NDRG2

Summary

NDRG2 (NDRG family member 2, HGNC:14460) is a protein-coding gene on chromosome 14q11.2, encoding Protein NDRG2 (Q9UN36). Contributes to the regulation of the Wnt signaling pathway.

This gene is a member of the N-myc downregulated gene family which belongs to the alpha/beta hydrolase superfamily. The protein encoded by this gene is a cytoplasmic protein that may play a role in neurite outgrowth. This gene may be involved in glioblastoma carcinogenesis. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 57447 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 141 total — 1 likely-pathogenic
• MANE Select transcript: NM_001320329

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14460
Approved symbol	NDRG2
Name	NDRG family member 2
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1248, SYLD
Ensembl gene	ENSG00000165795
Ensembl biotype	protein_coding
OMIM	605272
Entrez	57447

Gene structure

Transcript identifiers

Ensembl transcripts: 166 — 144 protein_coding, 16 retained_intron, 5 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000298684, ENST00000298687, ENST00000350792, ENST00000360463, ENST00000366204, ENST00000397844, ENST00000397847, ENST00000397851, ENST00000397853, ENST00000397858, ENST00000403829, ENST00000449431, ENST00000553442, ENST00000553503, ENST00000553563, ENST00000553567, ENST00000553593, ENST00000553741, ENST00000553784, ENST00000553793, ENST00000553862, ENST00000553867, ENST00000553900, ENST00000554094, ENST00000554104, ENST00000554143, ENST00000554277, ENST00000554379, ENST00000554398, ENST00000554415, ENST00000554419, ENST00000554472, ENST00000554483, ENST00000554489, ENST00000554531, ENST00000554561, ENST00000554833, ENST00000554893, ENST00000555026, ENST00000555142, ENST00000555158, ENST00000555384, ENST00000555650, ENST00000555657, ENST00000555695, ENST00000555733, ENST00000555767, ENST00000555869, ENST00000556008, ENST00000556147, ENST00000556329, ENST00000556366, ENST00000556420, ENST00000556457, ENST00000556561, ENST00000556688, ENST00000556716, ENST00000556924, ENST00000556974, ENST00000557113, ENST00000557149, ENST00000557167, ENST00000557169, ENST00000557182, ENST00000557198, ENST00000557264, ENST00000557274, ENST00000557305, ENST00000557318, ENST00000557353, ENST00000557416, ENST00000557616, ENST00000557633, ENST00000557669, ENST00000557676, ENST00000557728, ENST00000635386, ENST00000876703, ENST00000876704, ENST00000876705, ENST00000876706, ENST00000876707, ENST00000876708, ENST00000876709, ENST00000876710, ENST00000876711, ENST00000876712, ENST00000876713, ENST00000876714, ENST00000876715, ENST00000876716, ENST00000876717, ENST00000876718, ENST00000876719, ENST00000876720, ENST00000876721, ENST00000876722, ENST00000876723, ENST00000876724, ENST00000876725, ENST00000876726, ENST00000876727, ENST00000876728, ENST00000876729, ENST00000876730, ENST00000876731, ENST00000876732, ENST00000876733, ENST00000876734, ENST00000876735, ENST00000876736, ENST00000876737, ENST00000876738, ENST00000876739, ENST00000876740, ENST00000876741, ENST00000876742, ENST00000876743, ENST00000876744, ENST00000876745, ENST00000876746, ENST00000876747, ENST00000876748, ENST00000876749, ENST00000876750, ENST00000876751, ENST00000876752, ENST00000876753, ENST00000876754, ENST00000876755, ENST00000876756, ENST00000876757, ENST00000876758, ENST00000876759, ENST00000876760, ENST00000876761, ENST00000876762, ENST00000876763, ENST00000916511, ENST00000916512, ENST00000916513, ENST00000949233, ENST00000949234, ENST00000949235, ENST00000949236, ENST00000949237, ENST00000949238, ENST00000949239, ENST00000949240, ENST00000949241, ENST00000949242, ENST00000949243, ENST00000949244, ENST00000949245, ENST00000949246, ENST00000949247, ENST00000949248, ENST00000949249, ENST00000949250, ENST00000949251, ENST00000949252, ENST00000949253, ENST00000949254, ENST00000949255, ENST00000949256, ENST00000949257

RefSeq mRNA: 27 — MANE Select: NM_001320329 NM_001282211, NM_001282212, NM_001282213, NM_001282214, NM_001282215, NM_001282216, NM_001320329, NM_001354558, NM_001354559, NM_001354560, NM_001354561, NM_001354562, NM_001354564, NM_001354565, NM_001354566, NM_001354567, NM_001354568, NM_001354569, NM_001354570, NM_016250, NM_201535, NM_201536, NM_201537, NM_201538, NM_201539, NM_201540, NM_201541

CCDS: CCDS61384, CCDS61386, CCDS73613, CCDS9564, CCDS9565

Canonical transcript exons

ENST00000556147 — 16 exons

Exon	Start	End
ENSE00002483528	21024030	21025061
ENSE00003468972	21019920	21019976
ENSE00003472350	21021817	21021879
ENSE00003487896	21016772	21017762
ENSE00003498998	21022062	21022182
ENSE00003515684	21019116	21019160
ENSE00003530903	21020496	21020582
ENSE00003543970	21018204	21018239
ENSE00003571815	21017987	21018038
ENSE00003573728	21018763	21018814
ENSE00003587710	21023241	21023321
ENSE00003602873	21022864	21022905
ENSE00003668689	21018457	21018504
ENSE00003686954	21022392	21022497
ENSE00003789124	21019639	21019742
ENSE00003790250	21020784	21020844

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 99.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 76.3573 / max 3157.9856, expressed in 1158 samples.

FANTOM5 promoters (31 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142102	33.8151	1098
142105	33.2550	536
142103	5.1120	354
142104	0.4468	165
142083	0.4001	17
142099	0.3750	120
142094	0.3029	45
142086	0.2954	108
142091	0.2949	113
142090	0.2926	117

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	99.88	gold quality
amygdala	UBERON:0001876	99.82	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.82	gold quality
putamen	UBERON:0001874	99.78	gold quality
nucleus accumbens	UBERON:0001882	99.78	gold quality
hypothalamus	UBERON:0001898	99.78	gold quality
cerebellar cortex	UBERON:0002129	99.73	gold quality
cerebellar hemisphere	UBERON:0002245	99.73	gold quality
medial globus pallidus	UBERON:0002477	99.73	gold quality
caudate nucleus	UBERON:0001873	99.72	gold quality
prefrontal cortex	UBERON:0000451	99.71	gold quality
cerebellum	UBERON:0002037	99.71	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.71	gold quality
gastrocnemius	UBERON:0001388	99.70	gold quality
anterior cingulate cortex	UBERON:0009835	99.70	gold quality
cingulate cortex	UBERON:0003027	99.69	gold quality
spinal cord	UBERON:0002240	99.65	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.65	gold quality
peripheral nervous system	UBERON:0000010	99.64	gold quality
nerve	UBERON:0001021	99.64	gold quality
tibial nerve	UBERON:0001323	99.64	gold quality
right ovary	UBERON:0002118	99.64	gold quality
globus pallidus	UBERON:0001875	99.62	gold quality
left ovary	UBERON:0002119	99.61	gold quality
corpus callosum	UBERON:0002336	99.59	gold quality
substantia nigra	UBERON:0002038	99.58	gold quality
muscle of leg	UBERON:0001383	99.57	gold quality
endocervix	UBERON:0000458	99.56	gold quality
midbrain	UBERON:0001891	99.55	gold quality
right adrenal gland cortex	UBERON:0035827	99.55	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	1778.02
E-HCAD-25	yes	1234.94
E-MTAB-3929	yes	70.10
E-MTAB-10287	yes	57.02
E-GEOD-137537	yes	36.29
E-GEOD-134144	yes	34.59
E-MTAB-7316	yes	30.74
E-GEOD-135922	yes	28.42
E-HCAD-11	yes	27.83
E-MTAB-5061	yes	25.71
E-MTAB-8410	yes	23.27
E-HCAD-1	yes	17.32
E-CURD-112	yes	15.28
E-MTAB-6678	yes	10.82
E-MTAB-9801	yes	9.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HIF1A, MYC, NFKB, NFKBID, NR1H4, TP53, WT1, ZBTB17

miRNA regulators (miRDB)

56 targeting NDRG2, 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-9-5P	100.00	72.28	2361
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-12135	98.99	70.26	1814

Literature-anchored findings (GeneRIF, showing 40)

