ASAP1

Chr 8

ArfGAP with SH3 domain, ankyrin repeat and PH domain 1

Also known as: AMAP1, CENTB4, DDEF1, PAG2, PAP, ZG14P

The ASAP1 protein functions as a GTPase-activating protein that regulates ARF1 and ARF5 to coordinate membrane trafficking, cytoskeleton remodeling, and ciliogenesis. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability, developmental delay, and behavioral abnormalities. This gene is highly constrained against loss-of-function variants, indicating that ASAP1 mutations are likely to have significant clinical consequences.

Summary from RefSeq, UniProt
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0
Active trials
19
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.19
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryASAP1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.19LOEUF
pLI 1.000
Z-score 6.66
OE 0.10 (0.050.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.31Z-score
OE missense 0.62 (0.570.68)
375 obs / 603.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.10 (0.050.19)
00.351.4
Missense OE0.62 (0.570.68)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 6 / 63.1Missense obs/exp: 375 / 603.5Syn Z: -0.48
DN
0.4090th %ile
GOF
0.5169th %ile
LOF
0.71top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.19

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ASAP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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