NDRG4

Summary

NDRG4 (NDRG family member 4, HGNC:14466) is a protein-coding gene on chromosome 16q21, encoding Protein NDRG4 (Q9ULP0). Contributes to the maintenance of intracerebral BDNF levels within the normal range, which is necessary for the preservation of spatial learning and the resistance to neuronal cell death caused by ischemic stress.

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 is required for cell cycle progression and survival in primary astrocytes and may be involved in the regulation of mitogenic signalling in vascular smooth muscles cells. Alternative splicing results in multiple transcripts encoding different isoforms.

Source: NCBI Gene 65009 — RefSeq curated summary.

At a glance

• Gene–disease (curated): achromatopsia (Limited, GenCC)
• GWAS associations: 95
• Clinical variants (ClinVar): 121 total
• MANE Select transcript: NM_001242835

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14466
Approved symbol	NDRG4
Name	NDRG family member 4
Location	16q21
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1180, SMAP-8
Ensembl gene	ENSG00000103034
Ensembl biotype	protein_coding
OMIM	614463
Entrez	65009

Gene structure

Transcript identifiers

Ensembl transcripts: 69 — 48 protein_coding, 12 retained_intron, 5 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

ENST00000258187, ENST00000356752, ENST00000394279, ENST00000394282, ENST00000421602, ENST00000561681, ENST00000561720, ENST00000561724, ENST00000561730, ENST00000561738, ENST00000561779, ENST00000562350, ENST00000562725, ENST00000562731, ENST00000562764, ENST00000562930, ENST00000562999, ENST00000563022, ENST00000563209, ENST00000563317, ENST00000563799, ENST00000563978, ENST00000564126, ENST00000564207, ENST00000564486, ENST00000564867, ENST00000564960, ENST00000565088, ENST00000565304, ENST00000565430, ENST00000565434, ENST00000565981, ENST00000566041, ENST00000566061, ENST00000566065, ENST00000566192, ENST00000566265, ENST00000566585, ENST00000566618, ENST00000566656, ENST00000567063, ENST00000567454, ENST00000567667, ENST00000568005, ENST00000568424, ENST00000568464, ENST00000568640, ENST00000568999, ENST00000569026, ENST00000569404, ENST00000569408, ENST00000569539, ENST00000569578, ENST00000569923, ENST00000570248, ENST00000889963, ENST00000889964, ENST00000889965, ENST00000889966, ENST00000889967, ENST00000889968, ENST00000889969, ENST00000889970, ENST00000889971, ENST00000889972, ENST00000961840, ENST00000961841, ENST00000961842, ENST00000961843

RefSeq mRNA: 24 — MANE Select: NM_001242835 NM_001130487, NM_001242833, NM_001242834, NM_001242835, NM_001242836, NM_001363869, NM_001378332, NM_001378333, NM_001378334, NM_001378335, NM_001378336, NM_001378337, NM_001378338, NM_001378339, NM_001378340, NM_001378341, NM_001378342, NM_001378343, NM_001378344, NM_001378345, NM_001378346, NM_001378347, NM_020465, NM_022910

CCDS: CCDS10797, CCDS45500, CCDS55999, CCDS58465, CCDS58466, CCDS58467, CCDS86532

Canonical transcript exons

ENST00000570248 — 15 exons

Exon	Start	End
ENSE00001845395	58511422	58513619
ENSE00003470664	58507948	58507999
ENSE00003480812	58500143	58500269
ENSE00003481803	58503798	58503903
ENSE00003510081	58509154	58509189
ENSE00003545905	58506912	58507015
ENSE00003551969	58507808	58507864
ENSE00003581406	58509301	58509352
ENSE00003615931	58510645	58510683
ENSE00003640051	58506387	58506473
ENSE00003641131	58508962	58509009
ENSE00003644506	58504359	58504421
ENSE00003647446	58504154	58504274
ENSE00003675148	58506558	58506614
ENSE00003785894	58504589	58504649

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 99.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.9442 / max 1234.9450, expressed in 1261 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154458	24.9659	927
154454	6.4996	583
154456	3.8338	353
154455	2.3961	285
207908	1.0640	589
154453	0.6368	277
207905	0.4918	174
154450	0.3484	179
207906	0.1769	74
154452	0.1478	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.80	gold quality
cerebellar cortex	UBERON:0002129	99.77	gold quality
cerebellar hemisphere	UBERON:0002245	99.77	gold quality
cerebellum	UBERON:0002037	99.68	gold quality
pons	UBERON:0000988	99.57	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.57	gold quality
right frontal lobe	UBERON:0002810	99.53	gold quality
prefrontal cortex	UBERON:0000451	99.48	gold quality
apex of heart	UBERON:0002098	99.37	gold quality
nucleus accumbens	UBERON:0001882	99.35	gold quality
cerebellar vermis	UBERON:0004720	99.31	gold quality
caudate nucleus	UBERON:0001873	99.19	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.19	gold quality
frontal cortex	UBERON:0001870	99.16	gold quality
paraflocculus	UBERON:0005351	99.16	gold quality
frontal lobe	UBERON:0016525	99.16	gold quality
substantia nigra pars compacta	UBERON:0001965	99.13	gold quality
amygdala	UBERON:0001876	99.06	gold quality
cingulate cortex	UBERON:0003027	99.06	gold quality
anterior cingulate cortex	UBERON:0009835	99.05	gold quality
postcentral gyrus	UBERON:0002581	99.03	gold quality
superior vestibular nucleus	UBERON:0007227	99.03	gold quality
hypothalamus	UBERON:0001898	98.99	gold quality
parietal lobe	UBERON:0001872	98.95	gold quality
left ventricle myocardium	UBERON:0006566	98.94	gold quality
right adrenal gland cortex	UBERON:0035827	98.93	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.87	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.86	gold quality
heart left ventricle	UBERON:0002084	98.85	gold quality
neocortex	UBERON:0001950	98.84	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-8205	yes	194.44
E-HCAD-35	yes	53.71
E-MTAB-7316	yes	18.08
E-ANND-3	yes	10.15
E-MTAB-5061	yes	9.02
E-HCAD-25	yes	8.87
E-GEOD-93593	yes	8.31
E-GEOD-84465	yes	6.96
E-GEOD-137537	yes	6.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

100 targeting NDRG4, 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-8485	100.00	77.57	4731
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-139-5P	99.80	69.50	1399

Literature-anchored findings (GeneRIF, showing 30)

• Cloning and expression of the gene; specifically expressed in brain and heart (PMID:11936845)
• smap8 is involved in the regulation of mitogenic signalling in vascular smooth muscle cells, possibly in response to a homocysteine-induced injury [SMAP8] (PMID:12755708)
• NDRG4 overexpression enhances ERK activation (PMID:16408304)
• NDRG4 is a candidate tumor suppressor gene in colorectal cancer whose expression is frequently inactivated by promoter methylation. (PMID:19535783)
• NDRG4 is required for cell cycle progression and survival, thereby diverging in function from its tumor suppressive family member NDRG2 in astrocytes and GBM cells (PMID:19592488)
• expression of NDRG4 is downregulated in human gliomas. The glioma patients with lower NDRG4 expression have a poor prognosis. (PMID:22399192)
• Over expression of NDRG4 inhibited proliferation of GBM cells. (PMID:22489821)
• NDRG4 is involved in modulating cell proliferation, invasion, migration and angiogenesis in meningioma, and may play a valuable role as a molecular target in its treatment (PMID:22869042)
• summarizes the current research on NDRG3 and NDRG4,including the molecular structure, cellular and tissue distribution, biological function, and function in cancer. (PMID:23725756)
• Methylation level in stool decreases dramatically following colorectal cancer resection (PMID:24993691)
• A homozygous variant in NDRG4 may be the causative variant of the autosomal recessive form of infantile myofibromatosis. (PMID:25241110)
• Two downregulated genes, NDRG4 and GINS3, have been located in a genomic interval associated with cardiac repolarization in published GWASs and zebra fish knockout models (PMID:25520251)
• These findings bring novel insight to the roles of NDRG4 in meningioma progression (PMID:26053091)
• Data indicate that patients with tumor of reduced NDRG family member 4 protein (NDRG4) mRNA level had unfavorable disease-free and overall survival. (PMID:26515606)
• Study shows that NDRG4 was significantly up-regulated in glioblastomas (GBM) and seems to play a role in GBM prognosis. These results indicate that NDRG4 gene in MGMT-methylated cells is a putative tumor-suppressor gene and an oncogene in cells with unmethylated MGMT. (PMID:26976975)
• NDRG4 might play an important role during early pregnancy. (PMID:27175791)
• NDRG4 promoter hypermethylation contributed to the risk of gastric cancer and predicted a poor prognosis in Chinese gastric cancer patients. (PMID:28042954)
• NDRG4 - the biomarker of a currently in-use multi-target stool DNA test was commonly expressed in tumor tissue specimens, independent of Fecal Immunochemical Test result. (PMID:28044229)
• NDRG4 is exclusively expressed by central, peripheral and enteric neurons/nerves, suggesting a neuronal-specific role of this protein (PMID:28524415)
• Results indicate that NDRG family member 4 protein (NDRG4) could be a potential tumor suppressor and prognostic marker of gastric cancer. (PMID:29500881)
• NDRG4 Alleviates Abeta1-40 Induction of SH-SY5Y Cell Injury via Activation of BDNF-Inducing Signalling Pathways. (PMID:32166572)
• MiR-433 Regulates Myocardial Ischemia Reperfusion Injury by Targeting NDRG4 Via the PI3K/Akt Pathway. (PMID:32187107)
• TFPI2 and NDRG4 gene promoter methylation analysis in peripheral blood mononuclear cells are novel epigenetic noninvasive biomarkers for colorectal cancer diagnosis. (PMID:32196834)
• A loss-of-function mutation p.T256M in NDRG4 is implicated in the pathogenesis of pulmonary atresia with ventricular septal defect (PA/VSD) and tetralogy of Fallot (TOF). (PMID:33211401)
• Hypermethylation-mediated silencing of NDRG4 promotes pancreatic ductal adenocarcinoma by regulating mitochondrial function. (PMID:33298240)
• Identification of NDRG Family Member 4 (NDRG4) and CDC28 Protein Kinase Regulatory Subunit 2 (CKS2) as Key Prognostic Genes in Adrenocortical Carcinoma by Transcriptomic Analysis. (PMID:33667214)
• Loss of enteric neuronal Ndrg4 promotes colorectal cancer via increased release of Nid1 and Fbln2. (PMID:33890711)
• Highly sensitive fecal DNA testing of NDRG4 12b methylation is a promising marker for detection of colorectal precancerosis. (PMID:34564976)
• Errate: Identification of NDRG Family Member 4 (NDRG4) and CDC28 Protein Kinase Regulatory Subunit 2 (CKS2) as Key Prognostic Genes in Adrenocortical Carcinoma by Transcriptomic Analysis. (PMID:35899496)
• miR-23a-3p promotes the development of colon cancer by inhibiting the expression of NDRG4. (PMID:36374403)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndrg4	ENSDARG00000103937
mus_musculus	Ndrg4	ENSMUSG00000036564
rattus_norvegicus	Ndrg4	ENSRNOG00000012482
drosophila_melanogaster	CG2082	FBGN0027608
drosophila_melanogaster	MESK2	FBGN0043070
caenorhabditis_elegans	Y48G10A.3	WBGENE00013020
caenorhabditis_elegans		WBGENE00014213

Paralogs (3): NDRG3 (ENSG00000101079), NDRG1 (ENSG00000104419), NDRG2 (ENSG00000165795)

Protein

Protein identifiers

Protein NDRG4 — Q9ULP0 (reviewed: Q9ULP0)

Alternative names: Brain development-related molecule 1, N-myc downstream-regulated gene 4 protein, Vascular smooth muscle cell-associated protein 8

All UniProt accessions (34): Q9ULP0, A0A0S2Z5L7, A0A0S2Z5R7, B7Z9X4, H3BM40, H3BM44, H3BM83, H3BMG5, H3BMR6, H3BN53, H3BN97, H3BNB4, H3BNE7, H3BNK4, H3BNQ1, H3BNX9, H3BPH8, H3BPQ3, H3BPT6, H3BPY2, H3BQ01, H3BQ86, H3BQJ4, H3BR92, H3BRT9, H3BS80, H3BSC3, H3BST8, H3BU08, H3BU25, H3BUH4, H3BUK1, H3BVB0, H3BVF3

UniProt curated annotations — full annotation on UniProt →

Function. Contributes to the maintenance of intracerebral BDNF levels within the normal range, which is necessary for the preservation of spatial learning and the resistance to neuronal cell death caused by ischemic stress. May enhance growth factor-induced ERK1 and ERK2 phosphorylation, including that induced by PDGF and FGF. May attenuate NGF-promoted ELK1 phosphorylation in a microtubule-dependent manner.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Expressed predominantly in brain and heart (at protein level). In the brain, detected in astrocytes. Isoform 1 and isoform 2 are only expressed in brain. Isoform 3 is expressed in both heart and brain. Up-regulated in glioblastoma multiforme cells.

Post-translational modifications. Phosphorylated in an aortic smooth muscle cell line, following PDGF treatment.

Similarity. Belongs to the NDRG family.

Isoforms (8)

UniProt ID	Names	Canonical?
Q9ULP0-1	1, NDRG4-BVar	yes
Q9ULP0-2	2, NDRG4-B
Q9ULP0-3	3, NDRG4-H
Q9ULP0-4	4
Q9ULP0-5	5
Q9ULP0-6	6
Q9ULP0-7	7
Q9ULP0-8	8

RefSeq proteins (24): NP_001123959, NP_001229762, NP_001229763, NP_001229764, NP_001229765, NP_001350798, NP_001365261, NP_001365262, NP_001365263, NP_001365264, NP_001365265, NP_001365266, NP_001365267, NP_001365268, NP_001365269, NP_001365270, NP_001365271, NP_001365272, NP_001365273, NP_001365274, NP_001365275, NP_001365276, NP_065198, NP_075061 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004142	NDRG	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily

Pfam: PF03096

UniProt features (15 total): splice variant 7, modified residue 3, compositionally biased region 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULP0-F1	85.27	0.72

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 (3): 298, 317, 323

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 275 (showing top): GOBP_PLATELET_DERIVED_GROWTH_FACTOR_RECEPTOR_SIGNALING_PATHWAY, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_CELL_MIGRATION_INVOLVED_IN_HEART_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_NEGATIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_PROLIFERATION, GOBP_NEURON_MATURATION, GOBP_ASSOCIATIVE_LEARNING, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP

GO Biological Process (15): heart looping (GO:0001947), signal transduction (GO:0007165), visual learning (GO:0008542), negative regulation of platelet-derived growth factor receptor signaling pathway (GO:0010642), positive regulation of neuron projection development (GO:0010976), negative regulation of smooth muscle cell migration (GO:0014912), cell differentiation (GO:0030154), embryonic heart tube development (GO:0035050), clustering of voltage-gated sodium channels (GO:0045162), obsolete vesicle docking (GO:0048278), negative regulation of smooth muscle cell proliferation (GO:0048662), cardiac muscle cell proliferation (GO:0060038), cell migration involved in heart development (GO:0060973), positive regulation of ERK1 and ERK2 cascade (GO:0070374), regulation of endocytic recycling (GO:2001135)

