HCFC1R1

Summary

HCFC1R1 (host cell factor C1 regulator 1, HGNC:21198) is a protein-coding gene on chromosome 16p13.3, encoding Host cell factor C1 regulator 1 (Q9NWW0). Regulates HCFC1 activity by modulating its subcellular localization. It is a selective cancer dependency (DepMap: 10.4% of cell lines).

Located in nucleoplasm.

Source: NCBI Gene 54985 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 37 total
• Cancer dependency (DepMap): dependent in 10.4% of screened cell lines
• MANE Select transcript: NM_017885

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21198
Approved symbol	HCFC1R1
Name	host cell factor C1 regulator 1
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	HPIP, FLJ20568
Ensembl gene	ENSG00000103145
Ensembl biotype	protein_coding
OMIM	618818
Entrez	54985

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 3 retained_intron

ENST00000248089, ENST00000354679, ENST00000572355, ENST00000573095, ENST00000573842, ENST00000574151, ENST00000574980, ENST00000575214, ENST00000576921, ENST00000873953, ENST00000915425, ENST00000915426, ENST00000948613, ENST00000948614, ENST00000948615

RefSeq mRNA: 8 — MANE Select: NM_017885 NM_001002017, NM_001002018, NM_001288665, NM_001288666, NM_001288667, NM_001288668, NM_001308070, NM_017885

CCDS: CCDS10490, CCDS32375, CCDS73815, CCDS76810

Canonical transcript exons

ENST00000248089 — 4 exons

Exon	Start	End
ENSE00000664591	3023233	3023361
ENSE00002633761	3023847	3023942
ENSE00003498950	3023474	3023530
ENSE00003903302	3022625	3022998

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 99.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 149.8942 / max 1222.3032, expressed in 1827 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155987	110.6391	1812
155989	30.9809	1813
155986	3.6878	1158
155984	1.4808	716
155983	1.3209	680
155988	1.2341	668
155985	0.5506	322

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	99.14	gold quality
descending thoracic aorta	UBERON:0002345	99.01	gold quality
ascending aorta	UBERON:0001496	98.96	gold quality
thoracic aorta	UBERON:0001515	98.96	gold quality
nucleus accumbens	UBERON:0001882	98.72	gold quality
right coronary artery	UBERON:0001625	98.70	gold quality
anterior cingulate cortex	UBERON:0009835	98.68	gold quality
cingulate cortex	UBERON:0003027	98.67	gold quality
aorta	UBERON:0000947	98.65	gold quality
caudate nucleus	UBERON:0001873	98.56	gold quality
right frontal lobe	UBERON:0002810	98.51	gold quality
popliteal artery	UBERON:0002250	98.48	gold quality
tibial artery	UBERON:0007610	98.47	gold quality
putamen	UBERON:0001874	98.45	gold quality
apex of heart	UBERON:0002098	98.42	gold quality
gastrocnemius	UBERON:0001388	98.37	gold quality
metanephros cortex	UBERON:0010533	98.36	gold quality
amygdala	UBERON:0001876	98.35	gold quality
left coronary artery	UBERON:0001626	98.31	gold quality
coronary artery	UBERON:0001621	98.19	gold quality
muscle of leg	UBERON:0001383	98.14	gold quality
prefrontal cortex	UBERON:0000451	98.08	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.83	gold quality
body of uterus	UBERON:0009853	97.83	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.77	gold quality
left uterine tube	UBERON:0001303	97.68	gold quality
cerebellar hemisphere	UBERON:0002245	97.63	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.62	gold quality
muscle organ	UBERON:0001630	97.61	gold quality
cerebellar cortex	UBERON:0002129	97.60	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	33.90
E-CURD-112	yes	19.40
E-HCAD-11	yes	18.72
E-MTAB-10042	yes	9.39
E-GEOD-134144	yes	8.42
E-MTAB-7316	yes	7.64
E-ANND-3	yes	7.63

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF, GATA1

miRNA regulators (miRDB)

23 targeting HCFC1R1, 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-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-4277	98.34	67.17	1323
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-3909	97.55	66.78	887
HSA-MIR-493-3P	97.50	66.44	731
HSA-MIR-3121-5P	97.30	66.62	1146
HSA-MIR-10400-3P	97.29	64.66	597
HSA-MIR-4674	97.29	64.62	597
HSA-MIR-6834-5P	96.25	64.88	823
HSA-MIR-6796-5P	95.37	66.08	1120

