ABCA2

ATP binding cassette subfamily A member 2, the group of ATP binding cassette subfamily A

Basic information

Region (hg38): 9:137007233-137028915

Previous symbols: [ "ABC2" ]

Links

ENSG00000107331 ∙ NCBI:20 ∙ OMIM:600047 ∙ HGNC:32 ∙ Uniprot:Q9BZC7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• schizophrenia (Limited), mode of inheritance: Unknown
• intellectual developmental disorder with poor growth and with or without seizures or ataxia (Limited), mode of inheritance: AR
• intellectual developmental disorder with poor growth and with or without seizures or ataxia (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with poor growth and with or without seizures or ataxia	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	Craniofacial; Musculoskeletal; Neurologic	29302074; 30237576; 31047799

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ABCA2 gene.

• not provided (117 variants)
• Inborn genetic diseases (100 variants)
• Intellectual developmental disorder with poor growth and with or without seizures or ataxia (40 variants)
• ABCA2-related condition (6 variants)
• not specified (3 variants)
• Ataxia with Dysarthria (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ABCA2 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				49	12	61
missense			141	9	2	152
nonsense	1	2				3
start loss						0
frameshift	2	1				3
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region	1		2	7	2	12
non coding			4	1	16	21
Total	3	4	146	59	30

Variants in ABCA2

This is a list of pathogenic ClinVar variants found in the ABCA2 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-137007762-A-G		Intellectual developmental disorder with poor growth and with or without seizures or ataxia	Benign (Jul 14, 2021)
9-137007943-C-T		not specified	Uncertain significance (Sep 06, 2022)
9-137007963-G-A		not specified	Uncertain significance (Dec 20, 2023)
9-137008260-A-G		Intellectual developmental disorder with poor growth and with or without seizures or ataxia	Benign (Jul 14, 2021)
9-137008334-G-C		Intellectual developmental disorder with poor growth and with or without seizures or ataxia	Benign (Jul 14, 2021)
9-137008345-C-G		Intellectual developmental disorder with poor growth and with or without seizures or ataxia	Benign (Jul 14, 2021)
9-137008428-G-A		not specified	Likely benign (Jan 16, 2024)
9-137008444-T-C		not specified	Uncertain significance (Dec 13, 2022)
9-137008451-C-T		not specified	Uncertain significance (Jan 20, 2023)
9-137008453-G-A			Uncertain significance (Mar 22, 2023)
9-137008459-A-C		not specified	Uncertain significance (Dec 21, 2023)
9-137008467-G-A			Likely benign (Jan 01, 2024)
9-137008487-C-T		not specified	Uncertain significance (May 05, 2023)
9-137008501-G-A		not specified	Uncertain significance (Nov 30, 2022)
9-137008510-C-T		not specified	Uncertain significance (Jun 06, 2023)
9-137008515-C-T		ABCA2-related disorder	Likely benign (Apr 04, 2019)
9-137008516-C-T		ABCA2-related disorder • not specified	Uncertain significance (Apr 18, 2023)
9-137008517-G-A		not specified	Uncertain significance (Apr 12, 2022)
9-137008527-G-A		ABCA2-related disorder	Likely benign (Mar 05, 2019)
9-137008538-C-G		not specified	Uncertain significance (Oct 14, 2023)
9-137008556-C-T		not specified	Uncertain significance (Jan 30, 2024)
9-137008575-C-T			Likely benign (Jul 01, 2022)
9-137008616-C-G		Intellectual developmental disorder with poor growth and with or without seizures or ataxia	Uncertain significance (Mar 01, 2022)
9-137008616-C-T		not specified	Uncertain significance (Dec 03, 2021)
9-137008732-T-C		not specified	Uncertain significance (Oct 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ABCA2	protein_coding	protein_coding	ENST00000341511	49	21682

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.30e-10	124440	0	32	124472	0.000129

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.91	1029	1.58e+3	0.652	0.000113	15623
Missense in Polyphen		314	693.66	0.45267		6845
Synonymous	-3.36	849	733	1.16	0.0000593	5063
Loss of Function	8.92	12	115	0.104	0.00000549	1254

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000198	0.000193
Ashkenazi Jewish	0.000203	0.000199
East Asian	0.000167	0.000167
Finnish	0.000115	0.0000928
European (Non-Finnish)	0.000169	0.000151
Middle Eastern	0.000167	0.000167
South Asian	0.000171	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable transporter, its natural substrate has not been found yet. May have a role in macrophage lipid metabolism and neural development.
• Pathway: Lysosome - Homo sapiens (human);ABC transporters - Homo sapiens (human);ABC transporters in lipid homeostasis;Transport of small molecules;ABC-family proteins mediated transport (Consensus)

Recessive Scores

• pRec: 0.298

Intolerance Scores

• loftool: 0.00985
• rvis_EVS: -4.24
• rvis_percentile_EVS: 0.12

Haploinsufficiency Scores

• pHI: 0.346
• hipred: Y
• hipred_score: 0.639
• ghis: 0.636

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.888

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Abca2
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism 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); reproductive system phenotype; 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)

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;lipid metabolic process;lipid transport;regulation of intracellular cholesterol transport;response to drug;cholesterol homeostasis;response to steroid hormone;transmembrane transport;response to cholesterol
• Cellular component: lysosome;lysosomal membrane;endosome;microtubule organizing center;endosome membrane;membrane;integral component of membrane;cytoplasmic vesicle;ATP-binding cassette (ABC) transporter complex;intracellular membrane-bounded organelle
• Molecular function: nucleotide binding;lipid transporter activity;ATP binding;ATPase activity;ATPase activity, coupled to transmembrane movement of substances