DCAF8L2

Summary

DCAF8L2 (DDB1 and CUL4 associated factor 8 like 2, HGNC:31811) is a protein-coding gene on chromosome Xp21.3, encoding DDB1- and CUL4-associated factor 8-like protein 2 (P0C7V8).

Predicted to be located in nucleus. Predicted to be part of Cul4-RING E3 ubiquitin ligase complex. Predicted to be active in cytoplasm.

Source: NCBI Gene 347442 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 16 total
• MANE Select transcript: NM_001353450

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31811
Approved symbol	DCAF8L2
Name	DDB1 and CUL4 associated factor 8 like 2
Location	Xp21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000189186
Ensembl biotype	protein_coding
Entrez	347442

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000431122, ENST00000451261, ENST00000545306, ENST00000578111, ENST00000580017, ENST00000583068, ENST00000967437

RefSeq mRNA: 3 — MANE Select: NM_001353450 NM_001353448, NM_001353449, NM_001353450

CCDS: CCDS59162

Canonical transcript exons

ENST00000451261 — 5 exons

Exon	Start	End
ENSE00001672413	27746838	27749942
ENSE00001754885	27716088	27716171
ENSE00002685123	27631879	27632000
ENSE00002695506	27590344	27590440
ENSE00002712391	27677836	27677912

Expression profiles

Bgee: expression breadth broad, 23 present calls, max score 84.89.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0582 / max 50.9726, expressed in 6 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195811	0.0252	6
195810	0.0244	3
195812	0.0086	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	84.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.29	gold quality
left testis	UBERON:0004533	83.38	gold quality
testis	UBERON:0000473	80.85	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	66.89	gold quality
bone marrow cell	CL:0002092	57.21	gold quality
upper leg skin	UBERON:0004262	44.11	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
ovary	UBERON:0000992	41.94	gold quality
bone marrow	UBERON:0002371	41.78	gold quality
right ovary	UBERON:0002118	41.63	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
granulocyte	CL:0000094	41.38	silver quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
left ovary	UBERON:0002119	41.09	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
jejunum	UBERON:0002115	40.18	gold quality
sural nerve	UBERON:0015488	40.12	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.93

Regulation

Is transcription factor: no

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), DCAF8L1 (ENSG00000226372)

Protein

Protein identifiers

DDB1- and CUL4-associated factor 8-like protein 2 — P0C7V8 (reviewed: P0C7V8)

Alternative names: WD repeat-containing protein 42C

All UniProt accessions (2): J3QRI4, P0C7V8

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the WD repeat DCAF8 family.

RefSeq proteins (3): NP_001340377, NP_001340378, NP_001340379* (*=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 (16 total): repeat 7, region of interest 3, compositionally biased region 3, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0C7V8-F1	70.63	0.47

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 12 (showing top): LYF1_01, GOCC_TRANSFERASE_COMPLEX, GOCC_CUL4_RING_E3_UBIQUITIN_LIGASE_COMPLEX, GOCC_CULLIN_RING_UBIQUITIN_LIGASE_COMPLEX, GOCC_UBIQUITIN_LIGASE_COMPLEX, chrXp21, DESCARTES_MAIN_FETAL_ELF3_AGBL2_POSITIVE_CELLS, GOCC_INTRACELLULAR_PROTEIN_CONTAINING_COMPLEX, GSE2405_HEAT_KILLED_VS_LIVE_A_PHAGOCYTOPHILUM_STIM_NEUTROPHIL_24H_UP, GSE22601_DOUBLE_NEGATIVE_VS_DOUBLE_POSITIVE_THYMOCYTE_UP, GSE22601_IMMATURE_CD4_SINGLE_POSITIVE_VS_DOUBLE_POSITIVE_THYMOCYTE_UP, GSE16385_UNTREATED_VS_12H_ROSIGLITAZONE_TREATED_MACROPHAGE_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

310 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCAF8L2	SPATA31A6	Q5VVP1	544
DCAF8L2	DCAF12L2	Q5VW00	543
DCAF8L2	DCAF12L1	Q5VU92	474
DCAF8L2	SPATA31D1	Q6ZQQ2	434
DCAF8L2	FAM151A	Q8WW52	399
DCAF8L2	DPCD	Q9BVM2	399
DCAF8L2	SPNS3	Q6ZMD2	370
DCAF8L2	CCDC180	Q9P1Z9	370
DCAF8L2	A0A087WV05	A0A087WV05	367
DCAF8L2	CEP85	Q6P2H3	353
DCAF8L2	TOP6BL	Q8N6T0	351
DCAF8L2	WSCD2	Q2TBF2	351
DCAF8L2	CHIC1	Q5VXU3	336
DCAF8L2	PYROXD1	Q8WU10	324
DCAF8L2	BEND4	Q6ZU67	321

IntAct

5 interactions, top by confidence:

A	B	Type	Score
DCAF8L2	VASP	psi-mi:“MI:0915”(physical association)	0.400
DCAF8L2	POLR3D	psi-mi:“MI:0914”(association)	0.350
DCAF8L2	KCNN4	psi-mi:“MI:0914”(association)	0.350
DCAF8L2	TCP1	psi-mi:“MI:0914”(association)	0.350

BioGRID (198): VASP (Proximity Label-MS), MYO5B (Affinity Capture-MS), TRPC4AP (Affinity Capture-MS), POLR3D (Affinity Capture-MS), ACAD11 (Affinity Capture-MS), CUL4A (Affinity Capture-MS), CUL4B (Affinity Capture-MS), TCP1 (Affinity Capture-MS), DDB1 (Affinity Capture-MS), TSPYL4 (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT7 (Affinity Capture-MS), MTPAP (Affinity Capture-MS), MICU1 (Affinity Capture-MS), LEPREL2 (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, A1CU75, A1DNV8, A3LWH8, A5DAQ7, A7TL17, B0Y8S0, Q0CSP9, Q0UYV9, Q12510, Q1E6Q0, Q2HHH2, Q2UUT4, Q4WLU1, Q59S45, Q5B6U3, Q6BKH9, Q6C0U2, Q6CB13, Q6CT00, Q6FQU2, Q75BS7, Q7S1H9, Q58WW2, Q5R9B8, Q80ZK9, Q8N5D0, Q9DC22, A5DWF4, O74184, Q23256, Q9C1X1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1763 predictions. Top by Δscore:

Variant	Effect	Δscore
X:27656304:A:T	donor_gain	1.0000
X:27590439:TGGT:T	donor_loss	0.9900
X:27590441:G:C	donor_loss	0.9900
X:27590441:G:GG	donor_gain	0.9900
X:27590442:T:G	donor_loss	0.9900
X:27656101:GGAGA:G	donor_gain	0.9900
X:27677909:GGAG:G	donor_gain	0.9900
X:27677910:G:GT	donor_gain	0.9900
X:27677835:GATGT:G	acceptor_gain	0.9800
X:27679400:GGA:G	donor_gain	0.9800
X:27679401:GAG:G	donor_gain	0.9800
X:27746835:CAGAG:C	acceptor_gain	0.9800
X:27605453:ATTTG:A	acceptor_gain	0.9700
X:27677835:GAT:G	acceptor_gain	0.9700
X:27746834:CCAGA:C	acceptor_gain	0.9700
X:27746836:AGAGC:A	acceptor_gain	0.9700
X:27591761:A:T	donor_gain	0.9600
X:27656305:GA:G	donor_gain	0.9600
X:27663335:A:G	acceptor_gain	0.9600
X:27676986:G:GT	donor_gain	0.9600
X:27677834:A:AG	acceptor_gain	0.9600
X:27677835:G:GG	acceptor_gain	0.9600
X:27684107:ACT:A	acceptor_gain	0.9600
X:27746837:GA:G	acceptor_gain	0.9600
X:27590439:TG:T	donor_gain	0.9500
X:27590440:GG:G	donor_gain	0.9500
X:27605453:ATTT:A	acceptor_gain	0.9500
X:27658103:T:A	acceptor_gain	0.9500
X:27746836:A:AG	acceptor_gain	0.9500
X:27746837:G:C	acceptor_gain	0.9500

AlphaMissense

4201 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:27748075:T:G	Y394D	0.997
X:27748086:G:C	R397S	0.996
X:27748086:G:T	R397S	0.996
X:27748213:A:C	S440R	0.996
X:27748215:C:A	S440R	0.996
X:27748215:C:G	S440R	0.996
X:27747606:C:A	N237K	0.995
X:27747606:C:G	N237K	0.995
X:27747658:T:A	W255R	0.995
X:27747658:T:C	W255R	0.995
X:27747730:T:C	F279L	0.995
X:27747731:T:C	F279S	0.995
X:27747732:C:A	F279L	0.995
X:27747732:C:G	F279L	0.995
X:27748079:A:C	D395A	0.995
X:27748205:T:C	L437P	0.995
X:27748040:T:C	F382S	0.994
X:27748079:A:G	D395G	0.994
X:27748354:A:C	S487R	0.994
X:27748356:C:A	S487R	0.994
X:27748356:C:G	S487R	0.994
X:27747664:T:A	W257R	0.993
X:27747664:T:C	W257R	0.993
X:27747788:G:C	R298P	0.993
X:27747896:T:C	F334S	0.993
X:27747923:T:A	V343D	0.993
X:27747602:T:C	F236S	0.992
X:27747761:C:A	A289D	0.992
X:27748079:A:T	D395V	0.992
X:27748085:G:C	R397T	0.992

dbSNP variants (sampled 300 via entrez): RS1000019018 (X:27538023 A>C), RS1000019202 (X:27743630 A>G), RS1000024479 (X:27591292 A>T), RS1000040265 (X:27484073 C>G,T), RS1000050763 (X:27660080 C>T), RS1000072543 (X:27635074 G>A), RS1000087275 (X:27601995 G>T), RS1000097756 (X:27676369 A>C), RS1000102648 (X:27538072 C>G), RS1000134101 (X:27583325 A>G), RS1000151232 (X:27537774 G>C), RS1000154468 (X:27484775 T>G), RS1000161399 (X:27739013 C>A,G), RS1000208493 (X:27651431 T>C), RS1000226584 (X:27583307 T>C)

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

0 associations (top):

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	decreases methylation	1
bisphenol S	increases methylation	1
Leflunomide	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases methylation	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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