NDST1

Summary

NDST1 (N-deacetylase and N-sulfotransferase 1, HGNC:7680) is a protein-coding gene on chromosome 5q33.1, encoding Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1 (P52848). Essential bifunctional enzyme that catalyzes both the N-deacetylation and the N-sulfation of glucosamine (GlcNAc) of the glycosaminoglycan in heparan sulfate.

This gene encodes a member of the heparan sulfate/heparin GlcNAc N-deacetylase/ N-sulfotransferase family. The encoded enzyme is a type II transmembrane protein that resides in the Golgi apparatus. The encoded protein catalyzes the transfer of sulfate from 3’-phosphoadenosine 5’-phosphosulfate to nitrogen of glucosamine in heparan sulfate. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 3340 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability, autosomal recessive 46 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 307 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 28
• MANE Select transcript: NM_001543

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7680
Approved symbol	NDST1
Name	N-deacetylase and N-sulfotransferase 1
Location	5q33.1
Locus type	gene with protein product
Status	Approved
Aliases	NST1
Ensembl gene	ENSG00000070614
Ensembl biotype	protein_coding
OMIM	600853
Entrez	3340

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 26 protein_coding, 3 protein_coding_CDS_not_defined, 1 TEC

ENST00000261797, ENST00000518299, ENST00000518346, ENST00000519157, ENST00000521752, ENST00000522491, ENST00000523767, ENST00000524161, ENST00000624156, ENST00000891667, ENST00000891668, ENST00000891669, ENST00000891670, ENST00000891671, ENST00000891672, ENST00000891673, ENST00000891674, ENST00000891675, ENST00000891676, ENST00000891677, ENST00000937575, ENST00000937576, ENST00000937577, ENST00000937578, ENST00000937579, ENST00000965559, ENST00000965560, ENST00000965561, ENST00000965562, ENST00000965563

RefSeq mRNA: 2 — MANE Select: NM_001543 NM_001301063, NM_001543

CCDS: CCDS34277, CCDS75358

Canonical transcript exons

ENST00000261797 — 15 exons

Exon	Start	End
ENSE00000439232	150534867	150535021
ENSE00000841211	150532945	150533032
ENSE00000841214	150535700	150535885
ENSE00000972942	150527804	150528298
ENSE00001171009	150520868	150521767
ENSE00001198482	150539228	150539356
ENSE00001475116	150553213	150558211
ENSE00001475118	150551753	150551855
ENSE00001475119	150549678	150549787
ENSE00001475121	150548218	150548388
ENSE00001475122	150545312	150545486
ENSE00001475124	150542848	150542971
ENSE00001475127	150540082	150540264
ENSE00001507093	150541570	150541666
ENSE00001607679	150508131	150508226

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 96.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.3134 / max 146.4025, expressed in 1763 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59454	6.6628	1609
59451	5.0343	1538
59453	4.6441	1561
59456	2.5807	1298
59460	1.1697	402
59455	0.6810	465
59450	0.4914	305
59463	0.3704	151
59452	0.3276	122
59462	0.1193	58

