DCAF8L1

Summary

DCAF8L1 (DDB1 and CUL4 associated factor 8 like 1, HGNC:31810) is a protein-coding gene on chromosome Xp21.3, encoding DDB1- and CUL4-associated factor 8-like protein 1 (A6NGE4).

This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by Gly-His and Trp-Asp (GH-WD), which may facilitate the formation of heterotrimeric or multi-protein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene appears to represent an intronless retrocopy of a related multi-exon gene located on chromosome 1. However, the CDS of this intronless gene remains intact, it is conserved in other primate species, it is known to be transcribed, and it is therefore thought to encode a functional protein.

Source: NCBI Gene 139425 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 73 total — 2 pathogenic
• MANE Select transcript: NM_001017930

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31810
Approved symbol	DCAF8L1
Name	DDB1 and CUL4 associated factor 8 like 1
Location	Xp21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000226372
Ensembl biotype	protein_coding
Entrez	139425

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000441525

RefSeq mRNA: 1 — MANE Select: NM_001017930 NM_001017930

CCDS: CCDS35222

Canonical transcript exons

ENST00000441525 — 1 exons

Exon	Start	End
ENSE00001756126	27977992	27981449

Expression profiles

Bgee: expression breadth tissue_specific, 7 present calls, max score 80.64.

Top tissues by expression

129 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.64	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	72.61	gold quality
right testis	UBERON:0004534	59.50	gold quality
testis	UBERON:0000473	59.03	gold quality
left testis	UBERON:0004533	58.38	gold quality
colonic epithelium	UBERON:0000397	41.53	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
sural nerve	UBERON:0015488	36.00	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.41	gold quality
granulocyte	CL:0000094	34.19	gold quality
mucosa of transverse colon	UBERON:0004991	33.96	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
right ovary	UBERON:0002118	29.86	silver quality
prefrontal cortex	UBERON:0000451	29.36	gold quality
right uterine tube	UBERON:0001302	29.24	gold quality
liver	UBERON:0002107	28.99	gold quality
lymph node	UBERON:0000029	28.71	gold quality
tonsil	UBERON:0002372	28.55	gold quality
duodenum	UBERON:0002114	28.14	gold quality
leukocyte	CL:0000738	28.00	gold quality
placenta	UBERON:0001987	27.54	gold quality
monocyte	CL:0000576	27.52	gold quality
islet of Langerhans	UBERON:0000006	26.89	gold quality
blood	UBERON:0000178	26.71	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

90 targeting DCAF8L1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4503	99.85	71.45	1869

Literature-anchored findings (GeneRIF, showing 1)

• Functionally characterizes other DDB1- and CUL4-associated factors, including the DCAF8 factor which most closely resembles the product of this gene. (PMID:16949367)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dcaf8	ENSDARG00000000324
mus_musculus	Dcaf8l	ENSMUSG00000035395
rattus_norvegicus	AABR07038690.1	ENSRNOG00000003345
drosophila_melanogaster	CG8001	FBGN0035268

Paralogs (5): DCAF8 (ENSG00000132716), DCAF5 (ENSG00000139990), WDTC1 (ENSG00000142784), DCAF6 (ENSG00000143164), DCAF8L2 (ENSG00000189186)

Protein

Protein identifiers

DDB1- and CUL4-associated factor 8-like protein 1 — A6NGE4 (reviewed: A6NGE4)

Alternative names: WD repeat-containing protein 42B

All UniProt accessions (1): A6NGE4

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the WD repeat DCAF8 family.

RefSeq proteins (1): NP_001017930* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR045151	DCAF8	Family

Pfam: PF00400

UniProt features (13 total): repeat 7, compositionally biased region 2, region of interest 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NGE4-F1	74.03	0.51

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 31 (showing top): GOCC_TRANSFERASE_COMPLEX, GOCC_CUL4_RING_E3_UBIQUITIN_LIGASE_COMPLEX, GOCC_CULLIN_RING_UBIQUITIN_LIGASE_COMPLEX, GOCC_UBIQUITIN_LIGASE_COMPLEX, chrXp21, MIR3662, MIR607, MIR6867_5P, MIR5688, MIR3671, MIR302C_5P, MIR1305, MIR3065_5P, MIR7159_5P, MIR5700

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): cytoplasm (GO:0005737), Cul4-RING E3 ubiquitin ligase complex (GO:0080008)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

280 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCAF8L1	DCAF12L2	Q5VW00	567
DCAF8L1	DCAF12L1	Q5VU92	501
DCAF8L1	DPCD	Q9BVM2	430
DCAF8L1	SLC22A31	A6NKX4	430
DCAF8L1	CEP85	Q6P2H3	375
DCAF8L1	USF3	Q68DE3	348
DCAF8L1	ZFP64	Q9NTW7	323
DCAF8L1	ATP13A1	Q9HD20	323
DCAF8L1	CEP85L	Q5SZL2	323
DCAF8L1	SCO1	O75880	298
DCAF8L1	ADGRD1	Q6QNK2	295
DCAF8L1	ARPC1A	Q92747	279
DCAF8L1	RAPGEF2	Q9Y4G8	277
DCAF8L1	NAP1L4	Q99733	275
DCAF8L1	ERFE	Q4G0M1	272

IntAct

3 interactions, top by confidence:

A	B	Type	Score
DCAF8	DCAF8L1	psi-mi:“MI:0914”(association)	0.530

BioGRID (3): DCAF8L1 (Affinity Capture-MS), DCAF8L1 (Affinity Capture-MS), DCAF8L1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GLK3, A0A8I6ASZ5, A0A974CYQ5, A4PES0, A4QNA8, A6NGE4, D2HHP1, D2HWM5, D3Z3I0, E6ZIJ1, E9Q349, F1ND48, O57473, P0C7V8, P0DOY1, P43254, P47817, P93471, Q28I90, Q3TLR7, Q4KLI9, Q4V837, Q58WW2, Q5QJC2, Q5R9B8, Q5RHI5, Q5XII5, Q60525, Q64LD2, Q66JG1, Q66JT0, Q6DFE0, Q6KAU8, Q6NRH1, Q6P1W0, Q6PCD5, Q80ZK9, Q8CBW4, Q8CIK8, Q8N5D0

Diamond homologs: A6NGE4, P0C7V8, Q28I90, Q5R448, Q5TAQ9, Q5U2M6, Q6NRH1, Q8N7N5, Q9FNN2, Q12510, Q58WW2, Q5R9B8, Q6CT00, Q80ZK9, Q8N5D0, Q9DC22, A5DWF4, O74184, Q23256, Q9C1X1, A8X8C6, O94527, Q17963, Q4V8C4, Q5RE95, Q86VZ2, Q94BQ3, Q9D7H2, A3LXF0, Q59VP7, P38123, A8IZG4, B0DWM8, B0R0D7, B4KTK4, B6QC06, F1LTR1, G0S8H7, G0SA60, O16519

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

73 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	60
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1076228	NC_000023.10:g.(?27765013)(31697703_?)del	Pathogenic
3391949	GRCh37/hg19 Xp21.3-21.1(chrX:26309498-35255723)x1	Pathogenic

SpliceAI

25 predictions. Top by Δscore:

Variant	Effect	Δscore
X:27981176:A:AC	donor_gain	0.5400
X:27981180:C:CT	donor_gain	0.5200
X:27981181:C:CT	donor_gain	0.4800
X:27979500:G:C	donor_gain	0.4700
X:27981169:C:A	donor_gain	0.4700
X:27981075:CCT:C	donor_gain	0.4600
X:27981077:TTC:T	donor_gain	0.4000
X:27981100:CGTCT:C	donor_gain	0.3900
X:27981110:TGA:T	donor_gain	0.3600
X:27979499:A:AC	donor_gain	0.3500
X:27981102:TCTTC:T	donor_gain	0.3200
X:27981078:TC:T	donor_gain	0.3100
X:27978959:CCCA:C	acceptor_gain	0.2800
X:27978960:CCAC:C	acceptor_gain	0.2800
X:27981305:G:C	donor_gain	0.2800
X:27981306:C:CT	donor_gain	0.2700
X:27981117:T:A	donor_gain	0.2600
X:27981307:C:CT	donor_gain	0.2600
X:27981105:TC:T	donor_gain	0.2300
X:27981179:A:AC	donor_gain	0.2200
X:27981082:CCA:C	donor_gain	0.2100
X:27981162:C:CT	donor_gain	0.2100
X:27981076:CTT:C	donor_gain	0.2000
X:27981084:ATG:A	donor_gain	0.2000
X:27981090:T:A	donor_gain	0.2000

AlphaMissense

3976 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:27980111:G:C	S408R	0.992
X:27980111:G:T	S408R	0.992
X:27980113:T:G	S408R	0.992
X:27980251:A:C	Y362D	0.991
X:27979964:A:C	S457R	0.989
X:27979964:A:T	S457R	0.989
X:27979966:T:G	S457R	0.989
X:27979977:A:T	V453D	0.988
X:27980538:C:G	R266P	0.988
X:27980084:G:C	F417L	0.987
X:27980084:G:T	F417L	0.987
X:27980086:A:G	F417L	0.987
X:27980247:T:G	D363A	0.987
X:27979940:C:A	W465C	0.986
X:27979940:C:G	W465C	0.986
X:27979979:A:C	F452L	0.986
X:27979979:A:T	F452L	0.986
X:27979981:A:G	F452L	0.986
X:27980085:A:G	F417S	0.986
X:27980118:A:G	L406P	0.986
X:27980668:A:G	W223R	0.986
X:27980668:A:T	W223R	0.986
X:27980720:G:C	N205K	0.986
X:27980720:G:T	N205K	0.986
X:27980723:A:C	F204L	0.986
X:27980723:A:T	F204L	0.986
X:27980725:A:G	F204L	0.986
X:27979942:A:G	W465R	0.985
X:27979942:A:T	W465R	0.985
X:27980092:A:C	Y415D	0.985

dbSNP variants (sampled 300 via entrez): RS1001188837 (X:27982921 G>T), RS1002178761 (X:27978464 A>G), RS1002634546 (X:27977755 A>G), RS1004451559 (X:27978266 T>G), RS1004506846 (X:27977707 G>A), RS1004570272 (X:27982600 G>A), RS1004941262 (X:27982243 A>G), RS1006458769 (X:27982953 T>C), RS1008975087 (X:27979778 A>T), RS1009419390 (X:27981410 T>G), RS1010924661 (X:27979015 T>G), RS1013879798 (X:27983208 C>T), RS1015858863 (X:27982248 A>G), RS1016258991 (X:27982145 T>G), RS1016304497 (X:27982608 G>A)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:310200

GenCC curated gene-disease

Mondo (1): Duchenne muscular dystrophy (MONDO:0010679)

Orphanet (1): Duchenne muscular dystrophy (Orphanet:98896)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000824_23	Erectile dysfunction and prostate cancer treatment	8.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020388	Muscular Dystrophy, Duchenne	C05.651.534.500.300; C10.668.491.175.500.300; C16.320.322.562; C16.320.577.300

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00819845	PHASE4	UNKNOWN	Ramipril Versus Carvedilol in Duchenne and Becker Patients
NCT01422200	PHASE4	COMPLETED	Flu Vaccine Study in Neuromuscular Patients 2011
NCT01999075	PHASE4	COMPLETED	Stacking Exercises Aid the Decline in FVC and Sick Time
NCT04687020	PHASE4	ACTIVE_NOT_RECRUITING	Long-term Use of Viltolarsen in Boys With Duchenne Muscular Dystrophy in Clinical Practice (VILT-502)
NCT04708314	PHASE4	TERMINATED	An Open-Label Study of Golodirsen in Non-Ambulant Patients With Duchenne Muscular Dystrophy
NCT05412394	PHASE4	RECRUITING	Once Weekly Infant Corticosteroid Trial for DMD
NCT06713135	PHASE4	ACTIVE_NOT_RECRUITING	A Study on Safety and Effectiveness of Long-term Treatment With Vamorolone in Boys With Duchenne Muscular Dystrophy
NCT07542314	PHASE4	NOT_YET_RECRUITING	Study to Evaluate the Safety and Effectiveness of ELEVIDYS in Participants With Duchenne Muscular Dystrophy Treated in a Post-Marketing Setting
NCT00004646	PHASE3	COMPLETED	Phase III Randomized, Double-Blind Study of Prednisone for Duchenne Muscular Dystrophy
NCT00110669	PHASE3	COMPLETED	High-dose Prednisone in Duchenne Muscular Dystrophy
NCT00308113	PHASE3	TERMINATED	CoQ10 and Prednisone in Non-Ambulatory DMD
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT01247207	PHASE3	COMPLETED	Study of Ataluren in Previously Treated Participants With Nonsense Mutation Dystrophinopathy (nmDBMD)
NCT01557400	PHASE3	COMPLETED	Study of Ataluren for Previously Treated Participants With Nonsense Mutation Duchenne/Becker Muscular Dystrophy (nmDBMD) in Europe, Israel, Australia, and Canada
NCT01603407	PHASE3	COMPLETED	Finding the Optimum Regimen for Duchenne Muscular Dystrophy
NCT01648634	PHASE3	COMPLETED	Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
NCT02255552	PHASE3	COMPLETED	Study of Eteplirsen in DMD Patients
NCT02354352	PHASE3	COMPLETED	Therapeutic Potential for Aldosterone Inhibition in Duchenne Muscular Dystrophy
NCT02500381	PHASE3	COMPLETED	Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD)
NCT02814019	PHASE3	TERMINATED	A Phase III Double-blind Study With Idebenone in Patients With Duchenne Muscular Dystrophy (DMD) Taking Glucocorticoid Steroids
NCT02851797	PHASE3	COMPLETED	Clinical Study to Evaluate the Efficacy and Safety of Givinostat in Ambulant Patients With Duchenne Muscular Dystrophy
NCT03354039	PHASE3	COMPLETED	Tamoxifen in Duchenne Muscular Dystrophy
NCT03532542	PHASE3	TERMINATED	An Extension Study to Evaluate Casimersen or Golodirsen in Patients With Duchenne Muscular Dystrophy
NCT03603288	PHASE3	TERMINATED	Phase III Study With Idebenone in Patients With Duchenne Muscular Dystrophy (SIDEROS-E)
NCT03642145	PHASE3	WITHDRAWN	A Study of Deflazacort (Emflaza®) in Participants With Duchenne Muscular Dystrophy (DMD)
NCT03917719	PHASE3	TERMINATED	An Open-Label Extension Study of Edasalonexent in Boys With Duchenne Muscular Dystrophy
NCT04060199	PHASE3	COMPLETED	Study to Assess the Efficacy and Safety of Viltolarsen in Ambulant Boys With DMD (RACER53)
NCT04281485	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate the Safety and Efficacy of PF-06939926 for the Treatment of Duchenne Muscular Dystrophy
NCT04371666	PHASE3	TERMINATED	Phase 3 Trial of Pamrevlumab or Placebo With Systemic Corticosteroids in Participants With Non-ambulatory Duchenne Muscular Dystrophy (DMD)
NCT04587908	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study of TAS-205 in Patients With Duchenne Muscular Dystrophy（REACH-DMD）
NCT04632940	PHASE3	TERMINATED	Phase 3 Trial of Pamrevlumab or Placebo in Combination With Systemic Corticosteroids in Participants With Ambulatory DMD
NCT04768062	PHASE3	UNKNOWN	Study to Assess the Safety and Efficacy of Viltolarsen in Ambulant Boys With DMD (RACER53-X)
NCT05096221	PHASE3	COMPLETED	A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Participants With Duchenne Muscular Dystrophy (DMD)
NCT05689164	PHASE3	TERMINATED	A Study to Understand the Long-term Safety and Effects of an Experimental Gene Therapy for Duchenne Muscular Dystrophy.
NCT05881408	PHASE3	ACTIVE_NOT_RECRUITING	A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Non-Ambulatory and Ambulatory Participants With Duchenne Muscular Dystrophy (DMD)
NCT05933057	PHASE3	RECRUITING	Efficacy, Safety and Tolerability of Givinostat in Non-ambulant Patients With Duchenne Muscular Dystrophy
NCT05967351	PHASE3	ENROLLING_BY_INVITATION	A Long-term Follow-up Study of Participants Who Received Delandistrogene Moxeparvovec (SRP-9001) in a Previous Clinical Study
NCT07160634	PHASE3	RECRUITING	A Study of SGT-003 Gene Therapy in Ambulant Males With Duchenne Muscular Dystrophy (IMPACT DUCHENNE)
NCT07587242	PHASE3	NOT_YET_RECRUITING	A Phase 3 Study to Evaluate the Safety and Efficacy of AOC 1044 (Also Referred to as Delpacibart Zotadirsen) in Participants With DMD With Gene Mutations Amenable to Exon 44 Skipping