VCF2

Summary

VCF2 (VCP nuclear cofactor family member 2, HGNC:25085) is a protein-coding gene on chromosome Xp11.21, encoding Protein VCF2 (Q5XKR9). It is a selective cancer dependency (DepMap: 14.0% of cell lines).

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 34 total
• Cancer dependency (DepMap): dependent in 14.0% of screened cell lines
• MANE Select transcript: NM_001166701

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25085
Approved symbol	VCF2
Name	VCP nuclear cofactor family member 2
Location	Xp11.21
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20434
Ensembl gene	ENSG00000182518
Ensembl biotype	protein_coding
OMIM	301141
Entrez	90736

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000332132, ENST00000358460, ENST00000425133, ENST00000472571, ENST00000477847, ENST00000478918, ENST00000489298, ENST00000685693, ENST00000874380

RefSeq mRNA: 7 — MANE Select: NM_001166701 NM_001166699, NM_001166700, NM_001166701, NM_001166702, NM_001166703, NM_001166704, NM_138362

CCDS: CCDS35305, CCDS55422, CCDS55423, CCDS55424, CCDS55425, CCDS55426, CCDS94615

Canonical transcript exons

ENST00000685693 — 3 exons

Exon	Start	End
ENSE00003651792	55159129	55159228
ENSE00003926960	55161137	55161185
ENSE00003938170	55143102	55146311

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 94.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.7505 / max 157.8898, expressed in 1759 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199413	5.9191	1658
199412	3.7806	1581
199410	0.0507	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	94.67	gold quality
cortical plate	UBERON:0005343	91.31	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.10	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.62	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.18	gold quality
islet of Langerhans	UBERON:0000006	88.64	gold quality
spinal cord	UBERON:0002240	88.30	gold quality
ganglionic eminence	UBERON:0004023	88.00	gold quality
hypothalamus	UBERON:0001898	87.76	gold quality
anterior cingulate cortex	UBERON:0009835	87.48	gold quality
ventricular zone	UBERON:0003053	87.46	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.38	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.22	gold quality
smooth muscle tissue	UBERON:0001135	87.17	gold quality
prefrontal cortex	UBERON:0000451	87.16	gold quality
amygdala	UBERON:0001876	87.16	gold quality
right adrenal gland	UBERON:0001233	87.01	gold quality
right adrenal gland cortex	UBERON:0035827	86.93	gold quality
right frontal lobe	UBERON:0002810	86.81	gold quality
lower esophagus	UBERON:0013473	86.58	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.57	gold quality
rectum	UBERON:0001052	86.55	gold quality
left adrenal gland	UBERON:0001234	86.30	gold quality
putamen	UBERON:0001874	86.24	gold quality
adult mammalian kidney	UBERON:0000082	86.21	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.18	gold quality
gastrocnemius	UBERON:0001388	86.16	gold quality
muscle of leg	UBERON:0001383	86.04	gold quality
left adrenal gland cortex	UBERON:0035825	85.95	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.90
E-GEOD-83139	no	2.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting VCF2, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-6760-5P	98.87	66.73	1515

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 14.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• The FAM104 proteins VCF1/2 promote the nuclear localization of p97/VCP. (PMID:37713320)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Vcf1	ENSMUSG00000041629
rattus_norvegicus	Vcf2	ENSRNOG00000049908

Protein

Protein identifiers

Protein VCF2 — Q5XKR9 (reviewed: Q5XKR9)

Alternative names: VCP nuclear cofactor family member 2

All UniProt accessions (2): Q5XKR9, A0A8I5KUH0

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the VCF family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q5XKR9-1	1	yes
Q5XKR9-2	2
Q5XKR9-3	3
Q5XKR9-4	4
Q5XKR9-5	5
Q5XKR9-6	6

RefSeq proteins (7): NP_001160171, NP_001160172, NP_001160173, NP_001160174, NP_001160175, NP_001160176, NP_612371 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029222	VCF1/2-like	Family

Pfam: PF15434

UniProt features (11 total): splice variant 5, compositionally biased region 2, chain 1, region of interest 1, sequence conflict 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5XKR9-F1	61.07	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 51 (showing top): WANG_CLIM2_TARGETS_UP, GCM_NF2, CHANG_IMMORTALIZED_BY_HPV31_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, chrXp11, ZNF618_TARGET_GENES, ZSCAN31_TARGET_GENES, MIR302C_5P, MIR548AA_MIR548AP_3P_MIR548T_3P, MIR8068, MIR6127, MIR4700_5P, MIR3685, MIR6129, MIR6133

GO Biological Process (0):

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

292 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VCF2	ZNF717	Q9BY31	579
VCF2	PAGE2B	Q5JRK9	543
VCF2	A0A3B3IRQ3	A0A3B3IRQ3	541
VCF2	FRG2C	A6NGY1	515
VCF2	ANKRD36C	Q5JPF3	471
VCF2	KRTAP4-8	Q9BYQ9	447
VCF2	SLC35G6	P0C7Q6	447
VCF2	OR4C5	Q8NGB2	444
VCF2	MTRNR2L10	P0CJ77	431
VCF2	OR2T35	Q8NGX2	417
VCF2	POTEC	B2RU33	400
VCF2	KRTAP4-3	Q9BYR4	397
VCF2	FRG1	Q14331	396
VCF2	HYDIN	Q4G0P3	395
VCF2	KRTAP9-2	Q9BYQ4	394
VCF2	POTEM	A6NI47	394

IntAct

1 interactions, top by confidence:

BioGRID (3): FAM104B (Two-hybrid), FAM104B (Protein-peptide), FAM104B (Affinity Capture-RNA)

ESM2 similar proteins: A6NGY3, A6ZT44, A8MT66, A8MTZ7, B3LMW8, C7GKF3, D3UET8, O89085, P03238, P0CT86, P21739, P21740, P30927, P33199, P33483, P38305, P38839, P60167, Q05105, Q08270, Q12379, Q1KN14, Q1KN16, Q1KN19, Q1KN23, Q1X6X9, Q1X6Y3, Q1X6Y4, Q1X6Y5, Q1X6Y7, Q1X6Z0, Q1X6Z1, Q1X6Z2, Q1X6Z3, Q2KIJ1, Q4R6N4, Q4V7B4, Q5BL73, Q5XKR9, Q77M19

Diamond homologs: Q5XKR9, Q969W3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

561 predictions. Top by Δscore:

Variant	Effect	Δscore
X:55146307:GAAAA:G	acceptor_gain	1.0000
X:55146308:AAAA:A	acceptor_gain	1.0000
X:55146309:AAA:A	acceptor_gain	1.0000
X:55146310:AA:A	acceptor_gain	1.0000
X:55146311:AC:A	acceptor_loss	1.0000
X:55146312:C:CC	acceptor_gain	1.0000
X:55146312:CT:C	acceptor_loss	1.0000
X:55146313:T:G	acceptor_loss	1.0000
X:55159120:A:AC	donor_gain	1.0000
X:55159121:C:CC	donor_gain	1.0000
X:55159168:ATT:A	donor_gain	1.0000
X:55159170:T:TA	donor_gain	1.0000
X:55161133:TTA:T	donor_loss	1.0000
X:55161134:TA:T	donor_loss	1.0000
X:55161135:A:AC	donor_gain	1.0000
X:55161136:C:CC	donor_gain	1.0000
X:55161136:CCGTA:C	donor_gain	1.0000
X:55159226:TTC:T	acceptor_gain	0.9900
X:55159229:C:CC	acceptor_gain	0.9900
X:55146179:ACC:A	donor_gain	0.9800
X:55146180:CCC:C	donor_gain	0.9800
X:55159116:CCATA:C	donor_gain	0.9800
X:55159130:T:TA	donor_gain	0.9800
X:55159226:TTCCT:T	acceptor_loss	0.9800
X:55159227:TC:T	acceptor_gain	0.9800
X:55159228:CC:C	acceptor_gain	0.9800
X:55159228:CCTGA:C	acceptor_loss	0.9800
X:55159229:CTGA:C	acceptor_loss	0.9800
X:55159230:T:C	acceptor_loss	0.9800
X:55161136:CCG:C	donor_gain	0.9800

AlphaMissense

772 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:55159225:T:A	K8N	0.821
X:55159225:T:G	K8N	0.821
X:55159222:T:A	R9S	0.807
X:55159222:T:G	R9S	0.807
X:55159226:T:A	K8I	0.769
X:55159216:T:A	R11S	0.750
X:55159216:T:G	R11S	0.750
X:55159174:T:A	K25N	0.736
X:55159174:T:G	K25N	0.736
X:55159171:C:A	R26S	0.723
X:55159171:C:G	R26S	0.723
X:55159226:T:G	K8T	0.713
X:55146309:A:C	F41L	0.707
X:55146309:A:T	F41L	0.707
X:55146311:A:G	F41L	0.707
X:55159219:T:A	R10S	0.669
X:55159219:T:G	R10S	0.669
X:55159227:T:C	K8E	0.654
X:55159150:A:C	F33L	0.638
X:55159150:A:T	F33L	0.638
X:55159152:A:G	F33L	0.638
X:55159223:C:G	R9T	0.600
X:55146192:G:C	F80L	0.579
X:55146192:G:T	F80L	0.579
X:55146194:A:G	F80L	0.579
X:55159165:C:A	K28N	0.573
X:55159165:C:G	K28N	0.573
X:55161137:C:G	R7P	0.573
X:55159175:T:A	K25I	0.572

dbSNP variants (sampled 300 via entrez): RS1000010774 (X:55157380 A>G), RS1000466323 (X:55159733 A>G), RS1001335899 (X:55147406 C>T), RS1001628842 (X:55159938 A>G), RS1001682674 (X:55159361 T>A), RS1001806673 (X:55147995 T>C), RS1002196341 (X:55160017 C>T), RS1002226051 (X:55160449 G>A,C), RS1002549326 (X:55150481 C>T), RS1002564394 (X:55162522 CAGTT>C), RS1002919327 (X:55145166 T>C,G), RS1003252781 (X:55143057 G>A,T), RS1003301098 (X:55161904 A>G), RS1003339953 (X:55152927 C>G), RS1003416058 (X:55150080 A>G)

Disease associations

OMIM: gene MIM:301141 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003983_18	Male-pattern baldness	8.000000e-13
GCST006661_51	Male-pattern baldness	5.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
methylmercuric chloride	decreases expression	1
arsenite	affects binding, increases reaction	1
perfluorooctanoic acid	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
perfluorooctane sulfonic acid	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Acetaminophen	decreases expression	1
Vehicle Emissions	decreases reaction, increases expression	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Lithium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases reaction, increases expression	1

Clinical trials (associated diseases)

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