ABCD3

ATP binding cassette subfamily D member 3, the group of ATP binding cassette subfamily D|GOLD domain containing

Basic information

Region (hg38): 1:94418389-94518666

Previous symbols: [ "PXMP1" ]

Links

ENSG00000117528

∙ NCBI:5825 ∙ OMIM:170995 ∙ HGNC:67 ∙ Uniprot:P28288 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

congenital bile acid synthesis defect 5 (Limited), mode of inheritance: AR
congenital bile acid synthesis defect 5 (Limited), mode of inheritance: Unknown
congenital bile acid synthesis defect 5 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bile acid synthesis defect, congenital, 5	AR	Gastrointestinal	Early interventions, such as with bile replacement therapy, may be beneficial, though liver transplant may be necessary	Biochemical; Craniofacial; Gastrointestinal; Neurologic	1301993; 9199576; 10447258; 17092750; 25168382

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ABCD3 gene.

not_provided (123 variants)
not_specified (61 variants)
Congenital_bile_acid_synthesis_defect_5 (3 variants)
ABCD3-related_disorder (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ABCD3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002858.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	27 clinvar	4 clinvar	32
missense			91 clinvar	2 clinvar	1 clinvar	94
nonsense			2 clinvar			2
start loss						0
frameshift	1 clinvar		2 clinvar			3
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	1	0	98	29	5

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ABCD3	protein_coding	protein_coding	ENST00000370214	23	100290

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00784	0.992	125707	0	32	125739	0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.54	229	366	0.626	0.0000195	4292
Missense in Polyphen		53	139.32	0.38041		1560
Synonymous	0.821	111	123	0.906	0.00000611	1233
Loss of Function	4.75	14	50.3	0.278	0.00000312	541

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000151	0.000148
Ashkenazi Jewish	0.000596	0.000595
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000133	0.000132
Middle Eastern	0.00	0.00
South Asian	0.000144	0.000131
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

Function: FUNCTION: Probable transporter involved in the transport of branched-chain fatty acids and C27 bile acids into the peroxisome; the latter function is a crucial step in bile acid biosynthesis (PubMed:25168382). The nucleotide-binding fold acts as an ATP- binding subunit with ATPase activity (PubMed:11248239). {ECO:0000269|PubMed:11248239, ECO:0000269|PubMed:25168382}.;
Disease: DISEASE: Congenital bile acid synthesis defect 5 (CBAS5) [MIM:616278]: An autosomal recessive disorder characterized by hepatosplenomegaly, hepatic fibrosis, progressive liver failure, and accumulation of peroxisomal C27-bile acid intermediates in plasma. {ECO:0000269|PubMed:25168382}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Peroxisome - Homo sapiens (human);ABC transporters - Homo sapiens (human);Nuclear Receptors in Lipid Metabolism and Toxicity;ABC transporters in lipid homeostasis;Transport of small molecules;ABC-family proteins mediated transport (Consensus)

Recessive Scores

pRec: 0.297

Intolerance Scores

loftool: 0.115
rvis_EVS: -0.65
rvis_percentile_EVS: 16.44

Haploinsufficiency Scores

pHI: 0.715
hipred: Y
hipred_score: 0.649
ghis: 0.603

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.806

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Abcd3
Phenotype: homeostasis/metabolism phenotype; cellular phenotype; liver/biliary system phenotype;

Gene ontology

Biological process: fatty acid biosynthetic process;fatty acid beta-oxidation;peroxisome organization;response to organic cyclic compound;peroxisomal long-chain fatty acid import;response to drug;very long-chain fatty acid catabolic process;transmembrane transport
Cellular component: mitochondrion;peroxisome;peroxisomal membrane;peroxisomal matrix;cytosol;membrane;integral component of membrane;intracellular membrane-bounded organelle
Molecular function: long-chain fatty acid transporter activity;protein binding;ATP binding;ATPase activity;ATPase activity, coupled to transmembrane movement of substances;protein homodimerization activity;protein self-association