ASAP1

Chr 8

ArfGAP with SH3 domain, ankyrin repeat and PH domain 1

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

NCBI Gene: 50807 ENSG00000153317 OMIM: 605953

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes an ADP-ribosylation factor (ARF) GTPase-activating protein. The GTPase-activating activity is stimulated by phosphatidylinositol 4,5-biphosphate (PIP2), and is greater towards ARF1 and ARF5, and lesser for ARF6. This gene maybe involved in regulation of membrane trafficking and cytoskeleton remodeling. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.19

Clinical Summary— ASAP1

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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.

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ClinVar Variants

81 VUS of 122 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.19LOEUF

pLI 1.000

Z-score 6.66

OE 0.10 (0.05–0.19)

Highly constrained

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

Missense Constraint?

3.31Z-score

OE missense 0.62 (0.57–0.68)

375 obs / 603.5 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.10 (0.05–0.19)

0≤0.351.4

Missense OE?0.62 (0.57–0.68)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 6 / 63.1Missense obs/exp: 375 / 603.5Syn Z: -0.48

This gene — mechanism propensity

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

122 submitted variants in ClinVar

ClinVar

Classification Summary

VUS81

Likely Benign4

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	81	0	0	81
Likely Benign	2	0	2	4
Benign	0	1	1	2
Total	83	1	3	87

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

View in ClinVar →

56 pathogenic / likely-pathogenic (of 68) ClinVar copy-number / structural variants overlap ASAP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →