NRDC

Summary

NRDC (nardilysin convertase, HGNC:7995) is a protein-coding gene on chromosome 1p32.3, encoding Nardilysin (O43847). Cleaves peptide substrates on the N-terminus of arginine residues in dibasic pairs.

This gene encodes a zinc-dependent endopeptidase that cleaves peptide substrates at the N-terminus of arginine residues in dibasic moieties and is a member of the peptidase M16 family. This protein interacts with heparin-binding EGF-like growth factor and plays a role in cell migration and proliferation. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4898 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 55 total
• Druggable target: yes
• MANE Select transcript: NM_001101662

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7995
Approved symbol	NRDC
Name	nardilysin convertase
Location	1p32.3
Locus type	gene with protein product
Status	Approved
Aliases	hNRD1, hNRD2
Ensembl gene	ENSG00000078618
Ensembl biotype	protein_coding
OMIM	602651
Entrez	4898

Gene structure

Transcript identifiers

Ensembl transcripts: 49 — 40 protein_coding, 9 protein_coding_CDS_not_defined

ENST00000352171, ENST00000354831, ENST00000440943, ENST00000464385, ENST00000468722, ENST00000473805, ENST00000475310, ENST00000475715, ENST00000483007, ENST00000485608, ENST00000491410, ENST00000497358, ENST00000539524, ENST00000888744, ENST00000888745, ENST00000888746, ENST00000888747, ENST00000888748, ENST00000888749, ENST00000888750, ENST00000888751, ENST00000888752, ENST00000888753, ENST00000888754, ENST00000888755, ENST00000911773, ENST00000911774, ENST00000911775, ENST00000911776, ENST00000911777, ENST00000911778, ENST00000911779, ENST00000911780, ENST00000911781, ENST00000911782, ENST00000911783, ENST00000911784, ENST00000911785, ENST00000911786, ENST00000911787, ENST00000911788, ENST00000963644, ENST00000963645, ENST00000963646, ENST00000963647, ENST00000963648, ENST00000963649, ENST00000963650, ENST00000963651

RefSeq mRNA: 3 — MANE Select: NM_001101662 NM_001101662, NM_001242361, NM_002525

CCDS: CCDS41335, CCDS55599, CCDS559

Canonical transcript exons

ENST00000352171 — 31 exons

Exon	Start	End
ENSE00003459888	51792046	51792098
ENSE00003467678	51791578	51791661
ENSE00003471821	51821498	51821555
ENSE00003519359	51794472	51794610
ENSE00003529893	51814035	51814089
ENSE00003534998	51823664	51823786
ENSE00003543346	51800556	51800683
ENSE00003550955	51825287	51825382
ENSE00003558222	51810281	51810404
ENSE00003560752	51809315	51809401
ENSE00003561512	51819800	51819873
ENSE00003568231	51790900	51790990
ENSE00003571271	51794823	51794854
ENSE00003576336	51806794	51806913
ENSE00003590728	51811994	51812098
ENSE00003594065	51792377	51792424
ENSE00003608043	51840226	51840514
ENSE00003610779	51790533	51790649
ENSE00003615161	51814551	51814609
ENSE00003627824	51834017	51834170
ENSE00003648964	51789568	51789657
ENSE00003655365	51836131	51836212
ENSE00003661374	51827796	51827869
ENSE00003663752	51798249	51798411
ENSE00003666024	51803814	51803964
ENSE00003668388	51816312	51816389
ENSE00003672863	51805510	51805561
ENSE00003681806	51814693	51814813
ENSE00003690929	51818066	51818135
ENSE00003899116	51878275	51878727
ENSE00003900901	51789210	51789433

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.4315 / max 731.2733, expressed in 1820 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12324	35.7164	1819
201509	0.9079	465
12322	0.7978	469
12326	0.7472	423
12323	0.6985	427
12325	0.5637	323

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gluteal muscle	UBERON:0002000	99.33	gold quality
right testis	UBERON:0004534	98.96	gold quality
left testis	UBERON:0004533	98.94	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.92	gold quality
triceps brachii	UBERON:0001509	98.89	gold quality
gastrocnemius	UBERON:0001388	98.75	gold quality
muscle of leg	UBERON:0001383	98.59	gold quality
adenohypophysis	UBERON:0002196	98.46	gold quality
sperm	CL:0000019	98.39	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.38	gold quality
muscle organ	UBERON:0001630	98.37	gold quality
male germ cell	CL:0000015	98.31	gold quality
biceps brachii	UBERON:0001507	98.29	gold quality
pituitary gland	UBERON:0000007	98.28	gold quality
diaphragm	UBERON:0001103	98.23	gold quality
skin of leg	UBERON:0001511	98.23	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.23	gold quality
vastus lateralis	UBERON:0001379	98.15	gold quality
tibial nerve	UBERON:0001323	98.14	gold quality
skin of abdomen	UBERON:0001416	98.10	gold quality
skeletal muscle tissue	UBERON:0001134	97.99	gold quality
monocyte	CL:0000576	97.97	gold quality
lower esophagus mucosa	UBERON:0035834	97.95	gold quality
right lobe of liver	UBERON:0001114	97.89	gold quality
testis	UBERON:0000473	97.87	gold quality
mononuclear cell	CL:0000842	97.81	gold quality
right ovary	UBERON:0002118	97.77	gold quality
endocervix	UBERON:0000458	97.75	gold quality
body of tongue	UBERON:0011876	97.75	gold quality
zone of skin	UBERON:0000014	97.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TCF3

Literature-anchored findings (GeneRIF, showing 22)

• N-arginine dibasic convertase is a specific receptor for heparin-binding EGF-like growth factor (HB-EGF) that modulates HB-EGF-induced cell migration. (PMID:11432822)
• The acidic stretch of nardilysin, expressed as a fusion protein with glutathione S-transferase and compared to the native enzyme with respect to spermine binding, functions as an autonomous domain. (PMID:11478915)
• nardilysin (NRDc) is potently inhibited by heparin-binding epidermal growth factor-like growth factor (HB-EGF) (PMID:12095415)
• Nardilysin has an essential role in HB-EGF ectodomain shedding, which is regulated by the modulation of sheddase activity (PMID:16923819)
• We found high staining intensity in the hypothalamus, neocortex and brain stem nuclei. The cellular localization is almost exclusively confined to neurons. In pre- and perinatal human brain cortex, most neurons express the enzyme. (PMID:17442499)
• These results indicate the involvement of NRDc in ectodomain shedding of TNF-alpha. (PMID:18355445)
• Nardilysin convertase regulates the function of the maxi-K channel isoform mK44 in human myometrium. (PMID:19118164)
• mediates antigen processing that generates cytotoxic T cell epitopes (PMID:21151101)
• Several flanking SNPs of the top hits in the meta-analysis demonstrated borderline associations with alcohol dependence in the family sample for KIAA0040, NRD1 and THSD7B, respectively. (PMID:21703634)
• SH-SY5Y cells, stably transfected with green fluorescent protein-tagged-p42(IP4) show enhanced NRD protein expression already at an earlier time point after retinoic acid stimulation. (PMID:21801775)
• Tubulin potentiates the interaction of the metalloendopeptidase nardilysin with the neuronal scaffold protein p42IP4/centaurin-alpha1 (ADAP1). (PMID:21972134)
• Identification and characterization of nardilysin as a novel dimethyl H3K4-binding protein involved in transcriptional regulation. (PMID:22294699)
• These results demonstrate that gastric cancer cell growth is maintained by autonomous TNF-alpha-NF-kappaB and IL-6-STAT3 signalling, and that NRDc and ADAM proteases turn on these signalling cascades by stimulating ectodomain shedding of TNF-alpha. (PMID:22351606)
• NRD1 interacts with p53 mutant R273H (PMID:22653443)
• This study demonistrated that alcohol-dependent reduction of nardilysin in cell culture and nervous tissue points to an implication of the enzyme in the pathophysiology of alcoholism. (PMID:23219461)
• possible roles of nardilysin in Alzheimer disease, Down syndrome, schizophrenia, mood disorders, alcohol abuse, heroin addiction and cancer; show that nardilysin is a Janus-faced enzyme with regard to brain pathology– probably neuropathogenic in some diseases, but neuroprotective in others [review] (PMID:23604405)
• MRNA expression of NRD1 was upregulated in 56% of ESCC tissue samples. (PMID:24168165)
• Gene expression level of NRD1 is significantly higher in AD patients when compared to normal controls. (PMID:26943237)
• NRDC expression was reduced in infarcted regions in autopsy samples from acute myocardial ischemia patients. (PMID:28747015)
• Increased serum nardilysin at admission is associated with a higher risk of all-cause mortality for ST-elevation myocardial infarction patients. (PMID:30536341)
• Altered Levels of Negative Costimulatory Molecule V-Set Domain-Containing T-Cell Activation Inhibitor-1 (VTCN1) and Metalloprotease Nardilysin (NRD1) are Associated with Generalized Active Vitiligo. (PMID:35815687)
• CircNRD1 elevates THAP domain containing 11 through sequestering microRNA-421 to inhibit gastric cancer growth and tumorigenesis. (PMID:38602237)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	nrd1a	ENSDARG00000019596
danio_rerio	nrd1b	ENSDARG00000062372
mus_musculus	Nrdc	ENSMUSG00000053510
rattus_norvegicus	Nrdc	ENSRNOG00000007111
drosophila_melanogaster	Nrd1	FBGN0030344
drosophila_melanogaster	CG10588	FBGN0037037
caenorhabditis_elegans		WBGENE00011679

Paralogs (6): UQCRC1 (ENSG00000010256), PMPCB (ENSG00000105819), PITRM1 (ENSG00000107959), IDE (ENSG00000119912), UQCRC2 (ENSG00000140740), PMPCA (ENSG00000165688)

Protein

Protein identifiers

Nardilysin — O43847 (reviewed: O43847)

Alternative names: N-arginine dibasic convertase, Nardilysin convertase

All UniProt accessions (3): O43847, G3V1R5, H0Y5G9

UniProt curated annotations — full annotation on UniProt →

Function. Cleaves peptide substrates on the N-terminus of arginine residues in dibasic pairs. Is a critical activator of BACE1- and ADAM17-mediated pro-neuregulin ectodomain shedding, involved in the positive regulation of axonal maturation and myelination. Required for proper functioning of 2-oxoglutarate dehydrogenase (OGDH).

Subunit / interactions. Interacts with BACE1 and NRG1.

Subcellular location. Mitochondrion. Cell projection. Dendrite.

Tissue specificity. Primarily in adult heart, skeletal muscle, and testis and at much lower levels in other tissues.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the peptidase M16 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O43847-1	1, NRD1	yes
O43847-2	2, NRD2

RefSeq proteins (3): NP_001095132, NP_001229290, NP_002516 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001431	Pept_M16_Zn_BS	Binding_site
IPR007863	Peptidase_M16_C	Domain
IPR011249	Metalloenz_LuxS/M16	Homologous_superfamily
IPR011765	Pept_M16_N	Domain
IPR032632	Peptidase_M16_M	Domain
IPR050626	Peptidase_M16	Family

Pfam: PF00675, PF05193, PF16187

Enzyme classification (BRENDA):

• EC 3.4.24.61 — nardilysin (BRENDA: 3 organisms, 148 substrates, 55 inhibitors, 81 Km, 66 kcat entries)

Substrate kinetics (BRENDA)

63 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
2-AMINOBENZOYL-TPLVTLX1X2NAIIKQED(2,4-DINITROPHE	0.0005–0.0466	8
2-AMINOBENZOYL-GGFLRRVGQ-N[2,4-DINITROPHENYL]-ET	0.0002–0.03	7
2-AMINOBENZOYL-GGFIRKVGQ-ETHYLENEDIAMINE-2,4-DIN	0.0062–0.0072	2
2-AMINOBENZOYL-GGFLRKVGQ-ETHYLENEDIAMINE-2,4-DIN	0.0057–0.0065	2
2-AMINOBENZOYL-GGFYRKVGQ-ETHYLENEDIAMINE-2,4-DIN	0.0083–0.0094	2
SOMATOSTATIN-14	0.0005–0.008	2
SOMATOSTATIN-28	0.0055–0.043	2
[ALA17,TYR20]-SOMATOSTATIN-28-(10-20)-NH2	0.428	2
2-AMINOBENZOYL-GFSPFRSSRQED(2,4-DINITROPHENYL)	0.0019	1
2-AMINOBENZOYL-GGALRKVGQ-ETHYLENEDIAMINE-2,4-DIN	0.0074	1
2-AMINOBENZOYL-GGFARKVGQ-ETHYLENEDIAMINE-2,4-DIN	0.0061	1
2-AMINOBENZOYL-GGFFRKVGQ-ETHYLENEDIAMINE-2,4-DIN	0.0094	1
2-AMINOBENZOYL-GGFHRKVGQ-ETHYLENEDIAMINE-2,4-DIN	0.0044	1
2-AMINOBENZOYL-GGFIKKVGQ-ETHYLENEDIAMINE-2,4-DIN	0.0075	1
2-AMINOBENZOYL-GGFIKRVGQ-ETHYLENEDIAMINE-2,4-DIN	0.0074	1

UniProt features (22 total): sequence conflict 7, modified residue 3, binding site 3, sequence variant 2, region of interest 2, signal peptide 1, chain 1, splice variant 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43847-F1	83.20	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.

Catalytic / active sites (1): 236 (proton acceptor)

Ligand- & substrate-binding residues (3): 233; 237; 314

Post-translational modifications (3): 94, 96, 86

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 215 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, RNGTGGGC_UNKNOWN, PAX4_01, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_RESPONSE_TO_PEPTIDE, MORF_HDAC1, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOCC_CELL_SURFACE, GOBP_NEUROGENESIS, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_REGULATION_OF_MYELINATION, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, ACTGCAG_MIR173P, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (7): proteolysis (GO:0006508), positive regulation of myelination (GO:0031643), positive regulation of tumor necrosis factor production (GO:0032760), positive regulation of axonogenesis (GO:0050772), positive regulation of membrane protein ectodomain proteolysis (GO:0051044), negative regulation of cold-induced thermogenesis (GO:0120163), positive regulation of tumor necrosis factor-mediated signaling pathway (GO:1903265)

GO Molecular Function (8): metalloendopeptidase activity (GO:0004222), metal ion binding (GO:0046872), epidermal growth factor binding (GO:0048408), endopeptidase activator activity (GO:0061133), protein binding (GO:0005515), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787)

GO Cellular Component (6): mitochondrial matrix (GO:0005759), cytosol (GO:0005829), cell surface (GO:0009986), dendrite (GO:0030425), mitochondrion (GO:0005739), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
endopeptidase activity	2
cytoplasm	2
protein metabolic process	1
regulation of myelination	1
positive regulation of nervous system process	1
myelination	1
positive regulation of cellular process	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
axonogenesis	1
positive regulation of cell projection organization	1
positive regulation of neurogenesis	1
regulation of axonogenesis	1
membrane protein ectodomain proteolysis	1
positive regulation of protein catabolic process	1
positive regulation of proteolysis	1
regulation of membrane protein ectodomain proteolysis	1
negative regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
positive regulation of cytokine-mediated signaling pathway	1
regulation of tumor necrosis factor-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
metallopeptidase activity	1
cation binding	1
growth factor binding	1
hormone binding	1
peptidase activator activity	1
endopeptidase regulator activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
mitochondrion	1
intracellular organelle lumen	1
neuron projection	1
dendritic tree	1

Protein interactions and networks

STRING

1368 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NRDC	SETX	Q7Z333	951
NRDC	HBEGF	Q99075	948
NRDC	ADAP1	O75689	788
NRDC	THOP1	P52888	680
NRDC	TPP2	P29144	646
NRDC	EXOSC10	Q01780	539
NRDC	NRG1	P98202	528
NRDC	BACE1	P56817	522
NRDC	NLN	Q9BYT8	508
NRDC	GPATCH11	Q8N954	494
NRDC	RNPEP	Q9H4A4	490
NRDC	SH3D19	Q5HYK7	482
NRDC	YJU2B	P13994	467
NRDC	PITRM1	Q5JRX3	457
NRDC	ADAM17	P78536	454

IntAct

95 interactions, top by confidence:

A	B	Type	Score
LMO1	ZBTB43	psi-mi:“MI:0914”(association)	0.830
ASF1B	HAT1	psi-mi:“MI:0914”(association)	0.640
TP53	NRDC	psi-mi:“MI:0915”(physical association)	0.580
NRDC	TP53	psi-mi:“MI:0915”(physical association)	0.580
ZNF707	ZNF316	psi-mi:“MI:0914”(association)	0.530
CDRT15	CDRT15L2	psi-mi:“MI:0914”(association)	0.530
AURKAIP1	NRDC	psi-mi:“MI:0914”(association)	0.480
NRDC	BAIAP2	psi-mi:“MI:0915”(physical association)	0.400
METTL25	NRDC	psi-mi:“MI:0915”(physical association)	0.400
NRDC	NLGN3	psi-mi:“MI:0915”(physical association)	0.370
ATM	RBM47	psi-mi:“MI:0914”(association)	0.350
Haus1	LTF	psi-mi:“MI:0914”(association)	0.350
Smchd1	SETD1A	psi-mi:“MI:0914”(association)	0.350
Mtx2	NRDC	psi-mi:“MI:0914”(association)	0.350
KIF7	TBC1D31	psi-mi:“MI:0914”(association)	0.350
Fus	DDX3X	psi-mi:“MI:0914”(association)	0.350
ERP44	NRDC	psi-mi:“MI:0914”(association)	0.350
LGALS3BP	CEP290	psi-mi:“MI:0914”(association)	0.350
PCDHB15	HLA-A	psi-mi:“MI:0914”(association)	0.350
PDGFRA	RNPS1	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
FMC1	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
CHCHD2	POLRMT	psi-mi:“MI:0914”(association)	0.350

BioGRID (167): NRD1 (Affinity Capture-MS), NRD1 (Affinity Capture-RNA), NRD1 (Affinity Capture-RNA), NRD1 (Affinity Capture-MS), NRD1 (Affinity Capture-MS), NRD1 (Affinity Capture-MS), NRD1 (Affinity Capture-MS), NRD1 (Affinity Capture-MS), KPNA3 (Co-fractionation), NRD1 (Affinity Capture-MS), NRD1 (Proximity Label-MS), NRD1 (Affinity Capture-MS), NRD1 (Affinity Capture-MS), NRD1 (Affinity Capture-MS), NRD1 (Affinity Capture-MS)

ESM2 similar proteins: A9X1D0, B0VX69, B1MTJ4, B2KI88, B4F753, B5FW36, B7ZUF3, C1FXW2, E2RBS6, E9PTA2, G3V6U9, O43847, O54804, O94759, O95453, O95803, P11926, P20069, P27117, P47245, Q0P5M8, Q10713, Q13507, Q4R4U1, Q4R766, Q5R4H6, Q5R513, Q5R5F8, Q5RC51, Q5U4X8, Q61143, Q6AYT7, Q6GQK9, Q7SXS7, Q7TT45, Q86TU7, Q8BHG1, Q8N2K0, Q91WC0, Q91YD4

Diamond homologs: B8B0E2, F4HNU6, F4J3D9, O14077, O22941, O43847, P14735, P22817, P27508, P35559, P42789, P47245, Q06010, Q24K02, Q4WP38, Q5R4H6, Q69TY5, Q88QV3, Q8BHG1, Q9I2D2, Q9JHR7, P55174, Q10040, Q4W6B5, P40851, P45181, Q88A79, Q04805, Q40983, P05458, P11913, Q83QC3, Q8CVS2, Q8X6M8, Q8Z418, Q8ZMB5, Q9P7X1, P55679, Q00302, Q9Y8B5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

5125 predictions. Top by Δscore:

Variant	Effect	Δscore
1:51787710:TACA:T	acceptor_loss	1.0000
1:51787711:ACAG:A	acceptor_loss	1.0000
1:51787713:A:AG	acceptor_gain	1.0000
1:51787713:A:C	acceptor_loss	1.0000
1:51787714:G:GA	acceptor_gain	1.0000
1:51787714:GTT:G	acceptor_gain	1.0000
1:51787714:GTTA:G	acceptor_gain	1.0000
1:51787714:GTTAT:G	acceptor_gain	1.0000
1:51789429:ACAAC:A	acceptor_gain	1.0000
1:51789430:CAAC:C	acceptor_gain	1.0000
1:51789430:CAACC:C	acceptor_gain	1.0000
1:51789431:AAC:A	acceptor_gain	1.0000
1:51789432:AC:A	acceptor_gain	1.0000
1:51789433:CC:C	acceptor_gain	1.0000
1:51789434:C:CC	acceptor_gain	1.0000
1:51789445:C:CT	acceptor_gain	1.0000
1:51789566:A:AC	donor_gain	1.0000
1:51789567:C:CC	donor_gain	1.0000
1:51789659:T:C	acceptor_gain	1.0000
1:51789659:T:TC	acceptor_gain	1.0000
1:51790660:C:CT	acceptor_gain	1.0000
1:51790895:GTCAC:G	donor_loss	1.0000
1:51790896:TCA:T	donor_loss	1.0000
1:51790897:CAC:C	donor_loss	1.0000
1:51790898:ACCT:A	donor_loss	1.0000
1:51790986:CAGAA:C	acceptor_gain	1.0000
1:51790987:AGAA:A	acceptor_gain	1.0000
1:51790988:GAA:G	acceptor_gain	1.0000
1:51790989:AA:A	acceptor_gain	1.0000
1:51790990:AC:A	acceptor_loss	1.0000

