DCAF4L1

Summary

DCAF4L1 (DDB1 and CUL4 associated factor 4 like 1, HGNC:27723) is a protein-coding gene on chromosome 4p13, encoding DDB1- and CUL4-associated factor 4-like protein 1 (Q3SXM0).

Located in cytoplasm.

Source: NCBI Gene 285429 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 31 total
• MANE Select transcript: NM_001029955

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27723
Approved symbol	DCAF4L1
Name	DDB1 and CUL4 associated factor 4 like 1
Location	4p13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000182308
Ensembl biotype	protein_coding
Entrez	285429

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000333141

RefSeq mRNA: 1 — MANE Select: NM_001029955 NM_001029955

CCDS: CCDS33978

Canonical transcript exons

ENST00000333141 — 1 exons

Exon	Start	End
ENSE00001308497	41981756	41986465

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 97.05.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0651 / max 51.5388, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47508	0.0651	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.05	gold quality
oocyte	CL:0000023	96.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.51	gold quality
secondary oocyte	CL:0000655	94.05	gold quality
testis	UBERON:0000473	86.86	gold quality
sperm	CL:0000019	86.82	gold quality
right testis	UBERON:0004534	86.34	gold quality
left testis	UBERON:0004533	85.10	gold quality
buccal mucosa cell	CL:0002336	84.64	gold quality
gastrocnemius	UBERON:0001388	63.77	gold quality
muscle of leg	UBERON:0001383	62.30	gold quality
adult organism	UBERON:0007023	62.21	gold quality
hindlimb stylopod muscle	UBERON:0004252	60.15	gold quality
oviduct epithelium	UBERON:0004804	60.02	silver quality
granulocyte	CL:0000094	58.76	gold quality
islet of Langerhans	UBERON:0000006	56.30	gold quality
lower lobe of lung	UBERON:0008949	55.69	silver quality
heart left ventricle	UBERON:0002084	54.33	gold quality
leukocyte	CL:0000738	54.02	gold quality
monocyte	CL:0000576	53.90	gold quality
cardiac ventricle	UBERON:0002082	53.84	gold quality
adenohypophysis	UBERON:0002196	53.17	gold quality
pituitary gland	UBERON:0000007	52.60	gold quality
bone marrow cell	CL:0002092	52.50	gold quality
spleen	UBERON:0002106	52.31	gold quality
mucosa of stomach	UBERON:0001199	51.89	gold quality
right coronary artery	UBERON:0001625	51.89	gold quality
blood	UBERON:0000178	51.88	gold quality
heart	UBERON:0000948	51.40	gold quality
metanephros cortex	UBERON:0010533	51.14	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	30.02
E-ANND-3	yes	3.84
E-CURD-10	no	281.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

94 targeting DCAF4L1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-3941	99.86	70.54	2735

Cross-species orthologs

0 orthologs

Paralogs (26): PAFAH1B1 (ENSG00000007168), SNRNP40 (ENSG00000060688), WDR62 (ENSG00000075702), WDR7 (ENSG00000091157), TBL2 (ENSG00000106638), PAK1IP1 (ENSG00000111845), WDR75 (ENSG00000115368), DCAF4 (ENSG00000119599), DAW1 (ENSG00000123977), TEP1 (ENSG00000129566), AHI1 (ENSG00000135541), WDR38 (ENSG00000136918), MAPKBP1 (ENSG00000137802), POC1B (ENSG00000139323), NEDD1 (ENSG00000139350), COP1 (ENSG00000143207), WDR17 (ENSG00000150627), WDR43 (ENSG00000163811), POC1A (ENSG00000164087), WDR88 (ENSG00000166359), WDR81 (ENSG00000167716), DCAF4L2 (ENSG00000176566), WDR27 (ENSG00000184465), NWD1 (ENSG00000188039), WDR5 (ENSG00000196363), WDR5B (ENSG00000196981)

Protein

Protein identifiers

DDB1- and CUL4-associated factor 4-like protein 1 — Q3SXM0 (reviewed: Q3SXM0)

Alternative names: WD repeat-containing protein 21B

All UniProt accessions (1): Q3SXM0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm.

RefSeq proteins (1): NP_001025126* (*=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
IPR052254	CUL4-DDB1_E3_ligase_receptor	Family

Pfam: PF23761

UniProt features (5 total): repeat 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3SXM0-F1	85.13	0.47

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 26 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOCC_TRANSFERASE_COMPLEX, GOCC_CUL4_RING_E3_UBIQUITIN_LIGASE_COMPLEX, GOCC_CULLIN_RING_UBIQUITIN_LIGASE_COMPLEX, GOCC_UBIQUITIN_LIGASE_COMPLEX, MIR9983_3P, MIR4482_3P, MIR302B_5P, MIR302D_5P, GSE11864_UNTREATED_VS_CSF1_PAM3CYS_IN_MAC_DN, MIR4709_5P, MIR502_5P, BLANCO_MELO_MERS_COV_INFECTION_MCR5_CELLS_UP, BLANCO_MELO_COVID19_SARS_COV_2_LOW_MOI_INFECTION_A594_ACE2_EXPRESSING_CELLS_UP, BLANCO_MELO_COVID19_SARS_COV_2_INFECTION_A594_ACE2_EXPRESSING_CELLS_UP

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

288 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCAF4L1	TMEM33	P57088	431
DCAF4L1	GTF3C3	Q9Y5Q9	407
DCAF4L1	AP5S1	Q9NUS5	400
DCAF4L1	PAGE2B	Q5JRK9	397
DCAF4L1	UBALD1	Q8TB05	393
DCAF4L1	ZSCAN23	Q3MJ62	370
DCAF4L1	ZNF814	B7Z6K7	370
DCAF4L1	DDB1	Q16531	351
DCAF4L1	CHADL	Q6NUI6	349
DCAF4L1	AP5Z1	O43299	339
DCAF4L1	PODNL1	Q6PEZ8	325
DCAF4L1	RHOXF1	Q8NHV9	324
DCAF4L1	C11orf42	Q8N5U0	324
DCAF4L1	AP4S1	Q9Y587	322
DCAF4L1	AP3S2	P59780	321

IntAct

12 interactions, top by confidence:

A	B	Type	Score
COPS6	RHOBTB1	psi-mi:“MI:0914”(association)	0.730
DCAF4L1	CUL4A	psi-mi:“MI:0914”(association)	0.730
CUL4A	COPS2	psi-mi:“MI:0914”(association)	0.640
DCAF4L1	SNRPA1	psi-mi:“MI:0915”(physical association)	0.400
CUL4A	HAX1	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
COPS6	DDX3X	psi-mi:“MI:0914”(association)	0.350
DCAF4L1	PFDN6	psi-mi:“MI:0914”(association)	0.350
DCAF4L1	VWA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (28): CUL4A (Affinity Capture-MS), CUL4A (Affinity Capture-MS), CUL4B (Affinity Capture-MS), DCAF4L1 (PCA), DCAF4L1 (Proximity Label-MS), DCAF4L1 (Affinity Capture-MS), DCAF4L1 (Affinity Capture-MS), CUL4A (Affinity Capture-MS), CUL4B (Affinity Capture-MS), LONP1 (Affinity Capture-MS), PDRG1 (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT7 (Affinity Capture-MS), PFDN6 (Affinity Capture-MS), CCT5 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LI67, A0A1W2PR48, A0JP70, D3YYM4, F1LW30, O13034, O15040, O70173, Q15345, Q3SXM0, Q3UDP0, Q3UJB9, Q3ULW6, Q3V129, Q3ZAV8, Q58DC2, Q5F479, Q5JV73, Q5M9H0, Q5M9H1, Q5R6T6, Q5R9H2, Q68DX3, Q6IRN0, Q6NV72, Q6P2E9, Q6P4K6, Q6PCD5, Q6ZPG2, Q6ZW76, Q7TNH6, Q80TQ5, Q8BLD6, Q8C008, Q8C5V5, Q8CBW4, Q8CIK8, Q8IWE5, Q8JZL1, Q8K1C9

Diamond homologs: Q3SXM0, Q58DC2, Q8NA75, Q8WV16, Q8RXA7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

184 predictions. Top by Δscore:

