ATAD1

protein-coding

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

Gene summary

Predicted to enable ATP hydrolysis activity. Involved in extraction of mislocalized protein from mitochondrial outer membrane. Located in mitochondrial outer membrane and peroxisomal membrane. Implicated in hyperekplexia 4. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001321967.2

Inheritance

AR, AD

ClinVar variants

P:4U:86B:65

Top phenotype

Hyperekplexia 4

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr10:87,751,512-87,841,361

External References & Databases

Ensembl (ENSG00000138138)

Transcript & Mutation Effects

hg38 • Region Span ~89.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hyperekplexia 4STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0044330

Submitter: PanelApp Australia

hyperekplexia 4STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0044330

Submitter: Labcorp Genetics (formerly Invitae)

hereditary hyperekplexiaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0021022

Submitter: Orphanet

hyperekplexia 4MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0044330

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Hyperekplexia 4AR

Manifestation: Neurologic

Intervention: Neurologic

Rationale: The condition can include severe neurologic sequelae, and medical management (with perampanel, an AMPAR antagonist) has been reported as having some benefits in individuals

Refs: 28180185; 29390050; 29659736

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ATAD1 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 199

Inborn genetic diseasesTotal: 18

not specifiedTotal: 11

Hyperekplexia 4Total: 8

ATAD1-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001321967.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	63 clinvar	2 clinvar	67
missense			72 clinvar			72
nonsense		1 clinvar	2 clinvar			3
start loss						0
frameshift		2 clinvar	4 clinvar			6
splice donor/acceptor (+/-2bp)		1 clinvar	6 clinvar			7
Total	0	4	86	63	2	155

Highest pathogenic variant AF is 0.000022938566

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 150 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001321967.2	RefSeq	NP_001308896.1	9	MANE Select
ENST00000680024.1	Ensembl	ENSP00000506333.1	9	MANE Select
NM_001321968.2	RefSeq	NP_001308897.1	8	Standard
NM_001321969.2	RefSeq	NP_001308898.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Purine Nucleoside Phosphorylase Deficiency
Mercaptopurine Action Pathway
Azathioprine Action Pathway
Xanthine Dehydrogenase Deficiency (Xanthinuria)
Adenylosuccinate Lyase Deficiency

Biological Process

positive regulation of receptor internalization
learning
memory
negative regulation of synaptic transmission, glutamatergic
regulation of postsynaptic neurotransmitter receptor internalization

Molecular Function

ATP binding
ATPase activity

Cellular Component

peroxisomal membrane
membrane
cell junction
postsynaptic membrane
glutamatergic synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000308448
Coding exons: 9
Length: 89832
Individuals with no LoFs: 125723
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125737
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.10	116	200	0.581	0.0000103	2387
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000089	0.000088	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.130

Intolerance Scores

LoFtool: 0.255
RVIS EVS: -0.21
RVIS percentile EVS: 38.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.683

Gene Damage Prediction

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