NMNAT1
Chr 1ARnicotinamide nucleotide adenylyltransferase 1
Also known as: LCA9, NMNAT, PNAT1, SHILCA
This nuclear enzyme catalyzes the formation of NAD+ from nicotinamide mononucleotide and ATP, playing a critical role in nuclear energy metabolism and neuroprotection against axonal degeneration. Mutations cause Leber congenital amaurosis 9 (severe early-onset retinal dystrophy leading to blindness in infancy) and a multisystem disorder involving spondyloepiphyseal dysplasia, sensorineural hearing loss, and intellectual disability. Inheritance is autosomal recessive.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
279 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 17 | 10 | 41 | 0 | 68 |
Likely Pathogenic | 4 | 29 | 9 | 0 | 42 |
VUS | 3 | 73 | 17 | 0 | 93 |
Likely Benign | 0 | 2 | 20 | 38 | 60 |
Benign | 0 | 0 | 2 | 0 | 2 |
Conflicting | — | 9 | |||
| Total | 24 | 114 | 89 | 38 | 274 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NMNAT1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools