ABCD3

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

Basic information

Region (hg38): 1:94418388-94518666

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 (74 variants)
• Inborn genetic diseases (10 variants)
• Congenital bile acid synthesis defect 5 (3 variants)
• not specified (2 variants)
• ABCD3-related condition (1 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.

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				15	4	19
missense			33		1	34
nonsense			2			2
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			5	7	2	14
non coding			1	7	7	15
Total	0	0	36	22	12

Variants in ABCD3

This is a list of pathogenic ClinVar variants found in the ABCD3 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-94418486-C-T		not specified	Uncertain significance (Jan 03, 2024)
1-94418487-C-T			Likely benign (Dec 20, 2023)
1-94418512-A-T		not specified	Uncertain significance (Feb 05, 2024)
1-94418520-G-T			Likely benign (Jul 12, 2023)
1-94418521-C-G		not specified	Uncertain significance (Jun 06, 2023)
1-94418528-G-A		not specified	Uncertain significance (Jan 01, 1999)
1-94418532-C-T			Likely benign (Sep 01, 2023)
1-94418545-C-G			Uncertain significance (Sep 25, 2023)
1-94418558-A-T			Uncertain significance (Oct 26, 2023)
1-94418571-C-T			Likely benign (Nov 24, 2022)
1-94418575-C-T		not specified	Uncertain significance (Dec 16, 2023)
1-94418577-C-T			Likely benign (Jul 07, 2023)
1-94418608-T-C			Likely benign (Oct 23, 2023)
1-94458589-T-C			Likely benign (Dec 07, 2023)
1-94458592-T-C			Benign (Nov 25, 2023)
1-94458595-T-A			Benign (Jan 01, 2023)
1-94458618-G-A			Conflicting classifications of pathogenicity (Sep 03, 2023)
1-94458629-T-G			Uncertain significance (Dec 06, 2023)
1-94458662-T-A			Likely benign (Jul 09, 2022)
1-94464759-C-CT			Benign (Aug 24, 2023)
1-94464768-A-T			Likely benign (Jun 13, 2022)
1-94464782-G-T		Congenital bile acid synthesis defect 5	Benign (Dec 15, 2023)
1-94464784-A-G		not specified	Uncertain significance (Aug 12, 2021)
1-94464788-A-G		not specified	Uncertain significance (Jun 24, 2022)
1-94464789-G-A		not specified • Congenital bile acid synthesis defect 5	Benign (Feb 01, 2024)

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