NMNAT1

nicotinamide nucleotide adenylyltransferase 1, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 1:9943427-9985501

Previous symbols: [ "LCA9" ]

Links

ENSG00000173614 ∙ NCBI:64802 ∙ OMIM:608700 ∙ HGNC:17877 ∙ Uniprot:Q9HAN9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Leber congenital amaurosis 9 (Definitive), mode of inheritance: AR
• Leber congenital amaurosis 9 (Strong), mode of inheritance: AR
• cone-rod dystrophy (Supportive), mode of inheritance: AD
• Leber congenital amaurosis (Supportive), mode of inheritance: AD
• spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and leber congenital amaurosis (Limited), mode of inheritance: AR
• NMNAT1-related retinopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spondyloepiphyseal dysplasia, sensorineural hearing loss, intellectual developmental disorder, and Leber congenital amaurosis	AR	Audiologic/Otolaryngologic	Among other findings, the condition can include sensorineural hearing loss, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	22842227; 22842229; 22842230; 22842231; 32533184; 33668384

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NMNAT1 gene.

• Leber congenital amaurosis 9 (132 variants)
• not provided (20 variants)
• Retinal dystrophy (8 variants)
• Inborn genetic diseases (6 variants)
• Leber congenital amaurosis (3 variants)
• Spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and leber congenital amaurosis (2 variants)
• not specified (1 variants)
• 7 conditions (1 variants)
• Cone-rod dystrophy (1 variants)
• - (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NMNAT1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	28		29
missense	8	8	62	2	1	81
nonsense	4					4
start loss						0
frameshift	4		1			5
inframe indel						0
splice donor/acceptor (+/-2bp)	1	2	1			4
splice region				5		5
non coding			1	8	1	10
Total	17	10	66	38	2

Highest pathogenic variant AF is 0.000814

Variants in NMNAT1

This is a list of pathogenic ClinVar variants found in the NMNAT1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-9943500-G-A		Leber congenital amaurosis 9	Likely pathogenic (-)
1-9943501-G-C		Retinal dystrophy	Uncertain significance (May 12, 2019)
1-9943503-C-T		Leber congenital amaurosis 9	Pathogenic (-)
1-9943515-G-T		Leber congenital amaurosis 9	Likely pathogenic (-)
1-9943517-T-C			Uncertain significance (Mar 01, 2023)
1-9943519-A-G		Leber congenital amaurosis 9	Likely pathogenic (-)
1-9943525-C-T		Leber congenital amaurosis 9	Likely pathogenic (-)
1-9972074-A-G		Leber congenital amaurosis 9	Pathogenic (-)
1-9972085-C-T		Leber congenital amaurosis 9	Likely benign (Dec 31, 2023)
1-9972086-G-A		Leber congenital amaurosis 9	Uncertain significance (Oct 13, 2022)
1-9972091-G-T		Leber congenital amaurosis 9 • Inborn genetic diseases	Uncertain significance (May 17, 2023)
1-9972095-G-A		Leber congenital amaurosis 9	Uncertain significance (Oct 13, 2022)
1-9972096-A-C		Leber congenital amaurosis 9	Benign (Jan 24, 2024)
1-9972098-G-A		Leber congenital amaurosis 9	Pathogenic (Dec 19, 2021)
1-9972110-G-A		Retinal dystrophy • Leber congenital amaurosis 9	Conflicting classifications of pathogenicity (Nov 27, 2023)
1-9972111-C-A		Leber congenital amaurosis 9	Likely pathogenic (Mar 23, 2023)
1-9972111-C-G		Leber congenital amaurosis 9	Uncertain significance (Mar 29, 2022)
1-9972124-C-A			Uncertain significance (Jan 10, 2023)
1-9972126-A-G		Retinal dystrophy • Leber congenital amaurosis 9	Pathogenic/Likely pathogenic (Mar 17, 2024)
1-9972130-C-T		Leber congenital amaurosis 9	Likely benign (Dec 13, 2021)
1-9972132-T-A		Leber congenital amaurosis 9	Uncertain significance (Dec 22, 2023)
1-9972132-T-C		Leber congenital amaurosis 9	Uncertain significance (Mar 18, 2022)
1-9972139-C-T		Leber congenital amaurosis 9	Likely benign (Feb 24, 2022)
1-9972148-C-A		Leber congenital amaurosis 9	Likely benign (Jun 20, 2022)
1-9972151-G-A		Leber congenital amaurosis 9	Likely benign (Sep 22, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NMNAT1	protein_coding	protein_coding	ENST00000377205	4	42074

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0354	0.932	125728	0	19	125747	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.627	129	151	0.856	0.00000764	1838
Missense in Polyphen		52	59.939	0.86755		729
Synonymous	0.639	50	56.1	0.891	0.00000282	524
Loss of Function	1.85	4	10.4	0.383	4.39e-7	138

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000555	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000123	0.000123
Middle Eastern	0.0000555	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP (PubMed:17402747). Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate with the same efficiency (PubMed:17402747). Can use triazofurin monophosphate (TrMP) as substrate (PubMed:17402747). Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+) (PubMed:17402747). 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 (PubMed:17402747). Involved in the synthesis of ATP in the nucleus, together with PARP1, PARG and NUDT5 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257). Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NaADP(+) (PubMed:17402747). Protects against axonal degeneration following mechanical or toxic insults (By similarity). {ECO:0000250|UniProtKB:Q9EPA7, ECO:0000269|PubMed:17402747, ECO:0000269|PubMed:27257257}.
• Pathway: Nicotinate and nicotinamide metabolism - Homo sapiens (human);NAD Biosynthesis II (from tryptophan);NAD+ metabolism;NAD+ biosynthetic pathways;Vitamin B3 (nicotinate and nicotinamide) metabolism;Metabolism;Nicotinate Nicotinamide metabolism;Nicotinate metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;NAD salvage;NAD biosynthesis from 2-amino-3-carboxymuconate semialdehyde;NAD <i>de novo</i> biosynthesis;superpathway of tryptophan utilization (Consensus)

Intolerance Scores

• loftool: 0.300
• rvis_EVS: 0.15
• rvis_percentile_EVS: 64.32

Haploinsufficiency Scores

• pHI: 0.149
• hipred: Y
• hipred_score: 0.599
• ghis: 0.431

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.676

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nmnat1
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); pigmentation phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype

Gene ontology

• Biological process: NAD biosynthetic process;response to wounding;NAD metabolic process;'de novo' NAD biosynthetic process from aspartate;positive regulation of MAPK cascade;negative regulation of neuron apoptotic process;negative regulation of apoptotic DNA fragmentation;ATP generation from poly-ADP-D-ribose
• Cellular component: nucleus;nucleoplasm;cytoplasm;nuclear body
• Molecular function: nicotinamide-nucleotide adenylyltransferase activity;nicotinate-nucleotide adenylyltransferase activity;protein binding;ATP binding;identical protein binding