VCF1

Summary

VCF1 (VCP nuclear cofactor family member 1, HGNC:25918) is a protein-coding gene on chromosome 17q25.1, encoding Protein VCF1 (Q969W3).

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 68 total
• MANE Select transcript: NM_001098832

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25918
Approved symbol	VCF1
Name	VCP nuclear cofactor family member 1
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14775
Ensembl gene	ENSG00000133193
Ensembl biotype	protein_coding
OMIM	621109
Entrez	84923

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000403627, ENST00000405159, ENST00000579872, ENST00000580032, ENST00000581110, ENST00000583024, ENST00000583178, ENST00000923017, ENST00000947727

RefSeq mRNA: 5 — MANE Select: NM_001098832 NM_001098832, NM_001289410, NM_001289411, NM_001289412, NM_032837

CCDS: CCDS11693, CCDS45766, CCDS74143, CCDS74144

Canonical transcript exons

ENST00000405159 — 4 exons

Exon	Start	End
ENSE00002716429	73232086	73232394
ENSE00003623436	73212678	73212740
ENSE00003680637	73227165	73227264
ENSE00003928165	73207365	73209768

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 99.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.5455 / max 894.9366, expressed in 1824 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167899	40.0593	1822
167898	1.2761	645
167897	0.9603	534
167893	0.1904	74
167895	0.0214	4
167894	0.0212	11
167896	0.0169	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.60	gold quality
left testis	UBERON:0004533	97.90	gold quality
right testis	UBERON:0004534	97.66	gold quality
epithelial cell of pancreas	CL:0000083	97.16	gold quality
pancreatic ductal cell	CL:0002079	96.77	gold quality
testis	UBERON:0000473	96.24	gold quality
trabecular bone tissue	UBERON:0002483	94.14	gold quality
ileal mucosa	UBERON:0000331	93.37	gold quality
blood	UBERON:0000178	92.99	gold quality
bone marrow	UBERON:0002371	92.07	gold quality
upper arm skin	UBERON:0004263	91.80	gold quality
monocyte	CL:0000576	91.36	gold quality
leukocyte	CL:0000738	91.23	gold quality
gingival epithelium	UBERON:0001949	91.09	gold quality
tibialis anterior	UBERON:0001385	90.69	gold quality
oviduct epithelium	UBERON:0004804	90.49	gold quality
parotid gland	UBERON:0001831	90.41	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.98	gold quality
upper leg skin	UBERON:0004262	89.79	gold quality
gingiva	UBERON:0001828	89.70	gold quality
bone marrow cell	CL:0002092	88.80	gold quality
adult organism	UBERON:0007023	88.56	gold quality
nipple	UBERON:0002030	88.45	gold quality
endothelial cell	CL:0000115	88.13	gold quality
granulocyte	CL:0000094	88.08	gold quality
nasal cavity epithelium	UBERON:0005384	87.99	silver quality
skin of hip	UBERON:0001554	87.92	gold quality
calcaneal tendon	UBERON:0003701	87.57	gold quality
placenta	UBERON:0001987	87.49	gold quality
penis	UBERON:0000989	87.45	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	28.58
E-MTAB-10042	yes	25.83
E-HCAD-10	no	1.94
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

127 targeting VCF1, 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-6873-3P	100.00	71.42	2626
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-186-5P	99.99	70.83	3707
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-607	99.97	73.62	5593
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-30A-3P	99.87	69.74	2928

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
rattus_norvegicus	Vcf1	ENSRNOG00000002851
drosophila_melanogaster	CG31898	FBGN0051898

Protein

Protein identifiers

Protein VCF1 — Q969W3 (reviewed: Q969W3)

Alternative names: VCP nuclear cofactor family member 1

All UniProt accessions (4): Q969W3, J3KSI9, J3KT52, J3KT76

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the VCF family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q969W3-1	1	yes
Q969W3-2	2

RefSeq proteins (5): NP_001092302, NP_001276339, NP_001276340, NP_001276341, NP_116226 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029222	VCF1/2-like	Family

Pfam: PF15434

UniProt features (8 total): compositionally biased region 4, chain 1, region of interest 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969W3-F1	62.96	0.10

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 4

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 130 (showing top): RNGTGGGC_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GTGCCTT_MIR506, ATTCTTT_MIR186, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, TGCCTTA_MIR124A, ALCALA_APOPTOSIS, SCGGAAGY_ELK1_02, YOSHIMURA_MAPK8_TARGETS_DN, ATGAAGG_MIR205, GAGCCAG_MIR149, FEV_TARGET_GENES, IRF5_TARGET_GENES, NCOA2_TARGET_GENES, NFKBIA_TARGET_GENES

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

334 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VCF1	CCDC127	Q96BQ5	846
VCF1	CNOT10	Q9H9A5	775
VCF1	TADA2B	Q86TJ2	747
VCF1	MTO1	Q9Y2Z2	744
VCF1	SUPT7L	O94864	733
VCF1	ASB7	Q9H672	709
VCF1	XPNPEP1	Q9NQW7	633
VCF1	AARS1	P49588	622
VCF1	CSNK2A2	P19784	520
VCF1	SHISAL2A	Q6UWV7	520
VCF1	MTNAP1	Q9BSJ5	400
VCF1	PRXL2B	Q8TBF2	375
VCF1	ASB10	Q8WXI3	359
VCF1	RETREG2	Q8NC44	346
VCF1	AARS2	Q5JTZ9	337

IntAct

26 interactions, top by confidence:

A	B	Type	Score
UBXN2B	VCP	psi-mi:“MI:0914”(association)	0.910
VCP	VCF1	psi-mi:“MI:0915”(physical association)	0.850
VCF1	VCP	psi-mi:“MI:0915”(physical association)	0.850
UBXN2B	VCF1	psi-mi:“MI:0915”(physical association)	0.670
VCF1	SERPINH1	psi-mi:“MI:0915”(physical association)	0.560
VCF1	PRKACA	psi-mi:“MI:0915”(physical association)	0.560
VCF1	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
VCP	PRKN	psi-mi:“MI:0914”(association)	0.530
UBXN6	POR	psi-mi:“MI:0914”(association)	0.350
NSFL1C	UBXN2A	psi-mi:“MI:0914”(association)	0.350
VCF1	VCP	psi-mi:“MI:0915”(physical association)	0.000
UBXN2B	VCF1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (24): FAM104A (Two-hybrid), FAM104A (Affinity Capture-RNA), FAM104A (Affinity Capture-RNA), FAM104A (Affinity Capture-MS), FAM104A (Affinity Capture-MS), FAM104A (Affinity Capture-MS), NSFL1C (Affinity Capture-Western), FAM104A (Affinity Capture-Western), FAM104A (Affinity Capture-MS), FAM104A (Affinity Capture-MS), FAM104A (Affinity Capture-MS), FAM104A (Affinity Capture-MS), FAM104A (Affinity Capture-MS), FAM104A (Affinity Capture-MS), VCP (Two-hybrid)

ESM2 similar proteins: A0A2Z4LIS9, A6NI87, D4AAA5, F1N8V3, O15054, O35182, O75638, O76081, O93343, O94850, P03327, P06936, P0C6A0, P0DOD6, P15863, P24097, P79348, Q00587, Q00731, Q15583, Q1ZZU3, Q3U133, Q5GJ75, Q5IS58, Q5NCY0, Q5R7P6, Q5SSG4, Q5VV16, Q66HC8, Q68FX5, Q6K1E7, Q6NUN9, Q6UYE1, Q7TPK6, Q80UE6, Q80WJ1, Q86UU5, Q8HYS5, Q8K3M5, Q8N5Z5

Diamond homologs: Q5XKR9, Q969W3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 10 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	5	26.1×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1191 predictions. Top by Δscore:

Variant	Effect	Δscore
17:73209764:GAAGA:G	acceptor_gain	1.0000
17:73209766:AGA:A	acceptor_gain	1.0000
17:73209767:GA:G	acceptor_gain	1.0000
17:73209769:C:CC	acceptor_gain	1.0000
17:73227159:TCCTA:T	donor_loss	1.0000
17:73227160:CCTAC:C	donor_loss	1.0000
17:73227161:CTA:C	donor_loss	1.0000
17:73227162:TACC:T	donor_loss	1.0000
17:73227163:ACCT:A	donor_loss	1.0000
17:73227164:C:CG	donor_loss	1.0000
17:73227164:CCT:C	donor_gain	1.0000
17:73227207:T:TA	donor_gain	1.0000
17:73209765:AAGA:A	acceptor_gain	0.9900
17:73227159:T:TA	donor_gain	0.9900
17:73227261:TTTC:T	acceptor_gain	0.9900
17:73227262:TTCC:T	acceptor_loss	0.9900
17:73227263:TC:T	acceptor_gain	0.9900
17:73227263:TCC:T	acceptor_loss	0.9900
17:73227264:CC:C	acceptor_gain	0.9900
17:73227264:CCTGA:C	acceptor_loss	0.9900
17:73227265:CTGA:C	acceptor_loss	0.9900
17:73227266:T:C	acceptor_loss	0.9900
17:73227277:C:CT	acceptor_gain	0.9900
17:73232077:C:A	donor_gain	0.9900
17:73232080:TCTCA:T	donor_loss	0.9900
17:73232081:CTCA:C	donor_loss	0.9900
17:73232082:TCA:T	donor_loss	0.9900
17:73232083:CAC:C	donor_loss	0.9900
17:73232084:ACCT:A	donor_loss	0.9900
17:73232085:C:T	donor_loss	0.9900

AlphaMissense

1357 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:73209565:G:C	F175L	0.994
17:73209565:G:T	F175L	0.994
17:73209567:A:G	F175L	0.994
17:73209593:A:C	I166S	0.993
17:73209593:A:G	I166T	0.993
17:73209581:A:G	L170P	0.991
17:73209593:A:T	I166N	0.991
17:73209559:G:C	S177R	0.990
17:73209559:G:T	S177R	0.990
17:73209561:T:G	S177R	0.990
17:73209573:C:G	A173P	0.990
17:73209568:G:C	H174Q	0.989
17:73209568:G:T	H174Q	0.989
17:73209570:G:C	H174D	0.989
17:73209581:A:T	L170Q	0.989
17:73209566:A:G	F175S	0.986
17:73209589:G:C	N167K	0.984
17:73209589:G:T	N167K	0.984
17:73209557:A:G	L178P	0.982
17:73227210:T:A	K92N	0.980
17:73227210:T:G	K92N	0.980
17:73209590:T:A	N167I	0.978
17:73227258:C:A	R76S	0.977
17:73227258:C:G	R76S	0.977
17:73209570:G:T	H174N	0.976
17:73209566:A:C	F175C	0.974
17:73209603:A:C	Y163D	0.972
17:73227211:T:A	K92I	0.969
17:73209569:T:C	H174R	0.968
17:73227261:T:A	K75N	0.966

dbSNP variants (sampled 300 via entrez): RS1000025710 (17:73212974 G>A), RS1000125861 (17:73212338 A>G), RS1000215245 (17:73207469 C>G,T), RS1000415579 (17:73216427 G>A), RS1000668135 (17:73228844 C>T), RS1000929382 (17:73231396 C>T), RS1000992357 (17:73221456 C>G), RS1000999493 (17:73224190 G>A), RS1001196336 (17:73223713 A>G), RS1001235126 (17:73234254 A>G), RS1001439508 (17:73209510 G>A), RS1001512469 (17:73209137 T>C), RS1001553470 (17:73212625 T>C), RS1001624402 (17:73215817 C>T), RS1001708224 (17:73221110 G>T)

Disease associations

OMIM: gene MIM:621109 | disease phenotypes: MIM:611209

GenCC curated gene-disease

Mondo (1): COG1-congenital disorder of glycosylation (MONDO:0012637)

Orphanet (1): COG1-CDG (Orphanet:263508)

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST90002390_536	Mean corpuscular hemoglobin	6.000000e-15
GCST90002392_26	Mean corpuscular volume	2.000000e-16
GCST90002396_671	Mean reticulocyte volume	3.000000e-22
GCST90002397_585	Mean spheric corpuscular volume	1.000000e-19
GCST90002403_369	Red blood cell count	2.000000e-10
GCST90002404_175	Red cell distribution width	1.000000e-17
GCST90002405_388	Reticulocyte count	9.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count
EFO:0009188	Red cell distribution width
EFO:0007986	reticulocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535756	Congenital disorder of glycosylation, type 2G (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Acrolein	increases expression, increases abundance, affects cotreatment	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Ozone	increases abundance, affects cotreatment, increases expression	1
Smoke	decreases expression	1
Cyclosporine	increases expression	1
Volatile Organic Compounds	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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