FCF1

Summary

FCF1 (FCF1 rRNA-processing protein, HGNC:20220) is a protein-coding gene on chromosome 14q24.3, encoding rRNA-processing protein FCF1 homolog (Q9Y324). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. It is a common-essential gene (DepMap: required in 99.7% of cancer cell lines).

Enables RNA binding activity. Involved in ribosomal small subunit biogenesis. Part of small-subunit processome.

Source: NCBI Gene 51077 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 36 total
• Cancer dependency (DepMap): dependent in 99.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_015962

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20220
Approved symbol	FCF1
Name	FCF1 rRNA-processing protein
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Aliases	CGI-35, Bka, UTP24
Ensembl gene	ENSG00000119616
Ensembl biotype	protein_coding
Entrez	51077

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

ENST00000341162, ENST00000534938, ENST00000553615, ENST00000553673, ENST00000554064, ENST00000554590, ENST00000554973, ENST00000556814

RefSeq mRNA: 2 — MANE Select: NM_015962 NM_001318508, NM_015962

CCDS: CCDS81827, CCDS9832

Canonical transcript exons

ENST00000341162 — 8 exons

Exon	Start	End
ENSE00001374171	74734882	74738620
ENSE00003479813	74713485	74713552
ENSE00003530195	74723272	74723344
ENSE00003569042	74715951	74716099
ENSE00003590242	74713144	74713200
ENSE00003612315	74714872	74714943
ENSE00003632350	74734076	74734170
ENSE00003659076	74732731	74732818

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 95.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.8095 / max 1551.1857, expressed in 1797 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140578	32.8095	1797

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	95.99	gold quality
rectum	UBERON:0001052	93.53	gold quality
monocyte	CL:0000576	93.40	gold quality
amniotic fluid	UBERON:0000173	93.32	gold quality
mononuclear cell	CL:0000842	93.31	gold quality
leukocyte	CL:0000738	93.18	gold quality
islet of Langerhans	UBERON:0000006	93.04	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.90	gold quality
gingival epithelium	UBERON:0001949	92.83	gold quality
stromal cell of endometrium	CL:0002255	92.77	gold quality
calcaneal tendon	UBERON:0003701	92.49	gold quality
palpebral conjunctiva	UBERON:0001812	92.45	gold quality
endometrium	UBERON:0001295	91.77	gold quality
epithelium of nasopharynx	UBERON:0001951	91.62	gold quality
gall bladder	UBERON:0002110	91.59	gold quality
vermiform appendix	UBERON:0001154	91.41	gold quality
descending thoracic aorta	UBERON:0002345	91.10	gold quality
mammary duct	UBERON:0001765	90.99	gold quality
superficial temporal artery	UBERON:0001614	90.86	gold quality
ganglionic eminence	UBERON:0004023	90.78	gold quality
ventricular zone	UBERON:0003053	90.63	gold quality
popliteal artery	UBERON:0002250	90.56	gold quality
tibial artery	UBERON:0007610	90.55	gold quality
hair follicle	UBERON:0002073	90.47	gold quality
right coronary artery	UBERON:0001625	90.30	gold quality
lymph node	UBERON:0000029	90.26	gold quality
gingiva	UBERON:0001828	90.25	gold quality
cortical plate	UBERON:0005343	90.23	gold quality
ovary	UBERON:0000992	90.20	gold quality
aorta	UBERON:0000947	90.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

72 targeting FCF1, 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-4776-3P	100.00	68.73	1340
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-4679	99.76	69.19	1229

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 1)

• hUTP24 inactivation leads to aberrant processing of 18S rRNA 2 nucleotides downstream of the normal A1 cleavage site. (PMID:26237581)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fcf1	ENSDARG00000102333
mus_musculus	Fcf1	ENSMUSG00000021243
rattus_norvegicus	Fcf1	ENSRNOG00000004723
drosophila_melanogaster	Bka	FBGN0010520
caenorhabditis_elegans	F30A10.9	WBGENE00009266

Paralogs (1): UTP23 (ENSG00000147679)

Protein

Protein identifiers

rRNA-processing protein FCF1 homolog — Q9Y324 (reviewed: Q9Y324)

All UniProt accessions (8): Q9Y324, G3V1S4, G3V2M5, G3V3N8, G3V5D2, G3V5L8, G3V5S9, Q4FZ45

UniProt curated annotations — full annotation on UniProt →

Function. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.

Subunit / interactions. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.

Subcellular location. Nucleus. Nucleolus.

Similarity. Belongs to the UTP23/FCF1 family. FCF1 subfamily.

RefSeq proteins (2): NP_001305437, NP_057046* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002716	PIN_dom	Domain
IPR006984	Fcf1/UTP23	Family
IPR029060	PIN-like_dom_sf	Homologous_superfamily
IPR037503	Fcf1_PIN	Domain

Pfam: PF04900

UniProt features (4 total): chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7MQA	ELECTRON MICROSCOPY	2.7
7MQ8	ELECTRON MICROSCOPY	3.6
7MQ9	ELECTRON MICROSCOPY	3.87

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y324-F1	83.59	0.48

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6790901	rRNA modification in the nucleus and cytosol
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol

MSigDB gene sets: 103 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOBP_MATURATION_OF_SSU_RRNA, chr14q24, GOBP_MATURATION_OF_5_8S_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOBP_MATURATION_OF_SSU_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, TIEN_INTESTINE_PROBIOTICS_24HR_UP, CREB_Q3, GOBP_MATURATION_OF_5_8S_RRNA, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, REACTOME_METABOLISM_OF_RNA, GOCC_PRERIBOSOME, GOCC_SMALL_SUBUNIT_PROCESSOME, GOCC_NUCLEOLUS, GOCC_RIBONUCLEOPROTEIN_COMPLEX

GO Biological Process (5): endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000447), endonucleolytic cleavage in 5’-ETS of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000480), ribosomal small subunit biogenesis (GO:0042274), rRNA processing (GO:0006364), ribosome biogenesis (GO:0042254)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (4): nucleoplasm (GO:0005654), nucleolus (GO:0005730), small-subunit processome (GO:0032040), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	2
endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	2
ribonucleoprotein complex biogenesis	2
ribosome biogenesis	2
nuclear lumen	2
maturation of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	1
RNA processing	1
rRNA metabolic process	1
nucleic acid binding	1
binding	1
cellular anatomical structure	1
intracellular membraneless organelle	1
nucleolus	1
preribosome	1
t-UTP complex	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1855 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FCF1	DNTTIP2	Q5QJE6	965
FCF1	FAF1	Q9UNN5	847
FCF1	UTP3	Q9NQZ2	804
FCF1	RCL1	Q9Y2P8	728
FCF1	NOB1	Q9ULX3	727
FCF1	UTP14A	Q9BVJ6	722
FCF1	NOMO2	Q5JPE7	715
FCF1	NOMO3	P69849	713
FCF1	PDCD11	Q14690	708
FCF1	NOMO1	P78421	696
FCF1	BMS1	Q14692	690
FCF1	WDR46	O15213	665
FCF1	HEATR1	Q9H583	665
FCF1	UTP11	Q9Y3A2	628
FCF1	KRR1	Q13601	627

IntAct

50 interactions, top by confidence:

A	B	Type	Score
BCCIP	FCF1	psi-mi:“MI:0915”(physical association)	0.560
SPDYC	FCF1	psi-mi:“MI:0915”(physical association)	0.560
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL18	NOP56	psi-mi:“MI:0914”(association)	0.530
RPL30	RRP8	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
FCF1	MAGEB2	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
SRSF5	CBX6	psi-mi:“MI:0914”(association)	0.530
FCF1	P4HA1	psi-mi:“MI:0915”(physical association)	0.400
FCF1	SULT2B1	psi-mi:“MI:0914”(association)	0.350
SART3	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
DGCR8	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
CNBP	NOP56	psi-mi:“MI:0914”(association)	0.350
GPATCH4	NOP56	psi-mi:“MI:0914”(association)	0.350
RBM4B	ZNF324	psi-mi:“MI:0914”(association)	0.350
CACNA1C	IGLL5	psi-mi:“MI:0914”(association)	0.350
	GTPBP10	psi-mi:“MI:0914”(association)	0.350
PRKRA	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
SURF6	GTPBP10	psi-mi:“MI:0914”(association)	0.350
RPL7A	GTPBP10	psi-mi:“MI:0914”(association)	0.350
SRSF1		psi-mi:“MI:0914”(association)	0.350
FGFBP1		psi-mi:“MI:0914”(association)	0.350
RPL35		psi-mi:“MI:0914”(association)	0.350
RPL31	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
RPL11	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350

BioGRID (140): FCF1 (Affinity Capture-MS), FCF1 (Affinity Capture-MS), FCF1 (Reconstituted Complex), FCF1 (Affinity Capture-MS), FCF1 (Affinity Capture-MS), FCF1 (Affinity Capture-MS), FCF1 (Affinity Capture-MS), FCF1 (Affinity Capture-MS), PPL (Affinity Capture-MS), TREX2 (Affinity Capture-MS), SULT2B1 (Affinity Capture-MS), ENDOU (Affinity Capture-MS), EVPL (Affinity Capture-MS), IVL (Affinity Capture-MS), SERPINB5 (Affinity Capture-MS)

ESM2 similar proteins: A0JN39, A4FV84, B5DGH9, D2K760, D2SW95, D5LHJ0, F4JGR5, O14929, O60832, P11497, P23514, P42932, P50990, P53618, Q05AY2, Q13085, Q1LUA8, Q28559, Q2YDN6, Q32PD0, Q39097, Q3B8M3, Q3ZCI9, Q5M939, Q5R4J9, Q5R922, Q5RAP1, Q5RFQ0, Q5SWU9, Q5XIY6, Q5ZIA5, Q66HV4, Q6DRI1, Q6EE31, Q6P7L9, Q8BY71, Q8IWZ6, Q8IZH2, Q8K2G4, Q9BSC4

Diamond homologs: O13610, O74862, Q05498, Q08DU1, Q32PD0, Q55GM5, Q5RFQ0, Q9CTH6, Q9Y324, Q12339, Q9BRU9, Q9CX11

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Eukaryotic Translation Initiation	5	41.7×	8e-07
Cap-dependent Translation Initiation	5	41.7×	8e-07
SARS-CoV-1 modulates host translation machinery	5	41.7×	8e-07
Peptide chain elongation	11	37.7×	1e-13
Viral mRNA Translation	11	37.7×	1e-13
Eukaryotic Translation Elongation	5	37.6×	1e-06
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	11	37.3×	1e-13
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	5	36.7×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	11	37.7×	1e-12
ribosomal small subunit biogenesis	6	25.3×	1e-05
translation	11	20.9×	5e-10
rRNA processing	5	13.1×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1075 predictions. Top by Δscore:

Variant	Effect	Δscore
14:74713225:G:T	donor_gain	1.0000
14:74713257:G:GT	donor_gain	1.0000
14:74713549:GGCT:G	donor_gain	1.0000
14:74713550:GCTG:G	donor_gain	1.0000
14:74713605:GA:G	donor_gain	1.0000
14:74713606:A:G	donor_gain	1.0000
14:74714870:A:AG	acceptor_gain	1.0000
14:74714871:G:GA	acceptor_gain	1.0000
14:74714871:GTAAA:G	acceptor_gain	1.0000
14:74714939:GAAGT:G	donor_gain	1.0000
14:74714942:GT:G	donor_gain	1.0000
14:74715949:A:AG	acceptor_gain	1.0000
14:74715950:G:GG	acceptor_gain	1.0000
14:74716098:GT:G	donor_gain	1.0000
14:74732725:CTACA:C	acceptor_loss	1.0000
14:74732726:TACAG:T	acceptor_loss	1.0000
14:74732727:ACAGG:A	acceptor_loss	1.0000
14:74732728:CAG:C	acceptor_loss	1.0000
14:74732729:A:AG	acceptor_gain	1.0000
14:74732729:AG:A	acceptor_gain	1.0000
14:74732729:AGGA:A	acceptor_loss	1.0000
14:74732730:G:C	acceptor_loss	1.0000
14:74732730:G:GG	acceptor_gain	1.0000
14:74732730:GG:G	acceptor_gain	1.0000
14:74732814:CTCAG:C	donor_loss	1.0000
14:74732815:TCAG:T	donor_loss	1.0000
14:74732816:CAG:C	donor_loss	1.0000
14:74732817:AG:A	donor_loss	1.0000
14:74732818:G:GC	donor_loss	1.0000
14:74732820:T:A	donor_loss	1.0000

