ADNP

Chr 20AD

activity dependent neuroprotector homeobox

Also known as: ADNP1, HVDAS, MRD28

NCBI Gene: 23394 ENSG00000101126 UniProt: Q9H2P0 OMIM: 611386

This gene encodes a transcription factor containing homeobox and zinc finger domains that is upregulated by vasoactive intestinal peptide and modulates p53 activity to promote cell viability. Mutations cause Helsmoortel-van der Aa syndrome through an autosomal dominant inheritance pattern, predominantly through loss-of-function mechanisms. The gene shows extreme intolerance to loss-of-function variants, consistent with haploinsufficiency as the primary pathogenic mechanism.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Helsmoortel-van der Aa syndromeMIM #615873

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder · AD · ClinGen 2020

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — ADNP

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 56

1,284 rare PASS variants

Rare truncating (LoF)

1 in 1,300

44 rare PASS variants

Rare synonymous (reference)

1 in 79

629 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ADNP. 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 69	1 in 4,300
South Asian	~43k	1 in 49	1 in 1,900
Remaining (unassigned)	~30k	1 in 50	1 in 340
European (Finnish)	~27k	1 in 220	1 in 3,300
Admixed American	~22k	1 in 54	1 in 3,200
African / African American	~21k	1 in 58	1 in 1,200
East Asian	~20k	1 in 64	1 in 540
Ashkenazi Jewish	~13k	1 in 190	≈ 1 in 3,400
Middle Eastern	~2,884	1 in 66	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.

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

📖

GeneReview available — ADNP

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

ADNPHelsmoortel-Van Der Aa SyndromeAutism Spectrum Disorder

ADNP Syndrome: The Seaver Autism Center for Research and Treatment is Characterizing ADNP-related Neurodevelopmental Disorders Using Genetic, Medical, and Neuropsychological Measures.

RECRUITING

NCT03718936Icahn School of Medicine at Mount SinaiStarted 2017-11-14

16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING

NCT01238250Simons SearchlightStarted 2010-10

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3

PubTator3