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	96.12	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.88	gold quality
spinal cord	UBERON:0002240	93.33	gold quality
olfactory bulb	UBERON:0002264	93.33	gold quality
subthalamic nucleus	UBERON:0001906	93.07	gold quality
tendon of biceps brachii	UBERON:0008188	93.03	silver quality
inferior vagus X ganglion	UBERON:0005363	92.83	gold quality
right lobe of liver	UBERON:0001114	92.07	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.01	gold quality
dorsal plus ventral thalamus	UBERON:0001897	92.00	gold quality
tongue squamous epithelium	UBERON:0006919	91.97	silver quality
esophagus mucosa	UBERON:0002469	91.85	gold quality
inferior olivary complex	UBERON:0002127	91.59	gold quality
upper lobe of left lung	UBERON:0008952	91.55	gold quality
medulla oblongata	UBERON:0001896	91.27	gold quality
lateral globus pallidus	UBERON:0002476	91.21	gold quality
spleen	UBERON:0002106	91.15	gold quality
ventral tegmental area	UBERON:0002691	91.05	gold quality
parotid gland	UBERON:0001831	91.00	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	90.97	gold quality
upper lobe of lung	UBERON:0008948	90.92	gold quality
cervix squamous epithelium	UBERON:0006922	90.80	silver quality
cortical plate	UBERON:0005343	90.65	gold quality
sural nerve	UBERON:0015488	90.63	gold quality
type B pancreatic cell	CL:0000169	90.62	gold quality
right lung	UBERON:0002167	90.47	gold quality
superior vestibular nucleus	UBERON:0007227	90.26	gold quality
lower esophagus mucosa	UBERON:0035834	90.25	gold quality
ventricular zone	UBERON:0003053	90.04	gold quality
pons	UBERON:0000988	89.95	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.26
E-GEOD-99795	no	250.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

206 targeting NDST1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
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-6833-3P	100.00	70.63	3197
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-23A-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 13)

• Altered expression of NDST-1 mRNA in glomerular basement membrane in puromycin aminonucleoside nephrosis. (PMID:14966466)
• effect of targeted inactivation of the Ndst1 gene on the inflammatory response associated with allergic inflammation (PMID:19710461)
• the expression of the NDST-1 isoform was approximately equal at all stages of mast cell maturation (PMID:19915053)
• Inhibitory peptides of the sulfotransferase domain of the heparan sulfate enzyme, N-deacetylase-N-sulfotransferase-1. (PMID:20129923)
• MicroRNA-191 targets N-deacetylase/N-sulfotransferase 1 and promotes cell growth in human gastric carcinoma cell line MGC803 (PMID:21947487)
• These findings establish NDST1 as a target of miR-24 and demonstrate how such NDST1 suppression in endothelial cells results in reduced responsiveness to VEGFA (PMID:23884416)
• Our data confirm NDST1 mutations as a cause of autosomal recessive intellectual disability with a distinctive phenotype, and support an important function of NDST1 in human development. (PMID:25125150)
• Upregulation of NDST1 is associated with chemoresistance in breast cancer. (PMID:25156775)
• demonstrate the essential role of domain cooperation within NDST-1 in producing HS with specific domain structures (PMID:26109066)
• Compound heterozygous mutations in NDST1 were identified, in the heparan sulfate N deacetylatase domain of one allele and the sulfotransferase domain of the other allele. This report expands the phenotypic spectrum of Ndst1 deficiency in humans. (PMID:28211985)
• Among the genes enriched in this screening, the authors found that TM9SF2 is critical for N-sulfation of heparan sulfate and therefore for chikungunya virus infection because it is involved in the proper localization and stability of NDST1. (PMID:28404855)
• MiRNA-191 functions as an oncogene in primary glioblastoma by directly targeting NDST1. (PMID:31364126)
• Two Cases of Recessive Intellectual Disability Caused by NDST1 and METTL23 Variants. (PMID:32878022)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndst1a	ENSDARG00000062397
danio_rerio	NDST1	ENSDARG00000103606
mus_musculus	Ndst1	ENSMUSG00000054008
rattus_norvegicus	Ndst1	ENSRNOG00000019014

Paralogs (10): HS3ST1 (ENSG00000002587), HS3ST2 (ENSG00000122254), HS3ST3B1 (ENSG00000125430), NDST4 (ENSG00000138653), HS3ST3A1 (ENSG00000153976), HS3ST6 (ENSG00000162040), NDST3 (ENSG00000164100), NDST2 (ENSG00000166507), HS3ST4 (ENSG00000182601), HS3ST5 (ENSG00000249853)

Protein

Protein identifiers

Bifunctional heparan sulfate N-deacetylase/N-sulfotransferase 1 — P52848 (reviewed: P52848)

Alternative names: Glucosaminyl N-deacetylase/N-sulfotransferase 1, N-heparan sulfate sulfotransferase 1, [Heparan sulfate]-glucosamine N-sulfotransferase 1

All UniProt accessions (4): P52848, E5RG24, E5RG58, E5RGN9

UniProt curated annotations — full annotation on UniProt →

Function. Essential bifunctional enzyme that catalyzes both the N-deacetylation and the N-sulfation of glucosamine (GlcNAc) of the glycosaminoglycan in heparan sulfate. Modifies the GlcNAc-GlcA disaccharide repeating sugar backbone to make N-sulfated heparosan, a prerequisite substrate for later modifications in heparin biosynthesis. Plays a role in determining the extent and pattern of sulfation of heparan sulfate. Participates in biosynthesis of heparan sulfate that can ultimately serve as L-selectin ligands, thereby playing a role in inflammatory response. Required for the exosomal release of SDCBP, CD63 and syndecan. Lacks both N-deacetylase and N-sulfotransferase activities. Acts as a dominant negative on isoform 1, likely by changing the composition of enzyme complexes responsible for elongation and modification of heparan sulfates.

Subunit / interactions. Monomer. Interacts with heparan sulfate co-polymerase subunits EXT1 and EXT2. Interacts with NDST1 isoform 3. Interacts with heparan sulfate co-polymerase subunits EXT1 and EXT2. Interacts with NDST1 isoform 1.

Subcellular location. Golgi apparatus. trans-Golgi network membrane. cis-Golgi network membrane Golgi apparatus. cis-Golgi network membrane.

Tissue specificity. Widely expressed. Expression is most abundant in heart, liver and pancreas.

Disease relevance. Intellectual developmental disorder, autosomal recessive 46 (MRT46) [MIM:616116] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT46 manifestations include delayed psychomotor development apparent from infancy or early childhood, delayed or absent expressive speech, hypotonia, and therapy-responsive seizures in some patients. Behavioral abnormalities are variable and include aggression, self-injurious behavior, and sleep disturbances. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Glycan metabolism; heparan sulfate biosynthesis. Glycan metabolism; heparin biosynthesis.

Miscellaneous. The presence of 4 different heparan sulfate N-deacetylase/N-sulfotransferase enzymes in mammals, as well as differences in their enzyme activity suggest that some initiate heparan sulfate modification/sulfation reactions, whereas other later on fill in or extend already modified heparan sulfate sequences. The increased expression in several types of cancer is associated with shorter survival.

Similarity. Belongs to the sulfotransferase 1 family. NDST subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P52848-1	1, NDST1A	yes
P52848-2	2
P52848-3	3, NDST1B

RefSeq proteins (2): NP_001287992, NP_001534* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000863	Sulfotransferase_dom	Domain
IPR021930	Heparan_SO4_deacetylase_dom	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR037359	NST/OST	Family
IPR056793	HSNSD_N	Domain

Pfam: PF00685, PF12062, PF25119

Enzyme classification (BRENDA):

• EC 2.8.2.8 — [heparan sulfate]-glucosamine N-sulfotransferase (BRENDA: 11 organisms, 86 substrates, 14 inhibitors, 13 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
3’-PHOSPHOADENYLYLSULFATE	0.005–0.108	6
N-DEACETYLASE K5-POLYSACCHARIDE	0.0009–0.0224	3
N,O-DESULFOHEPARAN SULFATE TETRASACCHARIDE	2.5	1
N-DESULFOHEPARAN SULFATE	1.89	1
N-DESULFOHEPARIN	0.013	1

Catalyzed reactions (Rhea), 2 shown:

• alpha-D-glucosaminyl-heparan sulfate + 3’-phosphoadenylyl sulfate = N-sulfo-alpha-D-glucosaminyl-heparan sulfate + adenosine 3’,5’-bisphosphate + 2 H(+) (RHEA:21980)
• N-acetyl-alpha-D-glucosaminyl-heparan sulfate + H2O = alpha-D-glucosaminyl-heparan sulfate + acetate (RHEA:70587)

UniProt features (112 total): strand 38, helix 34, turn 9, sequence conflict 6, binding site 4, glycosylation site 4, sequence variant 4, splice variant 3, region of interest 3, topological domain 2, chain 1, disulfide bond 1, transmembrane region 1, mutagenesis site 1, active site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
1NST	X-RAY DIFFRACTION	2.3
8CD0	ELECTRON MICROSCOPY	2.42
8CCY	ELECTRON MICROSCOPY	2.7
8CHS	ELECTRON MICROSCOPY	3.15
9F6Z	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52848-F1	90.55	0.83

Antibody-complex structures (SAbDab): 2 — 8CD0, 8CHS

Functional residue map

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

Catalytic / active sites (1): 614 (for sulfotransferase activity)

Ligand- & substrate-binding residues (4): 817; 833–837; 614–618; 712

Disulfide bonds (1): 818–828

Glycosylation sites (4): 231, 351, 401, 667

Mutagenesis-validated functional residues (1):

Position	Phenotype
614	loss of heparan sulfate-glucosamine n-sulfotransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-2022928	HS-GAG biosynthesis
R-HSA-1430728	Metabolism
R-HSA-1630316	Glycosaminoglycan metabolism
R-HSA-1638091	Heparan sulfate/heparin (HS-GAG) metabolism
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives

MSigDB gene sets: 382 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_CORONARY_VASCULATURE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_INFLAMMATORY_RESPONSE, TTCCGTT_MIR191, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_EMBRYONIC_SKELETAL_SYSTEM_MORPHOGENESIS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_ARTERY_DEVELOPMENT

GO Biological Process (19): polysaccharide biosynthetic process (GO:0000271), cardiac septum development (GO:0003279), inflammatory response (GO:0006954), respiratory gaseous exchange by respiratory system (GO:0007585), cell population proliferation (GO:0008283), fibroblast growth factor receptor signaling pathway (GO:0008543), heparan sulfate proteoglycan biosynthetic process (GO:0015012), glycosaminoglycan metabolic process (GO:0030203), heparin proteoglycan biosynthetic process (GO:0030210), forebrain development (GO:0030900), midbrain development (GO:0030901), aorta development (GO:0035904), positive regulation of MAPK cascade (GO:0043410), positive regulation of smoothened signaling pathway (GO:0045880), embryonic neurocranium morphogenesis (GO:0048702), embryonic viscerocranium morphogenesis (GO:0048703), coronary vasculature development (GO:0060976), heart development (GO:0007507), animal organ morphogenesis (GO:0009887)

GO Molecular Function (9): heparan sulfate N-sulfotransferase activity (GO:0015016), deacetylase activity (GO:0019213), N-acetylglucosamine deacetylase activity (GO:0050119), heparan sulfate N-deacetylase activity (GO:0102140), catalytic activity (GO:0003824), protein binding (GO:0005515), sulfotransferase activity (GO:0008146), transferase activity (GO:0016740), hydrolase activity (GO:0016787)

GO Cellular Component (4): Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), trans-Golgi network membrane (GO:0032588), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Heparan sulfate/heparin (HS-GAG) metabolism	1
Metabolism of carbohydrates and carbohydrate derivatives	1
Glycosaminoglycan metabolism	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	3
protein O-linked glycosylation via xylose	2
brain development	2
embryonic morphogenesis	2
embryonic cranial skeleton morphogenesis	2
animal organ development	2
deacetylase activity	2
catalytic activity	2
polysaccharide metabolic process	1
macromolecule biosynthetic process	1
carbohydrate biosynthetic process	1
cardiac chamber development	1
defense response	1
multicellular organismal process	1
cellular process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to fibroblast growth factor stimulus	1
proteoglycan biosynthetic process	1
heparan sulfate proteoglycan metabolic process	1
aminoglycan metabolic process	1
heparin proteoglycan metabolic process	1
artery development	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
smoothened signaling pathway	1
regulation of smoothened signaling pathway	1
positive regulation of signal transduction	1
blood vessel development	1
heart development	1
circulatory system development	1
anatomical structure morphogenesis	1
heparan sulfate sulfotransferase activity	1
deacylase activity	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	1
carboxylic ester hydrolase activity	1
molecular_function	1
binding	1
transferase activity, transferring sulphur-containing groups	1
Golgi apparatus	1

