ABCD1

ATP binding cassette subfamily D member 1, the group of ATP binding cassette subfamily D

Basic information

Region (hg38): X:153724855-153744755

Previous symbols: [ "ALD" ]

Links

ENSG00000101986 ∙ NCBI:215 ∙ OMIM:300371 ∙ HGNC:61 ∙ Uniprot:P33897 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary spastic paraplegia (Strong), mode of inheritance: XL
• adrenoleukodystrophy (Strong), mode of inheritance: XL
• X-linked cerebral adrenoleukodystrophy (Definitive), mode of inheritance: XL
• Hirschsprung disease (Supportive), mode of inheritance: AD
• X-linked cerebral adrenoleukodystrophy (Supportive), mode of inheritance: XL
• adrenomyeloneuropathy (Supportive), mode of inheritance: XL
• adrenoleukodystrophy (Definitive), mode of inheritance: XL
• adrenoleukodystrophy (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Adrenoleukodystrophy	XL	Biochemical	For individuals with adrenal insufficiency, corticosteroid treatment is indicated; In asymptomatic individuals with ALD, medical treatment (eg, with oleic and erucic acids) may be beneficial in combination with dietary measures, though the benefit of such treatment in other affected individuals, such as symptomatic individuals, may not warrant such treatment; BMT/HSCT has been reported as effective if performed early, and gene therapy has been approved to treat some forms of the condition	Biochemical; Endocrine; Neurologic	169765; 61263; 965973; 200861; 200862; 218453; 7438498; 7436359; 6299222; 7202134; 6280106; 6387532; 2682348; 2309698; 7904210; 8094785; 8338333; 8441467; 7849723; 8040304; 7581394; 7825602; 8566952; 8636252; 9062496; 9183487; 10073906; 9894883; 11748843; 11085690; 11204280; 11916318; 11220738; 12210797; 12486501; 12913200; 15073029; 15812458; 16240348; 15668429; 16305618; 16380594; 16009761; 16313334; 17372139; 17353371; 18759549; 19892975; 20301491; 28976817

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ABCD1 gene.

• Adrenoleukodystrophy (1155 variants)
• not provided (357 variants)
• Inborn genetic diseases (91 variants)
• not specified (66 variants)
• ABCD1-related condition (22 variants)
• X-linked cerebral adrenoleukodystrophy (2 variants)
• X-linked spondyloepimetaphyseal dysplasia (2 variants)
• See cases (2 variants)
• History of neurodevelopmental disorder (2 variants)
• Primary adrenocortical insufficiency (1 variants)
• Encephalitis;Episodic vomiting;Myocarditis;Recurrent fever (1 variants)
• Abnormality of the nervous system (1 variants)
• Intellectual disability (1 variants)
• Peroxisome biogenesis disorder 2B (1 variants)
• Spastic gait;Spastic paraplegia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ABCD1 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			2	288	23	313
missense	47	130	294	46	17	534
nonsense	43	11	3		1	58
start loss	3					3
frameshift	72	29				101
inframe indel	4	8	15			27
splice donor/acceptor (+/-2bp)	20	12	2			34
splice region	1	1	13	27	3	45
non coding		1	38	58	24	121
Total	189	191	354	392	65

Highest pathogenic variant AF is 0.00000890

Variants in ABCD1

This is a list of pathogenic ClinVar variants found in the ABCD1 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-153724925-G-A		Adrenoleukodystrophy	Uncertain significance (Jan 13, 2018)
X-153725065-C-G		Adrenoleukodystrophy	Benign (Jan 13, 2018)
X-153725208-C-T		Adrenoleukodystrophy	Benign (Nov 07, 2021)
X-153725247-C-T		not specified • Adrenoleukodystrophy	Likely benign (Aug 24, 2017)
X-153725248-GGCAGCCAGCCCAGGTGACATGCCGGT-G		Adrenoleukodystrophy	Pathogenic (Aug 14, 2021)
X-153725257-C-T		Adrenoleukodystrophy	Uncertain significance (Jan 13, 2018)
X-153725267-A-G		Adrenoleukodystrophy	Pathogenic (Feb 05, 2019)
X-153725268-T-TG		Adrenoleukodystrophy	Pathogenic (Oct 30, 2023)
X-153725269-GC-TT		Adrenoleukodystrophy	Pathogenic (Dec 08, 2023)
X-153725272-G-A		Adrenoleukodystrophy	Likely benign (Oct 09, 2020)
X-153725272-G-T		Adrenoleukodystrophy	Likely benign (Oct 13, 2023)
X-153725273-GT-G		Adrenoleukodystrophy	Pathogenic (Jan 24, 2024)
X-153725273-GTGCTC-G			Likely pathogenic (Jul 05, 2022)
X-153725275-G-GC		Adrenoleukodystrophy	Likely pathogenic (Apr 20, 2018)
X-153725278-C-G		Adrenoleukodystrophy	Likely benign (Nov 15, 2021)
X-153725278-C-T		Adrenoleukodystrophy	Likely benign (May 13, 2023)
X-153725282-AGGCCCC-CT		Adrenoleukodystrophy	Pathogenic (Sep 11, 2017)
X-153725284-GC-G		Adrenoleukodystrophy	Pathogenic (Oct 06, 2021)
X-153725284-G-GC		Adrenoleukodystrophy	Likely pathogenic (Apr 24, 2023)
X-153725285-C-T		Adrenoleukodystrophy	Likely benign (Sep 10, 2023)
X-153725287-C-T		Adrenoleukodystrophy	Likely benign (Feb 16, 2023)
X-153725288-C-A		Adrenoleukodystrophy	Uncertain significance (Jan 12, 2018)
X-153725288-C-T		Adrenoleukodystrophy • Inborn genetic diseases	Uncertain significance (Oct 30, 2023)
X-153725295-G-A		Adrenoleukodystrophy	Pathogenic (Jan 19, 2023)
X-153725296-G-A		Adrenoleukodystrophy	Pathogenic (Mar 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ABCD1	protein_coding	protein_coding	ENST00000218104	10	19894

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00104	108694	1	1	108696	0.00000920

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.87	250	348	0.719	0.0000328	4682
Missense in Polyphen		46	115.36	0.39876		1535
Synonymous	0.441	151	158	0.955	0.0000153	1619
Loss of Function	4.13	0	19.9	0.00	0.00000134	331

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000305	0.0000211
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in the transport of free very-long-chain fatty acids (VLCFAs) as well as their CoA-esters across the peroxisomal membrane by acting as an ATP-specific binding subunit releasing ADP after ATP hydrolysis (PubMed:15682271, PubMed:11248239, PubMed:16946495). Thus, plays a role in regulation of VLCFAs and energy metabolism namely, in the degradation and biosynthesis of fatty acids by beta-oxidation, mitochondrial function and microsomal fatty acid elongation (PubMed:23671276). Involved in several processes; namely, controls the active myelination phase by negatively regulating the microsomal fatty acid elongation activity and may also play a role in axon and myelin maintenance. Controls also the cellular response to oxidative stress by regulating mitochondrial function like, mitochondrial oxidative phosphorylation and depolarization. And finally controls the inflammatory response by positively regulating peroxisomal beta-oxidation of VLCFAs (By similarity). {ECO:0000250|UniProtKB:P48410, ECO:0000269|PubMed:11248239, ECO:0000269|PubMed:15682271, ECO:0000269|PubMed:16946495, ECO:0000269|PubMed:23671276}.
• Disease: DISEASE: Adrenoleukodystrophy (ALD) [MIM:300100]: A peroxisomal metabolic disorder characterized by progressive multifocal demyelination of the central nervous system and by peripheral adrenal insufficiency (Addison disease). It results in mental deterioration, corticospinal tract dysfunction, and cortical blindness. Different clinical manifestations exist like: cerebral childhood ALD (CALD), adult cerebral ALD (ACALD), adrenomyeloneuropathy (AMN) and 'Addison disease only' (ADO) phenotype. {ECO:0000269|PubMed:10369742, ECO:0000269|PubMed:10480364, ECO:0000269|PubMed:10551832, ECO:0000269|PubMed:10737980, ECO:0000269|PubMed:10980539, ECO:0000269|PubMed:11248239, ECO:0000269|PubMed:11438993, ECO:0000269|PubMed:11810273, ECO:0000269|PubMed:15643618, ECO:0000269|PubMed:21700483, ECO:0000269|PubMed:21889498, ECO:0000269|PubMed:23651979, ECO:0000269|PubMed:26686776, ECO:0000269|PubMed:7581394, ECO:0000269|PubMed:7717396, ECO:0000269|PubMed:7825602, ECO:0000269|PubMed:7849723, ECO:0000269|PubMed:7904210, ECO:0000269|PubMed:8040304, ECO:0000269|PubMed:8566952, ECO:0000269|PubMed:8651290, ECO:0000269|PubMed:9452087}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=The promoter region of ABCD1 is deleted in the chromosome Xq28 deletion syndrome which involves ABCD1 and the neighboring gene BCAP31. {ECO:0000269|PubMed:11992258}.
• Pathway: Peroxisome - Homo sapiens (human);ABC transporters - Homo sapiens (human);Beta Oxidation of Very Long Chain Fatty Acids;Oxidation of Branched Chain Fatty Acids;Refsum Disease;Phytanic Acid Peroxisomal Oxidation;Adrenoleukodystrophy, X-linked;Carnitine-acylcarnitine translocase deficiency;Vitamin D Receptor Pathway;Metabolism of lipids;ABC transporters in lipid homeostasis;alpha-linolenic acid (ALA) metabolism;Linoleic acid (LA) metabolism;alpha-linolenic (omega3) and linoleic (omega6) acid metabolism;Beta-oxidation of very long chain fatty acids;Peroxisomal lipid metabolism;Metabolism;Fatty acid metabolism;Transport of small molecules;ABC-family proteins mediated transport (Consensus)

Recessive Scores

• pRec: 0.769

Intolerance Scores

• loftool: 0.0188
• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.54

Haploinsufficiency Scores

• pHI: 0.442
• hipred: Y
• hipred_score: 0.685
• ghis: 0.429

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.783

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Abcd1
• Phenotype: hematopoietic system phenotype; normal phenotype; 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; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune 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); vision/eye phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: abcd1
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: regulation of oxidative phosphorylation;fatty acid beta-oxidation;peroxisome organization;peroxisomal long-chain fatty acid import;fatty-acyl-CoA transport;peroxisomal membrane transport;fatty acid elongation;regulation of fatty acid beta-oxidation;positive regulation of fatty acid beta-oxidation;fatty acid beta-oxidation using acyl-CoA oxidase;alpha-linolenic acid metabolic process;very long-chain fatty-acyl-CoA catabolic process;long-chain fatty acid catabolic process;very long-chain fatty acid catabolic process;myelin maintenance;linoleic acid metabolic process;regulation of mitochondrial depolarization;transmembrane transport;fatty acid homeostasis;sterol homeostasis;negative regulation of cytokine production involved in inflammatory response;regulation of cellular response to oxidative stress;negative regulation of reactive oxygen species biosynthetic process;neuron projection maintenance;positive regulation of unsaturated fatty acid biosynthetic process
• Cellular component: cytoplasm;lysosomal membrane;peroxisome;peroxisomal membrane;integral component of peroxisomal membrane;endoplasmic reticulum membrane;cytosol;membrane;mitochondrial membrane;perinuclear region of cytoplasm
• Molecular function: transporter activity;long-chain fatty acid transporter activity;protein binding;ATP binding;fatty-acyl-CoA transmembrane transporter activity;ATPase activity;enzyme binding;ATPase activity, coupled to transmembrane movement of substances;identical protein binding;protein homodimerization activity;ADP binding