIT3/CHOP that is specifically produced in absence of stress, thereby preventing translation of downstream stress effector DDIT3/CHOP.

Subunit / interactions. Interacts with DDIT3 (isoform 1).

Subcellular location. Nucleus. Cytoplasm.

Isoforms (3)

UniProt ID	Names	Canonical?
P0DPQ6-1	AltDDIT3	yes
P35638-1	1
P35638-2	2

RefSeq proteins (8): NP_001181982, NP_001181983, NP_001181984, NP_001181985, NP_001181986, NP_001400570, NP_001400571, NP_004074* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004827	bZIP	Domain
IPR016670	DNA_damage_induc_transcript_3	Family

Pfam: PF07716

UniProt features (19 total): modified residue 6, region of interest 5, chain 2, compositionally biased region 2, domain 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DPQ6-F1	84.76	0.17
AF-P35638-F1	71.54	0.32

Functional residue map

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

Post-translational modifications (6): 15, 30, 31, 79, 82, 14

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-380994	ATF4 activates genes in response to endoplasmic reticulum stress
R-HSA-381183	ATF6 (ATF6-alpha) activates chaperone genes
R-HSA-9614657	FOXO-mediated transcription of cell death genes
R-HSA-9633012	Response of EIF2AK4 (GCN2) to amino acid deficiency
R-HSA-9648895	Response of EIF2AK1 (HRI) to heme deficiency

MSigDB gene sets: 534 (showing top): MODULE_52, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, GOBP_AXIS_SPECIFICATION, TSENG_IRS1_TARGETS_UP, PAX4_01, HARRIS_HYPOXIA, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, GOBP_NEGATIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS

GO Biological Process (54): diaphragm contraction (GO:0002086), ER overload response (GO:0006983), sensory perception of sound (GO:0007605), response to wounding (GO:0009611), gene expression (GO:0010467), endoplasmic reticulum unfolded protein response (GO:0030968), response to platelet-derived growth factor (GO:0036119), negative regulation of fat cell differentiation (GO:0045599), artery development (GO:0060840), response to caloric restriction (GO:0061771), intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059), calcium ion import (GO:0070509), vascular associated smooth muscle cell migration (GO:1904738), vascular associated smooth muscle cell proliferation (GO:1990874), negative regulation of transcription by RNA polymerase II (GO:0000122), blood vessel maturation (GO:0001955), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), DNA damage response (GO:0006974), response to unfolded protein (GO:0006986), anterior/posterior axis specification (GO:0009948), regulation of autophagy (GO:0010506), Wnt signaling pathway (GO:0016055), negative regulation of type II interferon production (GO:0032689), negative regulation of interleukin-17 production (GO:0032700), negative regulation of interleukin-4 production (GO:0032713), positive regulation of interleukin-8 production (GO:0032757), response to endoplasmic reticulum stress (GO:0034976), intracellular signal transduction (GO:0035556), PERK-mediated unfolded protein response (GO:0036499), ATF6-mediated unfolded protein response (GO:0036500), response to starvation (GO:0042594), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), positive regulation of neuron apoptotic process (GO:0043525), cell redox homeostasis (GO:0045454), negative regulation of myoblast differentiation (GO:0045662), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), release of sequestered calcium ion into cytosol (GO:0051209)

GO Molecular Function (16): DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), transcription corepressor activity (GO:0003714), cAMP response element binding protein binding (GO:0008140), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), leucine zipper domain binding (GO:0043522), protein heterodimerization activity (GO:0046982), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), transcription regulator inhibitor activity (GO:0140416), transcription regulator activator activity (GO:0140537), protein binding (GO:0005515)

GO Cellular Component (11): nucleus (GO:0005634), cytoplasm (GO:0005737), late endosome (GO:0005770), chromatin (GO:0000785), transcription regulator complex (GO:0005667), cytosol (GO:0005829), protein-DNA complex (GO:0032993), CHOP-C/EBP complex (GO:0036488), RNA polymerase II transcription regulator complex (GO:0090575), CHOP-ATF4 complex (GO:1990617), CHOP-ATF3 complex (GO:1990622)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
PERK regulates gene expression	1
ATF6 (ATF6-alpha) activates chaperones	1
FOXO-mediated transcription	1
Cellular response to starvation	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to endoplasmic reticulum stress	3
regulation of gene expression	3
transcription regulator activity	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
response to stress	2
blood vessel development	2
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
regulation of DNA-templated transcription	2
DNA-binding transcription factor binding	2
protein dimerization activity	2
protein-containing complex	2
RNA polymerase II transcription regulator complex	2
transcription regulator complex	2
nuclear protein-containing complex	2
involuntary skeletal muscle contraction	1
respiratory system process	1
ER-nucleus signaling pathway	1
cellular response to biotic stimulus	1
sensory perception of mechanical stimulus	1
macromolecule biosynthetic process	1
cellular response to unfolded protein	1
intracellular signal transduction	1
response to growth factor	1
fat cell differentiation	1
negative regulation of cell differentiation	1
regulation of fat cell differentiation	1
response to nutrient levels	1
intrinsic apoptotic signaling pathway	1
calcium ion transport	1
smooth muscle cell migration	1
smooth muscle cell proliferation	1
anatomical structure maturation	1
DNA-templated transcription	1
regulation of RNA biosynthetic process	1
cellular response to stress	1
response to topologically incorrect protein	1
nucleic acid binding	1

Protein interactions and networks

STRING

8 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DDIT3	BEST3	Q8N1M1	578
DDIT3	BEST2	Q8NFU1	349
DDIT3	BEST1	O76090	203
DDIT3	NES	P48681	199

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A0C5B5G6, A0A1D0BRC1, A0A2R8VHR8, B3SRS6, B3SRV8, C0H444, O22426, O24369, P03055, P04567, P06556, P06919, P0C5L9, P0C5N5, P0C5P8, P0CAR3, P0CJ71, P0DKI9, P0DPM5, P0DPN2, P0DPN6, P0DPP8, P0DPQ6, P0DSF6, P0DSG5, P0DSH6, P0DV19, P0DV21, P16607, P20326, P23053, P25430, P42456, P53175, P55959, P59036, P82452, Q02210, Q47268, Q6IM87

Diamond homologs: A0A2R8VHR8, P0DPQ6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

691 predictions. Top by Δscore:

Variant	Effect	Δscore
12:57517176:TCTTC:T	acceptor_loss	1.0000
12:57517177:CTTC:C	acceptor_gain	1.0000
12:57517180:CCTT:C	acceptor_loss	1.0000
12:57517181:C:CC	acceptor_gain	1.0000
12:57517181:C:CG	acceptor_loss	1.0000
12:57517182:T:A	acceptor_loss	1.0000
12:57517184:C:CT	acceptor_gain	1.0000
12:57517185:A:T	acceptor_gain	1.0000
12:57517191:A:AC	acceptor_gain	1.0000
12:57517191:A:C	acceptor_gain	1.0000
12:57517265:TTA:T	donor_loss	1.0000
12:57517266:TA:T	donor_loss	1.0000
12:57517267:A:AC	donor_gain	1.0000
12:57517267:A:AT	donor_loss	1.0000
12:57517268:C:CC	donor_gain	1.0000
12:57517268:CCT:C	donor_gain	1.0000
12:57517376:C:CT	acceptor_gain	1.0000
12:57517376:C:T	acceptor_gain	1.0000
12:57517377:G:T	acceptor_gain	1.0000
12:57517700:GTTTA:G	donor_loss	1.0000
12:57517701:TTTA:T	donor_loss	1.0000
12:57517702:TTA:T	donor_loss	1.0000
12:57517704:ACCT:A	donor_loss	1.0000
12:57517705:CCTG:C	donor_gain	1.0000
12:57517705:CCTGC:C	donor_loss	1.0000
12:57517752:CA:C	acceptor_gain	1.0000
12:57517754:C:CC	acceptor_gain	1.0000
12:57517178:TTC:T	acceptor_gain	0.9900
12:57517181:C:T	acceptor_gain	0.9900
12:57517302:C:CA	donor_gain	0.9900

AlphaMissense

1091 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:57516876:A:G	L148P	0.993
12:57516897:A:G	L141P	0.992
12:57517346:A:G	W21R	0.992
12:57517346:A:T	W21R	0.992
12:57517333:A:G	L25P	0.991
12:57516843:A:G	L159P	0.989
12:57516852:C:G	R156P	0.984
12:57516853:G:T	R156S	0.978
12:57516834:C:G	R162P	0.975
12:57517344:C:A	W21C	0.973
12:57517344:C:G	W21C	0.973
12:57517333:A:T	L25Q	0.971
12:57516918:A:G	L134P	0.970
12:57516840:A:T	I160N	0.968
12:57517337:C:G	D24H	0.967
12:57516847:C:G	A158P	0.966
12:57516852:C:A	R156L	0.965
12:57517343:A:C	Y22D	0.965
12:57516843:A:T	L159Q	0.963
12:57517333:A:C	L25R	0.958
12:57517336:T:G	D24A	0.957
12:57517342:T:G	Y22S	0.954
12:57517321:A:G	L29P	0.953
12:57516865:C:A	V152L	0.948
12:57516865:C:G	V152L	0.948
12:57517345:C:G	W21S	0.945
12:57516840:A:C	I160S	0.943
12:57516853:G:C	R156G	0.938
12:57516906:T:A	N138I	0.938
12:57517343:A:G	Y22H	0.937

dbSNP variants (sampled 300 via entrez): RS1000179989 (12:57519646 G>A,C), RS1000204759 (12:57519297 C>T), RS1000247810 (12:57518166 G>A), RS1000321044 (12:57518956 G>A,C,T), RS1000576589 (12:57520323 A>C,G), RS1000632053 (12:57519244 T>C), RS1001783325 (12:57518722 G>A), RS1002117148 (12:57520035 G>A,C), RS1002998215 (12:57523470 G>T), RS1003423249 (12:57520872 T>C,G), RS1004026494 (12:57522930 C>T), RS1004469897 (12:57519694 A>G), RS1004813828 (12:57518783 G>A,C,T), RS1004936408 (12:57518608 T>C), RS1006203584 (12:57519967 G>A)

Disease associations

OMIM: gene MIM:126337 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0001482	Subcutaneous nodule
HP:0002027	Abdominal pain
HP:0002579	Gastrointestinal dysmotility

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010703_209	Brain morphology (MOSTest)	2.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetylcysteine	affects cotreatment, decreases reaction, increases expression, increases reaction, increases abundance (+1 more)	34
Thapsigargin	increases expression, increases reaction, decreases response to substance, affects cotreatment, increases activity (+3 more)	32
Tunicamycin	affects cotreatment, increases reaction, increases activity, decreases reaction, increases expression	30
4-phenylbutyric acid	increases expression, increases phosphorylation, affects localization, increases reaction, affects expression (+2 more)	26
sodium arsenite	affects cotreatment, increases abundance, decreases reaction, increases expression, affects reaction (+3 more)	19
Cyclosporine	increases expression, affects expression, affects cotreatment, affects reaction, affects localization (+1 more)	16
Arsenic Trioxide	affects expression, affects response to substance, decreases reaction, increases expression, increases reaction (+3 more)	15
Cadmium Chloride	increases abundance, increases expression, decreases expression, decreases reaction	12
1-Methyl-4-phenylpyridinium	decreases reaction, affects expression, increases expression	11
Particulate Matter	affects cotreatment, affects expression, increases reaction, decreases expression, decreases reaction (+2 more)	11
Bortezomib	affects cotreatment, increases expression, increases reaction, affects reaction, decreases response to substance (+3 more)	10
Cisplatin	decreases expression, affects binding, increases reaction, decreases reaction, increases expression (+2 more)	10
bisphenol A	decreases reaction, increases expression, affects expression, decreases methylation	9
pyrazolanthrone	decreases reaction, increases expression	9
Capsaicin	affects localization, increases expression	9
Paraquat	decreases reaction, increases expression, increases reaction, affects cotreatment, affects expression (+1 more)	9
Resveratrol	decreases activity, decreases expression, decreases reaction, increases expression, increases reaction (+2 more)	8
Tobacco Smoke Pollution	affects expression, decreases reaction, increases expression, increases phosphorylation, increases activity (+1 more)	8
arsenite	decreases reaction, increases abundance, affects binding, increases reaction, increases expression	7
ochratoxin A	increases expression, increases reaction, decreases methylation, decreases reaction, affects reaction (+1 more)	7
salubrinal	decreases reaction, increases expression, increases reaction	7
Cadmium	decreases reaction, increases abundance, increases expression	7
Quercetin	affects reaction, affects cotreatment, increases cleavage, affects localization, decreases expression (+2 more)	7
methylselenic acid	affects reaction, increases expression, decreases reaction	6
perfluorooctanoic acid	increases activity, increases expression	6
hydroquinone	decreases reaction, increases expression, affects localization	6
Doxorubicin	increases reaction, decreases expression, affects reaction, decreases reaction, increases expression (+1 more)	6
ursodoxicoltaurine	affects localization, decreases reaction, increases expression	5
epigallocatechin gallate	affects localization, affects cotreatment, decreases reaction, increases expression	5
7-methyl-5-(1-((3-(trifluoromethyl)phenyl)acetyl)-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo(2,3-d)pyrimidin-4-amine	affects cotreatment, decreases reaction, increases abundance, increases expression, decreases expression	5

Cellosaurus cell lines

15 cell lines: 11 cancer cell line, 4 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A1VS	NCC-MLPS1-C1	Cancer cell line	Male
CVCL_AX37	HT1080 FUS-DDIT3-EGFP	Cancer cell line	Male
CVCL_B0YS	Abcam SW480 DDIT3 KO	Cancer cell line	Male
CVCL_B1PW	Abcam HeLa DDIT3 KO	Cancer cell line	Female
CVCL_C1GI	NCC-MLPS2-C1	Cancer cell line	Female
CVCL_C1GJ	NCC-MLPS3-C1	Cancer cell line	Female
CVCL_C8SV	HeLa S3 CHOP KO by CRISPR	Cancer cell line	Female
CVCL_C8SW	HeLa S3 CHOP KO by TALEN	Cancer cell line	Female
CVCL_C8SX	HeLa S3 CHOP/ATF4/ATF5 triple KO	Cancer cell line	Female
CVCL_DQ91	DL-221	Cancer cell line	Male

Clinical trials (associated diseases)

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