NUBP2

Summary

NUBP2 (NUBP iron-sulfur cluster assembly factor 2, cytosolic, HGNC:8042) is a protein-coding gene on chromosome 16p13.3, encoding Cytosolic Fe-S cluster assembly factor NUBP2 (Q9Y5Y2). Component of the cytosolic iron-sulfur (Fe/S) protein assembly (CIA) machinery. It is a selective cancer dependency (DepMap: 72.2% of cell lines).

This gene encodes an adenosine triphosphate (ATP) and metal-binding protein that is required for the assembly of cyotosolic iron-sulfur proteins. The encoded protein functions in a heterotetramer with nucleotide-binding protein 1 (NUBP1). Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 10101 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 87 total
• Cancer dependency (DepMap): dependent in 72.2% of screened cell lines
• MANE Select transcript: NM_012225

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8042
Approved symbol	NUBP2
Name	NUBP iron-sulfur cluster assembly factor 2, cytosolic
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	CFD1, CIAO6
Ensembl gene	ENSG00000095906
Ensembl biotype	protein_coding
OMIM	610779
Entrez	10101

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 9 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000262302, ENST00000562263, ENST00000563136, ENST00000563821, ENST00000564227, ENST00000565134, ENST00000565603, ENST00000565987, ENST00000566090, ENST00000566447, ENST00000567700, ENST00000568287, ENST00000568610, ENST00000568706, ENST00000568834, ENST00000569898, ENST00000881954, ENST00000942968

RefSeq mRNA: 3 — MANE Select: NM_012225 NM_001284501, NM_001284502, NM_012225

CCDS: CCDS10445, CCDS66898

Canonical transcript exons

ENST00000262302 — 7 exons

Exon	Start	End
ENSE00001359790	1782960	1783036
ENSE00001737040	1788569	1789186
ENSE00003593851	1787941	1788051
ENSE00003608495	1787677	1787831
ENSE00003618290	1786537	1786655
ENSE00003636766	1786757	1786955
ENSE00003671446	1788138	1788207

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 96.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.8229 / max 131.4301, expressed in 1820 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152133	31.8229	1820

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	96.88	gold quality
right lobe of liver	UBERON:0001114	94.80	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.42	gold quality
apex of heart	UBERON:0002098	94.33	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.94	gold quality
cerebellar hemisphere	UBERON:0002245	93.93	gold quality
cerebellum	UBERON:0002037	93.86	gold quality
cerebellar cortex	UBERON:0002129	93.83	gold quality
body of pancreas	UBERON:0001150	93.64	gold quality
fundus of stomach	UBERON:0001160	93.64	gold quality
right adrenal gland	UBERON:0001233	93.63	gold quality
gastrocnemius	UBERON:0001388	93.63	gold quality
left adrenal gland cortex	UBERON:0035825	93.61	gold quality
left adrenal gland	UBERON:0001234	93.59	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.58	gold quality
lower esophagus	UBERON:0013473	93.57	gold quality
granulocyte	CL:0000094	93.56	gold quality
skin of leg	UBERON:0001511	93.53	gold quality
mucosa of transverse colon	UBERON:0004991	93.53	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.43	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.43	gold quality
right adrenal gland cortex	UBERON:0035827	93.41	gold quality
body of stomach	UBERON:0001161	93.39	gold quality
skin of abdomen	UBERON:0001416	93.30	gold quality
zone of skin	UBERON:0000014	93.20	gold quality
prostate gland	UBERON:0002367	93.15	gold quality
pituitary gland	UBERON:0000007	93.14	gold quality
substantia nigra	UBERON:0002038	92.98	gold quality
muscle of leg	UBERON:0001383	92.97	gold quality
metanephros cortex	UBERON:0010533	92.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting NUBP2, 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-4492	99.87	68.25	3611
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-935	98.82	69.36	1072
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-4653-5P	97.22	67.72	1429
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-2277-3P	91.94	62.27	299
HSA-MIR-6889-5P	90.26	64.13	291

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 72.2% of screened cell lines.

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nubp2	ENSDARG00000055653
mus_musculus	Nubp2	ENSMUSG00000039183
rattus_norvegicus	Nubp2	ENSRNOG00000015090
drosophila_melanogaster	Nubp2	FBGN0037011

Paralogs (2): NUBP1 (ENSG00000103274), NUBPL (ENSG00000151413)

Protein

Protein identifiers

Cytosolic Fe-S cluster assembly factor NUBP2 — Q9Y5Y2 (reviewed: Q9Y5Y2)

Alternative names: Nucleotide-binding protein 2

All UniProt accessions (9): Q9Y5Y2, B7Z6P0, H3BMW1, H3BNF0, H3BNS4, H3BQE5, H3BQR2, H3BRE1, H3BRK5

UniProt curated annotations — full annotation on UniProt →

Function. Component of the cytosolic iron-sulfur (Fe/S) protein assembly (CIA) machinery. Required for maturation of extramitochondrial Fe-S proteins. The NUBP1-NUBP2 heterotetramer forms a Fe-S scaffold complex, mediating the de novo assembly of an Fe-S cluster and its transfer to target apoproteins. Negatively regulates cilium formation and structure.

Subunit / interactions. Heterotetramer of 2 NUBP1 and 2 NUBP2 chains. Interacts with KIFC1. Interacts with NUBP1.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Cilium axoneme. Centriole.

Tissue specificity. Widely expressed with highest expression in skeletal muscle.

Cofactor. Binds 4 [4Fe-4S] clusters per heterotetramer. Contains two stable clusters in the N-termini of NUBP1 and two labile, bridging clusters between subunits of the NUBP1-NUBP2 heterotetramer.

Similarity. Belongs to the Mrp/NBP35 ATP-binding proteins family. NUBP2/CFD1 subfamily.

RefSeq proteins (3): NP_001271430, NP_001271431, NP_036357* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000808	Mrp-like_CS	Conserved_site
IPR019591	Mrp/NBP35_ATP-bd	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR028600	NUBP2/Cfd1_eukaryotes	Family
IPR033756	YlxH/NBP35	Family

Pfam: PF10609

UniProt features (9 total): binding site 3, sequence variant 3, chain 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5Y2-F1	90.81	0.72

Functional residue map

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

Ligand- & substrate-binding residues (3): 22–29; 196; 199

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2564830	Cytosolic iron-sulfur cluster assembly

MSigDB gene sets: 100 (showing top): GOCC_MICROTUBULE_ORGANIZING_CENTER, GOCC_CENTROSOME, HAND1E47_01, GOBP_CELL_PROJECTION_ORGANIZATION, DANG_BOUND_BY_MYC, GOCC_SPINDLE, GOCC_CENTRIOLE, GOCC_CYTOPLASMIC_REGION, SANSOM_APC_MYC_TARGETS, BENPORATH_MYC_MAX_TARGETS, GOCC_CILIUM, NIKOLSKY_BREAST_CANCER_16P13_AMPLICON, GOMF_METAL_CLUSTER_BINDING, GOMF_ADENYL_NUCLEOTIDE_BINDING, GOMF_4_IRON_4_SULFUR_CLUSTER_BINDING

GO Biological Process (2): iron-sulfur cluster assembly (GO:0016226), cell projection organization (GO:0030030)

GO Molecular Function (7): nucleotide binding (GO:0000166), ATP binding (GO:0005524), metal ion binding (GO:0046872), iron-sulfur cluster binding (GO:0051536), 4 iron, 4 sulfur cluster binding (GO:0051539), ATP-dependent FeS chaperone activity (GO:0140663), protein binding (GO:0005515)

GO Cellular Component (12): nucleoplasm (GO:0005654), centriole (GO:0005814), cytosol (GO:0005829), axoneme (GO:0005930), spindle pole centrosome (GO:0031616), nucleus (GO:0005634), cytoplasm (GO:0005737), centrosome (GO:0005813), microtubule organizing center (GO:0005815), cytoskeleton (GO:0005856), cilium (GO:0005929), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
microtubule organizing center	2
intracellular membraneless organelle	2
metallo-sulfur cluster assembly	1
cellular component organization	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
metal cluster binding	1
iron-sulfur cluster binding	1
metallochaperone activity	1
ATP-dependent activity	1
binding	1
nuclear lumen	1
cytoplasm	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
spindle pole	1
centrosome	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
centriole	1
microtubule cytoskeleton	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