Protein interactions and networks

STRING

698 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NDST1	EXT2	Q93063	941
NDST1	SULT1C3	Q6IMI6	896
NDST1	SULT1C4	O75897	895
NDST1	SULT1B1	O43704	893
NDST1	EXT1	Q16394	879
NDST1	EXTL3	O43909	844
NDST1	HS2ST1	Q7LGA3	821
NDST1	HS6ST1	O60243	750
NDST1	GLCE	O94923	726
NDST1	TCOF1	Q13428	725
NDST1	K7EP71	K7EP71	695
NDST1	ANXA6	P08133	679
NDST1	UST	Q9Y2C2	668
NDST1	HS6ST2	Q96MM7	652
NDST1	RPS14	P06366	644

IntAct

46 interactions, top by confidence:

A	B	Type	Score
CD83	BTAF1	psi-mi:“MI:0914”(association)	0.530
NRROS	NDUFA3	psi-mi:“MI:0914”(association)	0.530
PLAUR	XRCC3	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
ANKH	FAM234B	psi-mi:“MI:0914”(association)	0.530
XRCC5	BACC1	psi-mi:“MI:0914”(association)	0.350
TMEM132A	WWP2	psi-mi:“MI:0914”(association)	0.350
Sidt2	PRSS1	psi-mi:“MI:0914”(association)	0.350
Brca1	SMCHD1	psi-mi:“MI:0914”(association)	0.350
PLAUR	DDX11L8	psi-mi:“MI:0914”(association)	0.350
TAZ	MANBA	psi-mi:“MI:0914”(association)	0.350
NAAA	NRP2	psi-mi:“MI:0914”(association)	0.350
	PLOD2	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
NAAA	POTEF	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
SCGB2A1	RAP1BL	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
RLN1	RTL8C	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
CEACAM8	PRRT4	psi-mi:“MI:0914”(association)	0.350
TAFAZZIN	MANBA	psi-mi:“MI:0914”(association)	0.350
C1orf54	AGRN	psi-mi:“MI:0914”(association)	0.350
HPN	TOR1A	psi-mi:“MI:0914”(association)	0.350
CD83	ABCD4	psi-mi:“MI:0914”(association)	0.350
NDST2	CLGN	psi-mi:“MI:0914”(association)	0.350
LCN6	COCH	psi-mi:“MI:0914”(association)	0.350
IDS	COCH	psi-mi:“MI:0914”(association)	0.350
NRROS	HS6ST1	psi-mi:“MI:0914”(association)	0.350

BioGRID (68): NDST1 (Affinity Capture-MS), NDST1 (Affinity Capture-MS), NDST1 (Affinity Capture-MS), NDST1 (Affinity Capture-MS), NDST1 (Affinity Capture-MS), NDST1 (Affinity Capture-MS), NDST1 (Affinity Capture-MS), NDST1 (Affinity Capture-MS), NDST1 (Affinity Capture-MS), NDST1 (Affinity Capture-MS), NDST1 (Affinity Capture-MS), NDST1 (Affinity Capture-MS), NDST1 (Affinity Capture-MS), NDST1 (Affinity Capture-MS), NDST1 (Positive Genetic)

ESM2 similar proteins: A0A1D5PUP4, A2AFS3, M0R7X9, O70472, O75882, O95803, P01134, P26012, P52799, P52848, P69849, Q02353, Q05204, Q0VCJ8, Q12841, Q13635, Q15155, Q3UHN9, Q3ZBS2, Q58D84, Q5EA46, Q5JPE7, Q5R9Y1, Q5U4X8, Q5VV63, Q5ZJB7, Q5ZMH6, Q61115, Q62356, Q62632, Q6A051, Q6GQK9, Q6GQT9, Q6P988, Q6UXG2, Q7Z5A7, Q86TD4, Q90693, Q91WE9, Q96CW9

Diamond homologs: O35310, O95803, O97583, P52848, P52849, P52850, Q02353, Q3UHN9, Q5GFD5, Q5U4X8, Q60V90, Q673U1, Q6GQK9, Q80W66, Q8BKN6, Q8BSL4, Q8IZT8, Q966W3, Q96QI5, Q9EQH7, Q9EQW8, Q9ESG5, Q9H3R1, Q9QZS6, Q9V3L1, Q9Y278, Q9Y661, Q9Y662, Q9Y663, O14792, Q55GK8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	156
Likely benign	95
Benign	21

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
161409	NM_001543.5(NDST1):c.2126G>A (p.Arg709Gln)	Pathogenic
161410	NM_001543.5(NDST1):c.1926G>T (p.Glu642Asp)	Pathogenic
161411	NM_001543.5(NDST1):c.1918T>C (p.Phe640Leu)	Likely pathogenic

SpliceAI

2321 predictions. Top by Δscore:

Variant	Effect	Δscore
5:150528290:G:GT	donor_gain	1.0000
5:150528296:AAG:A	donor_gain	1.0000
5:150528296:AAGGT:A	donor_loss	1.0000
5:150532941:CTAG:C	acceptor_loss	1.0000
5:150532943:A:AG	acceptor_gain	1.0000
5:150532944:G:A	acceptor_loss	1.0000
5:150532944:G:GG	acceptor_gain	1.0000
5:150532944:GGCC:G	acceptor_gain	1.0000
5:150532944:GGCCC:G	acceptor_gain	1.0000
5:150533031:AGGTA:A	donor_loss	1.0000
5:150533032:GGTA:G	donor_loss	1.0000
5:150533033:GT:G	donor_loss	1.0000
5:150533034:T:G	donor_loss	1.0000
5:150534861:CTGCA:C	acceptor_loss	1.0000
5:150534862:T:A	acceptor_gain	1.0000
5:150534862:TGCA:T	acceptor_loss	1.0000
5:150534863:GCA:G	acceptor_loss	1.0000
5:150534864:CA:C	acceptor_loss	1.0000
5:150534865:A:AG	acceptor_gain	1.0000
5:150534866:G:A	acceptor_loss	1.0000
5:150534866:G:GG	acceptor_gain	1.0000
5:150534866:GGT:G	acceptor_gain	1.0000
5:150535009:G:GT	donor_gain	1.0000
5:150535017:CTGTC:C	donor_gain	1.0000
5:150535018:TGTC:T	donor_gain	1.0000
5:150535019:GTC:G	donor_gain	1.0000
5:150535019:GTCG:G	donor_gain	1.0000
5:150535020:TC:T	donor_gain	1.0000
5:150535020:TCGT:T	donor_gain	1.0000
5:150535022:G:GG	donor_gain	1.0000

AlphaMissense

5800 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:150527963:T:A	W225R	1.000
5:150527963:T:C	W225R	1.000
5:150527973:T:C	F228S	1.000
5:150528135:G:A	G282D	1.000
5:150528234:T:C	L315P	1.000
5:150528246:A:T	D319V	1.000
5:150528248:G:C	D320H	1.000
5:150528248:G:T	D320Y	1.000
5:150528249:A:C	D320A	1.000
5:150528249:A:G	D320G	1.000
5:150528249:A:T	D320V	1.000
5:150528250:C:A	D320E	1.000
5:150528250:C:G	D320E	1.000
5:150532949:T:C	L338P	1.000
5:150534887:G:T	G373W	1.000
5:150534926:T:A	W386R	1.000
5:150534926:T:C	W386R	1.000
5:150534929:T:C	F387L	1.000
5:150534931:C:A	F387L	1.000
5:150534931:C:G	F387L	1.000
5:150534935:C:G	H389D	1.000
5:150534947:C:G	H393D	1.000
5:150534949:C:A	H393Q	1.000
5:150534949:C:G	H393Q	1.000
5:150534957:C:A	P396H	1.000
5:150534959:C:G	H397D	1.000
5:150535740:C:A	P431H	1.000
5:150535742:C:G	H432D	1.000
5:150535745:C:G	H433D	1.000
5:150535746:A:G	H433R	1.000

dbSNP variants (sampled 300 via entrez): RS1000093743 (5:150520917 C>T), RS1000131544 (5:150529613 A>C), RS1000142356 (5:150541566 T>G), RS1000200761 (5:150500412 G>A), RS1000305813 (5:150523529 C>T), RS1000306995 (5:150515466 C>T), RS1000312555 (5:150509149 C>G,T), RS1000394061 (5:150526258 T>G), RS1000498872 (5:150496014 T>C), RS1000504460 (5:150541865 C>T), RS1000535556 (5:150542297 A>G), RS1000571088 (5:150503305 G>A), RS1000594623 (5:150496438 C>T), RS1000616635 (5:150515133 A>G), RS1000635189 (5:150497243 G>A)

Disease associations

OMIM: gene MIM:600853 | disease phenotypes: MIM:616116

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, autosomal recessive 46	Strong	Autosomal recessive
autosomal recessive non-syndromic intellectual disability	Supportive	Autosomal recessive

Mondo (4): intellectual disability, autosomal recessive 46 (MONDO:0014499), cleft lip/palate (MONDO:0016044), intellectual disability (MONDO:0001071), autosomal recessive non-syndromic intellectual disability (MONDO:0019502)

Orphanet (3): Autosomal recessive non-syndromic intellectual disability (Orphanet:88616), Cleft lip/palate (Orphanet:199306), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

28 total (28 of 28 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000411	Protruding ear
HP:0000486	Strabismus
HP:0000639	Nystagmus
HP:0000664	Synophrys
HP:0000687	Widely spaced teeth
HP:0000713	Agitation
HP:0000718	Aggressive behavior
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001510	Growth delay
HP:0001520	Large for gestational age
HP:0001763	Pes planus
HP:0002119	Ventriculomegaly
HP:0002194	Delayed gross motor development
HP:0002360	Sleep disturbance
HP:0002465	Poor speech
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0010862	Delayed fine motor development
HP:0011463	Childhood onset
HP:0100716	Self-injurious behavior

