NMNAT1

Summary

NMNAT1 (nicotinamide nucleotide adenylyltransferase 1, HGNC:17877) is a protein-coding gene on chromosome 1p36.22, encoding Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1 (Q9HAN9). Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP. It is a selective cancer dependency (DepMap: 24.4% of cell lines).

This gene encodes an enzyme which catalyzes a key step in the biosynthesis of nicotinamide adenine dinucleotide (NAD). The encoded enzyme is one of several nicotinamide nucleotide adenylyltransferases, and is specifically localized to the cell nucleus. Activity of this protein leads to the activation of a nuclear deacetylase that functions in the protection of damaged neurons. Mutations in this gene have been associated with Leber congenital amaurosis 9. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene are located on chromosomes 1, 3, 4, 14, and 15.

Source: NCBI Gene 64802 — RefSeq curated summary.

At a glance

• Gene–disease (curated): NMNAT1-related retinopathy (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 233 total — 39 pathogenic, 28 likely-pathogenic
• Phenotypes (HPO): 84
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 24.4% of screened cell lines
• MANE Select transcript: NM_022787

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17877
Approved symbol	NMNAT1
Name	nicotinamide nucleotide adenylyltransferase 1
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Aliases	NMNAT, PNAT1
Ensembl gene	ENSG00000173614
Ensembl biotype	protein_coding
OMIM	608700
Entrez	64802

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000377205, ENST00000403197, ENST00000462686, ENST00000492735, ENST00000496751, ENST00000887500, ENST00000946962, ENST00000946963, ENST00000946964, ENST00000946965

RefSeq mRNA: 3 — MANE Select: NM_022787 NM_001297778, NM_001297779, NM_022787

CCDS: CCDS108, CCDS72698

Canonical transcript exons

ENST00000377205 — 5 exons

Exon	Start	End
ENSE00001180526	9981031	9981170
ENSE00001473095	9982301	9985498
ENSE00001682224	9975592	9975775
ENSE00002273780	9972018	9972188
ENSE00003849433	9943475	9943515

Expression profiles

Bgee: expression breadth ubiquitous, 225 present calls, max score 85.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.4643 / max 110.7990, expressed in 1801 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
541	10.4643	1801

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	85.19	gold quality
muscle of leg	UBERON:0001383	84.18	gold quality
mucosa of transverse colon	UBERON:0004991	83.98	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.45	gold quality
gastrocnemius	UBERON:0001388	83.38	gold quality
islet of Langerhans	UBERON:0000006	83.00	gold quality
monocyte	CL:0000576	82.85	gold quality
leukocyte	CL:0000738	82.40	gold quality
calcaneal tendon	UBERON:0003701	82.10	gold quality
stromal cell of endometrium	CL:0002255	82.05	gold quality
rectum	UBERON:0001052	81.63	gold quality
adrenal tissue	UBERON:0018303	81.45	gold quality
apex of heart	UBERON:0002098	80.81	gold quality
heart left ventricle	UBERON:0002084	80.65	gold quality
cardiac ventricle	UBERON:0002082	80.20	gold quality
right atrium auricular region	UBERON:0006631	79.45	gold quality
right adrenal gland	UBERON:0001233	79.42	gold quality
right adrenal gland cortex	UBERON:0035827	79.34	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	79.00	gold quality
heart	UBERON:0000948	78.65	gold quality
left adrenal gland	UBERON:0001234	78.49	gold quality
left adrenal gland cortex	UBERON:0035825	78.18	gold quality
smooth muscle tissue	UBERON:0001135	78.06	gold quality
transverse colon	UBERON:0001157	78.03	gold quality
adrenal gland	UBERON:0002369	77.86	gold quality
cardiac atrium	UBERON:0002081	77.79	gold quality
skeletal muscle tissue	UBERON:0001134	77.74	gold quality
adrenal cortex	UBERON:0001235	77.25	gold quality
adult mammalian kidney	UBERON:0000082	76.43	gold quality
right lobe of thyroid gland	UBERON:0001119	76.33	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

88 targeting NMNAT1, 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-3646	100.00	73.56	5283
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-124-3P	99.89	73.74	3043

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 24.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 36)

• By using a combination of single isomorphous replacement and density modification techniques, the human NMNAT structure was solved by x-ray crystallography to a 2.5-A resolution, revealing a hexamer that is composed of alpha/beta-topology subunits (PMID:11751893)
• structure determination and role in activating tiazofurin (PMID:11788603)
• Crystal structure of human nicotinamide mononucleotide adenylyltransferase in complex with NMN. (PMID:11959140)
• structural characterization of this human cytosolic enzyme and implicatons in NAD biosyntheesis (PMID:12574164)
• NMNAT1 is a nuclear protein, whereas NMNAT2 and -3 are localized to the Golgi complex and the mitochondria (PMID:16118205)
• depending on its state of phosphorylation, NMNAT-1 binds to activated, automodifying PARP-1 and thereby amplifies poly(ADP-ribosyl)ation (PMID:17360427)
• ATP binds before NMN with nuclear isozyme NMNAT1. NMNH conversion to NADH by NMNAT1 and NMNAT3 occurs at similar rates, conversion by NMNAT2 is much slower. (PMID:17402747)
• Nicotinamide mononucleotide adenylyl transferase 1 (Nmnat1) is important for axonal protection, since mutants with reduced enzymatic activity lack axon protective activity. (PMID:19403820)
• Neuronal expression of exogenous Nmnat1 protein localized to the cytosol is essential and sufficient to delay Wallerian degeneration; cytosolic Nmnat1 showed greatly enhanced axon protection compared with native (nuclear) Nmnat1. (PMID:19458223)
• analysis of isoform-specific targeting and interaction domains in human nicotinamide mononucleotide adenylyltransferases (PMID:20388704)
• Red blood cells represent the first human cell type with a remarkable predominance of NMNAT3 over NMNAT1; NMNAT2 is absent. (PMID:20457531)
• Axonal targeting of transgenic NMNAT activity is both necessary and sufficient to delay Wallerian degeneration; promoting axonal and synaptic delivery greatly enhances NMNAT1 effectiveness. (PMID:20926655)
• Study investigated the importance of NMNAT2’s central domain, which are postulated to be dispensable for catalytic activity, instead representing an isozyme-specific control domain within the overall architecture of NMNAT2. (PMID:20954240)
• nicotinamide mononucleotide adenylyltransferase (Nmnat) protein transduction into transected axons blocks axonal degeneration (PMID:21071441)
• Our studies link the enzymatic activities of NMNAT-1 and PARP-1 to the regulation of a set of common target genes through functional interactions at target gene promoters. (PMID:22334709)
• Mutations in NMNAT1 cause Leber congenital amaurosis with early-onset severe macular and optic atrophy. (PMID:22842229)
• A new disease mechanism underlying Leber congential amaurosis and the first link between endogenous NMNAT1 dysfunction and a human nervous system disorder. (PMID:22842230)
• mutations in nicotinamide nucleotide adenylyltransferase 1(NMNAT1) cause Leber congenital amaurosis (PMID:23351689)
• NMNAT1 deletion in tumors may contribute to transformation by increasing ribosomal RNA synthesis. (PMID:23737528)
• Data found pathogenic DNA variants in the genes RP1, USH2A, CNGB3, NMNAT1, CHM, and ABCA4, responsible for retinitis pigmentosa, Usher syndrome, achromatopsia, Leber congenital amaurosis, choroideremia, or recessive Stargardt/cone-rod dystrophy cases. (PMID:23940504)
• theNMNAT1 p.Glu257Lys variant is a hypomorphic variant that almost without exception causes leber congenital amaurosis (LCA) in combination with more severe NMNAT1 variants. (PMID:24830548)
• The aim of this study was to determine the occurrence and frequency of NMNAT1 mutations and associated phenotypes in different types of inherited retinal dystrophies. (PMID:24940029)
• NMNAT1, which encodes the nicotinamide mononucleotide adenylyltransferase 1, has been recently identified to be one of the LCA-causing genes. Our results expanded the spectrum of mutations in NMNAT1 (PMID:25988908)
• To study how mutations affect NMNAT1 function and ultimately lead to a retinal degeneration phenotype, we performed detailed analysis of Leber congenital amaurosis 9-associated NMNAT1 mutants. (PMID:26018082)
• Hidden Genetic Variation in LCA9-Associated Congenital Blindness Explained by 5’UTR Mutations and Copy-Number Variations of NMNAT1. (PMID:26316326)
• We confirmed a diagnosis of NMNAT1-associated Leber congenital amaurosis in two siblings through identification of the mutation (c.25G>A [p. Val9Met]) in a homozygous state. (PMID:26464178)
• Results associate a distinct retinal dystrophy phenotype with nicotinamide-nucleotide adenylyltransferase 1 protein (NMNAT1) mutation and suggest coiled-coil domain containing 66 (CCDC66) should not be considered a retinal dystrophy candidate gene. (PMID:28369829)
• Rare homozygous variant c.[271G > A] p.(Glu91Lys) and compound heterozygous variants c.[53 A > G];[769G > A] p.(Asn18Ser);(Glu257Lys) were identified in two cases of cone-rod dystrophy, respectively. (PMID:29184169)
• A NOVEL CASE SERIES OF NMNAT1-ASSOCIATED EARLY-ONSET RETINAL DYSTROPHY: EXTENDING THE PHENOTYPIC SPECTRUM. (PMID:30004997)
• An Alu-mediated duplication in NMNAT1, involved in NAD biosynthesis, causes a novel syndrome, SHILCA, affecting multiple tissues and organs. (PMID:32533184)
• Coats-like Exudative Vitreoretinopathy in NMNAT1 Leber Congenital Amaurosis. (PMID:34243968)
• Nuclear NAD(+) homeostasis governed by NMNAT1 prevents apoptosis of acute myeloid leukemia stem cells. (PMID:34290089)
• Clinical features and genetic spectrum of NMNAT1-associated retinal degeneration. (PMID:34837036)
• NMNAT1 and hereditary spastic paraplegia (HSP): expanding the phenotypic spectrum of NMNAT1 variants. (PMID:36871412)
• Lactate enhances NMNAT1 lactylation to sustain nuclear NAD[+] salvage pathway and promote survival of pancreatic adenocarcinoma cells under glucose-deprived conditions. (PMID:38467179)
• NMNAT1 Is Essential for Human iPS Cell Differentiation to the Retinal Lineage. (PMID:39446354)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nmnat1	ENSDARG00000105748
mus_musculus	Nmnat1	ENSMUSG00000028992
rattus_norvegicus	Nmnat1	ENSRNOG00000015962

Paralogs (2): NMNAT2 (ENSG00000157064), NMNAT3 (ENSG00000163864)

Protein

Protein identifiers

Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1 — Q9HAN9 (reviewed: Q9HAN9)

Alternative names: Nicotinamide-nucleotide adenylyltransferase 1, Nicotinate-nucleotide adenylyltransferase 1

All UniProt accessions (3): Q9HAN9, B1AN62, K7EPD7

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP. Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate with the same efficiency. Can use triazofurin monophosphate (TrMP) as substrate. Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+). For the pyrophosphorolytic activity, prefers NAD(+) and NaAD as substrates and degrades NADH, nicotinic acid adenine dinucleotide phosphate (NHD) and nicotinamide guanine dinucleotide (NGD) less effectively. Involved in the synthesis of ATP in the nucleus, together with PARP1, PARG and NUDT5. Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming. Also acts as a cofactor for glutamate and aspartate ADP-ribosylation by directing PARP1 catalytic activity to glutamate and aspartate residues on histones. Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NaADP(+). Protects against axonal degeneration following mechanical or toxic insults. Neural protection does not correlate with cellular NAD(+) levels but may still require enzyme activity.

Subunit / interactions. Homohexamer. Interacts with ADPRT/PARP1.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed with highest levels in skeletal muscle, heart and kidney. Also expressed in the liver pancreas and placenta. Widely expressed throughout the brain.

Disease relevance. Leber congenital amaurosis 9 (LCA9) [MIM:608553] A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. The disease is caused by variants affecting the gene represented in this entry. Spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and Leber congenital amaurosis (SHILCA) [MIM:619260] An autosomal recessive disorder characterized by early-onset retinal degeneration, sensorineural hearing loss, short stature due to spondyloepiphyseal dysplasia, and motor and intellectual delay. Brain imaging shows abnormalities including delayed myelination, leukoencephalopathy, and cerebellar hypoplasia. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activity is strongly inhibited by galotannin. Inhibited by P1-(adenosine-5’)-P4-(nicotinic-acid-riboside-5’)-tetraphosphate (Nap4AD).

Cofactor. Divalent metal cations. Zn(2+) confers higher activity as compared to Mg(2+).

Pathway. Cofactor biosynthesis; NAD(+) biosynthesis; NAD(+) from nicotinamide D-ribonucleotide: step 1/1. Cofactor biosynthesis; NAD(+) biosynthesis; deamido-NAD(+) from nicotinate D-ribonucleotide: step 1/1.

Similarity. Belongs to the eukaryotic NMN adenylyltransferase family.

RefSeq proteins (3): NP_001284707, NP_001284708, NP_073624* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004821	Cyt_trans-like	Domain
IPR005248	NadD/NMNAT	Family
IPR014729	Rossmann-like_a/b/a_fold	Homologous_superfamily
IPR045094	NMNAT_euk	Family
IPR051182	Euk_NMN_adenylyltrnsfrase	Family

Pfam: PF01467

Enzyme classification (BRENDA):

• EC 2.7.7.1 — nicotinamide-nucleotide adenylyltransferase (BRENDA: 35 organisms, 118 substrates, 59 inhibitors, 203 Km, 57 kcat entries)
• EC 2.7.7.18 — nicotinate-nucleotide adenylyltransferase (BRENDA: 18 organisms, 31 substrates, 52 inhibitors, 74 Km, 22 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ATP	0.0008–3.5	53
NMN	—	37
NICOTINAMIDE RIBONUCLEOTIDE	0.0029–178.5	32
ATP	0.0017–4	22
DIPHOSPHATE	0.083–166.6	13
NICOTINATE BETA-D-RIBONUCLEOTIDE	0.0358–2.8	12
NAD+	0.023–412.2	11
NICOTINIC ACID MONONUCLEOTIDE	0.0145–0.15	11
NMNH	0.13–0.304	6
DIPHOSPHATE	0.083–4.2	5
NAD+	0.069–1.7	5
NICOTINATE RIBONUCLEOTIDE	0.025–1.3	5
NICOTINATE RIBONUCLEOTIDE	0.08–5	4
NICOTINIC ACID RIBONUCLEOTIDE	0.011–0.323	4
NICOTINAMIDE MONONUCLEOTIDE	0.021–0.7	3

Catalyzed reactions (Rhea), 2 shown:

• beta-nicotinamide D-ribonucleotide + ATP + H(+) = diphosphate + NAD(+) (RHEA:21360)
• nicotinate beta-D-ribonucleotide + ATP + H(+) = deamido-NAD(+) + diphosphate (RHEA:22860)

UniProt features (85 total): sequence variant 28, binding site 26, helix 14, strand 7, turn 3, modified residue 2, sequence conflict 2, chain 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
1KQN	X-RAY DIFFRACTION	2.2
1KR2	X-RAY DIFFRACTION	2.3
1KKU	X-RAY DIFFRACTION	2.5
1KQO	X-RAY DIFFRACTION	2.5
1GZU	X-RAY DIFFRACTION	2.9
8QE8	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HAN9-F1	89.23	0.81

Functional residue map

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

Ligand- & substrate-binding residues (26): 24; 55; 57; 57; 58; 92; 92; 95; 95; 156–158; 156; 158 …

Post-translational modifications (2): 117, 119

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-196807	Nicotinate metabolism

MSigDB gene sets: 339 (showing top): GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PURINE_CONTAINING_COMPOUND_SALVAGE, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NADPLUS_METABOLIC_PROCESS, COUP_01, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, IRF7_01, GOBP_NUCLEOSIDE_TRIPHOSPHATE_METABOLIC_PROCESS, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN

GO Biological Process (17): nicotinamide metabolic process (GO:0006769), nucleotide biosynthetic process (GO:0009165), NAD+ biosynthetic process (GO:0009435), response to wounding (GO:0009611), NAD+ biosynthetic process via the salvage pathway (GO:0034355), positive regulation of MAPK cascade (GO:0043410), negative regulation of neuron apoptotic process (GO:0043524), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), negative regulation of apoptotic DNA fragmentation (GO:1902511), negative regulation of adipose tissue development (GO:1904178), positive regulation of adipose tissue development (GO:1904179), ATP generation from poly-ADP-D-ribose (GO:1990966), purine nucleotide metabolic process (GO:0006163), biosynthetic process (GO:0009058), pyridine nucleotide biosynthetic process (GO:0019363), organophosphate biosynthetic process (GO:0090407)

GO Molecular Function (10): nicotinamide-nucleotide adenylyltransferase activity (GO:0000309), nicotinate-nucleotide adenylyltransferase activity (GO:0004515), ATP binding (GO:0005524), identical protein binding (GO:0042802), protein ADP-ribosyltransferase-substrate adaptor activity (GO:0140768), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleotide metabolic process	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
adipose tissue development	2
regulation of adipose tissue development	2
adenylyltransferase activity	2
cellular anatomical structure	2
alkaloid metabolic process	1
pyridine-containing compound metabolic process	1
nucleoside phosphate biosynthetic process	1
purine nucleotide biosynthetic process	1
nicotinamide nucleotide biosynthetic process	1
NAD+ metabolic process	1
response to stress	1
NAD+ biosynthetic process	1
pyridine nucleotide salvage	1
purine nucleotide salvage	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
apoptotic DNA fragmentation	1
regulation of apoptotic DNA fragmentation	1
negative regulation of DNA catabolic process	1
negative regulation of developmental process	1
negative regulation of multicellular organismal process	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
macromolecule metabolic process	1
ATP metabolic process	1
purine-containing compound metabolic process	1
metabolic process	1
nucleotide biosynthetic process	1
pyridine-containing compound biosynthetic process	1
biosynthetic process	1
organophosphate metabolic process	1

Protein interactions and networks

STRING

2046 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NMNAT1	NAMPT	P43490	910
NMNAT1	UBE4B	O95155	894
NMNAT1	NAPRT	Q6XQN6	820
NMNAT1	SIRT1	Q96EB6	814
NMNAT1	NMRK1	Q9NWW6	812
NMNAT1	SARM1	Q6SZW1	795
NMNAT1	QPRT	Q15274	743
NMNAT1	NADSYN1	Q6IA69	675
NMNAT1	NADK	O95544	627
NMNAT1	BST1	Q10588	616
NMNAT1	AIPL1	Q9NZN9	607
NMNAT1	SLC12A8	A0AV02	594
NMNAT1	RDH12	Q96NR8	593
NMNAT1	GUCY2D	Q02846	580
NMNAT1	CLOCK	O15516	572
NMNAT1	NMRK2	Q9NPI5	572

