ABCA7

protein-coding

ATP binding cassette subfamily A member 7, the group of ATP binding cassette subfamily A

Gene summary

The 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 intra-cellular 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 full transporter has been detected predominantly in myelo-lymphatic tissues with the highest expression in peripheral leukocytes, thymus, spleen, and bone marrow. The function of this protein is not yet known; however, the expression pattern suggests a role in lipid homeostasis in cells of the immune system. [provided by RefSeq, Jul 2008]

MANE transcript

NM_019112.4

Inheritance

—

ClinVar variants

P:26U:393B:94

Top phenotype

ABCA7-related disorder

gnomAD constraint

pLI —, LoF o/e 0.9

Max pathogenic AF

—

Genomic locus

chr19:1,039,997-1,065,572

External References & Databases

Ensembl (ENSG00000064687)

Transcript & Mutation Effects

hg38 • Region Span ~25.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Alzheimer disease 9LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0012153

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ABCA7 variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 364

not providedTotal: 103

ABCA7-related disorderTotal: 41

Alzheimer disease 9Total: 35

Flexion contractureTotal: 3

Neuromuscular diseaseTotal: 2

Primary degenerative dementia of the Alzheimer type, presenile onsetTotal: 1

Amyotrophic lateral sclerosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_019112.4. 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		1 clinvar	7 clinvar	36 clinvar	6 clinvar	50
missense			364 clinvar	39 clinvar	9 clinvar	412
nonsense	1 clinvar	8 clinvar	4 clinvar	1 clinvar		14
start loss						0
frameshift	1 clinvar	10 clinvar	9 clinvar	2 clinvar	1 clinvar	23
splice donor/acceptor (+/-2bp)	1 clinvar	4 clinvar	9 clinvar			14
Total	3	23	393	78	16	513

Highest pathogenic variant AF is 0.0001555391

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_019112.4	RefSeq	NP_061985.2	46	MANE Select
ENST00000263094.11	Ensembl	ENSP00000263094.6	46	MANE Select
ENST00000435683.7	Ensembl	ENSP00000465322.2	13	Standard
ENST00000524850.5	Ensembl	ENSP00000431473.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

lipid transport
phagocytosis
memory
positive regulation of cholesterol efflux
peptide cross-linking

Molecular Function

transporter activity
lipid transporter activity
protein binding
ATP binding
ATPase activity

Cellular Component

Golgi membrane
phagocytic cup
Golgi apparatus
plasma membrane
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263094
Coding exons: 46
Length: 25470
Individuals with no LoFs: 124312
Homozygous LoFs: 2
Heterozygous LoFs: 1434
Defined: 125748
p: 0.00573

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.47	1516	1.36e+3	1.11	0.0000934	13509
Missense (PolyPhen)		521	481.43	1.0822		5228
Synonymous	-1.07	649	615	1.05	0.0000438	4708
Loss of Function	0.973	90	101	0.895	0.00000513	1043

Population LoF Frequency

Population	CAF	p-value	Status
African	0.015	0.014	notable
Latino/Admixed American	0.0060	0.0059	notable
Ashkenazi Jewish	0.0093	0.0087	notable
East Asian	0.0072	0.0069	notable
Finnish	0.0034	0.0020	notable
European (Non-Finnish)	0.0058	0.0052	notable
South Asian	0.0043	0.0041	notable
Other	0.0060	0.0054	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in phagocytosis by macrophages of apoptotic cells. Binds APOA1 and may function in apolipoprotein-mediated phospholipid efflux from cells. May also mediate cholesterol efflux. May regulate cellular ceramide homeostasis during keratinocytes differentiation. {ECO:0000269|PubMed:12917409, ECO:0000269|PubMed:12925201, ECO:0000269|PubMed:14570867, ECO:0000269|PubMed:14592415}.;
Disease: DISEASE: Alzheimer disease 9 (AD9) [MIM:608907]: A familial, late- onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C- terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death. {ECO:0000269|PubMed:25807283, ECO:0000269|PubMed:26141617}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.155

Intolerance Scores

LoFtool: 0.0339
RVIS EVS: -2.15
RVIS percentile EVS: 1.46

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.392

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High