AlphaMissense

1306 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:74715973:T:C	F56L	1.000
14:74715975:T:A	F56L	1.000
14:74715975:T:G	F56L	1.000
14:74715987:T:A	N60K	1.000
14:74715987:T:G	N60K	1.000
14:74716016:T:A	L70H	1.000
14:74716016:T:C	L70P	1.000
14:74716019:T:A	V71D	1.000
14:74716021:G:C	D72H	1.000
14:74716022:A:C	D72A	1.000
14:74716022:A:T	D72V	1.000
14:74716023:T:A	D72E	1.000
14:74716023:T:G	D72E	1.000
14:74716025:C:T	T73I	1.000
14:74716029:C:A	N74K	1.000
14:74716029:C:G	N74K	1.000
14:74716030:T:C	F75L	1.000
14:74716031:T:C	F75S	1.000
14:74716032:T:A	F75L	1.000
14:74716032:T:G	F75L	1.000
14:74716034:T:A	I76N	1.000
14:74716038:C:A	N77K	1.000
14:74716038:C:G	N77K	1.000
14:74716042:T:C	S79P	1.000
14:74716043:C:A	S79Y	1.000
14:74716043:C:T	S79F	1.000
14:74716086:T:G	C93W	1.000
14:74716088:T:C	L94P	1.000
14:74716099:T:C	C98R	1.000
14:74723273:T:G	C98W	1.000

dbSNP variants (sampled 300 via entrez): RS1000124777 (14:74712467 A>G), RS1000189115 (14:74718623 G>A), RS1000231869 (14:74718909 T>C), RS1000337272 (14:74724604 T>G), RS1000727506 (14:74718270 T>C,G), RS1000777200 (14:74732444 C>T), RS1000816969 (14:74723480 G>A,C), RS1001122403 (14:74723049 T>C), RS1001152739 (14:74737991 C>A), RS1001329237 (14:74719512 A>G), RS1001560726 (14:74725522 G>A), RS1001597350 (14:74719860 A>C), RS1001840898 (14:74735854 A>T), RS1001892890 (14:74724063 C>A), RS1002073442 (14:74719250 A>G)

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

6 associations (top):

Study	Trait	p-value
GCST005237_3	Mood instability	1.000000e-06
GCST005238_3	Mood instability	3.000000e-09
GCST010002_156	Refractive error	7.000000e-25
GCST010396_47	Gut microbiota (bacterial taxa, hurdle binary method)	7.000000e-06
GCST012354_47	Anxiety	3.000000e-16
GCST012355_13	Depression	3.000000e-18

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008475	mood instability measurement
EFO:0007874	gut microbiome measurement
EFO:0009863	anxiety measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, affects cotreatment, decreases expression, increases abundance, increases expression	3
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
bisphenol A	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Irinotecan	affects expression	1
Temozolomide	decreases expression	1
Atrazine	increases expression	1
Cadmium	increases abundance, increases expression	1
Coumestrol	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Formaldehyde	decreases expression	1
Ribonucleotides	affects binding	1
Valproic Acid	decreases expression	1
Acrylamide	increases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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