NAPRT

Chr 8

nicotinate phosphoribosyltransferase

Also known as: NAPRT1, PP3856

NCBI Gene: 93100 ENSG00000147813 UniProt: Q6XQN6 OMIM: 611552

Nicotinic acid phosphoribosyltransferase catalyzes the first step in NAD biosynthesis from nicotinic acid, converting nicotinic acid and 5-phospho-D-ribose 1-phosphate to beta-nicotinate D-ribonucleotide in an ATP-dependent reaction. Biallelic mutations cause pellagra-like dermatitis with neurologic and psychiatric manifestations, inherited in an autosomal recessive pattern. The gene shows tolerance to loss-of-function variants, consistent with the recessive inheritance pattern of associated disease.

OMIM ResearchSummary from RefSeq, UniProt

Nicotinic acid (NA; niacin) is converted by nicotinic acid phosphoribosyltransferase (NAPRT; EC 2.4.2.11) to NA mononucleotide (NaMN), which is then converted to NA adenine dinucleotide (NaAD), and finally to nicotinamide adenine dinucleotide (NAD), which serves as a coenzyme in cellular redox reactions and is an essential component of a variety of processes in cellular metabolism including response to stress (Hara et al., 2007).[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.43

Clinical Summary— NAPRT

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

104 VUS of 150 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.43LOEUF

pLI 0.000

Z-score -0.16

OE 1.03 (0.76–1.43)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.62Z-score

OE missense 1.10 (1.00–1.21)

331 obs / 300.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.03 (0.76–1.43)

0≤0.351.4

Missense OE?1.10 (1.00–1.21)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 27 / 26.1Missense obs/exp: 331 / 300.9Syn Z: -1.21

This gene — mechanism propensity

0.6163th %ile

GOF

0.6737th %ile

LOF

0.3260th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

150 submitted variants in ClinVar

ClinVar

Classification Summary

VUS104

Likely Benign7

Benign2

104

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	103	0	0	104
Likely Benign	0	6	0	1	7
Benign	0	0	1	1	2
Total	1	109	1	2	113

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

60 pathogenic / likely-pathogenic (of 65) ClinVar copy-number / structural variants overlap NAPRT — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →