ATAD3A

ATPase family AAA domain containing 3A, the group of AAA ATPases

Basic information

Region (hg38): 1:1512162-1534685

Links

ENSG00000197785 ∙ NCBI:55210 ∙ OMIM:612316 ∙ HGNC:25567 ∙ Uniprot:Q9NVI7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal (Strong), mode of inheritance: AR
• Harel-Yoon syndrome (Definitive), mode of inheritance: Semidominant
• Harel-Yoon syndrome (Moderate), mode of inheritance: AD
• pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal (Moderate), mode of inheritance: AR
• Harel-Yoon syndrome (Strong), mode of inheritance: AD
• Harel-Yoon syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Harel-Yoon syndrome; Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Cardiovascular; Craniofacial; Musculoskeletal; Ophthalmologic; Neurologic; Pulmonary	27640307; 28549128; 29053797

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATAD3A gene.

• Harel-Yoon syndrome (2 variants)
• Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal (2 variants)
• Congenital cerebellar hypoplasia (1 variants)
• not provided (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATAD3A 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			1	30	5	36
missense	1	3	136	9	5	154
nonsense	2	3	2			7
start loss		1				1
frameshift		4	1			5
inframe indel			4	1		5
splice donor/acceptor (+/-2bp)		5	1			6
splice region			8	6	2	16
non coding	1		10	2	11	24
Total	4	16	155	42	21

Highest pathogenic variant AF is 0.0000197

Variants in ATAD3A

This is a list of pathogenic ClinVar variants found in the ATAD3A region.

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

Position	Type	Phenotype	Significance	ClinVar
1-1512268-C-T			Uncertain significance (Nov 15, 2022)
1-1512270-T-A			Likely pathogenic (Sep 12, 2023)
1-1512287-A-C			Uncertain significance (Mar 31, 2022)
1-1512287-A-G		Harel-Yoon syndrome	Benign/Likely benign (Aug 01, 2024)
1-1512296-G-A		Inborn genetic diseases	Uncertain significance (Jan 22, 2024)
1-1512305-G-A		Inborn genetic diseases	Uncertain significance (Jul 05, 2023)
1-1512307-T-A			Likely benign (Apr 01, 2023)
1-1512313-C-T			Benign (Dec 14, 2017)
1-1512320-C-T			Uncertain significance (Jan 21, 2022)
1-1512338-C-T			Uncertain significance (May 06, 2022)
1-1512374-G-C			Uncertain significance (Dec 16, 2022)
1-1512376-G-C		not specified	Benign (Jan 24, 2024)
1-1512393-C-T			Uncertain significance (Sep 22, 2022)
1-1512396-C-A		Inborn genetic diseases	Uncertain significance (Mar 25, 2024)
1-1512399-A-G		Harel-Yoon syndrome	Uncertain significance (Oct 19, 2021)
1-1512412-C-G		Inborn genetic diseases	Uncertain significance (Jan 02, 2024)
1-1512418-C-G		Harel-Yoon syndrome	Uncertain significance (-)
1-1512423-C-T		Harel-Yoon syndrome	Uncertain significance (Aug 25, 2022)
1-1512426-C-T		Harel-Yoon syndrome • not specified • Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal	Conflicting classifications of pathogenicity (Apr 04, 2024)
1-1512436-G-A			Likely benign (Dec 27, 2017)
1-1512441-CCGCCAAGGCGGCG-C			Uncertain significance (Dec 31, 2019)
1-1512447-A-T		Inborn genetic diseases	Uncertain significance (Jan 19, 2024)
1-1512453-C-T		Inborn genetic diseases	Uncertain significance (Jul 11, 2024)
1-1512459-A-C		Inborn genetic diseases	Uncertain significance (Dec 17, 2021)
1-1512464-G-C		Inborn genetic diseases	Uncertain significance (Aug 09, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATAD3A	protein_coding	protein_coding	ENST00000378755	16	22537

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.09e-9	0.987	125701	0	41	125742	0.000163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0126	401	402	0.998	0.0000293	4053
Missense in Polyphen		77	101.61	0.75776		1122
Synonymous	-0.993	188	171	1.10	0.0000126	1285
Loss of Function	2.35	19	33.7	0.564	0.00000194	368

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000595	0.000589
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000163	0.000163
Finnish	0.0000467	0.0000462
European (Non-Finnish)	0.000145	0.000141
Middle Eastern	0.000163	0.000163
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential for mitochondrial network organization, mitochondrial metabolism and cell growth at organism and cellular level. May play an important role in mitochondrial protein synthesis. May also participate in mitochondrial DNA replication. May bind to mitochondrial DNA D-loops and contribute to nucleoid stability. Required for enhanced channeling of cholesterol for hormone-dependent steroidogenesis. {ECO:0000269|PubMed:17210950, ECO:0000269|PubMed:20154147, ECO:0000269|PubMed:22453275}.
• Disease: DISEASE: Harel-Yoon syndrome (HAYOS) [MIM:617183]: A syndrome characterized by global developmental delay, hypotonia, intellectual disability, and axonal neuropathy. Some patients have optic atrophy and hypertrophic cardiomyopathy. HAYOS inheritance can be autosomal dominant or autosomal recessive. {ECO:0000269|PubMed:27640307}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.0950
• rvis_EVS: 0.12
• rvis_percentile_EVS: 62.21

Haploinsufficiency Scores

• pHI: 0.301
• hipred: N
• hipred_score: 0.407
• ghis: 0.518

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.735

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Atad3a
• Phenotype: muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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: regulation of cell growth;mitochondrion organization;negative regulation of apoptotic process
• Cellular component: mitochondrion;mitochondrial inner membrane;integral component of membrane;mitochondrial nucleoid
• Molecular function: ATP binding;zinc ion binding