NMNAT3

Chr 3

nicotinamide nucleotide adenylyltransferase 3

Also known as: FKSG76, PNAT-3, PNAT3

NCBI Gene: 349565 ENSG00000163864 UniProt: Q96T66 OMIM: 608702

This gene encodes a member of the nicotinamide/nicotinic acid mononucleotide adenylyltransferase family. These enzymes use ATP to catalyze the synthesis of nicotinamide adenine dinucleotide or nicotinic acid adenine dinucleotide from nicotinamide mononucleotide or nicotinic acid mononucleotide, respectively. The encoded protein is localized to mitochondria and may also play a neuroprotective role as a molecular chaperone. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.85

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.85LOEUF

pLI 0.000

Z-score -0.60

OE 1.22 (0.75–1.85)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.16Z-score

OE missense 1.04 (0.90–1.20)

133 obs / 128.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.22 (0.75–1.85)

0≤0.351.4

Missense OE?1.04 (0.90–1.20)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 10 / 8.2Missense obs/exp: 133 / 128.0Syn Z: 0.61

Background carrier burden — how many people carry a rare variant somewhere in NMNAT3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 79

521 rare PASS variants

Rare truncating (LoF)

1 in 670

84 rare PASS variants

Rare synonymous (reference)

1 in 150

200 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NMNAT3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 660
South Asian	~43k	1 in 82	1 in 410
Remaining (unassigned)	~30k	1 in 77	1 in 790
European (Finnish)	~27k	1 in 800	1 in 950
Admixed American	~22k	1 in 70	1 in 570
African / African American	~21k	1 in 120	1 in 520
East Asian	~20k	1 in 98	1 in 1,000
Ashkenazi Jewish	~13k	1 in 790	≈ 1 in 6,300
Middle Eastern	~2,884	1 in 110	≈ 1 in 940

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 2 of 5 coding exons well covered in gnomAD exomes; exons 3, 4, 6 marginal. Genomes: all 5.? see exons ↓