DCAF4L2

Summary

DCAF4L2 (DDB1 and CUL4 associated factor 4 like 2, HGNC:26657) is a protein-coding gene on chromosome 8q21.3, encoding DDB1- and CUL4-associated factor 4-like protein 2 (Q8NA75).

Predicted to be part of Cul4-RING E3 ubiquitin ligase complex.

Source: NCBI Gene 138009 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 74 total
• MANE Select transcript: NM_152418

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26657
Approved symbol	DCAF4L2
Name	DDB1 and CUL4 associated factor 4 like 2
Location	8q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000176566
Ensembl biotype	protein_coding
OMIM	620421
Entrez	138009

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000319675

RefSeq mRNA: 1 — MANE Select: NM_152418 NM_152418

CCDS: CCDS6245

Canonical transcript exons

ENST00000319675 — 1 exons

Exon	Start	End
ENSE00001260087	87870747	87874015

Expression profiles

Bgee: expression breadth broad, 27 present calls, max score 95.07.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1315 / max 29.7541, expressed in 27 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93837	0.0768	19
93836	0.0370	18
93838	0.0177	11

Top tissues by expression

199 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	95.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.74	gold quality
secondary oocyte	CL:0000655	91.01	gold quality
oocyte	CL:0000023	82.47	gold quality
right testis	UBERON:0004534	81.31	gold quality
testis	UBERON:0000473	81.25	gold quality
left testis	UBERON:0004533	79.44	gold quality
myocardium	UBERON:0002349	67.08	gold quality
buccal mucosa cell	CL:0002336	65.78	gold quality
tendon of biceps brachii	UBERON:0008188	64.97	silver quality
adult organism	UBERON:0007023	63.77	gold quality
lower lobe of lung	UBERON:0008949	61.17	silver quality
medial globus pallidus	UBERON:0002477	60.26	gold quality
pericardium	UBERON:0002407	56.24	silver quality
sperm	CL:0000019	56.03	silver quality
cartilage tissue	UBERON:0002418	54.57	gold quality
Brodmann (1909) area 46	UBERON:0006483	52.31	gold quality
nasal cavity epithelium	UBERON:0005384	51.04	gold quality
pharyngeal mucosa	UBERON:0000355	47.53	silver quality
vastus lateralis	UBERON:0001379	44.80	gold quality
quadriceps femoris	UBERON:0001377	44.69	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	44.57	gold quality
biceps brachii	UBERON:0001507	43.88	gold quality
deltoid	UBERON:0001476	43.57	gold quality
oviduct epithelium	UBERON:0004804	43.46	gold quality
substantia nigra pars reticulata	UBERON:0001966	43.02	silver quality
mucosa of sigmoid colon	UBERON:0004993	42.43	gold quality
skin of hip	UBERON:0001554	42.36	silver quality
trabecular bone tissue	UBERON:0002483	42.36	gold quality
heart right ventricle	UBERON:0002080	42.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	28.70
E-ANND-3	yes	2.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

69 targeting DCAF4L2, 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-5692A	100.00	74.40	6850
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-548AH-5P	99.52	69.73	2626

Literature-anchored findings (GeneRIF, showing 2)

• In addition, eight genes classified as ‘second tier’ hits in the original study (PAX7, THADA, COL8A1/FILIP1L, DCAF4L2, GADD45G, NTN1, RBFOX3 and FOXE1) showed evidence of linkage and association in this replication sample. (PMID:23512105)
• LncRNA ST8SIA6-AS1 promotes hepatocellular carcinoma progression by regulating MAGEA3 and DCAF4L2 expression. (PMID:33012505)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dcaf4	ENSMUSG00000021222
rattus_norvegicus	Dcaf4	ENSRNOG00000008399

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), DCAF4L1 (ENSG00000182308), WDR27 (ENSG00000184465), NWD1 (ENSG00000188039), WDR5 (ENSG00000196363), WDR5B (ENSG00000196981)

Protein

Protein identifiers

DDB1- and CUL4-associated factor 4-like protein 2 — Q8NA75 (reviewed: Q8NA75)

Alternative names: WD repeat-containing protein 21C

All UniProt accessions (1): Q8NA75

RefSeq proteins (1): NP_689631* (*=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 (3 total): repeat 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NA75-F1	85.17	0.49

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 30 (showing top): NIKOLSKY_BREAST_CANCER_8Q12_Q22_AMPLICON, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOCC_TRANSFERASE_COMPLEX, GOCC_CUL4_RING_E3_UBIQUITIN_LIGASE_COMPLEX, GOCC_CULLIN_RING_UBIQUITIN_LIGASE_COMPLEX, GOCC_UBIQUITIN_LIGASE_COMPLEX, chr8q21, MARTENS_TRETINOIN_RESPONSE_UP, CBX5_TARGET_GENES, TRIP13_TARGET_GENES, MIR520D_5P, MIR524_5P, MIR3688_3P, MIR548AT_5P, MIR4762_3P

GO Biological Process (0):

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

GO Cellular Component (1): Cul4-RING E3 ubiquitin ligase complex (GO:0080008)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cullin-RING ubiquitin ligase complex	1

Protein interactions and networks

STRING

472 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCAF4L2	ASB7	Q9H672	447
DCAF4L2	TMTC2	Q8N394	431
DCAF4L2	CYRIA	Q9H0Q0	419
DCAF4L2	ARHGAP29	Q52LW3	415
DCAF4L2	C2CD4D	B7Z1M9	399
DCAF4L2	DDB1	Q16531	380
DCAF4L2	IRF6	O14896	380
DCAF4L2	ELP4	Q96EB1	377
DCAF4L2	WDR89	Q96FK6	370
DCAF4L2	ZNF701	Q9NV72	370
DCAF4L2	DDHD1	Q8NEL9	356
DCAF4L2	OR2B11	Q5JQS5	354
DCAF4L2	TRIOBP	Q9H2D6	354
DCAF4L2	VAX1	Q5SQQ9	353
DCAF4L2	Q6GMV1	Q6GMV1	350

IntAct

5 interactions, top by confidence:

A	B	Type	Score
DCAF4L2	CLUH	psi-mi:“MI:0914”(association)	0.530
NUDC	DCAF4L2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (56): COPS2 (Affinity Capture-MS), CLUH (Affinity Capture-MS), CCT6B (Affinity Capture-MS), PYGL (Affinity Capture-MS), CUL4B (Affinity Capture-MS), CUL4A (Affinity Capture-MS), CLUH (Affinity Capture-MS), PYGL (Affinity Capture-MS), CUL4B (Affinity Capture-MS), CUL4A (Affinity Capture-MS), DDB1 (Affinity Capture-MS), CUL4A (Affinity Capture-MS), COPS4 (Affinity Capture-MS), PPM1B (Affinity Capture-MS), ANXA2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8GXY4, A0A1L8I2C5, A1A5R7, A6PWY4, A9X1C6, B1ANS9, B2KIQ4, D3Z3I0, E9Q7R9, F1QHZ6, O13286, O74845, O94411, P26309, P43254, P51956, P93471, Q09786, Q4V837, Q5R6T6, Q5TKR9, Q5XHI9, Q5ZKI7, Q6DTM3, Q6GM71, Q6GPU3, Q6VZ17, Q7Z2W4, Q80Z32, Q86VD1, Q86Y33, Q8BZ21, Q8CDP0, Q8K3E5, Q8L4H0, Q8N157, Q8N4N8, Q8NA75, Q8NDM7, Q8NEM8

Diamond homologs: A0JPH4, A1C7E4, A1CBP8, A1D7I5, A1DDL6, A1DHW6, A2QCU8, A2QEV8, A2R3Z3, A2RRU4, A4R3M4, A4RJV3, A5DGL8, A6QM06, A6ZMK5, A6ZQL5, A6ZZZ8, A7ETB3, A7TMF9, A7TNS8, A8PTE4, B0XTS1, B0XYC8, B2B766, B4GSH1, B4JB43, B6Q4Z5, B8NGT5, C4JPW9, C5FWH1, C7Z6H2, O08653, O42937, O48716, O54929, P0CS44, P0CS45, P36130, P40217, P47025

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	12
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

11 predictions. Top by Δscore:

Variant	Effect	Δscore
8:87872740:T:TA	donor_gain	0.6300
8:87872738:CTT:C	donor_gain	0.4000
8:87872648:C:CA	donor_gain	0.3200
8:87872655:C:T	donor_gain	0.3000
8:87872737:A:AC	donor_gain	0.2900
8:87872738:C:CC	donor_gain	0.2900
8:87873370:C:A	acceptor_gain	0.2700
8:87873369:ACTG:A	acceptor_gain	0.2400
8:87873940:T:TA	donor_gain	0.2200
8:87872644:AGCAC:A	donor_gain	0.2100
8:87872680:A:C	donor_gain	0.2100

AlphaMissense

2570 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:87873369:A:C	S201R	0.995
8:87873369:A:T	S201R	0.995
8:87873371:T:G	S201R	0.995
8:87872949:C:A	W341C	0.988
8:87872949:C:G	W341C	0.988
8:87872951:A:G	W341R	0.986
8:87872951:A:T	W341R	0.986
8:87872969:C:G	D335H	0.986
8:87873276:A:C	F232L	0.986
8:87873276:A:T	F232L	0.986
8:87873278:A:G	F232L	0.986
8:87873404:A:G	W190R	0.986
8:87873404:A:T	W190R	0.986
8:87873578:A:G	W132R	0.983
8:87873578:A:T	W132R	0.983
8:87872968:T:G	D335A	0.982
8:87872796:G:C	F392L	0.981
8:87872796:G:T	F392L	0.981
8:87872798:A:G	F392L	0.981
8:87872955:T:A	R339S	0.981
8:87872955:T:G	R339S	0.981
8:87872968:T:A	D335V	0.980
8:87873576:C:A	W132C	0.980
8:87873576:C:G	W132C	0.980
8:87873249:A:C	N241K	0.979
8:87873249:A:T	N241K	0.979
8:87872868:G:C	F368L	0.978
8:87872868:G:T	F368L	0.978
8:87872870:A:G	F368L	0.978
8:87872967:G:C	D335E	0.978

dbSNP variants (sampled 300 via entrez): RS1000220604 (8:87872142 C>G), RS1000821195 (8:87870915 A>G), RS1000947558 (8:87871655 A>C,T), RS1001237121 (8:87871289 A>G), RS1001504252 (8:87874274 C>G), RS1002630688 (8:87874095 A>C,G), RS1002679986 (8:87874304 T>C), RS1002817398 (8:87870912 T>C), RS1003181574 (8:87875413 C>G), RS1003197420 (8:87871293 G>A,T), RS1004494844 (8:87874930 A>G), RS1004690446 (8:87871772 A>G), RS1005622125 (8:87875792 T>C), RS1005937382 (8:87875430 T>A,C), RS1006089810 (8:87870597 T>C,G)

Disease associations

OMIM: gene MIM:620421 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002765_3	Optic disc area	2.000000e-08
GCST002765_8	Optic disc area	2.000000e-08
GCST004166_15	Nonsyndromic cleft lip with cleft palate	9.000000e-12
GCST009411_13	Optic disc area	2.000000e-08
GCST009462_98	Optic disc size	5.000000e-14
GCST009464_4	Facial morphology	5.000000e-08
GCST010922_5	Hip bone mineral density and total body fat mass (bivariate analysis)	6.000000e-12
GCST012337_18	Nonsyndromic cleft lip with or without cleft palate	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0003959	cleft lip
EFO:0007702	hip bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation	1
CGP 52608	affects binding, increases reaction	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	increases methylation	1
Endosulfan	decreases expression	1
Valproic Acid	increases expression	1
Sodium Selenite	decreases expression	1

Clinical trials (associated diseases)

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