NUFIP1

Summary

NUFIP1 (nuclear FMR1 interacting protein 1, HGNC:8057) is a protein-coding gene on chromosome 13q14.12, encoding FMR1-interacting protein NUFIP1 (Q9UHK0). Binds RNA. It is a selective cancer dependency (DepMap: 72.6% of cell lines).

This gene encodes a nuclear RNA binding protein that contains a C2H2 zinc finger motif and a nuclear localization signal. This protein is associated with the nuclear matrix in perichromatin fibrils and, in neurons, localizes to the cytoplasm in association with endoplasmic reticulum ribosomes. This protein interacts with the fragile X mental retardation protein (FMRP), the tumor suppressor protein BRCA1, upregulates RNA polymerase II transcription, and is involved in box C/D snoRNP biogenesis. A pseudogene of this gene resides on chromosome 6q12.

Source: NCBI Gene 26747 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 107 total
• Cancer dependency (DepMap): dependent in 72.6% of screened cell lines
• MANE Select transcript: NM_012345

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8057
Approved symbol	NUFIP1
Name	nuclear FMR1 interacting protein 1
Location	13q14.12
Locus type	gene with protein product
Status	Approved
Aliases	NUFIP, Rsa1
Ensembl gene	ENSG00000083635
Ensembl biotype	protein_coding
OMIM	604354
Entrez	26747

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000379161

RefSeq mRNA: 1 — MANE Select: NM_012345 NM_012345

CCDS: CCDS9393

Canonical transcript exons

ENST00000379161 — 10 exons

Exon	Start	End
ENSE00000490194	44943442	44943674
ENSE00000490200	44959381	44959574
ENSE00000534769	44979190	44979266
ENSE00000681955	44949722	44949838
ENSE00000681976	44965844	44965936
ENSE00000681983	44979890	44979952
ENSE00000681986	44980722	44980820
ENSE00000681989	44982072	44982154
ENSE00000817277	44939249	44941322
ENSE00001479938	44989025	44989471

Expression profiles

Bgee: expression breadth ubiquitous, 223 present calls, max score 90.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.0436 / max 137.5056, expressed in 1795 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137075	12.7857	1794
137074	0.2580	108

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	90.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.23	gold quality
secondary oocyte	CL:0000655	86.93	gold quality
oocyte	CL:0000023	84.55	gold quality
cortical plate	UBERON:0005343	80.27	gold quality
ventricular zone	UBERON:0003053	79.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.91	gold quality
ganglionic eminence	UBERON:0004023	78.41	gold quality
Brodmann (1909) area 23	UBERON:0013554	77.62	gold quality
gastrocnemius	UBERON:0001388	76.71	gold quality
muscle of leg	UBERON:0001383	76.27	gold quality
adrenal tissue	UBERON:0018303	75.85	gold quality
calcaneal tendon	UBERON:0003701	75.68	gold quality
islet of Langerhans	UBERON:0000006	75.42	gold quality
CA1 field of hippocampus	UBERON:0003881	74.97	gold quality
hindlimb stylopod muscle	UBERON:0004252	74.91	gold quality
tibialis anterior	UBERON:0001385	74.24	silver quality
middle temporal gyrus	UBERON:0002771	74.24	silver quality
muscle organ	UBERON:0001630	74.16	gold quality
prefrontal cortex	UBERON:0000451	74.07	gold quality
stromal cell of endometrium	CL:0002255	74.03	gold quality
primary visual cortex	UBERON:0002436	74.02	gold quality
popliteal artery	UBERON:0002250	73.13	gold quality
tibial artery	UBERON:0007610	73.12	gold quality
biceps brachii	UBERON:0001507	72.37	silver quality
entorhinal cortex	UBERON:0002728	72.23	silver quality
left adrenal gland	UBERON:0001234	72.07	gold quality
aorta	UBERON:0000947	71.97	gold quality
descending thoracic aorta	UBERON:0002345	71.92	gold quality
left coronary artery	UBERON:0001626	71.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.44
E-MTAB-7008	no	104.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

114 targeting NUFIP1, 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-4283	100.00	66.42	2097
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-765	99.84	68.24	2442

