ADNP

activity dependent neuroprotector homeobox, the group of ZF class homeoboxes and pseudogenes

Basic information

Region (hg38): 20:50888916-50931437

Links

ENSG00000101126 ∙ NCBI:23394 ∙ OMIM:611386 ∙ HGNC:15766 ∙ Uniprot:Q9H2P0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder (Definitive), mode of inheritance: AD
• ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder (Strong), mode of inheritance: AD
• ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder (Definitive), mode of inheritance: AD
• ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder (Supportive), mode of inheritance: Unknown
• ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Helsmoortel-van der Aa syndrome	AD	Cardiovascular	Individuals have been described with congenital heart anomalies, and awareness may enable early diagnosis and management	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	24531329; 25057125

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADNP gene.

• not provided (52 variants)
• ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder (34 variants)
• Inborn genetic diseases (11 variants)
• ADNP-related disorder (2 variants)
• Intellectual disability (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADNP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			35	82	17	134
missense		3	236	63	6	308
nonsense	20	6				26
start loss	1	1				2
frameshift	58	23	2			83
inframe indel			12	3		15
splice donor/acceptor (+/-2bp)		1				1
splice region			4			4
non coding	1		10	5	5	21
Total	80	34	295	153	28

Variants in ADNP

This is a list of pathogenic ClinVar variants found in the ADNP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-50889829-C-T			Likely benign (Sep 01, 2023)
20-50889934-G-A			Likely benign (Apr 01, 2024)
20-50891355-T-G		ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder	Benign (Jul 14, 2021)
20-50891406-T-TA			Likely pathogenic (Jan 31, 2017)
20-50891410-C-T		ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder	Uncertain significance (Oct 24, 2019)
20-50891412-T-C			Uncertain significance (Feb 18, 2020)
20-50891414-T-C			Likely benign (Oct 22, 2023)
20-50891421-C-T			Uncertain significance (Nov 19, 2021)
20-50891422-T-C			Uncertain significance (Oct 31, 2023)
20-50891433-C-A		Inborn genetic diseases	Uncertain significance (Jul 26, 2022)
20-50891434-C-T		not specified	Uncertain significance (Aug 24, 2023)
20-50891435-G-A		not specified • ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder • Inborn genetic diseases • ADNP-related disorder	Benign/Likely benign (Jan 29, 2024)
20-50891434-C-CGG		ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder	not provided (-)
20-50891448-T-C		ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder	Uncertain significance (Apr 23, 2021)
20-50891452-T-C			Uncertain significance (Jan 17, 2023)
20-50891456-C-A		Inborn genetic diseases	Likely benign (Jul 02, 2019)
20-50891465-T-TC		ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder	Uncertain significance (May 21, 2018)
20-50891466-C-CCAT		ADNP-related disorder	Uncertain significance (Nov 15, 2022)
20-50891475-A-G			Uncertain significance (Nov 01, 2023)
20-50891476-T-C			Uncertain significance (Jul 29, 2023)
20-50891478-T-C		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jul 07, 2023)
20-50891491-C-T			Likely benign (Oct 13, 2023)
20-50891492-C-T			Uncertain significance (Aug 30, 2023)
20-50891497-CCTCA-C		ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder	Pathogenic (Sep 22, 2023)
20-50891507-A-T			Conflicting classifications of pathogenicity (Oct 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADNP	protein_coding	protein_coding	ENST00000396029	3	42374

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000489	125733	0	6	125739	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.07	439	579	0.758	0.0000300	7343
Missense in Polyphen		57	189.87	0.3002		2552
Synonymous	-3.92	288	215	1.34	0.0000118	2066
Loss of Function	5.61	1	38.7	0.0259	0.00000227	486

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Potential transcription factor. May mediate some of the neuroprotective peptide VIP-associated effects involving normal growth and cancer proliferation.

Recessive Scores

• pRec: 0.133

Intolerance Scores

• loftool: 0.00689
• rvis_EVS: -1.41
• rvis_percentile_EVS: 4.13

Haploinsufficiency Scores

• pHI: 0.904
• hipred: Y
• hipred_score: 0.591
• ghis: 0.689

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.881

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Adnp
• Phenotype: embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: adnpa
• Affected structure: blood cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;short-term memory;response to carbohydrate;response to inorganic substance;negative regulation of gene expression;regulation of protein ADP-ribosylation;cGMP-mediated signaling;cellular response to extracellular stimulus;negative regulation of protein binding;activation of protein kinase activity;nitric oxide homeostasis;negative regulation of neuron apoptotic process;estrous cycle;positive regulation of axon extension;positive regulation of peptidyl-tyrosine phosphorylation;negative regulation of synaptic transmission;positive regulation of synapse assembly
• Cellular component: extracellular space;nucleus;cytoplasm;axon;dendrite;neuronal cell body
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;chromatin binding;copper ion binding;protein binding;peptide binding;beta-tubulin binding