IntAct

199 interactions, top by confidence:

A	B	Type	Score
NMNAT1	NMNAT1	psi-mi:“MI:0915”(physical association)	0.850
RNASE1	RNH1	psi-mi:“MI:0914”(association)	0.850
CDCA4	PPP2R1A	psi-mi:“MI:0914”(association)	0.790
NMNAT1	KPNA2	psi-mi:“MI:0915”(physical association)	0.780
KPNA2	NMNAT1	psi-mi:“MI:0915”(physical association)	0.780
SART1	PRPF6	psi-mi:“MI:0914”(association)	0.750
BANP	NMNAT1	psi-mi:“MI:0915”(physical association)	0.740
POLR2D	MED19	psi-mi:“MI:0914”(association)	0.730
NMNAT1	CCNC	psi-mi:“MI:0915”(physical association)	0.670
CCNC	NMNAT1	psi-mi:“MI:0915”(physical association)	0.670
TDO2	NMNAT1	psi-mi:“MI:0915”(physical association)	0.670
H1-1	RRP8	psi-mi:“MI:0914”(association)	0.640
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
NMNAT1	PCYT1A	psi-mi:“MI:0915”(physical association)	0.640

BioGRID (179): NMNAT1 (Two-hybrid), NMNAT1 (Two-hybrid), NMNAT1 (Two-hybrid), SIRT1 (Affinity Capture-Western), NMNAT1 (Affinity Capture-Western), SIRT1 (Reconstituted Complex), NMNAT1 (Affinity Capture-MS), PCYT1A (Affinity Capture-MS), CDC5L (Affinity Capture-MS), NMNAT1 (Affinity Capture-MS), NMNAT1 (Affinity Capture-MS), NMNAT1 (Affinity Capture-MS), NMNAT1 (Synthetic Lethality), NMNAT1 (Affinity Capture-MS), NMNAT1 (Two-hybrid)

ESM2 similar proteins: A0A0G2K344, A0JMU5, A1A4L5, A2PYH4, A2RUV5, A4IH61, A8Y5H7, B3M1E1, B3P4N5, B4GZ20, B4HJC0, B4JXV2, B4KA23, B4LVS8, B4NKI9, B4PVH6, B4QVW6, O18475, O94830, P32871, P42336, P42337, P42338, Q0HA29, Q0VC59, Q0VD50, Q13057, Q29B63, Q2TBM9, Q3U213, Q5RBL5, Q5SNQ7, Q6PC93, Q80VJ4, Q80Y20, Q80Y98, Q8BNJ3, Q8BTI9, Q8C0L9, Q922E4

Diamond homologs: A4IH61, A8ZXR7, B0TGU9, F4K687, Q0HA29, Q0VC59, Q0VD50, Q5RBL5, Q6PC93, Q7UFN6, Q8BNJ3, Q96T66, Q99JR6, Q9BZQ4, Q9EPA7, Q9HAN9, Q9UT53, Q9VC03, P53204, P91851, Q06178, Q0DWH7, B5EEI3, A3DEU4, A6V0A4, B0K413, B0KAB6, B0KJY4, B1J134, B1YKR5, B4U7J9, B9M0D7, C1A4H9, Q1AVU4, Q2JNW7, Q2JWZ1, Q2LU86, Q2S0V3, Q3A1E1, Q3MAP9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 149 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Influenza Infection	8	15.3×	2e-06
Peptide chain elongation	11	15.2×	2e-08
Viral mRNA Translation	11	15.2×	2e-08
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	11	15.0×	2e-08
Selenocysteine synthesis	11	14.4×	2e-08
Eukaryotic Translation Termination	11	14.4×	2e-08
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	11	14.1×	2e-08
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	11	14.1×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of DNA recombination	5	43.9×	1e-05
chromosome condensation	5	32.9×	4e-05
NLS-bearing protein import into nucleus	5	31.4×	5e-05
cytoplasmic translation	11	15.9×	7e-08
ribosomal small subunit biogenesis	8	14.2×	1e-05
rRNA processing	10	11.1×	6e-06
translation	12	9.6×	2e-06
nucleosome assembly	8	8.8×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	39
Likely pathogenic	28
Uncertain significance	82
Likely benign	56
Benign	2

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1050789	NM_022787.4(NMNAT1):c.299+526_*968dup	Pathogenic
1050790	NM_022787.4(NMNAT1):c.439+5G>T	Pathogenic
1071528	NC_000001.10:g.(?10027411)(10042759_?)del	Pathogenic
1412405	NM_022787.4(NMNAT1):c.393_394del (p.Glu131fs)	Pathogenic
1424174	NM_022787.4(NMNAT1):c.676del (p.Ile226fs)	Pathogenic
1426207	NC_000001.10:g.(?10035630)(10041248_?)del	Pathogenic
1435359	NM_022787.4(NMNAT1):c.116-2A>G	Pathogenic
1437729	NM_022787.4(NMNAT1):c.469del (p.Ala157fs)	Pathogenic
1451670	NC_000001.10:g.(?10041069)(10041248_?)del	Pathogenic
1459432	NM_022787.4(NMNAT1):c.255G>A (p.Trp85Ter)	Pathogenic
2081952	NM_022787.4(NMNAT1):c.165C>G (p.Tyr55Ter)	Pathogenic
2131219	NM_022787.4(NMNAT1):c.648G>A (p.Trp216Ter)	Pathogenic
2426774	NC_000001.10:g.(?10032132)(10032266_?)del	Pathogenic
2426775	NC_000001.10:g.(?10032132)(10035853_?)del	Pathogenic
2426776	NC_000001.10:g.(?10027411)(10045246_?)del	Pathogenic
2426777	NC_000001.10:g.(?10041069)(10042759_?)del	Pathogenic
265453	NM_022787.4(NMNAT1):c.507G>A (p.Trp169Ter)	Pathogenic
2733823	NM_022787.4(NMNAT1):c.721C>T (p.Pro241Ser)	Pathogenic
2856865	NM_022787.4(NMNAT1):c.282_283del (p.Glu94fs)	Pathogenic
2919586	NM_022787.4(NMNAT1):c.254G>A (p.Trp85Ter)	Pathogenic
3247741	NC_000001.11:g.(?9981031)(9982701_?)dup	Pathogenic
37132	NM_022787.4(NMNAT1):c.838T>C (p.Ter280Gln)	Pathogenic
37133	NM_022787.4(NMNAT1):c.619C>T (p.Arg207Trp)	Pathogenic
37135	NM_022787.4(NMNAT1):c.817A>G (p.Asn273Asp)	Pathogenic
37138	NM_022787.4(NMNAT1):c.710G>T (p.Arg237Leu)	Pathogenic
37139	NM_022787.4(NMNAT1):c.457C>G (p.Leu153Val)	Pathogenic
37140	NM_022787.4(NMNAT1):c.25G>A (p.Val9Met)	Pathogenic
3774486	NM_022787.4(NMNAT1):c.140T>A (p.Ile47Asn)	Pathogenic
464669	NC_000001.11:g.(?9981011)(9982721_?)del	Pathogenic
813197	NM_022787.4(NMNAT1):c.629T>C (p.Ile210Thr)	Pathogenic

SpliceAI

808 predictions. Top by Δscore:

Variant	Effect	Δscore
1:9972014:GTA:G	acceptor_loss	1.0000
1:9972015:TAGAC:T	acceptor_loss	1.0000
1:9972016:A:AG	acceptor_gain	1.0000
1:9972016:AGAC:A	acceptor_loss	1.0000
1:9972017:G:GA	acceptor_gain	1.0000
1:9972017:GA:G	acceptor_gain	1.0000
1:9972017:GAC:G	acceptor_gain	1.0000
1:9972017:GACA:G	acceptor_gain	1.0000
1:9972017:GACAA:G	acceptor_gain	1.0000
1:9972152:T:TA	donor_gain	1.0000
1:9972186:CAGGT:C	donor_loss	1.0000
1:9972188:GG:G	donor_loss	1.0000
1:9972189:GT:G	donor_loss	1.0000
1:9972190:T:A	donor_loss	1.0000
1:9975588:CTAG:C	acceptor_loss	1.0000
1:9975590:A:AC	acceptor_loss	1.0000
1:9975590:AG:A	acceptor_gain	1.0000
1:9975591:G:C	acceptor_loss	1.0000
1:9975591:GG:G	acceptor_gain	1.0000
1:9975591:GGA:G	acceptor_gain	1.0000
1:9975591:GGAA:G	acceptor_gain	1.0000
1:9975629:T:A	acceptor_gain	1.0000
1:9975715:TGG:T	donor_gain	1.0000
1:9981029:A:AG	acceptor_gain	1.0000
1:9981030:G:GG	acceptor_gain	1.0000
1:9981112:G:GT	donor_gain	1.0000
1:9982299:A:AG	acceptor_gain	1.0000
1:9982300:G:GG	acceptor_gain	1.0000
1:9982300:GCT:G	acceptor_gain	1.0000
1:9982300:GCTGT:G	acceptor_gain	1.0000

AlphaMissense

1841 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:9972122:T:C	F17L	0.993
1:9972124:C:A	F17L	0.993
1:9972124:C:G	F17L	0.993
1:9972127:T:A	N18K	0.993
1:9972127:T:G	N18K	0.993
1:9975750:T:A	W92R	0.992
1:9975750:T:C	W92R	0.992
1:9982366:T:A	W169R	0.991
1:9982366:T:C	W169R	0.991
1:9972129:C:A	P19H	0.989
1:9975604:T:A	V43D	0.989
1:9982541:G:C	R227P	0.989
1:9975752:G:C	W92C	0.988
1:9975752:G:T	W92C	0.988
1:9982368:G:C	W169C	0.988
1:9982368:G:T	W169C	0.988
1:9972128:C:T	P19S	0.987
1:9972150:G:C	R26T	0.987
1:9975655:T:C	L60P	0.987
1:9972151:G:C	R26S	0.986
1:9972151:G:T	R26S	0.986
1:9972165:C:A	A31D	0.985
1:9975694:C:A	A73D	0.985
1:9975684:G:C	A70P	0.984
1:9982546:G:C	A229P	0.984
1:9972105:T:A	L11H	0.983
1:9975621:T:C	S49P	0.982
1:9975625:C:A	P50H	0.982
1:9975711:T:A	W79R	0.982
1:9975711:T:C	W79R	0.982

dbSNP variants (sampled 300 via entrez): RS1000014112 (1:9950776 T>C), RS1000023223 (1:9996037 C>A,G,T), RS1000077845 (1:9950475 A>G,T), RS1000110109 (1:9980483 C>T), RS1000131011 (1:9942980 C>T), RS1000140613 (1:9944556 C>T), RS1000141202 (1:9980737 A>G), RS1000166236 (1:9967848 T>G), RS1000274119 (1:9942590 A>G,T), RS1000274896 (1:9975320 G>T), RS1000320587 (1:9974319 G>A), RS1000377735 (1:9943474 T>C), RS1000414687 (1:9982014 C>T), RS1000578831 (1:9987496 G>A), RS1000609001 (1:9976604 A>G)

Disease associations

OMIM: gene MIM:608700 | disease phenotypes: MIM:608553, MIM:619260, MIM:120970, MIM:204000

GenCC curated gene-disease

Disease	Classification	Inheritance
Leber congenital amaurosis 9	Definitive	Autosomal recessive
NMNAT1-related retinopathy	Strong	Autosomal recessive
cone-rod dystrophy	Supportive	Autosomal dominant
Leber congenital amaurosis	Supportive	Autosomal dominant
spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and leber congenital amaurosis	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
NMNAT1-related retinopathy	Definitive	AR

Mondo (9): Leber congenital amaurosis 9 (MONDO:0012056), spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and leber congenital amaurosis (MONDO:0031007), inherited retinal dystrophy (MONDO:0019118), pathologic nystagmus (MONDO:0004843), retinal disorder (MONDO:0005283), cone-rod dystrophy (MONDO:0015993), Leber congenital amaurosis (MONDO:0018998), NMNAT1-related retinopathy (MONDO:0800101), cone dystrophy (MONDO:0000455)

Orphanet (5): Leber congenital amaurosis (Orphanet:65), Spondyloepiphyseal dysplasia-sensorineural hearing loss-intellectual disability-Leber congenital amaurosis syndrome (Orphanet:611207), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Cone rod dystrophy (Orphanet:1872), Progressive cone dystrophy (Orphanet:1871)

HPO phenotypes

84 total (30 of 84 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000154	Wide mouth
HP:0000280	Coarse facial features
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000505	Visual impairment
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract
HP:0000529	Progressive visual loss
HP:0000540	Hypermetropia
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000550	Undetectable electroretinogram
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000577	Exotropia
HP:0000603	Central scotoma
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000664	Synophrys
HP:0000666	Horizontal nystagmus
HP:0000729	Autistic behavior
HP:0001105	Retinal atrophy
HP:0001116	Macular pseudocoloboma
HP:0001141	Severely reduced visual acuity
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003818_38	Resting heart rate	1.000000e-07

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D000077765	Cone Dystrophy	C11.270.151; C11.768.216
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D009759	Nystagmus, Pathologic	C10.292.562.675; C11.590.400
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
C536603	Amaurosis congenita of Leber, type 9 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4802016 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
Cadmium Chloride	decreases expression, increases expression	3
bisphenol A	affects expression, increases abundance, decreases expression, affects cotreatment	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
ginger extract	affects cotreatment, affects expression, increases abundance	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
decabromobiphenyl ether	decreases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases abundance, increases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	increases abundance, increases expression	1
puag-haad	decreases reaction, increases expression	1
di-n-butylphosphoric acid	affects expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Resveratrol	increases reaction, increases expression, affects binding, affects cotreatment, decreases reaction	1
Fulvestrant	decreases reaction, increases reaction, affects binding, affects cotreatment	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Vehicle Emissions	increases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	increases phosphorylation	1
Catechin	affects cotreatment, decreases expression	1
Estradiol	decreases reaction, increases expression, affects binding, increases reaction	1
Ivermectin	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4775912	Binding	Binding affinity to NMNAT1 in PMA-differentiated human THP-1 cells incubated for 2 hrs by SDS-PAGE and LC-MS/MS analysis	Berberine Directly Targets the NEK7 Protein to Block the NEK7-NLRP3 Interaction and Exert Anti-inflammatory Activity. — J Med Chem

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_D1P7	Abcam K-562 NMNAT1 KO	Cancer cell line	Female
CVCL_D2KT	Abcam Raji NMNAT1 KO	Cancer cell line	Male
CVCL_D8RG	Ubigene HCT 116 NMNAT1 KO	Cancer cell line	Male
CVCL_WQ10	Abcam Jurkat NMNAT1 KO	Cancer cell line	Male
CVCL_WR23	KSCBi011-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
NCT00999609	PHASE3	ACTIVE_NOT_RECRUITING	Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis
NCT06891443	PHASE3	RECRUITING	Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT01373476	PHASE2	COMPLETED	Multicentre, Randomized, Controlled Trial of Qideng Mingmu Capsule in The Treatment of Diabetic Retinopathy
NCT01793090	PHASE2	COMPLETED	EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment
NCT00516477	PHASE1	COMPLETED	Safety Study in Subjects With Leber Congenital Amaurosis
NCT00821340	PHASE1	COMPLETED	Clinical Trial of Gene Therapy for Leber Congenital Amaurosis Caused by RPE65 Mutations
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT06467344	PHASE1/PHASE2	RECRUITING	Study to Evaluate ACDN-01 in ABCA4-related Stargardt Retinopathy (STELLAR)
NCT06789445	PHASE1/PHASE2	RECRUITING	A Study to Investigate the Safety of OpCT-001 in Adults Who Have Primary Photoreceptor Disease (CLARICO)
NCT00427180	Not specified	UNKNOWN	IRIS PILOT - Extended Pilot Study With a Retinal Implant System
NCT01864486	Not specified	COMPLETED	Restoring Vision With the Intelligent Retinal Implant System (IRIS V1)in Patients With Retinal Dystrophy
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT02670980	Not specified	COMPLETED	Compensation for Blindness With the Intelligent Retinal Implant System (IRIS V2) in Patients With Retinal Dystrophy
NCT04658251	Not specified	TERMINATED	Study of New Mutations in Cone Disorders
NCT05355415	Not specified	RECRUITING	Adaptive Optics Imaging of Outer Retinal Diseases
NCT06445322	Not specified	RECRUITING	Prescreening Study to Identify Potential Stargardt Participants for ACDN-01 Clinical Trials (STARPATH)
NCT07548944	Not specified	RECRUITING	Observational Study to Investigate the Short-term Effects of Transcorneal Electrical Stimulation on Visual Performance
NCT03913143	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Efficacy, Safety, Tolerability and Exposure After a Repeat-dose of Sepofarsen (QR-110) in LCA10 (ILLUMINATE)
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT00749957	PHASE1/PHASE2	COMPLETED	Phase 1/2 Safety and Efficacy Study of AAV-RPE65 Vector to Treat Leber Congenital Amaurosis
NCT01208389	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Phase 1 Follow-on Study of AAV2-hRPE65v2 Vector in Subjects With Leber Congenital Amaurosis (LCA) 2
NCT01496040	PHASE1/PHASE2	COMPLETED	Clinical Gene Therapy Protocol for the Treatment of Retinal Dystrophy Caused by Defects in RPE65
NCT02781480	PHASE1/PHASE2	COMPLETED	Clinical Trial of Gene Therapy for the Treatment of Leber Congenital Amaurosis (LCA)
NCT03913130	PHASE1/PHASE2	TERMINATED	Extension Study to Study PQ-110-001 (NCT03140969)
NCT03920007	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study of Subretinally Injected ATSN-101 Administered in Patients With Leber Congenital Amaurosis Caused by Biallelic Mutations in GUCY2D
NCT05203939	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study to Assess the Safety and Efficacy of OCU400 for Retinitis Pigmentosa and Leber Congenital Amaurosis
NCT05906953	PHASE1/PHASE2	RECRUITING	Safety and Efficacy Trial of HG004 for Leber Congenital Amaurosis Related to Rpe65 Gene Mutations (STAR)
NCT06088992	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Leber Congenital Amaurosis Inherited Blindness of Gene Therapy Trial(LIGHT)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02575430	Not specified	COMPLETED	Natural History Study in Inherited Retinal Disease Subjects Caused by Mutations in RPE65 or LRAT
NCT02714816	Not specified	COMPLETED	Natural History Study of Patients With Leber Congenital Amaurosis Associated With Mutations in RPE65