• Cloning and expression of the gene; highly expressed in adult skeletal muscle and brain (PMID:11936845)
• Down-Regulation of N-Myc downstream-regulated gene 2 is associated with glioblastoma (PMID:12845671)
• NDRG2 is upregulated at both the RNA and protein levels in Alzheimer disease brains; expression in affected brains is revealed in cortical pyramidal neurons, senile plaques and cellular processes of dystrophic neurons. (PMID:15207261)
• results identify NDRG1 and NDRG2 as physiological substrates for SGK1, and demonstrate that phosphorylation of NDRG1 by SGK1 primes it for phosphorylation by GSK3 (PMID:15461589)
• NDRG2 gene might express differently between normal tissues and cancer tissues, and might play an important role in the development of pancreatic cancer and liver cancer. (PMID:15526377)
• Data identify NDRG2 as the first specific candidate tumor suppressor gene on chromosome 14q that is inactivated during meningioma progression. (PMID:16103061)
• NDRG2 expression is repressed by Myc via Miz-1-dependent interaction with the NDRG2 core promoter (PMID:17050536)
• modulation of Ndrg2 level influences the cell cycle process together with MSP58 (PMID:17109818)
• describe for the first time, the mechanisms involved in NDRG2 gene down-regulation (PMID:17470364)
• These results show that the expression of the NDRG2 gene is directly or indirectly induced by WT1, and provide the first insights into transcriptional regulation of the NDRG2 gene, including demonstration of a novel splice variant. (PMID:17688410)
• Together, these data demonstrate that NDRG2 expression in breast cancer cells is able to inhibit STAT3 activation via SOCS1 induction in a p38 MAPK dependent manner. (PMID:17888401)
• The NDRG2 is able to preserve ALCAM expression during DC differentiation from monocytes under cytokine culture conditions and that its expression helps DC maintain costimulatory signals necessary for T cell stimulation. (PMID:17911180)
• expression of NDRG2 is down-regulated at a late stage during colorectal carcinogenesis. (PMID:17935612)
• This study suggests that NDRG2 is a Hif-1 target gene and closely related with hypoxia-induced apoptosis in A549 cells. (PMID:18209490)
• results suggest that NDRG2 can inhibit extracellular matrix-based, Rho-driven tumor cell invasion and migration and thereby play important roles in suppressing tumor metastasis in hepatocellular carcinoma (PMID:18519680)
• NDRG2 might play an important role in the carcinogenesis and development of clear cell renal cell carcinoma and may function as a tumor suppressor in clear cell renal cell carcinoma (PMID:18591767)
• NDRG2 expression in colon cancer was not correlated with age, sex, metastasis of lymph node, or depth of infiltration, while it was correlated to the histology grading. (PMID:18636358)
• NDRG2 as a candidate tumor suppressor gene that is epigenetically silenced in the majority of primary glioblastomas, but not in lower grade astrocytomas and secondary glioblastomas. (PMID:18709645)
• NDRG2 modulates intracellular signals to control cell cycle through the regulation of cyclin D1 expression via phosphorylation pathway and down-regulation of AP-1 (PMID:18844221)
• Reduced expression in human thyroid cancer (PMID:18940011)
• NDRG2 expression is highly responsive to different stress conditions in skeletal muscle and suggest that the level of NDRG2 expression may be critical to myoblast growth and differentiation. (PMID:19204049)
• Loss of NDRG2 is associated with colon adenocarcinoma. (PMID:19237607)
• NDRG2 expression significantly suppresses tumor invasion by inhibiting MMP activities, which are regulated through the NF-kappaB signaling (PMID:19336468)
• Ndrg2 protein levels increased from poor-differentiated to well-differentiated carcinomas. (PMID:19434539)
• BMP-4 induced by NDRG2 expression inhibits the metastatic potential of breast cancer cells, especially via suppression of MMP-9 activity. (PMID:19450561)
• NDRG2 may play a role during the differentiation of colorectal cancer cells. (PMID:19483300)
• NDRG2, was significantly higher expressed in normal macrophages compared to primary acute myeloid leukemia cells (PMID:19775754)
• NDRG2 is a candidate tumor-suppressor gene for oral squamous-cell carcinoma (OSCC)development and probably contributes to the tumorigenesis of OSCC partly via the modulation of Akt signaling. (PMID:20045673)
• NDRG2 contribute to hypoxia-induced radioresistance of cervical cancer Hela cells (PMID:20206160)
• NDRG2 played an important role in the proliferation of esophageal squamous cell carcinoma (ESCC) cells and the expression of NDRG2 in ESCC was closely related with the prognosis. (PMID:20331630)
• NDRG2 might have a pivotal role as one of intrinsic factors for the modulation of p38 MAPK phosphorylation, and subsequently involve in controlling of IL-10 production. (PMID:20438703)
• NDRG2 gene expression is down-regulated in atypical and recurrent meningiomas. (PMID:20607352)
• Data show that NDRG2 and GFAP had an increased number of phosphospectra in FTLD. (PMID:20886841)
• Present research provides the first evidence that decreased NDRG2 mRNA expression in primary human CRC might be a powerful, independent predictor of recurrence and outcome. (PMID:21220491)
• Data show that NDRG2 mRNA is statistically significantly down-regulated in breast cancer. (PMID:21226903)
• Structural analysis suggests that NDRG2 is a nonenzymatic member of the ABH superfamily, because it lacks the catalytic signature residues and has an occluded substrate-binding site. (PMID:21247902)
• these results suggest that NDRG2 expression is regulated by promoter methylation and miR-650 in human colorectal cancer cells. (PMID:21352815)
• Data show that the expression of the NDRG2 genes was low in the three PCA cell lines. (PMID:21623166)
• results suggest that Ndrg2 may regulate astroglial activation through the suppression of cell proliferation and stabilization of cell morphology (PMID:21672576)
• Our findings indicate that NDRG2 and CD24 regulate HCC adhesion, migration and invasion. (PMID:21676268)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndrg2	ENSDARG00000011170
mus_musculus	Ndrg2	ENSMUSG00000004558
rattus_norvegicus	Ndrg2	ENSRNOG00000010389
drosophila_melanogaster	CG2082	FBGN0027608
drosophila_melanogaster	MESK2	FBGN0043070
caenorhabditis_elegans	Y48G10A.3	WBGENE00013020
caenorhabditis_elegans		WBGENE00014213

Paralogs (3): NDRG3 (ENSG00000101079), NDRG4 (ENSG00000103034), NDRG1 (ENSG00000104419)

Protein

Protein identifiers

Protein NDRG2 — Q9UN36 (reviewed: Q9UN36)

Alternative names: N-myc downstream-regulated gene 2 protein, Protein Syld709613

All UniProt accessions (43): A0A0U1RR50, Q9UN36, G3V237, G3V239, G3V271, G3V280, G3V285, G3V2A6, G3V2I9, G3V2S0, G3V2T2, G3V2Y3, G3V358, G3V383, G3V392, G3V3C3, G3V3D5, G3V3L1, G3V3P1, G3V3P6, G3V3X2, G3V3X3, G3V420, G3V4S2, G3V4S9, G3V4T9, G3V4X3, G3V552, G3V578, G3V5A6, G3V5B5, G3V5B7, G3V5D7, G3V5G0, G3V5G7, G3V5H8, G3V5L7, G3V5P9, G3V5S0, G3V5V9, H0YJ56, H0YJT9, H7C0X0

UniProt curated annotations — full annotation on UniProt →

Function. Contributes to the regulation of the Wnt signaling pathway. Down-regulates CTNNB1-mediated transcriptional activation of target genes, such as CCND1, and may thereby act as tumor suppressor. May be involved in dendritic cell and neuron differentiation.

Subunit / interactions. Interacts with CTNNB1.

Subcellular location. Cytoplasm. Perinuclear region. Cell projection. Growth cone.

Tissue specificity. Highly expressed in brain, heart, skeletal muscle and salivary gland, and moderately in kidney and liver. Expressed in dendritic cells, but not in other blood cells. Expression levels are low in pancreatic and liver cancer tissues; absent in meningioma. Expressed in low-grade gliomas but present at low levels in glioblastoma. Isoform 1 and isoform 2 are present in brain neurons and up-regulated in Alzheimer disease (at protein level).

