DCAF12L2

Summary

DCAF12L2 (DDB1 and CUL4 associated factor 12 like 2, HGNC:32950) is a protein-coding gene on chromosome Xq25, encoding DDB1- and CUL4-associated factor 12-like protein 2 (Q5VW00).

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 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 9. However, the CDS of this intronless gene remains intact, it is conserved in other mammalian species, it is known to be transcribed, and it is therefore thought to encode a functional protein.

Source: NCBI Gene 340578 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 66 total
• Cancer driver (intOGen): activating (oncogene-like) across 4 cancer types
• MANE Select transcript: NM_001013628

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32950
Approved symbol	DCAF12L2
Name	DDB1 and CUL4 associated factor 12 like 2
Location	Xq25
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000198354
Ensembl biotype	protein_coding
Entrez	340578

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000360028

RefSeq mRNA: 1 — MANE Select: NM_001013628 NM_001013628

CCDS: CCDS43991

Canonical transcript exons

ENST00000360028 — 1 exons

Exon	Start	End
ENSE00001421022	126163499	126166289

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 87.19.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6633 / max 111.1441, expressed in 268 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200422	0.5059	242
200421	0.1574	63

Top tissues by expression

237 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	87.19	gold quality
corpus epididymis	UBERON:0004359	83.37	gold quality
cauda epididymis	UBERON:0004360	77.81	gold quality
ventricular zone	UBERON:0003053	71.82	gold quality
cortical plate	UBERON:0005343	70.86	gold quality
prefrontal cortex	UBERON:0000451	67.42	gold quality
right testis	UBERON:0004534	67.35	gold quality
hypothalamus	UBERON:0001898	66.75	gold quality
left uterine tube	UBERON:0001303	66.65	gold quality
testis	UBERON:0000473	66.31	gold quality
ganglionic eminence	UBERON:0004023	65.87	gold quality
left testis	UBERON:0004533	65.50	gold quality
smooth muscle tissue	UBERON:0001135	65.15	gold quality
caput epididymis	UBERON:0004358	65.06	gold quality
cartilage tissue	UBERON:0002418	63.43	silver quality
Brodmann (1909) area 9	UBERON:0013540	62.28	gold quality
body of uterus	UBERON:0009853	62.19	gold quality
anterior cingulate cortex	UBERON:0009835	61.87	gold quality
pancreatic ductal cell	CL:0002079	61.61	silver quality
fallopian tube	UBERON:0003889	61.15	gold quality
right ovary	UBERON:0002118	61.07	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	60.43	gold quality
endothelial cell	CL:0000115	60.17	gold quality
neocortex	UBERON:0001950	60.04	gold quality
frontal cortex	UBERON:0001870	59.52	gold quality
left ovary	UBERON:0002119	59.25	gold quality
ovary	UBERON:0000992	58.74	gold quality
calcaneal tendon	UBERON:0003701	58.32	gold quality
seminal vesicle	UBERON:0000998	57.93	gold quality
nucleus accumbens	UBERON:0001882	57.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting DCAF12L2, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-4325	99.49	72.20	1342

Literature-anchored findings (GeneRIF, showing 1)

• Functionally characterizes other DDB1- and CUL4-associated factors, including the DCAF12 factor which most closely resembles the product of this gene. (PMID:16949367)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dcaf12l1	ENSMUSG00000045284
mus_musculus	Dcaf12l2	ENSMUSG00000050926
rattus_norvegicus	Dcaf12l1	ENSRNOG00000023458
rattus_norvegicus	Dcaf12l2	ENSRNOG00000031533

Paralogs (2): DCAF12 (ENSG00000198876), DCAF12L1 (ENSG00000198889)

Protein

Protein identifiers

DDB1- and CUL4-associated factor 12-like protein 2 — Q5VW00 (reviewed: Q5VW00)

Alternative names: WD repeat-containing protein 40C

All UniProt accessions (1): Q5VW00

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the WD repeat DCAF12 family.

RefSeq proteins (1): NP_001013650* (*=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
IPR051191	DCAF12	Family
IPR056151	Beta-prop_DCAF12	Domain

Pfam: PF23760

UniProt features (11 total): repeat 7, chain 1, sequence variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VW00-F1	80.48	0.53

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 16 (showing top): GOCC_TRANSFERASE_COMPLEX, GOCC_CUL4_RING_E3_UBIQUITIN_LIGASE_COMPLEX, GOCC_CULLIN_RING_UBIQUITIN_LIGASE_COMPLEX, GOCC_UBIQUITIN_LIGASE_COMPLEX, chrXq25, PEDRIOLI_MIR31_TARGETS_DN, GSE14415_TCONV_VS_FOXP3_KO_INDUCED_TREG_UP, GSE13547_WT_VS_ZFX_KO_BCELL_ANTI_IGM_STIM_12H_UP, MIR7110_3P, MIR6835_3P, MIR544B, MIR3137, GSE12003_4D_VS_8D_CULTURE_MIR223_KO_BM_PROGENITOR_UP, GOCC_INTRACELLULAR_PROTEIN_CONTAINING_COMPLEX, GSE6259_33D1_POS_VS_DEC205_POS_SPLENIC_DC_UP

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

332 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCAF12L2	PRSS45P	Q7RTY3	598
DCAF12L2	DCAF8L1	A6NGE4	567
DCAF12L2	DCAF8L2	P0C7V8	543
DCAF12L2	RNF113B	Q8IZP6	475
DCAF12L2	MCTP1	Q6DN14	470
DCAF12L2	CPXCR1	Q8N123	447
DCAF12L2	ZNF157	P51786	418
DCAF12L2	FARP1	Q9Y4F1	402
DCAF12L2	MRGPRX4	Q96LA9	397
DCAF12L2	RNF44	Q7L0R7	395
DCAF12L2	GMPR	P36959	379
DCAF12L2	LONRF3	Q496Y0	378
DCAF12L2	GLT1D1	Q96MS3	372
DCAF12L2	TCEAL9	Q9UHQ7	372
DCAF12L2	KLHL4	Q9C0H6	370

IntAct

13 interactions, top by confidence:

A	B	Type	Score
COPS6	RHOBTB1	psi-mi:“MI:0914”(association)	0.730
CCT2	TXNDC9	psi-mi:“MI:0914”(association)	0.730
CUL4A	COPS2	psi-mi:“MI:0914”(association)	0.640
DCAF12L2	CETN3	psi-mi:“MI:0914”(association)	0.640
CCT3	TXNDC9	psi-mi:“MI:0914”(association)	0.640
CBX6	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
CUL4A	HAX1	psi-mi:“MI:0914”(association)	0.350
COPS6	DDX3X	psi-mi:“MI:0914”(association)	0.350
FGF8	ANKHD1-EIF4EBP3	psi-mi:“MI:0914”(association)	0.350

BioGRID (148): DCAF12L1 (Affinity Capture-MS), RCOR1 (Affinity Capture-MS), RCOR3 (Affinity Capture-MS), LONP1 (Affinity Capture-MS), CETN3 (Affinity Capture-MS), CUL4B (Affinity Capture-MS), CETN2 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), DCAF12L2 (Proximity Label-MS), RCOR1 (Affinity Capture-MS), CETN3 (Affinity Capture-MS), LONP1 (Affinity Capture-MS), DCAF12L1 (Affinity Capture-MS), RCOR3 (Affinity Capture-MS), PFDN2 (Affinity Capture-MS)

ESM2 similar proteins: A2AKB9, A2RRH5, A2RRU4, A2SXS5, A6QM06, O60346, O88559, P30291, P97260, Q08BB3, Q0P5I0, Q12770, Q3B7L5, Q3MHH0, Q3UHE1, Q4R3J7, Q5E9I8, Q5FW06, Q5M9G8, Q5MNU5, Q5QP82, Q5R7H5, Q5T6F0, Q5VW00, Q5ZJL7, Q63ZP7, Q69Z89, Q6AX81, Q6GQT6, Q6NS60, Q6NWH1, Q6P809, Q6ZWB6, Q8AVS9, Q8BGW4, Q8BGZ3, Q8CHE4, Q8NHY2, Q8QZS3, Q8TEB1

Diamond homologs: Q08BB3, Q3MHH0, Q4R3J7, Q5F3R7, Q5T6F0, Q5VU92, Q5VW00, Q63ZP7, Q6AX81, Q6P809, Q8BGW4, Q8BGZ3, Q8CBW4, Q9VGE3, Q9AV81

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 4 cancer types — COAD, GBM, LUAD, PRAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

49 predictions. Top by Δscore:

Variant	Effect	Δscore
X:126164929:C:CT	acceptor_gain	0.5200
X:126164930:A:T	acceptor_gain	0.4300
X:126164929:C:T	acceptor_gain	0.4000
X:126164876:C:CT	donor_gain	0.3800
X:126164771:T:A	donor_gain	0.3500
X:126164978:T:C	donor_gain	0.3500
X:126164872:TGTGC:T	donor_gain	0.3200
X:126165592:C:CT	donor_gain	0.3200
X:126164774:T:TA	donor_gain	0.3100
X:126165591:C:CT	donor_gain	0.3100
X:126164784:T:TA	donor_gain	0.2900
X:126164977:A:AC	donor_gain	0.2900
X:126165597:G:A	donor_gain	0.2900
X:126164877:C:CT	donor_gain	0.2800
X:126164829:C:T	donor_gain	0.2700
X:126164859:G:C	donor_gain	0.2600
X:126164728:C:CA	donor_gain	0.2500
X:126165039:A:AT	acceptor_gain	0.2500
X:126165040:T:TT	acceptor_gain	0.2500
X:126164956:C:T	acceptor_gain	0.2400
X:126165216:CCTCG:C	donor_gain	0.2400
X:126164800:A:C	acceptor_gain	0.2300
X:126164827:G:A	donor_gain	0.2300
X:126164833:A:C	donor_gain	0.2300
X:126164867:ACG:A	donor_gain	0.2300
X:126164868:CGC:C	donor_gain	0.2300
X:126165774:G:A	donor_gain	0.2300
X:126164536:A:C	donor_gain	0.2200
X:126164857:CAGCG:C	donor_gain	0.2200
X:126164858:AGCGA:A	donor_gain	0.2200

AlphaMissense

2983 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:126165612:A:G	W105R	0.999
X:126165612:A:T	W105R	0.999
X:126165295:G:C	S210R	0.998
X:126165295:G:T	S210R	0.998
X:126165297:T:G	S210R	0.998
X:126165622:G:C	F101L	0.998
X:126165622:G:T	F101L	0.998
X:126165624:A:G	F101L	0.998
X:126165267:A:G	W220R	0.997
X:126165267:A:T	W220R	0.997
X:126165321:A:G	W202R	0.997
X:126165321:A:T	W202R	0.997
X:126165610:C:A	W105C	0.997
X:126165610:C:G	W105C	0.997
X:126164541:A:G	W462R	0.996
X:126164541:A:T	W462R	0.996
X:126164954:C:T	G324D	0.996
X:126165431:G:T	A165D	0.996
X:126164862:A:G	S355P	0.995
X:126165396:A:C	Y177D	0.995
X:126165584:C:T	G114D	0.995
X:126165628:C:A	K99N	0.995
X:126165628:C:G	K99N	0.995
X:126164960:G:T	A322D	0.994
X:126165060:A:G	W289R	0.994
X:126165060:A:T	W289R	0.994
X:126165577:C:A	K116N	0.994
X:126165577:C:G	K116N	0.994
X:126165611:C:G	W105S	0.994
X:126164558:C:T	G456E	0.993

dbSNP variants (sampled 300 via entrez): RS1002096068 (X:126164051 T>C), RS1002695991 (X:126166531 T>A), RS1003179191 (X:126166839 T>G), RS1003824887 (X:126167745 GA>G,GAA), RS1003960250 (X:126166499 G>A), RS1005954983 (X:126163429 C>G,T), RS1006545114 (X:126165711 C>A,G), RS1006649059 (X:126163771 C>T), RS1007006106 (X:126163101 T>G), RS1009635549 (X:126165526 G>A), RS1010670001 (X:126167798 G>T), RS1011402257 (X:126167472 C>T), RS1012042297 (X:126166604 C>G,T), RS10126452 (X:126165484 G>C,T), RS1013076599 (X:126165746 A>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

3 associations (top):

Study	Trait	p-value
GCST008155_6	Waist-hip ratio	6.000000e-06
GCST008159_61	Waist-to-hip ratio adjusted for BMI	5.000000e-06
GCST012466_6	Autism spectrum disorder	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004343	waist-hip ratio
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, decreases expression	3
Panobinostat	affects cotreatment, decreases expression	2
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Copper	affects cotreatment, decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Mercuric Chloride	affects cotreatment, increases expression	1
Methotrexate	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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