ADNP

Chr 20AD

activity dependent neuroprotector homeobox

Also known as: ADNP1, HVDAS, MRD28

NCBI Gene: 23394ENSG00000101126UniProt: Q9H2P0OMIM: 611386

Vasoactive intestinal peptide is a neuroprotective factor that has a stimulatory effect on the growth of some tumor cells and an inhibitory effect on others. This gene encodes a protein that is upregulated by vasoactive intestinal peptide and may be involved in its stimulatory effect on certain tumor cells. The encoded protein contains one homeobox and nine zinc finger domains, suggesting that it functions as a transcription factor. This gene is also upregulated in normal proliferative tissues. Finally, the encoded protein may increase the viability of certain cell types through modulation of p53 activity. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
LOFmechanismADLOEUF 0.121 OMIM phenotype
Clinical Summary— ADNP
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Gene-Disease Validity (ClinGen)
ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.12LOEUF
pLI 1.000
Z-score 5.61
OE 0.03 (0.01–0.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
2.07Z-score
OE missense 0.76 (0.70–0.82)
439 obs / 579.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.03 (0.01–0.12)
0≤0.351.4
Missense OE?0.76 (0.70–0.82)
0≤0.61.4
Synonymous OE?1.34
0≤1.21.6
LoF obs/exp: 1 / 38.7Missense obs/exp: 439 / 579.4Syn Z: -3.92
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveADNP-related neurodevelopmental disorder (Helsmoortel-Van der Aa Syndrome)LOFAD

This gene — mechanism propensity

DN
0.19100th %ile
GOF
0.1799th %ile
LOF
0.85top 5%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · 1 literature citation · LOEUF 0.12 · ClinGen HI: Sufficient evidence for dosage pathogenicity
DN1 literature citation

Literature Evidence

DNHelsmoortel et al. (2014) noted that mutations in other SWI/SNF components of the BAF complex, such as SMARCB1 (601607) and ARID1B (614556), have been identified in patients with intellectual disability, and hypothesized that the ADNP mutations cause a dominant-negative effect on the recruitment of 1
LOFHere, we extended the ADNP syndrome phenotype describing skin abnormalities in both a patient with ADNP syndrome and an Adnp haploinsufficient mice.2

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

References

  1. 1.PMID 24531329 ↗
  2. 2.PMID 30679581 ↗

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ADNP · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients