NYAP2

Chr 2

neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adaptor 2

Also known as: KIAA1486

NCBI Gene: 57624 ENSG00000144460 UniProt: Q9P242

The protein activates PI3K and recruits the WAVE1 complex to regulate neuronal morphogenesis. Mutations cause autosomal recessive intellectual disability with autistic features. The gene shows low constraint against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

ResearchSummary from RefSeq, UniProt

Predicted to be involved in neuron projection morphogenesis and phosphatidylinositol 3-kinase/protein kinase B signal transduction. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.71

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.71LOEUF

pLI 0.000

Z-score 2.65

OE 0.42 (0.26–0.71)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.79Z-score

OE missense 0.89 (0.81–0.97)

360 obs / 404.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.42 (0.26–0.71)

0≤0.351.4

Missense OE?0.89 (0.81–0.97)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 10 / 24.0Missense obs/exp: 360 / 404.7Syn Z: -0.03

Background carrier burden — how many people carry a rare variant somewhere in NYAP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 78

945 rare PASS variants

Rare truncating (LoF)

1 in 3,900

60 rare PASS variants

Rare synonymous (reference)

1 in 74

413 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NYAP2. 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 99	1 in 4,300
South Asian	~43k	1 in 60	1 in 8,400
Remaining (unassigned)	~30k	1 in 73	≈ 1 in 15,000
European (Finnish)	~27k	1 in 310	1 in 1,600
Admixed American	~22k	1 in 97	1 in 1,900
African / African American	~21k	1 in 67	≈ 1 in 9,200
East Asian	~20k	1 in 79	1 in 1,500
Ashkenazi Jewish	~13k	1 in 210	1 in 2,500
Middle Eastern	~2,884	1 in 89	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 ↓