2158 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUBP2	FOXRED1	Q96CU9	797
NUBP2	ACO1	P21399	795
NUBP2	CIAO1	O76071	721
NUBP2	CIAO3	Q9H6Q4	709
NUBP2	GAPDH	P00354	622
NUBP2	RHOA	P06749	606
NUBP2	NDOR1	Q9UHB4	583
NUBP2	ACTB	P02570	582
NUBP2	PXDNL	A1KZ92	542
NUBP2	PXDN	Q92626	541
NUBP2	CIAPIN1	Q6FI81	537
NUBP2	NUBP1	P53384	528
NUBP2	ALB	P02768	520
NUBP2	ABCB7	O75027	501
NUBP2	NFS1	Q9Y697	499

IntAct

69 interactions, top by confidence:

A	B	Type	Score
NUBP1	NUBP2	psi-mi:“MI:0915”(physical association)	0.670
RAF1	CALU	psi-mi:“MI:0914”(association)	0.640
RNASEH2C	RNASEH2A	psi-mi:“MI:0914”(association)	0.640
NUBPL	NUBP2	psi-mi:“MI:0915”(physical association)	0.600
NUBP2		psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	NUBP2	psi-mi:“MI:0915”(physical association)	0.560
NUBP2	TNS2	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	NUBP2	psi-mi:“MI:0915”(physical association)	0.560
	NUBP2	psi-mi:“MI:0915”(physical association)	0.560
TNS2	NUBP2	psi-mi:“MI:0915”(physical association)	0.560
NUBP2	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
NUBP2	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-1	NUBP2	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	NUBP2	psi-mi:“MI:0915”(physical association)	0.560
TGM1	NUBP2	psi-mi:“MI:0915”(physical association)	0.560
MDFI	NUBP2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-8	NUBP2	psi-mi:“MI:0915”(physical association)	0.560
INCA1	NUBP2	psi-mi:“MI:0915”(physical association)	0.560
NUBP2	PTGER4	psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
MAD2L2		psi-mi:“MI:0914”(association)	0.350
QPCT	NUBP1	psi-mi:“MI:0914”(association)	0.350
ENG	IGKV2-28	psi-mi:“MI:0914”(association)	0.350
RHOA	PPP6C	psi-mi:“MI:0914”(association)	0.350
SMYD2	HSPA4L	psi-mi:“MI:0914”(association)	0.350

BioGRID (188): TENC1 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), NUBP2 (Affinity Capture-MS), NUBP2 (Affinity Capture-MS), CDK5 (Co-fractionation), UCK1 (Co-fractionation), NUBP2 (Proximity Label-MS), NUBP2 (Affinity Capture-MS), NUBP2 (Affinity Capture-RNA), NUBP2 (Affinity Capture-MS), NUBP2 (Affinity Capture-MS), NUBP2 (Affinity Capture-MS), NUBP2 (Affinity Capture-MS)

ESM2 similar proteins: A3CXI2, A5UKT8, A6VGG2, A7IB61, B8BM09, C6E6X6, O27728, O77507, O83985, P25453, P27865, P37383, P37384, P50265, P62215, P70099, P74503, P74646, P94102, P95547, Q06609, Q08297, Q12U80, Q14565, Q1AW43, Q27297, Q2KJ94, Q2LPL5, Q2NHD1, Q39009, Q40134, Q61880, Q67EU8, Q6L8L5, Q79PF4, Q7EAG4, Q7GBF7, Q7GBF8, Q7U8R3, Q7V5W7

Diamond homologs: A1C4X8, A1C7T4, A4QNM5, A7RUD5, A7SE07, A8PW87, A8WWQ7, A9V7A1, B0X4N8, B0XDJ0, B3M9R3, B3MU92, B3NIP2, B3NNJ9, B3RPX4, B4G8R5, B4H7P4, B4I540, B4IAD1, B4IUH5, B4IYG8, B4JBI7, B4KHX1, B4KY56, B4LGB4, B4LUF5, B4N1C3, B4N4D9, B4P9A8, B4PES4, B4Q7F5, B4QJ46, B6K1G6, O94442, P0C8Q1, P0CO88, P0CO89, P0CO90, P0CO91, P40558

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NUBP2	“form complex”	“NUBP1-NUBP2 iron-sulfur cluster assembly scaffold complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1199 predictions. Top by Δscore:

Variant	Effect	Δscore
16:1786530:C:A	acceptor_gain	1.0000
16:1786532:CCCA:C	acceptor_loss	1.0000
16:1786534:CA:C	acceptor_loss	1.0000
16:1786535:A:AG	acceptor_gain	1.0000
16:1786535:A:C	acceptor_loss	1.0000
16:1786536:G:GA	acceptor_gain	1.0000
16:1786536:GA:G	acceptor_gain	1.0000
16:1786536:GAGC:G	acceptor_gain	1.0000
16:1786652:GAAG:G	donor_gain	1.0000
16:1786654:AGGT:A	donor_loss	1.0000
16:1786656:GTGAG:G	donor_loss	1.0000
16:1787674:CAGC:C	acceptor_loss	1.0000
16:1787675:A:AG	acceptor_gain	1.0000
16:1787675:A:C	acceptor_loss	1.0000
16:1787675:AGC:A	acceptor_gain	1.0000
16:1787676:G:A	acceptor_loss	1.0000
16:1787676:G:GT	acceptor_gain	1.0000
16:1787676:GC:G	acceptor_gain	1.0000
16:1787676:GCG:G	acceptor_gain	1.0000
16:1787676:GCGC:G	acceptor_gain	1.0000
16:1787676:GCGCT:G	acceptor_gain	1.0000
16:1787827:CCCAG:C	donor_loss	1.0000
16:1787830:AG:A	donor_loss	1.0000
16:1787831:GG:G	donor_loss	1.0000
16:1787832:GTAGC:G	donor_loss	1.0000
16:1787833:T:G	donor_loss	1.0000
16:1787935:CCGCA:C	acceptor_loss	1.0000
16:1787936:CGCAG:C	acceptor_loss	1.0000
16:1787938:CAGGC:C	acceptor_loss	1.0000
16:1787939:A:AG	acceptor_gain	1.0000

AlphaMissense

1747 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:1786603:A:T	K28I	0.998
16:1787709:T:A	W123R	0.997
16:1787709:T:C	W123R	0.997
16:1786605:A:C	S29R	0.996
16:1786607:C:A	S29R	0.996
16:1786607:C:G	S29R	0.996
16:1786893:C:T	S91F	0.996
16:1787711:G:C	W123C	0.996
16:1787711:G:T	W123C	0.996
16:1787728:T:C	L129P	0.996
16:1788021:T:A	N190K	0.996
16:1788021:T:G	N190K	0.996
16:1786589:G:C	K23N	0.995
16:1786589:G:T	K23N	0.995
16:1786600:G:A	G27E	0.995
16:1786604:A:C	K28N	0.995
16:1786604:A:T	K28N	0.995
16:1786776:A:T	D52V	0.995
16:1786790:A:C	S57R	0.995
16:1786792:T:A	S57R	0.995
16:1786792:T:G	S57R	0.995
16:1786951:A:C	K110N	0.995
16:1786951:A:T	K110N	0.995
16:1787736:G:C	D132H	0.995
16:1786602:A:C	K28Q	0.994
16:1786602:A:G	K28E	0.994
16:1786777:C:A	D52E	0.994
16:1786777:C:G	D52E	0.994
16:1786950:A:T	K110I	0.994
16:1787818:T:A	V159D	0.994

dbSNP variants (sampled 300 via entrez): RS1000588840 (16:1789289 T>A,C), RS1000740118 (16:1787956 G>A,C), RS1001138988 (16:1784052 C>A,T), RS1001367563 (16:1787796 C>A,T), RS1001400199 (16:1787990 C>CG), RS1001868867 (16:1783851 G>A,T), RS1001869356 (16:1788179 G>A), RS1002054788 (16:1784607 T>C), RS1002250848 (16:1783589 A>C), RS1002479993 (16:1783220 C>G,T), RS1002539505 (16:1784787 C>T), RS1003003991 (16:1781528 G>T), RS1003041007 (16:1788433 G>A,T), RS1003051504 (16:1781757 C>T), RS1003085610 (16:1785778 C>T)

Disease associations

OMIM: gene MIM:610779 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000937_1	Insulin-like growth factors	1.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004626	IGFBP-3 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Ozone	affects expression, affects cotreatment, increases oxidation, increases abundance	3
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	increases oxidation, increases abundance, affects cotreatment	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Aspirin	decreases expression	2
aristolochic acid I	increases expression	1
2,4,6-tribromophenol	decreases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
tetrahydropalmatine	decreases expression	1
beta-lapachone	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
MT19c compound	decreases expression	1
Decitabine	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1
Ivermectin	decreases expression	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Dronabinol	decreases expression	1

Clinical trials (associated diseases)

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