GADD45A

Summary

GADD45A (growth arrest and DNA damage inducible alpha, HGNC:4095) is a protein-coding gene on chromosome 1p31.3, encoding Growth arrest and DNA damage-inducible protein GADD45 alpha (P24522). In T-cells, functions as a regulator of p38 MAPKs by inhibiting p88 phosphorylation and activity.

This gene is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The protein encoded by this gene responds to environmental stresses by mediating activation of the p38/JNK pathway via MTK1/MEKK4 kinase. The DNA damage-induced transcription of this gene is mediated by both p53-dependent and -independent mechanisms. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

Source: NCBI Gene 1647 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 15 total
• MANE Select transcript: NM_001924

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4095
Approved symbol	GADD45A
Name	growth arrest and DNA damage inducible alpha
Location	1p31.3
Locus type	gene with protein product
Status	Approved
Aliases	GADD45
Ensembl gene	ENSG00000116717
Ensembl biotype	protein_coding
OMIM	126335
Entrez	1647

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 retained_intron

ENST00000370985, ENST00000370986, ENST00000460575, ENST00000484245, ENST00000617962, ENST00000648742, ENST00000650283

RefSeq mRNA: 3 — MANE Select: NM_001924 NM_001199741, NM_001199742, NM_001924

CCDS: CCDS55605, CCDS640, CCDS72806

Canonical transcript exons

ENST00000370986 — 4 exons

Exon	Start	End
ENSE00000774372	67686350	67686587
ENSE00000774373	67686025	67686126
ENSE00001677170	67687661	67688334
ENSE00001867603	67685201	67685538

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.1831 / max 757.1166, expressed in 1822 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3412	59.4952	1819
3415	4.8760	1622
3417	1.1500	664
3414	1.0433	631
3413	0.3323	156
3416	0.1990	69
3411	0.0873	50

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
descending thoracic aorta	UBERON:0002345	98.63	gold quality
vena cava	UBERON:0004087	98.61	gold quality
ascending aorta	UBERON:0001496	98.58	gold quality
thoracic aorta	UBERON:0001515	98.58	gold quality
aorta	UBERON:0000947	98.17	gold quality
popliteal artery	UBERON:0002250	97.89	gold quality
tibial artery	UBERON:0007610	97.88	gold quality
renal glomerulus	UBERON:0000074	97.68	gold quality
metanephric glomerulus	UBERON:0004736	97.66	gold quality
kidney epithelium	UBERON:0004819	97.51	gold quality
adult mammalian kidney	UBERON:0000082	97.45	gold quality
cartilage tissue	UBERON:0002418	97.44	gold quality
left coronary artery	UBERON:0001626	97.39	gold quality
right coronary artery	UBERON:0001625	97.36	gold quality
seminal vesicle	UBERON:0000998	97.32	gold quality
type B pancreatic cell	CL:0000169	97.28	gold quality
coronary artery	UBERON:0001621	97.08	gold quality
nephron tubule	UBERON:0001231	97.01	gold quality
kidney	UBERON:0002113	96.61	gold quality
gastrocnemius	UBERON:0001388	96.43	gold quality
omental fat pad	UBERON:0010414	96.37	gold quality
peritoneum	UBERON:0002358	96.33	gold quality
cortex of kidney	UBERON:0001225	96.32	gold quality
pericardium	UBERON:0002407	96.32	gold quality
decidua	UBERON:0002450	96.10	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.03	gold quality
calcaneal tendon	UBERON:0003701	95.86	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.84	gold quality
metanephros	UBERON:0000081	95.72	gold quality
left ventricle myocardium	UBERON:0006566	95.71	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-GEOD-114530	yes	2287.18
E-HCAD-38	yes	2163.97
E-GEOD-124472	yes	1658.74
E-MTAB-10018	yes	531.32
E-MTAB-8142	yes	91.58
E-MTAB-10287	yes	47.22
E-HCAD-10	yes	29.64
E-GEOD-84465	yes	27.22
E-MTAB-6701	yes	21.65
E-HCAD-13	yes	7.43
E-GEOD-130148	yes	4.67
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ASCL1, ATF2, ATF3, ATM, BHLHE41, BRCA1, CEBPA, CEBPB, CEBPD, CEBPG, DDIT3, E2F4, EGR1, ESR2, FOXC1, FOXO1, FOXO3, FOXO4, HES1, JUN, JUND, LITAF, MAX, MEF2D, MYC, NACC1, NFIC, NFKB1, NFKBIA, NFYA, NKX3-1, NR2C2, NR3C2, OVOL1, PAX5, POU2F1, POU5F1, PPARG, RUNX1

miRNA regulators (miRDB)

77 targeting GADD45A, 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-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4698	99.84	71.41	4303

Literature-anchored findings (GeneRIF, showing 40)

• immunodepletion of Oct-1 and NF-YA proteins or mutations in the OCT-1 and CAAT motifs disrupt BRCA1 binding to the GADD45 promoter (PMID:11777930)
• Early induction of CDKN1A (p21) and GADD45 mRNA by a low dose of ionizing radiation is due to their dose-dependent post-transcriptional regulation. (PMID:11893252)
• GADD 45 may play an important role in melanoma progression (PMID:12168790)
• GADD45a has a role in pancreatic cancer [review] (PMID:12171872)
• role in G2-M arrest is associated with altered subcellular distribution of cyclin B1 and is independent of p38 kinase activity (PMID:12483522)
• GADD45 is an important mediator for the tumor-suppressing activity of 1,25-dihydroxyvitamin D3 in human ovarian cancer cells (PMID:14506229)
• Gadd45a transcription is repressed through ZBRK1 binding to a specific sequence in intron 3 (PMID:14517299)
• Histone deacetylase inhibitors can induce Gadd45 through its promoter without the need for functional p53, and both Oct-1 and NF-Y concertedly participate in trichostatin A-induced activation of the gadd45 promoter. (PMID:14586402)
• 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)
• Silencing of GADD45gamma, a negative regulator of cell growth, is most likely responsible for conferring a selective growth advantage during tumour evolution and outgrowth (PMID:14647444)
• Akt and P70S6K phosphorylation and Gadd45 levels are modulated by GPx-1 in tumor cells (PMID:15203190)
• Inhibition of GADD45alpha and gamma in cancer cells by small interfering RNA abrogates apoptosis induction by the inhibitor of NF-kappaB (PMID:15353598)
• a novel association of B23 and Gadd45a and implicate B23 as an important regulator in Gadd45a nuclear import. (PMID:15644315)
• The CpG island associated with GADD45a was analysed Four CpG’s, located approximately 700 bp upstream of the transcriptional start site are methylated in the majority of breast cancer cell lines and primary tumors (PMID:15735726)
• Expression of CDKN1A and Gadd45 proteins acting on cell cycle checkpoints and DNA repair in PCa relative to the presence of oxidative DNA damage was measured. (PMID:15736438)
• Gadd45a is involved in the induction of apoptosis, inhibiting microtubule stability and inducing Bim translocation to mitochondria. (PMID:15899854)
• We conclude that the GADD45A gene is not involved in meningioma tumorigenesis. (PMID:16157202)
• findings provide evidence that GADD45alpha contributes to pancreatic cancer cell proliferation and viability (PMID:16353139)
• Gadd45a interacts with aurora-A and inhibits its kinase activity (PMID:16772293)
• The overall median mRNA expression level of Gadd45 was approximately 10-fold lower in tumor tissues than in matching normal lung tissues. High intratumoral Gadd45 expression was significantly associated with a poorer histological grading. (PMID:16827157)
• p53 preferentially occupied the promoters of growth arrest genes p21 and GADD45 in senescent normal human diploid fibroblasts. (PMID:16951143)
• Reverse-transcription polymerase chain reaction confirmed increased expression of GADD45A, BTG2, PDE4B, and CEBPD and downregulation of TOB1 in skeletal muscle intradialysis. (PMID:16997058)
• In support of the idea that checkpoint activation and apoptosis induction are functionally linked, we show that Bax activation by Vpr was ablated when ATR or GADD45alpha was knocked down (PMID:17140287)
• Establish MDA-7/IL-24 and GADD45alpha and GADD45gamma as critical mediators of apoptosis and growth arrest in response to NSAIDs in cancer cells. (PMID:17178890)
• Overexpression of Gadd45a is associated with pancreatic cancer (PMID:17230496)
• Fucoxanthin induced G1 arrest in HepG2 and DU145 cells and GADD45A may be involved in fucoxanthin-induced G1 arrest in cancer cels. (PMID:17436581)
• Induction of GADD45A expression might play a role in mediating the apoptotic response of ovarian cancer cells to the synthetic retinoid CD437. (PMID:17474084)
• Gadd45a-deficient human colon cancer cells exhibited slow base excision repair after treatment with methyl methanesulfonate, a pure base-damaging agent. (PMID:17599061)
• in growth-arrested cells, As(3+) is still capable of inducing GADD45 alpha expression through an IRES-dependent translational regulation (PMID:17616671)
• UVB-induced Gadd45a overexpression protects melanoma cells from apoptosis, both by causing a G2 cell cycle arrest and by inhibiting the mitochondrial apoptotic pathway. (PMID:17703175)
• We propose that BARD1 reduces BRCA1 transcriptional activity, and that this at least partly involves BRCA1/BARD1 E3 ubiquitin ligase activity, which is disrupted by the C61G mutation. (PMID:18243530)
• enhanced phosphorylation of p38 and p53 (ser15) in ZS cells was normalized after suppression of Gadd45 by siRNA (PMID:18296737)
• characterization of the entire coding sequence, intron/exon boundaries, and p53- and ZNF350-binding sequences of this potential breast cancer susceptibility candidate gene in a sample set of 96 women affected with breast cancer (PMID:18350249)
• we were unable to substantiate a functional role of GADD45A in DNA demethylation (PMID:18369439)
• GADD45 alpha knockdown attenuated the G(2) arrest induced by AKT inhibition in soft tissue sarcoma cells. (PMID:18413758)
• Epigenetic inactivation by methylation of GADD45A gene is associated with osteosarcoma (PMID:18472964)
• MMR-dependent intrinsic apoptosis is p53-independent, but stimulated by hMLH1/c-Abl/p73alpha/GADD45alpha retrograde signaling (PMID:18480060)
• Review GADD45a-GFP GreenScreen HC genotoxicity screening assay. (PMID:18611122)
• GADD45alpha is an essential component of many metabolic pathways that control proliferating cancer cells, it presents itself as an emerging drug target worthy of further investigation. (PMID:18760377)
• Flow cytometric analysis revealed significant G2/M arrest in cells transfected with either Gadd45alpha or Gadd45gamma. Importantly, we found that expression of either Gadd45alpha or Gadd45gamma activated P38 and JNK kinase pathways to induce G2/M arrest. (PMID:19048389)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gadd45aa	ENSDARG00000043581
danio_rerio	gadd45ab	ENSDARG00000104571
mus_musculus	Gadd45a	ENSMUSG00000036390
rattus_norvegicus	Gadd45a	ENSRNOG00000005615
drosophila_melanogaster	Gadd45	FBGN0033153

Paralogs (2): GADD45B (ENSG00000099860), GADD45G (ENSG00000130222)

Protein

Protein identifiers

Growth arrest and DNA damage-inducible protein GADD45 alpha — P24522 (reviewed: P24522)

Alternative names: DNA damage-inducible transcript 1 protein

All UniProt accessions (4): P24522, A0A087WZQ0, A0A3B3ITF9, A5JUZ3

UniProt curated annotations — full annotation on UniProt →

Function. In T-cells, functions as a regulator of p38 MAPKs by inhibiting p88 phosphorylation and activity. Might affect PCNA interaction with some CDK (cell division protein kinase) complexes; stimulates DNA excision repair in vitro and inhibits entry of cells into S phase.

Subunit / interactions. Interacts with MAPK14. Predominantly monomeric but also forms dimers and other oligomers as concentration increases. Interacts with GADD45GIP1. Interacts weakly with PCNA. Interacts with AURKA, likely to compete with dimerization.

Subcellular location. Nucleus.

Induction. By UV irradiation, X-rays, growth arrest and alkylating agents. The induction is mediated by some kinase(s) other than PKC.

Similarity. Belongs to the GADD45 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P24522-1	1	yes
P24522-2	2

RefSeq proteins (3): NP_001186670, NP_001186671, NP_001915* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004038	Ribosomal_eL8/eL30/eS12/Gad45	Domain
IPR024824	GADD45	Family
IPR029064	Ribosomal_eL30-like_sf	Homologous_superfamily

Pfam: PF01248

UniProt features (18 total): helix 7, strand 4, turn 3, chain 1, modified residue 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2KG4	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P24522-F1	81.65	0.46

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 (1): 2

Mutagenesis-validated functional residues (1):

Position	Phenotype
77	abolishes dimerization.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6804114	TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest
R-HSA-9617828	FOXO-mediated transcription of cell cycle genes

MSigDB gene sets: 642 (showing top): AGGAAGC_MIR5163P, AP1_01, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_REGULATION_OF_PHOSPHORYLATION, SWEET_KRAS_ONCOGENIC_SIGNATURE, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, BIOCARTA_ATM_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_BLOOD_VESSEL_ENDOTHELIAL_CELL_MIGRATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, KEGG_MAPK_SIGNALING_PATHWAY, TTTGTAG_MIR520D, GOBP_PEPTIDYL_SERINE_MODIFICATION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP

GO Biological Process (18): regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0000079), negative regulation of transcription by RNA polymerase II (GO:0000122), DNA repair (GO:0006281), apoptotic process (GO:0006915), centrosome cycle (GO:0007098), negative regulation of angiogenesis (GO:0016525), negative regulation of peptidyl-serine phosphorylation of STAT protein (GO:0033140), signal transduction in response to DNA damage (GO:0042770), positive regulation of apoptotic process (GO:0043065), negative regulation of blood vessel endothelial cell migration (GO:0043537), positive regulation of JNK cascade (GO:0046330), regulation of cell cycle (GO:0051726), cellular response to mechanical stimulus (GO:0071260), cellular response to ionizing radiation (GO:0071479), negative regulation of protein serine/threonine kinase activity (GO:0071901), positive regulation of p38MAPK cascade (GO:1900745), positive regulation of reactive oxygen species metabolic process (GO:2000379), DNA damage response (GO:0006974)

GO Molecular Function (5): kinase binding (GO:0019900), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), promoter-specific chromatin binding (GO:1990841), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear speck (GO:0016607)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
TP53 Regulates Transcription of Cell Cycle Genes	1
FOXO-mediated transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of protein serine/threonine kinase activity	2
DNA damage response	2
positive regulation of MAPK cascade	2
protein dimerization activity	2
cellular anatomical structure	2
cyclin-dependent protein serine/threonine kinase activity	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
DNA metabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell cycle process	1
microtubule organizing center organization	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
negative regulation of peptidyl-serine phosphorylation	1
regulation of peptidyl-serine phosphorylation of STAT protein	1
serine phosphorylation of STAT protein	1
intracellular signal transduction	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
negative regulation of endothelial cell migration	1
blood vessel endothelial cell migration	1
regulation of blood vessel endothelial cell migration	1
JNK cascade	1
regulation of JNK cascade	1
cell cycle	1
regulation of cellular process	1
response to mechanical stimulus	1
cellular response to abiotic stimulus	1
cellular response to external stimulus	1
response to ionizing radiation	1
cellular response to radiation	1
protein serine/threonine kinase activity	1
negative regulation of protein kinase activity	1
p38MAPK cascade	1

Protein interactions and networks

STRING

2282 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GADD45A	MAP3K4	Q9Y6R4	988
GADD45A	TDG	Q13569	983
GADD45A	GADD45GIP1	Q8TAE8	980
GADD45A	TET1	Q8NFU7	947
GADD45A	CDKN1A	P38936	926
GADD45A	TP53	P04637	913
GADD45A	APEX1	P27695	911
GADD45A	CDK1	P06493	851
GADD45A	MDM2	Q00987	797
GADD45A	CCNB1	P14635	783
GADD45A	DDIT3	P35638	774
GADD45A	ATM	Q13315	746
GADD45A	ATF3	P18847	729
GADD45A	CARM1	Q86X55	712
GADD45A	BRCA1	P38398	710

IntAct

106 interactions, top by confidence:

A	B	Type	Score
GADD45A	DCTN2	psi-mi:“MI:0915”(physical association)	0.740
MAP3K4	GADD45A	psi-mi:“MI:0915”(physical association)	0.680
GADD45A	GADD45GIP1	psi-mi:“MI:0407”(direct interaction)	0.590
GADD45GIP1	GADD45A	psi-mi:“MI:0915”(physical association)	0.590
GADD45A	PCNA	psi-mi:“MI:0915”(physical association)	0.590
PCNA	GADD45A	psi-mi:“MI:0915”(physical association)	0.590
GADD45A	CNOT9	psi-mi:“MI:0915”(physical association)	0.560
GADD45A	PARVG	psi-mi:“MI:0915”(physical association)	0.560
DYNC1H1	GADD45A	psi-mi:“MI:0915”(physical association)	0.560
KLK6	GADD45A	psi-mi:“MI:0915”(physical association)	0.560
MTOR	GADD45A	psi-mi:“MI:0914”(association)	0.560
MTOR	GADD45A	psi-mi:“MI:0915”(physical association)	0.560
GADD45A	ERCC5	psi-mi:“MI:0407”(direct interaction)	0.540
GADD45A	ERCC5	psi-mi:“MI:0915”(physical association)	0.540
TDG	GADD45A	psi-mi:“MI:0915”(physical association)	0.520
GADD45A	TDG	psi-mi:“MI:0915”(physical association)	0.520
GADD45A	MAP2K6	psi-mi:“MI:0915”(physical association)	0.520
MAP2K6	GADD45A	psi-mi:“MI:2364”(proximity)	0.520
NUCB2	GADD45A	psi-mi:“MI:0915”(physical association)	0.510
GADD45A	SH3GLB1	psi-mi:“MI:0915”(physical association)	0.510

BioGRID (163): PCNA (Affinity Capture-Western), APEX1 (Affinity Capture-Western), ING4 (Affinity Capture-Western), ING4 (Co-localization), MTOR (Reconstituted Complex), GADD45A (Affinity Capture-Western), STAT3 (Affinity Capture-Western), PCNA (Reconstituted Complex), AURKA (Reconstituted Complex), CDK1 (Affinity Capture-Western), DCTN2 (Two-hybrid), GADD45A (Affinity Capture-MS), GADD45A (Co-localization), GADD45A (Affinity Capture-Western), GADD45A (Affinity Capture-Western)

ESM2 similar proteins: A0A1L1SUL6, A3KFX0, F1LQY6, O43272, O75208, O75293, O95257, P22339, P24522, P24523, P48316, P48317, P50747, Q1HAQ0, Q1LVW0, Q28955, Q2KIX1, Q2KJ58, Q2NL34, Q3TFD2, Q3UMR5, Q3ZBN6, Q5E9A5, Q5R812, Q60GI5, Q64311, Q68FT1, Q6DDJ3, Q6DFV5, Q6DJB3, Q6NYU2, Q7T0P6, Q7Z6G3, Q80YV4, Q8K1Z0, Q8NE86, Q8R1C6, Q8R1T1, Q8TBN0, Q8VDG3

Diamond homologs: O75293, O95257, P22339, P24522, P24523, P48316, P48317, Q2KIX1, Q3ZBN6, Q5E9A5, Q60GI5, Q9WTQ7, Q9Z111, Q9SMI3, A4YIL9, A6UT51, A8A912, B1Y9V4, B8D6E8, C5A1V9, G1SFR8, O13019, O14062, O59936, O74322, O97249, P25398, P46405, P47840, P48589, P49196, P62008, P62009, P63323, P63324, P80455, P84175, Q03253, Q4J8P1, Q54PX9

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
GADD45A	down-regulates	MAPK14	binding
TP53	“up-regulates quantity by expression”	GADD45A	“transcriptional regulation”
GADD45A	down-regulates	CyclinB/CDK1	binding
GADD45A	“down-regulates activity”	CDK11A	binding
GADD45A	down-regulates	CDK1	binding
HNRNPU	“up-regulates quantity by stabilization”	GADD45A	“post transcriptional regulation”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

459 predictions. Top by Δscore:

Variant	Effect	Δscore
1:67686123:ACGT:A	donor_gain	1.0000
1:67686125:GT:G	donor_gain	1.0000
1:67686125:GTGTA:G	donor_loss	1.0000
1:67686127:G:GA	donor_loss	1.0000
1:67686127:G:GG	donor_gain	1.0000
1:67686128:T:G	donor_loss	1.0000
1:67686348:A:AG	acceptor_gain	1.0000
1:67686348:AGC:A	acceptor_gain	1.0000
1:67686349:G:GG	acceptor_gain	1.0000
1:67686349:GC:G	acceptor_gain	1.0000
1:67686349:GCG:G	acceptor_gain	1.0000
1:67686379:T:A	acceptor_gain	1.0000
1:67686382:C:CA	acceptor_gain	1.0000
1:67686584:GACG:G	donor_gain	1.0000
1:67686586:CGGTA:C	donor_loss	1.0000
1:67686588:G:GA	donor_loss	1.0000
1:67686588:G:GG	donor_gain	1.0000
1:67686589:T:G	donor_loss	1.0000
1:67687659:A:AG	acceptor_gain	1.0000
1:67687660:G:GG	acceptor_gain	1.0000
1:67685536:AAGG:A	donor_loss	0.9900
1:67685539:G:GA	donor_loss	0.9900
1:67686020:TGTAG:T	acceptor_loss	0.9900
1:67686021:GTAGG:G	acceptor_loss	0.9900
1:67686022:TA:T	acceptor_loss	0.9900
1:67686023:AG:A	acceptor_gain	0.9900
1:67686024:GG:G	acceptor_gain	0.9900
1:67686122:AACGT:A	donor_gain	0.9900
1:67686341:T:A	acceptor_gain	0.9900
1:67686344:CCCCA:C	acceptor_loss	0.9900

AlphaMissense

1082 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:67686095:G:A	G39R	1.000
1:67686095:G:C	G39R	1.000
1:67686095:G:T	G39W	1.000
1:67686096:G:A	G39E	1.000
1:67686111:C:A	A44D	1.000
1:67686372:T:C	C57R	1.000
1:67686374:C:G	C57W	1.000
1:67686421:T:C	I73T	1.000
1:67686423:C:G	H74D	1.000
1:67686433:T:A	L77Q	1.000
1:67686433:T:C	L77P	1.000
1:67686444:T:C	F81L	1.000
1:67686446:T:A	F81L	1.000
1:67686446:T:G	F81L	1.000
1:67686449:C:G	C82W	1.000
1:67686096:G:T	G39V	0.999
1:67686107:G:C	A43P	0.999
1:67686120:T:A	L47H	0.999
1:67686120:T:C	L47P	0.999
1:67686373:G:A	C57Y	0.999
1:67686421:T:A	I73N	0.999
1:67686421:T:G	I73S	0.999
1:67686426:T:C	F75L	0.999
1:67686428:C:A	F75L	0.999
1:67686428:C:G	F75L	0.999
1:67686441:G:C	A80P	0.999
1:67686445:T:C	F81S	0.999
1:67686447:T:C	C82R	0.999
1:67686448:G:A	C82Y	0.999
1:67686472:T:C	L90P	0.999

dbSNP variants (sampled 300 via entrez): RS1000335833 (1:67688351 CTT>C), RS1000857155 (1:67683584 A>G), RS1001516263 (1:67688697 T>TGTGCAAAG), RS1001776325 (1:67685763 T>G), RS1002689055 (1:67684068 T>C), RS1002715012 (1:67684356 G>T), RS1002725168 (1:67684940 T>A,C,G), RS1003187441 (1:67684673 C>T), RS1003689192 (1:67685429 GCGC>G), RS1003718776 (1:67685652 G>A), RS1003959934 (1:67685067 C>G,T), RS1004134061 (1:67683272 C>G,T), RS1004847643 (1:67685933 G>C), RS1005064705 (1:67685364 G>A,T), RS1006067437 (1:67684070 T>C)