AlphaMissense

7658 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:51789647:A:G	L1060P	1.000
1:51790546:C:G	R1052P	1.000
1:51790583:A:G	W1040R	1.000
1:51790583:A:T	W1040R	1.000
1:51790630:A:G	L1024P	1.000
1:51790639:A:G	L1021P	1.000
1:51790957:A:C	F998L	1.000
1:51790957:A:T	F998L	1.000
1:51790959:A:G	F998L	1.000
1:51791608:A:T	V977D	1.000
1:51791617:C:T	G974E	1.000
1:51791618:C:G	G974R	1.000
1:51791618:C:T	G974R	1.000
1:51791653:A:T	V962D	1.000
1:51791660:A:G	Y960H	1.000
1:51792046:C:T	G959E	1.000
1:51792047:C:A	G959W	1.000
1:51792047:C:G	G959R	1.000
1:51792047:C:T	G959R	1.000
1:51792061:G:A	T954I	1.000
1:51792064:C:G	R953P	1.000
1:51792065:G:C	R953G	1.000
1:51792067:A:G	L952P	1.000
1:51792067:A:T	L952H	1.000
1:51792075:A:C	F949L	1.000
1:51792075:A:T	F949L	1.000
1:51792076:A:C	F949C	1.000
1:51792076:A:G	F949S	1.000
1:51792077:A:C	F949V	1.000
1:51792077:A:G	F949L	1.000

dbSNP variants (sampled 300 via entrez): RS1000009422 (1:51843977 T>C), RS1000039176 (1:51832498 T>C,G), RS1000055976 (1:51835111 G>A), RS1000137268 (1:51846176 G>A,T), RS1000152468 (1:51857975 T>C), RS1000178492 (1:51877648 G>A), RS1000184365 (1:51815021 C>T), RS1000225767 (1:51829415 T>C), RS1000229074 (1:51877431 C>A,G,T), RS1000242800 (1:51788718 G>T), RS1000303178 (1:51844135 G>A), RS1000316918 (1:51802030 G>A), RS1000349585 (1:51851807 A>G), RS1000354926 (1:51847828 G>A,C), RS1000356374 (1:51842651 CA>C,CAA)

Disease associations

OMIM: gene MIM:602651 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90000025_922	Appendicular lean mass	2.000000e-10
GCST90020028_529	Hip circumference adjusted for BMI	3.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724615 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.41	Kd	3858	nM	CHEMBL5653589
5.34	ED50	4579	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 8 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148888: Binding affinity to human NRD1 incubated for 45 mins by Kinobead based pull down assay	kd	3.8583	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
cobaltous chloride	decreases expression, increases expression	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	increases oxidation, increases abundance, affects cotreatment	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
bufotalin	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
tributyltin	decreases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	increases expression	1
ochratoxin A	increases expression	1
bleomycetin	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
LDN 193189	decreases expression, affects cotreatment	1
Acetaminophen	decreases expression	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Benzo(a)pyrene	decreases expression	1
Dinitrochlorobenzene	affects binding	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Formaldehyde	decreases expression	1
Gallic Acid	decreases expression	1
Ivermectin	decreases expression	1
Thimerosal	increases expression	1
Valproic Acid	affects expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651930	Binding	Binding affinity to human NRD1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3CS	Abcam HEK293T NRDC KO	Transformed cell line	Female
CVCL_TB08	HAP1 NRD1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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