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004131_47	Inflammatory bowel disease	3.000000e-15
GCST004132_24	Crohn’s disease	2.000000e-19
GCST005855_1	Cholangiocarcinoma in primary sclerosing cholangitis	1.000000e-06
GCST006585_2707	Blood protein levels	2.000000e-06
GCST90000025_22	Appendicular lean mass	3.000000e-09
GCST90002398_5	Neutrophil count	2.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass
EFO:0004833	neutrophil count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, increases expression	3
Valproic Acid	decreases expression, decreases methylation	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Acetaminophen	decreases expression, increases expression	2
Cyclosporine	decreases expression, decreases methylation	2
bisphenol F	affects cotreatment, increases methylation	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
bisphenol A	decreases expression	1
trichostatin A	affects expression	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Bucladesine	affects cotreatment, increases expression	1
Folic Acid	affects expression	1
Methyl Methanesulfonate	increases expression	1
Methylcholanthrene	affects binding, increases reaction	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Dronabinol	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Aflatoxin B1	increases methylation	1
Medroxyprogesterone Acetate	affects cotreatment, increases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04234971	PHASE4	RECRUITING	Cost Effectiveness in Alveolar Bone Grafting in Patients With Cleft Lip and Palate
NCT04771156	PHASE4	RECRUITING	Ketorolac in Palatoplasty
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT03766217	PHASE3	COMPLETED	Bone Tissue Engineering With Dental Pulp Stem Cells for Alveolar Cleft Repair
NCT06284434	PHASE3	RECRUITING	Liposomal Bupivacaine Use in Alveolar Bone Graft Patients
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00930124	PHASE2	COMPLETED	Cleft Orthognathic Surgery Versus Distraction Osteogenesis - Which is Better?
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT06408337	PHASE1/PHASE2	RECRUITING	Phase I-IIa, to Evaluate the Safety, Feasibility, and Efficacy of the Use of BIOCLEFT in the Treatment of Cleft Palate.
NCT00070811	Not specified	COMPLETED	Assessing the Results of Lip Surgery in Patients With Cleft Lip and Palate
NCT00156442	Not specified	COMPLETED	A Study to Examine the Relationship Between Sleep Apnea and Cleft Lip/Palate
NCT01601171	Not specified	RECRUITING	Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
NCT01871623	Not specified	UNKNOWN	One-Piece Le Fort I Osteotomy Versus Segmental Le Fort I Osteotomy
NCT01932164	Not specified	COMPLETED	Use of Mesenchymal Stem Cells for Alveolar Bone Tissue Engineering for Cleft Lip and Palate Patients
NCT02702869	Not specified	ENROLLING_BY_INVITATION	Allied Cleft & Craniofacial Quality-Improvement and Research Network (ACCQUIREnet)
NCT02789787	Not specified	COMPLETED	Clinical Effectiveness of Late Maxillary Protraction for Cleft Lip and Palate
NCT02845193	Not specified	COMPLETED	Effect of Novel Nasoalveolar Molding Techniques on Parents’ Satisfaction and Short Term Treatment Outcomes in Unilateral Cleft Lip and Palate Infants: A Randomized Controlled Trial
NCT02881606	Not specified	COMPLETED	Evaluation of the Clinical Effectiveness of Naso-alveolar Molding (NAM) Versus Computer Aided Design NAM (CAD/NAM) in Infants With Bilateral Cleft Lip and Palate: A Randomized Clinical Trial
NCT03011489	Not specified	UNKNOWN	Parent’s Satisfaction and Evaluation of Postsurgical Outcomes in Unilateral Cleft Lip / Palate Newly Born Infants With / Without Vacuum Formed Nasoalveolar Molding Aligners : A Controlled Clinical Trial
NCT03065686	Not specified	RECRUITING	Identification of Genetic Factors Implicated in Orofacial Cleft Using Whole Exome Sequencing
NCT03165331	Not specified	UNKNOWN	Online Psychosocial Support for Young People With a Visible Difference: A Randomised Control Study
NCT03217890	Not specified	UNKNOWN	the Relationship Between Cleft Lip and / or Palate (Different Types) and ABO Blood Groups.
NCT03308266	Not specified	COMPLETED	Electromyographic Analysis of the Masticatory Muscles in Cleft Lip and Palate Children With Temporomandibular Disorders
NCT03395015	Not specified	COMPLETED	Efficacy of Maxillo-facial Treatment on Cleft Lip and Palate Patients Faces: Aesthetic Considerations
NCT03514563	Not specified	TERMINATED	Three Dimensional Facial Growth Analysis
NCT03563495	Not specified	COMPLETED	Tissue Engineered Constructs for Alveolar Cleft Repair
NCT03582111	Not specified	COMPLETED	Ultrasound Diagnosis of Cleft Lip and Palate
NCT03686761	Not specified	COMPLETED	Periodontal Changes Following Mid Maxillary Distraction
NCT03708406	Not specified	COMPLETED	Otologic and Rhinologic Outcomes in Children With Clef Palate