GO Molecular Function (2): molecular_function (GO:0003674), protein binding (GO:0005515)

GO Cellular Component (7): cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), cell projection membrane (GO:0031253), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
heart development	2
plasma membrane region	2
embryonic heart tube morphogenesis	1
determination of heart left/right asymmetry	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
visual behavior	1
associative learning	1
negative regulation of signal transduction	1
regulation of platelet-derived growth factor receptor signaling pathway	1
platelet-derived growth factor receptor signaling pathway	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
smooth muscle cell migration	1
regulation of smooth muscle cell migration	1
negative regulation of cell migration	1
cellular developmental process	1
tube development	1
embryonic organ development	1
epithelium development	1
neuronal ion channel clustering	1
negative regulation of cell population proliferation	1
smooth muscle cell proliferation	1
regulation of smooth muscle cell proliferation	1
striated muscle cell proliferation	1
cardiac muscle tissue growth	1
cell migration	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
regulation of intracellular transport	1
endocytic recycling	1
regulation of vesicle-mediated transport	1
binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1526 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NDRG4	BMP3	P12645	840
NDRG4	SEPTIN9	Q9UHD8	697
NDRG4	MYCN	P04198	600
NDRG4	TFPI2	P48307	598
NDRG4	POPDC1	Q8NE79	585
NDRG4	KRAS	P01116	579
NDRG4	SDC2	P34741	544
NDRG4	SFRP2	Q96HF1	542
NDRG4	C9orf50	Q5SZB4	516
NDRG4	RNF207	Q6ZRF8	507
NDRG4	GINS3	Q9BRX5	451
NDRG4	VIM	P08670	450
NDRG4	ALX4	Q9H161	437
NDRG4	NOS1AP	O75052	430
NDRG4	HLTF	Q14527	422

IntAct

27 interactions, top by confidence:

A	B	Type	Score
ARL6IP1	NDRG4	psi-mi:“MI:0915”(physical association)	0.560
AGTRAP	NDRG4	psi-mi:“MI:0915”(physical association)	0.560
CMTM5	NDRG4	psi-mi:“MI:0915”(physical association)	0.560
RABAC1	NDRG4	psi-mi:“MI:0915”(physical association)	0.560
NDRG4	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.560
NDRG4	CMTM5	psi-mi:“MI:0915”(physical association)	0.560
NDRG4	RABAC1	psi-mi:“MI:0915”(physical association)	0.560
NDRG4	AGTRAP	psi-mi:“MI:0915”(physical association)	0.560
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
NUFIP1	PDE2A	psi-mi:“MI:0914”(association)	0.530
NDRG4	UFSP2	psi-mi:“MI:0915”(physical association)	0.400
NDRG4	APLNR	psi-mi:“MI:0915”(physical association)	0.370
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
TEX101	NDUFA4	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CACNA1C	IGLL5	psi-mi:“MI:0914”(association)	0.350
GPM6A	KIF2A	psi-mi:“MI:0914”(association)	0.350
HAX1	DNM1L	psi-mi:“MI:0914”(association)	0.350
DNAAF2	DNM1L	psi-mi:“MI:0914”(association)	0.350
FXYD3	TNPO2	psi-mi:“MI:0914”(association)	0.350
FXYD1	SPINK4	psi-mi:“MI:0914”(association)	0.350

BioGRID (69): NDRG4 (Two-hybrid), NDRG4 (Two-hybrid), NDRG4 (Two-hybrid), CMTM5 (Two-hybrid), NDRG4 (Affinity Capture-MS), NDRG4 (Affinity Capture-MS), NDRG4 (Affinity Capture-MS), NDRG4 (Affinity Capture-MS), NDRG4 (Affinity Capture-MS), NDRG4 (Affinity Capture-MS), NDRG4 (Affinity Capture-MS), TP53 (Affinity Capture-Western), RABAC1 (Affinity Capture-Western), RTN3 (Two-hybrid), AGTRAP (Two-hybrid)

ESM2 similar proteins: A0A2R8QFQ6, A0A2R8RWN9, A0JN27, A5PKD9, B5DFK7, D3Z7P3, G3MWR8, O94925, P13264, Q01098, Q08DW9, Q14722, Q28528, Q28D01, Q2HJ19, Q2YDM2, Q4R766, Q5JUK3, Q5NVE6, Q5RIC0, Q5SRY7, Q5TA45, Q5XIJ5, Q5ZIN0, Q5ZJ01, Q5ZJX1, Q67FW5, Q6DCC5, Q6DD70, Q6DEY3, Q6GL10, Q6PCB6, Q6ZPR4, Q7RTP6, Q7ZVZ7, Q8BTG7, Q8C6G8, Q8CJ19, Q8N2K0, Q8TF64

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	28
Benign	31

Top pathogenic / likely-pathogenic (0)

SpliceAI

2054 predictions. Top by Δscore:

Variant	Effect	Δscore
16:58503904:G:GG	donor_gain	1.0000
16:58504272:GGG:G	donor_gain	1.0000
16:58504273:GG:G	donor_gain	1.0000
16:58504273:GGG:G	donor_gain	1.0000
16:58504274:GG:G	donor_gain	1.0000
16:58504354:TGCA:T	acceptor_loss	1.0000
16:58504356:CAG:C	acceptor_loss	1.0000
16:58504357:A:C	acceptor_loss	1.0000
16:58504419:CGGG:C	donor_loss	1.0000
16:58504420:GG:G	donor_gain	1.0000
16:58504420:GGGTG:G	donor_loss	1.0000
16:58504421:GG:G	donor_gain	1.0000
16:58504421:GGTG:G	donor_loss	1.0000
16:58504422:G:GG	donor_gain	1.0000
16:58504423:TGA:T	donor_loss	1.0000
16:58504424:GA:G	donor_loss	1.0000
16:58504650:G:GG	donor_gain	1.0000
16:58506403:T:TA	acceptor_gain	1.0000
16:58506475:T:A	donor_loss	1.0000
16:58506881:T:TA	acceptor_gain	1.0000
16:58506884:A:AG	acceptor_gain	1.0000
16:58506884:AT:A	acceptor_gain	1.0000
16:58506885:T:G	acceptor_gain	1.0000
16:58506893:T:G	acceptor_gain	1.0000
16:58506897:T:G	acceptor_gain	1.0000
16:58506903:T:TA	acceptor_gain	1.0000
16:58506904:G:A	acceptor_gain	1.0000
16:58506907:CCTAG:C	acceptor_loss	1.0000
16:58506910:A:AG	acceptor_gain	1.0000
16:58506911:G:GG	acceptor_gain	1.0000

AlphaMissense

2312 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:58506411:G:T	G133W	1.000
16:58506463:C:A	A150D	1.000
16:58507970:G:T	G234W	1.000
16:58508981:T:C	L250P	1.000
16:58509005:T:C	L258P	1.000
16:58509328:T:C	Y281H	1.000
16:58509340:G:C	G285R	1.000
16:58503874:T:A	I33N	0.999
16:58503877:T:C	L34P	0.999
16:58503895:G:A	G40D	0.999
16:58504235:C:A	A70D	0.999
16:58504385:T:C	L92P	0.999
16:58504605:G:C	G110R	0.999
16:58504606:G:A	G110D	0.999
16:58504612:G:A	G112E	0.999
16:58504623:G:A	G116R	0.999
16:58504623:G:C	G116R	0.999
16:58504624:G:A	G116E	0.999
16:58504636:T:C	L120P	0.999
16:58506411:G:A	G133R	0.999
16:58506411:G:C	G133R	0.999
16:58506412:G:A	G133E	0.999
16:58506415:T:C	L134P	0.999
16:58506421:T:C	L136P	0.999
16:58506450:T:A	W146R	0.999
16:58506450:T:C	W146R	0.999
16:58507962:T:C	L231P	0.999
16:58507965:T:A	V232E	0.999
16:58507970:G:A	G234R	0.999
16:58507970:G:C	G234R	0.999

