ABCA2

protein-coding

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

Gene summary

The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. This protein is highly expressed in brain tissue and may play a role in macrophage lipid metabolism and neural development. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

ABC2

MANE transcript

NM_001606.5

Inheritance

ClinVar variants

P:17U:488B:217

Top phenotype

Intellectual developmental disorder with poor growth and with or without seizures or ataxia

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr9:137,007,234-137,028,915

External References & Databases

Ensembl (ENSG00000107331)

Transcript & Mutation Effects

hg38 • Region Span ~21.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder with poor growth and with or without seizures or ataxiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032930

Submitter: Labcorp Genetics (formerly Invitae)

intellectual developmental disorder with poor growth and with or without seizures or ataxiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032930

Submitter: PanelApp Australia

intellectual developmental disorder with poor growth and with or without seizures or ataxiaMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032930

Submitter: G2P

schizophreniaLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0005090

Submitter: Labcorp Genetics (formerly Invitae)

intellectual developmental disorder with poor growth and with or without seizures or ataxiaMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032930

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Intellectual developmental disorder with poor growth and with or without seizures or ataxiaAR

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 29302074; 30237576; 31047799

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ABCA2 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 616

not providedTotal: 236

ABCA2-related disorderTotal: 55

Intellectual developmental disorder with poor growth and with or without seizures or ataxiaTotal: 54

Ataxia with DysarthriaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001606.5. 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			10 clinvar	180 clinvar	7 clinvar	197
missense			465 clinvar	28 clinvar	2 clinvar	495
nonsense	2 clinvar	4 clinvar	2 clinvar			8
start loss						0
frameshift	5 clinvar	3 clinvar				8
splice donor/acceptor (+/-2bp)	1 clinvar	2 clinvar	11 clinvar			14
Total	8	9	488	208	9	722

Highest pathogenic variant AF is 6.855692e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001606.5	RefSeq	NP_001597.2	49	MANE Select
ENST00000341511.11	Ensembl	ENSP00000344155.6	49	MANE Select
NM_001411042.1	RefSeq	NP_001397971.1	48	Standard
NM_212533.3	RefSeq	NP_997698.1	49	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Lysosome - Homo sapiens (human)
ABC transporters - Homo sapiens (human)
ABC transporters in lipid homeostasis
Transport of small molecules
ABC-family proteins mediated transport

Biological Process

regulation of transcription by RNA polymerase II
lipid metabolic process
lipid transport
regulation of intracellular cholesterol transport
response to drug

Molecular Function

nucleotide binding
lipid transporter activity
ATP binding
ATPase activity
ATPase activity, coupled to transmembrane movement of substances

Cellular Component

lysosome
lysosomal membrane
endosome
microtubule organizing center
endosome membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000341511
Coding exons: 49
Length: 21682
Individuals with no LoFs: 124440
Homozygous LoFs: 0
Heterozygous LoFs: 32
Defined: 124472
p: 0.000129

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	4.91	1029	1.58e+3	0.652	0.000113	15623
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00020	0.00019	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00017	0.00017	rare
Finnish	0.00012	0.000093	rare
European (Non-Finnish)	0.00017	0.00015	rare
South Asian	0.00017	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.298

Intolerance Scores

LoFtool: 0.00985
RVIS EVS: -4.24
RVIS percentile EVS: 0.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.888

Gene Damage Prediction

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