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• HPIP regulates HCF-1 activity by modulating its subcellular localization (PMID:12235138)
• HPIP is upregulated in colorectal cancer and regulates colorectal cancer cell proliferation, apoptosis and invasion (PMID:25800793)
• HPIP promotes thyroid cancer cell growth, migration and epithelial mesenchymal transformation through activating PI3K/AKT signaling pathway. (PMID:26463629)
• HPIP overexpression is an independent predictor of platinum-based chemotherapy resistance in epithelial ovarian neoplasms. (PMID:27818289)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hcfc1r1	ENSMUSG00000023904
rattus_norvegicus	Hcfc1r1	ENSRNOG00000003542

Protein

Protein identifiers

Host cell factor C1 regulator 1 — Q9NWW0 (reviewed: Q9NWW0)

Alternative names: HCF-1 beta-propeller-interacting protein

All UniProt accessions (4): Q9NWW0, I3L174, I3L1N5, J3KNY1

UniProt curated annotations — full annotation on UniProt →

Function. Regulates HCFC1 activity by modulating its subcellular localization. Overexpression of HCFC1R1 leads to accumulation of HCFC1 in the cytoplasm. HCFC1R1-mediated export may provide the pool of cytoplasmic HCFC1 required for import of virion-derived VP16 into the nucleus.

Subunit / interactions. Interacts with HCFC1.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Widely expressed.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NWW0-1	1	yes
Q9NWW0-2	2

RefSeq proteins (8): NP_001002017, NP_001002018, NP_001275594, NP_001275595, NP_001275596, NP_001275597, NP_001294999, NP_060355* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029195	HCFC1R1	Family

Pfam: PF15226

UniProt features (7 total): mutagenesis site 2, chain 1, region of interest 1, short sequence motif 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NWW0-F1	62.44	0.02

Functional residue map

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

Mutagenesis-validated functional residues (2):

Position	Phenotype
76–79	loss of interaction with hcfc1.
117–119	reduces nuclear export.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 161 (showing top): RNGTGGGC_UNKNOWN, KOBAYASHI_EGFR_SIGNALING_24HR_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOLDRATH_IMMUNE_MEMORY, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MENSE_HYPOXIA_UP, GGGTGGRR_PAX4_03, SP1_Q2_01, AACWWCAANK_UNKNOWN, ONKEN_UVEAL_MELANOMA_UP, RGTTAMWNATT_HNF1_01, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, DOANE_RESPONSE_TO_ANDROGEN_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, TGANTCA_AP1_C

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (3): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
nuclear lumen	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

406 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HCFC1R1	THOC6	Q86W42	513
HCFC1R1	YIPF3	Q9GZM5	506
HCFC1R1	FLYWCH2	Q96CP2	491
HCFC1R1	PP2D1	A8MPX8	458
HCFC1R1	BICDL2	A1A5D9	456
HCFC1R1	E4F1	Q66K89	454
HCFC1R1	C1QTNF12	Q5T7M4	448
HCFC1R1	SH3TC1	Q8TE82	429
HCFC1R1	ANKEF1	Q9NU02	421
HCFC1R1	TMEM235	A6NFC5	418
HCFC1R1	FLYWCH1	Q4VC44	414
HCFC1R1	TMEM71	Q6P5X7	398
HCFC1R1	GFER	P55789	366
HCFC1R1	SYNGR2	O43760	361
HCFC1R1	PRSS33	Q8NF86	353

IntAct

3 interactions, top by confidence:

A	B	Type	Score
HCFC1R1	OGT	psi-mi:“MI:0914”(association)	0.350
HMP19	HCFC1R1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): HCFC1 (Affinity Capture-MS), OGT (Affinity Capture-MS), HCFC1 (Affinity Capture-Western), OGT (Affinity Capture-MS), HCFC1 (Affinity Capture-MS), APP (Reconstituted Complex)

ESM2 similar proteins: A0A1B0GUS0, A0A5F9ZHS7, A7E346, A7MB34, A8MZG2, B2RU40, D4A9R4, O08574, O75593, P0C1Z6, P0CG20, Q0VG99, Q0ZCJ7, Q17QH7, Q29RM2, Q2KIS6, Q2M2S6, Q2M3G4, Q2NL68, Q32LE6, Q3U1J1, Q5JXC2, Q5R815, Q5SW24, Q61660, Q63247, Q6NZ36, Q6PBC9, Q6ZN01, Q6ZRI6, Q7TN08, Q7Z591, Q80VF6, Q86WR7, Q8BG26, Q8BP99, Q8BXQ8, Q8IYS4, Q8N9Y4, Q8NAV2

Diamond homologs: Q2M2S6, Q80V38, Q9CYQ5, Q9NWW0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

457 predictions. Top by Δscore:

Variant	Effect	Δscore
16:3024083:G:GT	donor_gain	1.0000
16:3023228:CCTA:C	donor_loss	0.9900
16:3023229:CTAC:C	donor_loss	0.9900
16:3023230:TAC:T	donor_loss	0.9900
16:3023231:ACCTG:A	donor_loss	0.9900
16:3023232:C:T	donor_loss	0.9900
16:3023472:A:AC	donor_gain	0.9900
16:3023473:C:CC	donor_gain	0.9900
16:3023473:CTG:C	donor_gain	0.9900
16:3023843:GCACC:G	donor_loss	0.9900
16:3023845:ACC:A	donor_loss	0.9900
16:3023358:CTCC:C	acceptor_gain	0.9800
16:3023360:CC:C	acceptor_gain	0.9800
16:3023361:CC:C	acceptor_gain	0.9800
16:3023904:C:A	donor_gain	0.9800
16:3023359:TCC:T	acceptor_gain	0.9700
16:3023360:CCC:C	acceptor_gain	0.9700
16:3023360:CCCT:C	acceptor_loss	0.9700
16:3023361:CCTGG:C	acceptor_loss	0.9700
16:3023362:C:CC	acceptor_gain	0.9700
16:3024088:C:T	donor_gain	0.9700
16:3024084:A:T	donor_gain	0.9600
16:3022995:GCTCC:G	acceptor_loss	0.9500
16:3022996:CTC:C	acceptor_gain	0.9500
16:3022998:CCTAG:C	acceptor_loss	0.9500
16:3022999:CTA:C	acceptor_loss	0.9500
16:3023000:T:A	acceptor_loss	0.9500
16:3023226:AACCT:A	donor_loss	0.9500
16:3023227:ACCTA:A	donor_loss	0.9500
16:3023845:A:AC	donor_gain	0.9500

AlphaMissense

881 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:3023340:A:C	F58L	0.978
16:3023340:A:T	F58L	0.978
16:3023342:A:G	F58L	0.978
16:3022973:A:G	W103R	0.971
16:3022973:A:T	W103R	0.971
16:3023311:A:G	F68S	0.971
16:3022971:C:A	W103C	0.969
16:3022971:C:G	W103C	0.969
16:3022951:A:G	I110T	0.960
16:3023310:G:C	F68L	0.960
16:3023310:G:T	F68L	0.960
16:3023312:A:G	F68L	0.960
16:3023346:C:A	K56N	0.952
16:3023346:C:G	K56N	0.952
16:3023298:G:C	S72R	0.945
16:3023298:G:T	S72R	0.945
16:3023300:T:G	S72R	0.945
16:3022939:A:T	L114H	0.925
16:3023311:A:C	F68C	0.922
16:3022951:A:C	I110S	0.914
16:3023302:A:G	L71P	0.911
16:3023494:C:A	K44N	0.910
16:3023494:C:G	K44N	0.910
16:3022951:A:T	I110N	0.909
16:3022939:A:G	L114P	0.904
16:3023341:A:G	F58S	0.901
16:3022972:C:G	W103S	0.892
16:3023937:A:G	I2T	0.888
16:3023341:A:C	F58C	0.887
16:3023322:C:A	M64I	0.881

dbSNP variants (sampled 300 via entrez): RS1000616190 (16:3023970 T>C), RS1000918889 (16:3023716 G>A,C), RS1000950947 (16:3022677 C>T), RS1001001726 (16:3023017 G>A,C), RS1001940172 (16:3023534 G>A,C), RS1002006199 (16:3022250 G>A,C,T), RS1002542776 (16:3023368 A>G), RS1003810930 (16:3022219 G>C), RS1003846663 (16:3026212 G>C), RS1003914622 (16:3022459 C>G,T), RS1004892878 (16:3022571 C>T), RS1005175924 (16:3022284 C>T), RS1005928905 (16:3024847 C>A,G), RS1006689737 (16:3024101 C>A,G,T), RS1007325493 (16:3024017 G>A,C)

Disease associations

OMIM: gene MIM:618818 | 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

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
methylmercuric chloride	decreases expression, increases expression	3
cobaltous chloride	decreases expression, increases expression, decreases reaction	2
Decitabine	decreases expression, decreases reaction, affects expression	2
Smoke	decreases expression, decreases reaction	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
bisphenol A	decreases expression	1
beta-lapachone	decreases expression	1
zinc chloride	decreases reaction, increases expression	1
sodium arsenite	decreases expression	1
cupric chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
entinostat	increases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	increases expression	1
MT19c compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases expression	1
Cisplatin	affects expression	1
Cytarabine	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2YI	Abcam HEK293T HCFC1R1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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