DCAF8

DDB1 and CUL4 associated factor 8, the group of DDB1 and CUL4 associated factors|WD repeat domain containing

Basic information

Region (hg38): 1:160215714-160262549

Previous symbols: [ "WDR42A" ]

Links

ENSG00000132716 ∙ NCBI:50717 ∙ OMIM:615820 ∙ HGNC:24891 ∙ Uniprot:Q5TAQ9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• giant axonal neuropathy 2 (Limited), mode of inheritance: AD
• giant axonal neuropathy 2 (Supportive), mode of inheritance: AD
• giant axonal neuropathy 2 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Giant axonal neuropathy 2, autosomal dominant	AD	Cardiovascular	Individuals have been described with cardiomyopathy, and awareness may allow early management	Cardiovascular; Neurologic	3859241; 24500646

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DCAF8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DCAF8 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				7	1	8
missense			25	2		27
nonsense			2			2
start loss						0
frameshift						0
inframe indel					2	2
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding				1		1
Total	0	0	27	10	3

Variants in DCAF8

This is a list of pathogenic ClinVar variants found in the DCAF8 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-160217659-G-A		Giant axonal neuropathy 2	Uncertain significance (Aug 30, 2022)
1-160217660-A-G		not specified	Uncertain significance (Sep 12, 2023)
1-160217702-G-A		not specified	Uncertain significance (Jun 06, 2023)
1-160217707-C-T		Neurofibromatosis, type 1	Uncertain significance (Oct 19, 2023)
1-160218452-A-G		not specified	Likely benign (Nov 10, 2023)
1-160222710-G-A		not specified	Uncertain significance (Mar 04, 2024)
1-160224518-A-G		DCAF8-related disorder	Conflicting classifications of pathogenicity (Jun 05, 2019)
1-160225090-G-A			Likely benign (Dec 31, 2019)
1-160225101-C-A			Uncertain significance (Apr 01, 2024)
1-160225634-T-C		not specified	Uncertain significance (Jun 11, 2021)
1-160231312-C-T		not specified	Uncertain significance (May 30, 2024)
1-160231339-T-C		not specified	Uncertain significance (Sep 06, 2022)
1-160237131-T-G		not specified	Uncertain significance (Oct 03, 2022)
1-160237135-G-A		DCAF8-related disorder	Uncertain significance (May 16, 2023)
1-160237145-G-A		Giant axonal neuropathy 2	Pathogenic (Mar 11, 2014)
1-160238649-C-T		Giant axonal neuropathy 2 • DCAF8-related disorder	Benign/Likely benign (Feb 14, 2022)
1-160238662-G-A			Uncertain significance (Feb 04, 2020)
1-160238682-T-C		DCAF8-related disorder	Benign (Dec 31, 2019)
1-160238694-G-A			Likely benign (Nov 05, 2018)
1-160239654-C-A		not specified	Uncertain significance (May 04, 2022)
1-160239746-C-T		not specified	Uncertain significance (Apr 29, 2024)
1-160239750-G-A		not specified	Uncertain significance (Oct 12, 2022)
1-160239778-G-A		DCAF8-related disorder	Likely benign (Feb 18, 2019)
1-160239808-G-A			Likely benign (Dec 01, 2023)
1-160239861-G-T		not specified	Uncertain significance (Aug 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DCAF8	protein_coding	protein_coding	ENST00000368073	12	69416

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000396	125741	0	4	125745	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.15	191	359	0.532	0.0000213	3940
Missense in Polyphen		13	65.69	0.1979		765
Synonymous	1.38	109	129	0.845	0.00000686	1137
Loss of Function	4.85	2	31.3	0.0639	0.00000180	339

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000943	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex. {ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:16964240}.
• Disease: DISEASE: Giant axonal neuropathy 2, autosomal dominant (GAN2) [MIM:610100]: An autosomal dominant peripheral axonal neuropathy characterized by onset of distal sensory impairment with lower extremity muscle weakness and atrophy after the second decade. Clinical features include foot deformities apparent in childhood, and cardiomyopathy in severely affected individuals. Sural nerve biopsy shows giant axonal swelling with neurofilament accumulation. {ECO:0000269|PubMed:24500646}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Post-translational protein modification;Metabolism of proteins;Neddylation (Consensus)

Recessive Scores

• pRec: 0.108

Intolerance Scores

• rvis_EVS: -0.65
• rvis_percentile_EVS: 16.36

Haploinsufficiency Scores

• pHI: 0.266
• hipred: Y
• hipred_score: 0.519
• ghis: 0.592

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.781

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dcaf8

Gene ontology

• Biological process: protein ubiquitination;post-translational protein modification
• Cellular component: nucleus;nucleoplasm;cytoplasm;mitochondrion;cytosol;Cul4-RING E3 ubiquitin ligase complex
• Molecular function: protein binding