ADAP1

Chr 7

ArfGAP with dual PH domains 1

Also known as: CENTA1, GCS1L, p42IP4

NCBI Gene: 11033ENSG00000105963UniProt: O75689

Enables GTPase activator activity. Predicted to be involved in cell surface receptor signaling pathway. Located in cytosol; nucleus; and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

117
ClinVar variants
39
Pathogenic / LP
0.53
pLI score
0
Active trials
Clinical Summary— ADAP1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.53) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 66 VUS of 117 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.44LOEUF
pLI 0.533
Z-score 3.59
OE 0.21 (0.11–0.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.89Z-score
OE missense 0.83 (0.74–0.94)
188 obs / 225.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.21 (0.11–0.44)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.74–0.94)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.65
0≤1.21.6
LoF obs/exp: 5 / 24.0Missense obs/exp: 188 / 225.5Syn Z: -4.92

ClinVar Variant Classifications

117 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic1
VUS66
Likely Benign4
Benign7
Conflicting1
38
Pathogenic
1
Likely Pathogenic
66
VUS
4
Likely Benign
7
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
38
0
38
Likely Pathogenic
0
0
1
0
1
VUS
0
51
15
0
66
Likely Benign
0
2
1
1
4
Benign
0
0
6
1
7
Conflicting
—1
Total053612117

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

View in ClinVar →

Protein Context — Lollipop Plot

ADAP1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Oncogenic fusion transcript analysis identified ADAP1-NOC4L, potentially associated with metastatic colorectal cancer.
Talebi A et al.·Cancer Med
2023
Identification of shared loci associated with both Crohn's disease and leprosy in East Asians.
Jung S et al.·Hum Mol Genet
2022Meta-analysis
Recombinant Human Adenovirus Type 5 (H101) Intra-Tumor Therapy in Patients with Persistent, Recurrent, or Metastatic Cervical Cancer: Genomic Profiling Relating to Clinical Efficacy.
Zhang Q et al.·Drug Des Devel Ther
2023Cohort
Genomic profiles of colorectal carcinoma with liver metastases and newly identified fusion genes.
Oga T et al.·Cancer Sci
2019
Gene expression correlations in human cancer cell lines define molecular interaction networks for epithelial phenotype.
Kohn KW et al.·PLoS One
2014
Multisite learning of high-dimensional heterogeneous data with applications to opioid use disorder study of 15,000 patients across 5 clinical sites.
Liu X et al.·Sci Rep
2022Cohort
Prognosis related miRNAs, DNA methylation, and epigenetic interactions in lung adenocarcinoma.
Liu H et al.·Neoplasma
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools