ABCD1
ATP binding cassette subfamily D member 1, the group of ATP binding cassette subfamily D
Basic information
Region (hg38): X:153724856-153744755
Previous symbols: [ "ALD" ]
Links
Phenotypes
GenCC
Source:
- 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:
| 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
- Adrenoleukodystrophy (180 variants)
- not provided (58 variants)
- Inborn genetic diseases (7 variants)
- ABCD1-related disorder (6 variants)
- not specified (2 variants)
- Primary adrenocortical insufficiency (1 variants)
- X-linked spondyloepimetaphyseal dysplasia (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 | 324 | 24 | 350 | |||
| missense | 55 | 140 | 306 | 57 | 14 | 572 |
| nonsense | 44 | 11 | 58 | |||
| start loss | 3 | |||||
| frameshift | 79 | 31 | 112 | |||
| inframe indel | 10 | 13 | 30 | |||
| splice donor/acceptor (+/-2bp) | 20 | 13 | 34 | |||
| splice region | 1 | 1 | 13 | 34 | 4 | 53 |
| non coding | 38 | 80 | 25 | 144 | ||
| Total | 208 | 206 | 365 | 461 | 63 |
Highest pathogenic variant AF is 0.00000888
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 | Conflicting classifications of pathogenicity (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:
| 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:
- 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