Similarity. Belongs to the NDRG family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9UN36-1	1, NDRG2ins	yes
Q9UN36-2	2, NDRG2var
Q9UN36-3	3
Q9UN36-4	4
Q9UN36-5	5
Q9UN36-6	6

RefSeq proteins (27): NP_001269140, NP_001269141, NP_001269142, NP_001269143, NP_001269144, NP_001269145, NP_001307258, NP_001341487, NP_001341488, NP_001341489, NP_001341490, NP_001341491, NP_001341493, NP_001341494, NP_001341495, NP_001341496, NP_001341497, NP_001341498, NP_001341499, NP_057334, NP_963293, NP_963294, NP_963831, NP_963832, NP_963833, NP_963834, NP_963835 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004142	NDRG	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily

Pfam: PF03096

UniProt features (63 total): modified residue 17, helix 15, strand 9, sequence conflict 7, splice variant 5, region of interest 2, sequence variant 2, turn 2, initiator methionine 1, chain 1, mutagenesis site 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2XMR	X-RAY DIFFRACTION	2
2XMS	X-RAY DIFFRACTION	2.15
2XMQ	X-RAY DIFFRACTION	2.81

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UN36-F1	84.26	0.70

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 (17): 332, 334, 335, 338, 344, 348, 350, 352, 353, 355, 357, 370, 2, 20, 326, 328, 330

Mutagenesis-validated functional residues (1):

Position	Phenotype
186	decreased interaction with ctnnb1. abolishes down-regulation of wnt signaling.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 318 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, FXR_IR1_Q6, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GOBP_NEGATIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_PROLIFERATION, RORA1_01, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, TGACCTY_ERR1_Q2, MEF2_02, GOBP_MUSCLE_CELL_PROLIFERATION, GGGTGGRR_PAX4_03, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, SREBP1_02, AACWWCAANK_UNKNOWN, NFKB_Q6

GO Biological Process (11): negative regulation of cytokine production (GO:0001818), signal transduction (GO:0007165), regulation of vascular endothelial growth factor production (GO:0010574), Wnt signaling pathway (GO:0016055), substantia nigra development (GO:0021762), cell differentiation (GO:0030154), negative regulation of ERK1 and ERK2 cascade (GO:0070373), regulation of platelet-derived growth factor production (GO:0090361), negative regulation of vascular associated smooth muscle cell proliferation (GO:1904706), vascular associated smooth muscle cell proliferation (GO:1990874), nervous system development (GO:0007399)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (9): nucleus (GO:0005634), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), growth cone (GO:0030426), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
regulation of cytokine production	3
cytoplasm	3
intracellular membrane-bounded organelle	2
cytokine production	1
negative regulation of gene expression	1
negative regulation of multicellular organismal process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
vascular endothelial growth factor production	1
cell surface receptor signaling pathway	1
midbrain development	1
neural nucleus development	1
cellular developmental process	1
negative regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
platelet-derived growth factor production	1
negative regulation of smooth muscle cell proliferation	1
regulation of vascular associated smooth muscle cell proliferation	1
vascular associated smooth muscle cell proliferation	1
smooth muscle cell proliferation	1
system development	1
binding	1
intracellular anatomical structure	1
endomembrane system	1
site of polarized growth	1
distal axon	1
extracellular vesicle	1

Protein interactions and networks

STRING

1128 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NDRG2	STK38L	Q9Y2H1	929
NDRG2	MYCN	P04198	868
NDRG2	NF2	P35240	433
NDRG2	WSB1	Q9Y6I7	405
NDRG2	DNAJC17	Q9NVM6	398
NDRG2	PPM1N	Q8N819	379
NDRG2	PPM1D	O15297	378
NDRG2	CSNK2A2IP	A0A1B0GTH6	370
NDRG2	SGK1	O00141	366
NDRG2	PHOX2B	Q99453	362
NDRG2	HSP90AA1	P07900	361
NDRG2	TMEM14A	Q9Y6G1	337
NDRG2	PIBF1	Q8WXW3	320
NDRG2	GCSAM	Q8N6F7	319
NDRG2	GFAP	P14136	318
NDRG2	TP53	P04637	318

IntAct

38 interactions, top by confidence:

A	B	Type	Score
ATP1A1	ATP1B1	psi-mi:“MI:0914”(association)	0.910
ESR1	NDRG2	psi-mi:“MI:0407”(direct interaction)	0.530
ESR1	NDRG2	psi-mi:“MI:0915”(physical association)	0.530
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
SSBP2	CLEC18A	psi-mi:“MI:0914”(association)	0.530
LRRTM4	AP3B1	psi-mi:“MI:0914”(association)	0.530
NDRG2	AGTR1	psi-mi:“MI:0915”(physical association)	0.370
NDRG2	CCR4	psi-mi:“MI:0915”(physical association)	0.370
MAPT	LANCL1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
KLHL11	PIPSL	psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	A2ML1	psi-mi:“MI:0914”(association)	0.350
CDK15	A2ML1	psi-mi:“MI:0914”(association)	0.350
RIPPLY3	A2ML1	psi-mi:“MI:0914”(association)	0.350
HCN1	A2ML1	psi-mi:“MI:0914”(association)	0.350
NDRG2	HSPA8	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
NRSN1	IGLC7	psi-mi:“MI:0914”(association)	0.350
SSUH2	IGLC7	psi-mi:“MI:0914”(association)	0.350
RNF115	IGLC7	psi-mi:“MI:0914”(association)	0.350
PIGT	A2ML1	psi-mi:“MI:0914”(association)	0.350
C18orf21	A2ML1	psi-mi:“MI:0914”(association)	0.350
PINK1	A2ML1	psi-mi:“MI:0914”(association)	0.350
FNDC5	A2ML1	psi-mi:“MI:0914”(association)	0.350
AGPAT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
PHF11	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (58): HSPA8 (Affinity Capture-MS), BAG5 (Affinity Capture-MS), NDRG1 (Affinity Capture-MS), NDRG2 (Affinity Capture-MS), NDRG2 (Biochemical Activity), NDRG2 (Proximity Label-MS), NDRG2 (Affinity Capture-MS), NDRG2 (Affinity Capture-MS), NDRG1 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), RABAC1 (Reconstituted Complex), NDRG2 (Affinity Capture-Western), RABAC1 (Two-hybrid), NDRG2 (Two-hybrid), NDRG2 (Two-hybrid)

ESM2 similar proteins: A0A8M1NHK4, A0AV96, A1L1G1, B2RYD2, B2RYJ8, B4F7E7, E2QY99, O46036, O95758, P86049, Q08BH5, Q22708, Q292F9, Q3US41, Q3ZBA8, Q4U2V3, Q5PR98, Q5R5P4, Q5R9H4, Q5RBN6, Q5XK84, Q5YD48, Q5ZLR4, Q66H68, Q66KM2, Q6DEZ7, Q7JUR6, Q7ZVR8, Q7ZY29, Q7ZY73, Q804S5, Q86X55, Q8BHD7, Q8IVH8, Q8JHF4, Q8K0G8, Q8TBY0, Q8VBU2, Q91WT8, Q923K9

Diamond homologs: A5A6K6, A7MB28, Q3SYX0, Q3ZBA8, Q4R4K0, Q4R4Q3, Q55BX3, Q5PR98, Q5RA95, Q5RBN6, Q62433, Q640Z1, Q641F2, Q66IG4, Q66KM2, Q6AYR2, Q6DFS4, Q6DIX1, Q6DJD3, Q6GQL1, Q6JE36, Q7ZWV3, Q7ZY73, Q8BTG7, Q8VBU2, Q92597, Q9ASU8, Q9FJT7, Q9QYF9, Q9QYG0, Q9UGV2, Q9ULP0, Q9UN36, Q9Z2L9, Q9ZUN1, A1AGT6, A1JMX1, A7ZSU1, A8A5M0, A8GCT3

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
SGK1	up-regulates	NDRG2	phosphorylation
DAPK1	“up-regulates activity”	NDRG2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	107
Likely benign	7
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1326312	GRCh37/hg19 14q11.2(chr14:20925965-23649548)x3	Likely pathogenic

SpliceAI

4462 predictions. Top by Δscore:

Variant	Effect	Δscore
14:21017763:C:CC	acceptor_gain	1.0000
14:21017978:GATAC:G	donor_loss	1.0000
14:21017979:ATAC:A	donor_loss	1.0000
14:21017980:TACT:T	donor_loss	1.0000
14:21017981:ACTC:A	donor_loss	1.0000
14:21017982:CTC:C	donor_loss	1.0000
14:21017983:TCA:T	donor_loss	1.0000
14:21017984:CA:C	donor_loss	1.0000
14:21017985:A:AC	donor_gain	1.0000
14:21017986:C:CT	donor_gain	1.0000
14:21017986:CT:C	donor_gain	1.0000
14:21018035:CTGG:C	acceptor_gain	1.0000
14:21018036:TGG:T	acceptor_gain	1.0000
14:21018037:GG:G	acceptor_gain	1.0000
14:21018039:C:CC	acceptor_gain	1.0000
14:21018042:C:CT	acceptor_gain	1.0000
14:21018043:G:T	acceptor_gain	1.0000
14:21018047:G:C	acceptor_gain	1.0000
14:21018047:G:GC	acceptor_gain	1.0000
14:21018201:CA:C	donor_loss	1.0000
14:21018202:A:AT	donor_loss	1.0000
14:21018203:C:CT	donor_loss	1.0000
14:21018256:C:CT	acceptor_gain	1.0000
14:21018256:C:T	acceptor_gain	1.0000
14:21018260:C:CT	acceptor_gain	1.0000
14:21018261:A:T	acceptor_gain	1.0000
14:21019112:TTACC:T	donor_loss	1.0000
14:21019113:TACCT:T	donor_loss	1.0000
14:21019114:A:AT	donor_loss	1.0000
14:21019158:CGG:C	acceptor_gain	1.0000

AlphaMissense

2408 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:21018011:A:G	Y309H	1.000
14:21018457:C:A	K287N	1.000
14:21018457:C:G	K287N	1.000
14:21018461:A:G	L286P	1.000
14:21018791:C:A	G262V	1.000
14:21018791:C:T	G262E	1.000
14:21020519:A:G	W178R	1.000
14:21020519:A:T	W178R	1.000
14:21020554:A:G	L166P	1.000
14:21017747:A:G	M322T	0.999
14:21017992:C:A	G315V	0.999
14:21017992:C:T	G315D	0.999
14:21017993:C:G	G315R	0.999
14:21017998:C:T	G313D	0.999
14:21017999:C:A	G313C	0.999
14:21017999:C:G	G313R	0.999
14:21018000:T:A	Q312H	0.999
14:21018000:T:G	Q312H	0.999
14:21018006:G:C	F310L	0.999
14:21018006:G:T	F310L	0.999
14:21018008:A:G	F310L	0.999
14:21018010:T:C	Y309C	0.999
14:21018010:T:G	Y309S	0.999
14:21018011:A:C	Y309D	0.999
14:21018012:C:A	K308N	0.999
14:21018012:C:G	K308N	0.999
14:21018014:T:C	K308E	0.999
14:21018019:G:T	A306D	0.999
14:21018028:A:G	L303P	0.999
14:21018217:G:T	P295H	0.999

dbSNP variants (sampled 300 via entrez): RS1000119394 (14:21032810 G>A), RS1000132361 (14:21036977 A>G), RS1000324285 (14:21066019 C>T), RS1000438847 (14:21065775 C>A), RS1000546604 (14:21046177 G>A), RS1000639146 (14:21052685 G>T), RS1000652751 (14:21049930 C>A,T), RS1000754233 (14:21044137 G>A), RS1000770832 (14:21019298 G>A,C), RS1000806350 (14:21058978 G>A), RS1000901232 (14:21016352 A>G), RS1000938776 (14:21061210 G>A,T), RS1000939884 (14:21046465 G>A,C), RS1000955476 (14:21065065 G>C), RS1000975098 (14:21022765 G>A,C,T)

Disease associations

OMIM: gene MIM:605272 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003818_18	Resting heart rate	4.000000e-20
GCST005787_31	Heart rate response to exercise	2.000000e-06
GCST008156_144	Hip circumference adjusted for BMI	9.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009184	heart rate response to exercise
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects expression	5
sodium arsenite	affects methylation, decreases methylation, increases expression	4
Ethinyl Estradiol	affects expression, decreases expression	3
Valproic Acid	affects expression, decreases methylation, increases expression	3
Cyclosporine	decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	2
Nickel	decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
FR900359	affects phosphorylation	1
testosterone enanthate	affects expression	1
alpha phellandrene	increases expression	1
uranyl acetate	affects expression	1
nickel sulfate	increases expression	1
ciglitazone	affects binding, increases expression	1
Am 580	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
abrine	decreases expression	1
1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone	increases phosphorylation	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Rosiglitazone	decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression	1
Antimony	decreases expression	1
Antimony Potassium Tartrate	decreases expression	1
Caffeine	affects phosphorylation	1

Clinical trials (associated diseases)

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