Disease associations

OMIM: gene MIM:126335 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST004076_12	Optic disc area	2.000000e-06
GCST004076_26	Optic disc area	4.000000e-08
GCST006011_87	Mean corpuscular volume	8.000000e-09
GCST006444_18	Bone mineral density (hip)	7.000000e-06
GCST008363_15	Offspring birth weight	2.000000e-08
GCST009462_18	Optic disc size	8.000000e-16
GCST90002401_346	Platelet distribution width	2.000000e-10
GCST90002403_8	Red blood cell count	2.000000e-13

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007702	hip bone mineral density
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0007984	platelet component distribution width
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects expression, affects cotreatment, decreases expression, decreases response to substance, decreases reaction (+4 more)	17
Benzo(a)pyrene	increases expression, affects expression, affects cotreatment, decreases reaction	16
sodium arsenite	affects cotreatment, affects localization, decreases sumoylation, affects expression, increases abundance (+4 more)	15
Arsenic Trioxide	affects expression, decreases methylation, increases expression, increases reaction	9
Fluorouracil	affects reaction, increases reaction, increases expression, affects response to substance, increases response to substance	9
Cadmium Chloride	increases abundance, increases expression	9
bisphenol A	affects expression, affects cotreatment, increases expression, decreases expression	8
Doxorubicin	decreases expression, increases expression, decreases reaction, affects reaction	8
Estradiol	affects expression, affects cotreatment, increases expression, decreases expression	7
Aflatoxin B1	increases expression	7
Particulate Matter	increases expression, decreases expression, affects cotreatment, affects expression, increases reaction (+1 more)	7
Cadmium	increases abundance, increases expression	6
Tobacco Smoke Pollution	affects expression, increases expression	6
Valproic Acid	affects cotreatment, increases expression	6
Cyclosporine	affects cotreatment, affects expression, increases expression	6
Etoposide	increases expression, increases response to substance, decreases reaction	5
Paraquat	affects cotreatment, increases expression	5
methylmercuric chloride	increases expression, affects cotreatment	4
Acetaminophen	decreases reaction, affects reaction, increases expression	4
Methotrexate	affects cotreatment, increases expression	4
Quercetin	decreases expression, increases expression, affects cotreatment	4
trichostatin A	affects cotreatment, increases expression	3
arsenite	increases expression, decreases reaction, increases reaction, affects reaction	3
cobaltous chloride	affects cotreatment, increases expression	3
ochratoxin A	decreases expression, increases expression	3
benz(a)anthracene	increases expression, affects cotreatment	3
dibenzo(a,l)pyrene	affects cotreatment, increases expression	3
arsenic trichloride	affects binding, increases reaction, increases expression, increases stability, affects response to substance (+1 more)	3
cylindrospermopsin	affects cotreatment, increases expression	3
Resveratrol	increases expression	3

Cellosaurus cell lines

9 cell lines: 4 cancer cell line, 4 embryonic stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_3786	RKO-AS45-1	Cancer cell line	Sex unspecified
CVCL_A2E8	SEES3-1V human GADD45A, clone1	Embryonic stem cell	Male
CVCL_A2E9	SEES3-1V human GADD45A, clone2	Embryonic stem cell	Male
CVCL_A2F0	SEES3-1V human GADD45A, clone3	Embryonic stem cell	Male
CVCL_A2YB	WAe001-A-59	Embryonic stem cell	Male
CVCL_D7QG	Ubigene A-549 GADD45A KO	Cancer cell line	Male
CVCL_D8LS	Ubigene HCT 116 GADD45A KO	Cancer cell line	Male
CVCL_D9FB	Ubigene HEK293 GADD45A KO	Transformed cell line	Female
CVCL_E0DM	Ubigene HeLa GADD45A KO	Cancer cell line	Female

Clinical trials (associated diseases)

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