Variant	Effect	Δscore
4:41983026:G:GT	donor_gain	0.9800
4:41983030:T:G	donor_gain	0.9600
4:41983109:GGG:G	donor_gain	0.9300
4:41983110:GGG:G	donor_gain	0.9300
4:41983030:TTAA:T	donor_gain	0.8900
4:41982873:G:GT	donor_gain	0.8600
4:41982993:T:TA	donor_gain	0.8400
4:41983117:GTGT:G	donor_gain	0.8100
4:41983118:TGTT:T	donor_gain	0.8100
4:41982281:GTTCT:G	donor_gain	0.7900
4:41982282:TTCTT:T	donor_gain	0.7900
4:41982957:G:GT	donor_gain	0.7900
4:41982994:G:GA	donor_gain	0.7900
4:41982921:G:GT	donor_gain	0.7800
4:41983026:G:T	donor_gain	0.7800
4:41982172:TG:T	donor_gain	0.7700
4:41982668:A:T	donor_gain	0.7700
4:41982921:G:T	donor_gain	0.7500
4:41982765:G:GT	donor_gain	0.7400
4:41982980:C:G	donor_gain	0.7000
4:41982954:C:T	donor_gain	0.6800
4:41982167:G:GT	donor_gain	0.6400
4:41982173:GA:G	donor_gain	0.6200
4:41982174:AA:A	donor_gain	0.6200
4:41982168:A:T	donor_gain	0.6000
4:41983110:GG:G	donor_gain	0.5800
4:41983111:GG:G	donor_gain	0.5800
4:41983119:GTTA:G	donor_gain	0.5800
4:41983027:A:T	donor_gain	0.5700
4:41983107:CAGGG:C	donor_loss	0.5700

AlphaMissense

2581 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:41982393:A:C	S201R	0.994
4:41982395:T:A	S201R	0.994
4:41982395:T:G	S201R	0.994
4:41982813:T:A	W341R	0.990
4:41982813:T:C	W341R	0.990
4:41982360:T:A	W190R	0.986
4:41982360:T:C	W190R	0.986
4:41982681:T:A	W297R	0.986
4:41982681:T:C	W297R	0.986
4:41982783:G:C	A331P	0.986
4:41982815:G:C	W341C	0.984
4:41982815:G:T	W341C	0.984
4:41982486:T:C	F232L	0.983
4:41982488:T:A	F232L	0.983
4:41982488:T:G	F232L	0.983
4:41982795:G:C	D335H	0.980
4:41982809:A:C	R339S	0.979
4:41982809:A:T	R339S	0.979
4:41982683:G:C	W297C	0.977
4:41982683:G:T	W297C	0.977
4:41982220:T:C	L143P	0.975
4:41982186:T:A	W132R	0.973
4:41982186:T:C	W132R	0.973
4:41982667:G:T	G292V	0.972
4:41982796:A:C	D335A	0.971
4:41982784:C:A	A331E	0.970
4:41982796:A:T	D335V	0.970
4:41982797:C:A	D335E	0.969
4:41982797:C:G	D335E	0.969
4:41982805:C:A	T338K	0.968

dbSNP variants (sampled 300 via entrez): RS1000410786 (4:41981634 T>C), RS1001674645 (4:41981027 C>T), RS1001957709 (4:41981351 A>C), RS1002522322 (4:41986077 C>G), RS1002677299 (4:41979759 G>A), RS1002960824 (4:41980094 T>C), RS1003050761 (4:41986729 G>A,T), RS1003192274 (4:41986340 T>C), RS1003490562 (4:41981652 C>G,T), RS1003810658 (4:41984739 T>C), RS1004308327 (4:41981977 G>A), RS1005162394 (4:41986677 T>A), RS1005257393 (4:41980982 T>G), RS1005521679 (4:41986446 A>C,G), RS1006016732 (4:41986325 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005355_3	Helping behaviour (self reported)	5.000000e-07
GCST005355_5	Helping behaviour (self reported)	3.000000e-06
GCST005839_40	Depression	3.000000e-09
GCST009600_120	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	3.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, increases expression	3
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
licochalcone B	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Acetaminophen	decreases expression	1
Demecolcine	increases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Niclosamide	decreases expression	1
Potassium Chloride	decreases response to substance, increases expression	1
Dronabinol	decreases response to substance, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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