dbSNP variants (sampled 300 via entrez): RS1000032497 (16:58467014 C>G), RS1000069529 (16:58485218 T>C), RS1000092623 (16:58490282 C>T), RS1000121632 (16:58484947 T>C), RS1000142028 (16:58478248 G>A), RS1000217548 (16:58462574 C>A,T), RS1000251413 (16:58468653 G>A), RS1000275070 (16:58506294 G>A), RS1000306353 (16:58495824 C>T), RS1000319381 (16:58495821 C>T), RS1000323998 (16:58505443 A>T), RS1000337032 (16:58496134 G>A), RS1000402563 (16:58463317 CAA>C), RS1000412474 (16:58463413 G>C), RS1000478645 (16:58501167 G>A,T)

Disease associations

OMIM: gene MIM:614463 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
achromatopsia	Limited	Autosomal recessive

Mondo (2): hepatoblastoma (MONDO:0018666), achromatopsia (MONDO:0018852)

Orphanet (1): Hepatoblastoma (Orphanet:449)

HPO phenotypes

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

GWAS associations

95 associations (top):

Study	Trait	p-value
GCST000363_9	QT interval	3.000000e-25
GCST000364_9	QT interval	7.000000e-25
GCST000561_18	Electrocardiographic traits	1.000000e-06
GCST001580_3	QT interval	1.000000e-07
GCST006803_60	Schizophrenia	2.000000e-10
GCST010135_44	Oily fish consumption	2.000000e-08
GCST010140_34	Pork consumption	2.000000e-08
GCST010796_3426	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-42
GCST010796_3427	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-44
GCST010796_3428	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-44
GCST010796_3429	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-44
GCST010796_3451	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-22
GCST010796_3452	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-21
GCST010796_3453	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-21
GCST010796_3454	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-23
GCST010796_3455	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-25
GCST010796_3456	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-26
GCST010796_3457	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-24
GCST010796_3458	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-23
GCST010796_3459	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-26
GCST010796_3460	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-29
GCST010796_3461	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-30
GCST010796_3462	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-30
GCST010796_3463	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-29
GCST010796_3464	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-29
GCST010796_3465	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-32
GCST010796_3466	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-34
GCST010796_3467	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-36
GCST010796_3468	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-38
GCST010796_3469	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-38

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004682	QT interval
EFO:0008111	diet measurement
EFO:0004327	electrocardiography

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018197	Hepatoblastoma	C04.557.435.380

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, increases expression, affects expression	8
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	4
Tetrachlorodibenzodioxin	increases expression	3
sodium arsenite	increases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Cisplatin	affects cotreatment, increases expression, affects expression	2
Nickel	decreases expression	2
Cyclosporine	decreases expression, decreases methylation, increases expression	2
Cadmium Chloride	increases abundance, increases expression, decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
afuresertib	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
uranyl acetate	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, decreases expression	1
arsenite	decreases expression, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT03017326	PHASE3	ACTIVE_NOT_RECRUITING	Paediatric Hepatic International Tumour Trial
NCT03533582	PHASE3	ACTIVE_NOT_RECRUITING	Cisplatin and Combination Chemotherapy in Treating Children and Young Adults With Hepatoblastoma or Liver Cancer After Surgery
NCT04478292	PHASE3	RECRUITING	A Multi-institutional Study for Treatment of Children With Newly Diagnosed Hepatoblastoma Using a Modified PHITT Strategy
NCT01154816	PHASE2	COMPLETED	Alisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia
NCT02011126	PHASE2	WITHDRAWN	Imetelstat Sodium in Treating Younger Patients With Relapsed or Refractory Solid Tumors
NCT02867592	PHASE2	ACTIVE_NOT_RECRUITING	Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors
NCT03155620	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03210714	PHASE2	ACTIVE_NOT_RECRUITING	Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213652	PHASE2	ACTIVE_NOT_RECRUITING	Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
NCT03213665	PHASE2	COMPLETED	Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
NCT03213678	PHASE2	COMPLETED	Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213704	PHASE2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03220035	PHASE2	COMPLETED	Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)
NCT03233204	PHASE2	COMPLETED	Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
NCT03526250	PHASE2	COMPLETED	Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)
NCT03698994	PHASE2	ACTIVE_NOT_RECRUITING	Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
NCT04195555	PHASE2	ACTIVE_NOT_RECRUITING	Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
NCT04284774	PHASE2	ACTIVE_NOT_RECRUITING	Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04320888	PHASE2	ACTIVE_NOT_RECRUITING	Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
NCT05302921	PHASE2	COMPLETED	Neoadjuvant Dual Checkpoint Inhibition and Cryoablation in Relapsed/Refractory Pediatric Solid Tumors
NCT06638931	PHASE2	RECRUITING	Agnostic Therapy in Rare Solid Tumors
NCT07300449	PHASE2	RECRUITING	A Prospective Multicenter Clinical Study of SCCG Protocol and ctDNA 5hmc in Predicting the Chemotherapy Sensitivity and Monitoring the Recurrence and Metastasis of Hepatoblastoma in Children and Adolescents
NCT01331135	PHASE1	COMPLETED	Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors
NCT02390843	PHASE1	COMPLETED	Simvastatin With Topotecan and Cyclophosphamide in Relapsed and/or Refractory Pediatric Solid and CNS Tumors
NCT03618381	PHASE1	ACTIVE_NOT_RECRUITING	EGFR806 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults
NCT04093648	PHASE1	WITHDRAWN	T Cells co- Expressing a Second Generation Glypican 3-specific Chimeric Antigen Receptor With Cytokines Interleukin-21 and 15 as Immunotherapy for Patients With Liver Cancer (TEGAR)
NCT04308330	PHASE1	RECRUITING	Vorinostat in Combination With Chemotherapy in Relapsed/Refractory Solid Tumors and CNS Malignancies
NCT04337177	PHASE1	ACTIVE_NOT_RECRUITING	Flavored, Oral Irinotecan VAL-413 (Orotecan®) Given With Temozolomide for Treatment of Recurrent Pediatric Solid Tumors
NCT04483778	PHASE1	ACTIVE_NOT_RECRUITING	B7H3 CAR T Cell Immunotherapy for Recurrent/Refractory Solid Tumors in Children and Young Adults
NCT04897321	PHASE1	RECRUITING	B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)
NCT06198296	PHASE1	RECRUITING	Immunotherapy For Adults With GPC3-Positive Solid Tumors Using IL-15 and IL-21 Armored GPC3-CAR T Cells
NCT07148050	PHASE1	RECRUITING	Immunotherapy for Solid Tumor Malignancies in Pediatrics Using Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor T Cells
NCT01648452	PHASE1/PHASE2	COMPLETED	CNTF Implants for CNGB3 Achromatopsia
NCT02599922	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGB3 Achromatopsia (A Clarity Clinical Trial)
NCT02610582	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy of rAAV.hCNGA3 Gene Therapy in Patients With CNGA3-linked Achromatopsia
NCT02935517	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGA3 Achromatopsia (A Clarity Clinical Trial)
NCT03001310	PHASE1/PHASE2	COMPLETED	Gene Therapy for Achromatopsia (CNGB3)
NCT03758404	PHASE1/PHASE2	COMPLETED	Gene Therapy for Achromatopsia (CNGA3)
NCT04041232	EARLY_PHASE1	SUSPENDED	PBA Use for Treatment of ATF6-/- Patients