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 72.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• NUFIP is associated with preinitiation complexes, open transcription complexes, and elongation complexes and facilitates ATP-dependent dissociation of hyperphosphorylated pol II from open transcription complexes in vitro (PMID:15107825)
• Results solve the structure of a complex resulting from interaction between protein fragments of human NUFIP1 and its cofactor ZNHIT3, and emphasize their imbrication. Also, it seems that the complexes involving NUFIP1, ZNHIT3, and SNU13 share strong structural similarities between human and yeast, suggesting that the initial steps of the box C/D snoRNP assembly process are conserved among species. (PMID:27594683)
• NUFIP1 is a receptor for the selective autophagy of ribosomes. (PMID:29700228)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nufip1	ENSDARG00000101024
mus_musculus	Nufip1	ENSMUSG00000022009
rattus_norvegicus	Nufip1	ENSRNOG00000001033
drosophila_melanogaster	Nufip	FBGN0036812

Protein

Protein identifiers

FMR1-interacting protein NUFIP1 — Q9UHK0 (reviewed: Q9UHK0)

Alternative names: Nuclear FMR1-interacting protein 1, Nuclear FMRP-interacting protein 1

All UniProt accessions (1): Q9UHK0

UniProt curated annotations — full annotation on UniProt →

Function. Binds RNA.

Subunit / interactions. Interacts with FMR1. Interacts with ZNHIT3. Interacts with NOP2, NOP56 and RUVBL1.

Subcellular location. Nucleus.

Tissue specificity. Expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon, peripheral blood leukocyte, heart, brain, placenta, lung, liver, skeletal muscle, kidney, and pancreas.

RefSeq proteins (1): NP_036477* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR019496	NUFIP1_cons_dom	Domain
IPR039136	NUFIP1-like	Family

Pfam: PF10453

UniProt features (14 total): modified residue 4, region of interest 3, compositionally biased region 2, chain 1, zinc finger region 1, sequence variant 1, helix 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5L85	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHK0-F1	55.91	0.04

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 (4): 342, 403, 338, 340

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 173 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, MORF_HDAC2, PUJANA_CHEK2_PCC_NETWORK, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GAZDA_DIAMOND_BLACKFAN_ANEMIA_ERYTHROID_UP, CREB_Q3, MARTINEZ_RESPONSE_TO_TRABECTEDIN_DN, PUJANA_BREAST_CANCER_LIT_INT_NETWORK, DANG_BOUND_BY_MYC, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, chr13q14, GOCC_SYNAPSE, GOCC_PRESYNAPTIC_ACTIVE_ZONE, GOCC_PRESYNAPSE

GO Biological Process (3): box C/D snoRNP assembly (GO:0000492), RNA processing (GO:0006396), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (8): RNA binding (GO:0003723), zinc ion binding (GO:0008270), protein-macromolecule adaptor activity (GO:0030674), identical protein binding (GO:0042802), ATPase binding (GO:0051117), protein binding (GO:0005515), snoRNA binding (GO:0030515), metal ion binding (GO:0046872)

GO Cellular Component (11): fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), perichromatin fibrils (GO:0005726), nucleolus (GO:0005730), transcription elongation factor complex (GO:0008023), nuclear matrix (GO:0016363), protein-containing complex (GO:0032991), presynaptic active zone (GO:0048786), pre-snoRNP complex (GO:0070761), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
nuclear lumen	3
protein binding	2
small nucleolar ribonucleoprotein complex assembly	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
nucleic acid binding	1
transition metal ion binding	1
molecular adaptor activity	1
enzyme binding	1
binding	1
RNA binding	1
cation binding	1
nucleolus	1
intracellular membrane-bounded organelle	1
nuclear chromosome	1
chromatin	1
intracellular membraneless organelle	1
nucleoplasm	1
nuclear protein-containing complex	1
cellular_component	1
presynapse	1
ribonucleoprotein complex	1
cell junction	1

Protein interactions and networks

STRING

1262 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUFIP1	ZNHIT3	Q15649	971
NUFIP1	FXR1	P51114	959
NUFIP1	FMR1	Q06787	946
NUFIP1	NUFIP2	Q7Z417	939
NUFIP1	FXR2	P51116	938
NUFIP1	CYFIP1	Q7L576	899
NUFIP1	SNU13	P55769	871
NUFIP1	ZNHIT6	Q9NWK9	847
NUFIP1	PIH1D1	Q9NWS0	790
NUFIP1	CYFIP2	Q96F07	748
NUFIP1	NOP58	Q9Y2X3	734
NUFIP1	NUCLEOLIN	P19338	709
NUFIP1	YBX1	P16990	696
NUFIP1	FHDC1	Q9C0D6	668
NUFIP1	PRPF31	Q8WWY3	615

IntAct

58 interactions, top by confidence:

A	B	Type	Score
NUFIP1	ZNHIT3	psi-mi:“MI:0915”(physical association)	0.840
ZNHIT3	NUFIP1	psi-mi:“MI:0915”(physical association)	0.840
NUFIP1	ZNHIT3	psi-mi:“MI:0914”(association)	0.840
NOP58	NOP56	psi-mi:“MI:0914”(association)	0.640
NUFIP1	NOP58	psi-mi:“MI:0914”(association)	0.600
NUFIP1	ZNHIT6	psi-mi:“MI:0915”(physical association)	0.560
NUFIP1	Ruvbl1	psi-mi:“MI:0915”(physical association)	0.560
ZNF324B	ZNF316	psi-mi:“MI:0914”(association)	0.530
RSBN1	SETD1A	psi-mi:“MI:0914”(association)	0.530
NUFIP1	PDE2A	psi-mi:“MI:0914”(association)	0.530
SNU13	NUFIP1	psi-mi:“MI:0915”(physical association)	0.500
NUFIP1	SNU13	psi-mi:“MI:0914”(association)	0.500
	NUFIP1	psi-mi:“MI:0407”(direct interaction)	0.410
Snu13		psi-mi:“MI:0915”(physical association)	0.400
NUFIP1	NUFIP1	psi-mi:“MI:0915”(physical association)	0.400
Ruvbl2	NUFIP1	psi-mi:“MI:0915”(physical association)	0.400
NOP56	NUFIP1	psi-mi:“MI:0915”(physical association)	0.400
NUFIP1	YWHAZ	psi-mi:“MI:0915”(physical association)	0.400
Ruvbl1	AAR2	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
NXF2B	MEIOC	psi-mi:“MI:0914”(association)	0.350
NUFIP1	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.350
RPL13	IPO5	psi-mi:“MI:0914”(association)	0.350
PPAN	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
GPATCH4	NOP56	psi-mi:“MI:0914”(association)	0.350

BioGRID (321): NCAM1 (Affinity Capture-MS), CRMP1 (Affinity Capture-MS), DPYSL3 (Affinity Capture-MS), DPYSL2 (Affinity Capture-MS), DPYSL5 (Affinity Capture-MS), STXBP1 (Affinity Capture-MS), ATP4A (Affinity Capture-MS), RAB14 (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), GPM6B (Affinity Capture-MS), HIST1H1B (Affinity Capture-MS), DNM1L (Affinity Capture-MS), HIST1H2BL (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), CNTN1 (Affinity Capture-MS)

ESM2 similar proteins: A0JNH9, A1L2T6, A2A3V1, A7E3D8, A8MT70, A9C3N6, A9JRX0, B0CM36, B1AX39, B1WC15, E7FAP1, F1R983, O95447, P0DPK0, P23497, P46100, Q09003, Q0IIM1, Q0P5X5, Q28EG9, Q2KIN0, Q3UHX0, Q4R3Q7, Q5H9M0, Q5T5J6, Q5U2Y9, Q5ZLE9, Q66H73, Q6GNV6, Q6GQJ2, Q6IE81, Q6IE82, Q6PG04, Q6ZPI0, Q6ZUT1, Q76FK4, Q7TSG3, Q7YQM3, Q7YQM4, Q80WQ8

Diamond homologs: Q641W3, Q9QXX8, Q9UHK0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 61 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
Major pathway of rRNA processing in the nucleolus and cytosol	6	11.6×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal small subunit biogenesis	5	22.3×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	8
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1495 predictions. Top by Δscore:

Variant	Effect	Δscore
13:44941319:GAAG:G	acceptor_gain	1.0000
13:44941321:AG:A	acceptor_gain	1.0000
13:44941323:C:CC	acceptor_gain	1.0000
13:44941335:T:C	acceptor_gain	1.0000
13:44943438:TTACC:T	donor_loss	1.0000
13:44943439:TAC:T	donor_loss	1.0000
13:44943441:C:A	donor_loss	1.0000
13:44943671:GTTT:G	acceptor_gain	1.0000
13:44943672:TTT:T	acceptor_gain	1.0000
13:44943673:TT:T	acceptor_gain	1.0000
13:44943675:C:CA	acceptor_loss	1.0000
13:44943675:C:CC	acceptor_gain	1.0000
13:44943676:T:C	acceptor_loss	1.0000
13:44943679:G:C	acceptor_gain	1.0000
13:44943679:G:GC	acceptor_gain	1.0000
13:44943681:G:C	acceptor_gain	1.0000
13:44943681:G:GC	acceptor_gain	1.0000
13:44943684:A:AC	acceptor_gain	1.0000
13:44943684:A:C	acceptor_gain	1.0000
13:44949836:ACTC:A	acceptor_loss	1.0000
13:44949837:CT:C	acceptor_gain	1.0000
13:44949838:TC:T	acceptor_loss	1.0000
13:44949839:C:CC	acceptor_gain	1.0000
13:44949839:CTG:C	acceptor_loss	1.0000
13:44965837:AGCTT:A	donor_loss	1.0000
13:44965838:GCTTA:G	donor_loss	1.0000
13:44965839:CTTAC:C	donor_loss	1.0000
13:44965840:TTACC:T	donor_loss	1.0000
13:44965841:TACC:T	donor_loss	1.0000
13:44965842:A:AC	donor_gain	1.0000

AlphaMissense

3299 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:44979207:C:A	W239C	1.000
13:44979207:C:G	W239C	1.000
13:44979209:A:G	W239R	1.000
13:44979209:A:T	W239R	1.000
13:44979952:A:G	C199R	1.000
13:44980780:C:T	C179Y	1.000
13:44980781:A:G	C179R	1.000
13:44980789:C:T	C176Y	1.000
13:44980790:A:G	C176R	1.000
13:44941321:A:G	L458P	0.999
13:44979195:T:A	R243S	0.999
13:44979195:T:G	R243S	0.999
13:44979196:C:G	R243T	0.999
13:44979204:C:A	R240S	0.999
13:44979204:C:G	R240S	0.999
13:44979208:C:G	W239S	0.999
13:44979901:G:C	H216D	0.999
13:44979909:A:T	V213D	0.999
13:44979924:G:T	A208E	0.999
13:44979929:A:C	F206L	0.999
13:44979929:A:T	F206L	0.999
13:44979931:A:G	F206L	0.999
13:44979935:G:C	C204W	0.999
13:44979936:C:G	C204S	0.999
13:44979937:A:G	C204R	0.999
13:44979937:A:T	C204S	0.999
13:44979951:C:G	C199S	0.999
13:44979952:A:T	C199S	0.999
13:44980728:A:C	H196Q	0.999
13:44980728:A:T	H196Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000047000 (13:44941262 T>C), RS1000093761 (13:44981461 G>A), RS1000133887 (13:44991239 G>C), RS1000218329 (13:44943851 A>G), RS1000258829 (13:44959411 G>A), RS1000419777 (13:44952898 C>G), RS1000453214 (13:44971525 T>C), RS1000509538 (13:44949536 A>G), RS1000608021 (13:44971104 T>A,C), RS1000636297 (13:44951690 G>A), RS1000700308 (13:44965996 A>G), RS1000710035 (13:44959177 C>T), RS1000745792 (13:44956647 C>G), RS1000802325 (13:44988675 G>C), RS1000871653 (13:44962706 C>T)

Disease associations

OMIM: gene MIM:604354 | 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
GCST001834_2	Oleic acid (18:1n-9) levels	1.000000e-06
GCST002805_11	Body mass index	7.000000e-06
GCST005790_27	Rosacea symptom severity	5.000000e-06
GCST010002_185	Refractive error	5.000000e-09
GCST010242_257	HDL cholesterol levels	1.000000e-09
GCST010242_65	HDL cholesterol levels	4.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005937	longitudinal BMI measurement
EFO:0009180	rosacea severity measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Cisplatin	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
deoxynivalenol	increases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	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
perfluorohexanesulfonic acid	decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression, affects cotreatment	1
MT19c compound	increases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Methapyrilene	increases methylation	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Urethane	decreases expression	1
Propofol	affects response to substance, affects cleavage, affects expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases expression	1

Clinical trials (associated diseases)

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