AASDHPPT

Chr 11

aminoadipate-semialdehyde dehydrogenase-phosphopantetheinyl transferase

Also known as: AASD-PPT, ACPS, CGI-80, LYS2, LYS5

NCBI Gene: 60496 ENSG00000149313 UniProt: Q9NRN7 OMIM: 607756

The protein encoded by this gene is similar to Saccharomyces cerevisiae LYS5, which is required for the activation of the alpha-aminoadipate dehydrogenase in the biosynthetic pathway of lysine. Yeast alpha-aminoadipate dehydrogenase converts alpha-biosynthetic-aminoadipate semialdehyde to alpha-aminoadipate. It has been suggested that defects in the human gene result in pipecolic acidemia. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.72

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.72LOEUF

pLI 0.034

Z-score 2.34

OE 0.34 (0.18–0.72)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.46Z-score

OE missense 0.90 (0.79–1.03)

151 obs / 167.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.34 (0.18–0.72)

0≤0.351.4

Missense OE?0.90 (0.79–1.03)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 5 / 14.7Missense obs/exp: 151 / 167.8Syn Z: 0.23

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

403 rare PASS variants

Rare truncating (LoF)

1 in 1,800

71 rare PASS variants

Rare synonymous (reference)

1 in 520

126 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for AASDHPPT. 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 300	1 in 1,800
South Asian	~43k	1 in 180	1 in 3,900
Remaining (unassigned)	~30k	1 in 170	1 in 4,300
European (Finnish)	~27k	1 in 620	1 in 1,600
Admixed American	~22k	1 in 130	1 in 2,200
African / African American	~21k	1 in 210	≈ 1 in 4,600
East Asian	~20k	1 in 190	1 in 380
Ashkenazi Jewish	~13k	≈ 1 in 3,300	none seen
Middle Eastern	~2,884	1 in 310	none seen

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): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