ATAD1

ATPase family AAA domain containing 1, the group of AAA ATPases

Basic information

Region (hg38): 10:87751512-87841361

Links

ENSG00000138138

∙ NCBI:84896 ∙ OMIM:614452 ∙ HGNC:25903 ∙ Uniprot:Q8NBU5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

hyperekplexia 4 (Moderate), mode of inheritance: AR
hyperekplexia 4 (Strong), mode of inheritance: AR
hereditary hyperekplexia (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperekplexia 4	AR	Neurologic	The condition can include severe neurologic sequelae, and medical management (with perampanel, an AMPAR antagonist) has been reported as having some benefits in individuals	Neurologic	28180185; 29390050; 29659736

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATAD1 gene.

not_provided (189 variants)
Inborn_genetic_diseases (18 variants)
Hyperekplexia_4 (7 variants)
ATAD1-related_disorder (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATAD1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001321967.2. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	56 clinvar	2 clinvar	59
missense			69 clinvar			69
nonsense		1 clinvar	2 clinvar			3
start loss						0
frameshift		1 clinvar	4 clinvar			5
splice donor/acceptor (+/-2bp)	1 clinvar		4 clinvar			5
Total	1	2	80	56	2

Highest pathogenic variant AF is 0.0000229386

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATAD1	protein_coding	protein_coding	ENST00000308448	9	89832

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00134	0.992	125723	0	14	125737	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.10	116	200	0.581	0.0000103	2387
Missense in Polyphen		25	65.586	0.38118		749
Synonymous	0.383	62	66.0	0.940	0.00000336	670
Loss of Function	2.36	8	19.2	0.418	0.00000104	221

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000580	0.0000580
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000546	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000891	0.0000879
Middle Eastern	0.0000546	0.0000544
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

Function: FUNCTION: ATPase that plays a critical role in regulating the surface expression of AMPA receptors (AMPAR), thereby regulating synaptic plasticity and learning and memory. Required for NMDA- stimulated AMPAR internalization and inhibition of GRIA1 and GRIA2 recycling back to the plasma membrane; these activities are ATPase-dependent (By similarity). {ECO:0000250}.;
Disease: DISEASE: Hyperekplexia 4 (HKPX4) [MIM:618011]: An autosomal recessive severe neurologic disorder apparent from birth. HKPX4 is characterized by little if any development, hypertonia, early- onset refractory seizures in some patients, and respiratory failure resulting in early death, mostly in the first months of life. {ECO:0000269|PubMed:28180185, ECO:0000269|PubMed:29390050, ECO:0000269|PubMed:29659736}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Purine Nucleoside Phosphorylase Deficiency;Mercaptopurine Action Pathway;Azathioprine Action Pathway;Xanthine Dehydrogenase Deficiency (Xanthinuria);Adenylosuccinate Lyase Deficiency;AICA-Ribosiduria;Thioguanine Action Pathway;Adenine phosphoribosyltransferase deficiency (APRT);Mitochondrial DNA depletion syndrome;Myoadenylate deaminase deficiency;Purine Metabolism;Molybdenum Cofactor Deficiency;Adenosine Deaminase Deficiency;Gout or Kelley-Seegmiller Syndrome;Lesch-Nyhan Syndrome (LNS);Xanthinuria type I;Xanthinuria type II (Consensus)

Recessive Scores

pRec: 0.130

Intolerance Scores

loftool: 0.255
rvis_EVS: -0.21
rvis_percentile_EVS: 38.28

Haploinsufficiency Scores

pHI: 0.351
hipred: Y
hipred_score: 0.765
ghis: 0.672

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.683

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Atad1
Phenotype: growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); 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);

Gene ontology

Biological process: positive regulation of receptor internalization;learning;memory;negative regulation of synaptic transmission, glutamatergic;regulation of postsynaptic neurotransmitter receptor internalization
Cellular component: peroxisomal membrane;membrane;cell junction;postsynaptic membrane;glutamatergic synapse
Molecular function: ATP binding;ATPase activity