NABP1

Summary

NABP1 (nucleic acid binding protein 1, HGNC:26232) is a protein-coding gene on chromosome 2q32.3, encoding SOSS complex subunit B2 (Q96AH0). Component of the SOSS complex, a multiprotein complex that functions downstream of the MRN complex to promote DNA repair and G2/M checkpoint.

Single-stranded DNA (ssDNA)-binding proteins, such as OBFC2A, are ubiquitous and essential for a variety of DNA metabolic processes, including replication, recombination, and detection and repair of damage (Richard et al., 2008 [PubMed 18449195]).

Source: NCBI Gene 64859 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 35 total
• Phenotypes (HPO): 36
• MANE Select transcript: NM_001031716

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26232
Approved symbol	NABP1
Name	nucleic acid binding protein 1
Location	2q32.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22833, DKFZp667M1322, FLJ13624, MGC111163, SSB2, hSSB2, SOSS-B2
Ensembl gene	ENSG00000173559
Ensembl biotype	protein_coding
OMIM	612103
Entrez	64859

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 9 nonsense_mediated_decay, 5 protein_coding, 3 retained_intron

ENST00000307834, ENST00000307849, ENST00000409510, ENST00000410026, ENST00000425611, ENST00000435931, ENST00000451500, ENST00000462712, ENST00000462824, ENST00000491331, ENST00000674172, ENST00000674187, ENST00000674262, ENST00000674360, ENST00000674406, ENST00000674414, ENST00000970387

RefSeq mRNA: 2 — MANE Select: NM_001031716 NM_001031716, NM_001254736

CCDS: CCDS33352, CCDS58745

Canonical transcript exons

ENST00000425611 — 6 exons

Exon	Start	End
ENSE00001182209	191678136	191678705
ENSE00003537219	191683729	191683804
ENSE00003596607	191681946	191682017
ENSE00003618674	191678990	191679128
ENSE00003625513	191684230	191684296
ENSE00003914789	191685599	191686943

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 98.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 118.6035 / max 6156.9318, expressed in 1821 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
24369	66.8342	1819
24372	40.1723	1790
24370	8.3028	1044
24371	1.2805	443
24368	1.0990	470
24375	0.4337	184
24374	0.4328	191
24377	0.3854	130
24373	0.0482	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.35	gold quality
amniotic fluid	UBERON:0000173	97.73	gold quality
esophagus squamous epithelium	UBERON:0006920	97.21	gold quality
parietal pleura	UBERON:0002400	95.95	gold quality
oocyte	CL:0000023	95.56	gold quality
spleen	UBERON:0002106	95.13	gold quality
stromal cell of endometrium	CL:0002255	95.04	gold quality
lower esophagus mucosa	UBERON:0035834	95.01	gold quality
epithelium of nasopharynx	UBERON:0001951	94.45	gold quality
decidua	UBERON:0002450	94.07	gold quality
sperm	CL:0000019	93.87	gold quality
omental fat pad	UBERON:0010414	93.66	gold quality
peritoneum	UBERON:0002358	93.64	gold quality
blood	UBERON:0000178	93.28	gold quality
adipose tissue of abdominal region	UBERON:0007808	93.19	gold quality
visceral pleura	UBERON:0002401	92.96	gold quality
pleura	UBERON:0000977	92.94	gold quality
jejunal mucosa	UBERON:0000399	92.81	gold quality
oral cavity	UBERON:0000167	92.77	gold quality
granulocyte	CL:0000094	92.27	gold quality
pericardium	UBERON:0002407	92.27	gold quality
germinal epithelium of ovary	UBERON:0001304	92.01	gold quality
monocyte	CL:0000576	91.91	gold quality
lymph node	UBERON:0000029	91.83	gold quality
tibia	UBERON:0000979	91.54	gold quality
mononuclear cell	CL:0000842	91.53	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.42	gold quality
leukocyte	CL:0000738	91.38	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.31	gold quality
adipose tissue	UBERON:0001013	91.15	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-9435	yes	4708.28
E-MTAB-7051	yes	3330.31
E-CURD-114	yes	1712.60
E-HCAD-56	yes	1695.16
E-MTAB-9154	yes	1567.52
E-MTAB-8142	yes	93.60
E-CURD-88	yes	38.43
E-HCAD-1	yes	32.49
E-GEOD-135922	yes	24.86
E-MTAB-9221	yes	24.79
E-MTAB-8410	yes	15.67
E-GEOD-137537	yes	15.11
E-GEOD-130148	yes	6.22
E-CURD-135	no	4341.33
E-HCAD-8	no	3254.74

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• hSSB1 and hSSB2 form two separate complexes with similar structures, and both complexes participate in DNA damage response. (PMID:19605351)
• SNPs rs11903757, with closest proximity to NABP1 and SDPR, and rs966423 in DIRC3, were associated with survival in laryngeal squamous cell carcinoma patients. (PMID:27793000)
• hSSB2 (NABP1) is required for the recruitment of RPA during the cellular response to DNA UV damage. (PMID:34642383)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nabp1a	ENSDARG00000004692
danio_rerio	nabp1b	ENSDARG00000043685
mus_musculus	Nabp1	ENSMUSG00000026107
rattus_norvegicus	Nabp1	ENSRNOG00000015416
drosophila_melanogaster	CG5181	FBGN0031909

Paralogs (1): NABP2 (ENSG00000139579)

Protein

Protein identifiers

SOSS complex subunit B2 — Q96AH0 (reviewed: Q96AH0)

Alternative names: Nucleic acid-binding protein 1, Oligonucleotide/oligosaccharide-binding fold-containing protein 2A, Sensor of single-strand DNA complex subunit B2, Sensor of ssDNA subunit B2, Single-stranded DNA-binding protein 2

All UniProt accessions (3): Q96AH0, F8WAF5, H7C0W4

UniProt curated annotations — full annotation on UniProt →

Function. Component of the SOSS complex, a multiprotein complex that functions downstream of the MRN complex to promote DNA repair and G2/M checkpoint. In the SOSS complex, acts as a sensor of single-stranded DNA that binds to single-stranded DNA, in particular to polypyrimidines. The SOSS complex associates with DNA lesions and influences diverse endpoints in the cellular DNA damage response including cell-cycle checkpoint activation, recombinational repair and maintenance of genomic stability. Required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs) and ATM-dependent signaling pathways.

Subunit / interactions. Component of the SOSS complex, composed of SOSS-B (SOSS-B1/NABP2 or SOSS-B2/NABP1), SOSS-A/INTS3 and SOSS-C/INIP. SOSS complexes containing SOSS-B1/NABP2 are more abundant than complexes containing SOSS-B2/NABP1.

Subcellular location. Nucleus.

Similarity. Belongs to the SOSS-B family. SOSS-B2 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96AH0-1	1	yes
Q96AH0-2	2
Q96AH0-3	3

RefSeq proteins (2): NP_001026886, NP_001241665 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR048970	OB_Ssb-like	Domain
IPR051231	SOSS-B	Family

Pfam: PF21473

UniProt features (9 total): splice variant 3, compositionally biased region 2, chain 1, DNA-binding region 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96AH0-F1	74.31	0.53

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6807505	RNA polymerase II transcribes snRNA genes
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 422 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE45365_NK_CELL_VS_BCELL_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, AAGCAAT_MIR137, GOBP_RESPONSE_TO_IONIZING_RADIATION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, XU_GH1_AUTOCRINE_TARGETS_UP, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, KENNY_CTNNB1_TARGETS_UP, GOBP_MITOTIC_G2_M_TRANSITION_CHECKPOINT, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, MARTINEZ_RB1_TARGETS_UP, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN

GO Biological Process (5): double-strand break repair via homologous recombination (GO:0000724), DNA repair (GO:0006281), DNA damage response (GO:0006974), response to ionizing radiation (GO:0010212), mitotic G2/M transition checkpoint (GO:0044818)

GO Molecular Function (4): DNA binding (GO:0003677), single-stranded DNA binding (GO:0003697), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (6): chromosome, telomeric region (GO:0000781), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), site of double-strand break (GO:0035861), SOSS complex (GO:0070876)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleic acid binding	2
cellular anatomical structure	2
recombinational repair	1
double-strand break repair	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
response to radiation	1
mitotic cell cycle checkpoint signaling	1
negative regulation of G2/M transition of mitotic cell cycle	1
DNA binding	1
binding	1
chromosomal region	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
site of DNA damage	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

594 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NABP1	INTS3	Q68E01	843
NABP1	INIP	Q9NRY2	762
NABP1	FIP1L1	Q6UN15	577
NABP1	RBM41	Q96IZ5	523
NABP1	LARP4	Q71RC2	518
NABP1	IRF2BP2	Q7Z5L9	507
NABP1	PRKAR1A	P10644	506
NABP1	NUMA1	Q14980	506
NABP1	FAM181B	A6NEQ2	500
NABP1	RPUSD4	Q96CM3	499
NABP1	RIPK3	Q9Y572	497
NABP1	NOL6	Q9H6R4	481
NABP1	CAVIN2	O95810	459
NABP1	DDX18	Q9NVP1	458
NABP1	PLK2	Q9NYY3	453

IntAct

39 interactions, top by confidence:

A	B	Type	Score
NABP1	RBMX	psi-mi:“MI:0915”(physical association)	0.720
RBMX	NABP1	psi-mi:“MI:0915”(physical association)	0.720
INIP	INTS3	psi-mi:“MI:0914”(association)	0.630
INTS3	NABP1	psi-mi:“MI:0914”(association)	0.620
NABP1	INTS3	psi-mi:“MI:0914”(association)	0.620
INTS3	NABP1	psi-mi:“MI:0915”(physical association)	0.620
INTS3	NABP1	psi-mi:“MI:0407”(direct interaction)	0.620
TFCP2	NABP1	psi-mi:“MI:0915”(physical association)	0.560
MKRN3	NABP1	psi-mi:“MI:0915”(physical association)	0.560
NABP1	KHDRBS2	psi-mi:“MI:0915”(physical association)	0.560
NABP1	QKI	psi-mi:“MI:0915”(physical association)	0.560
NABP1	TFCP2	psi-mi:“MI:0915”(physical association)	0.560
KHDRBS2	NABP1	psi-mi:“MI:0915”(physical association)	0.560
QKI	NABP1	psi-mi:“MI:0915”(physical association)	0.560
NABP1	MKRN3	psi-mi:“MI:0915”(physical association)	0.560
REL	NABP1	psi-mi:“MI:0915”(physical association)	0.560
NABP1	PURB	psi-mi:“MI:0915”(physical association)	0.560
NABP1	TRIM7	psi-mi:“MI:0915”(physical association)	0.560
NABP1	COPS3	psi-mi:“MI:0915”(physical association)	0.560
TP53	NABP1	psi-mi:“MI:0915”(physical association)	0.400
NABP1	XPO1	psi-mi:“MI:0914”(association)	0.350
NABP1	DBT	psi-mi:“MI:0914”(association)	0.350
NABP1	RBMX	psi-mi:“MI:0915”(physical association)	0.000
NABP1	REL	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (38): NABP1 (Two-hybrid), NABP1 (Two-hybrid), NABP1 (Two-hybrid), NABP1 (Two-hybrid), KHDRBS2 (Two-hybrid), NABP1 (Reconstituted Complex), POLR2A (Affinity Capture-MS), PPP2R1A (Affinity Capture-MS), XPO1 (Affinity Capture-MS), INTS6 (Affinity Capture-MS), ASTE1 (Affinity Capture-MS), GOLT1B (Affinity Capture-MS), CPSF3L (Affinity Capture-MS), AGGF1 (Affinity Capture-MS), INIP (Affinity Capture-MS)

ESM2 similar proteins: A5D7P8, A6QLK2, F1LQ48, O55047, O95628, P25916, P35226, P59326, P97855, Q08CW1, Q0VCY1, Q0VCZ3, Q12906, Q13148, Q13283, Q1ECX4, Q32KX7, Q32LC7, Q3SWT1, Q3ZBD9, Q4R5D9, Q5FVP2, Q5PRC7, Q5R601, Q5R8L2, Q5RB87, Q5SDR3, Q5U2U0, Q5ZLN5, Q64213, Q66K94, Q6DE02, Q6NRF9, Q86UE8, Q8BGW5, Q8BT14, Q8C0V0, Q8R2Y9, Q90ZY6, Q91YT7

Diamond homologs: A5D7P8, A6QLK2, Q3SWT1, Q54X41, Q5FVP2, Q5PRC7, Q66K94, Q6DE02, Q6NRF9, Q8BGW5, Q8R2Y9, Q96AH0, Q9BQ15, Q9VM17

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

995 predictions. Top by Δscore:

Variant	Effect	Δscore
2:191678701:GATAG:G	donor_gain	1.0000
2:191678979:A:G	acceptor_gain	1.0000
2:191679125:GAGG:G	donor_gain	1.0000
2:191679127:GG:G	donor_gain	1.0000
2:191679128:GG:G	donor_gain	1.0000
2:191681941:TCTA:T	acceptor_loss	1.0000
2:191681942:CTAG:C	acceptor_loss	1.0000
2:191681943:TA:T	acceptor_loss	1.0000
2:191681944:A:AG	acceptor_gain	1.0000
2:191681944:AG:A	acceptor_gain	1.0000
2:191681945:G:GT	acceptor_gain	1.0000
2:191681945:GG:G	acceptor_gain	1.0000
2:191681945:GGT:G	acceptor_gain	1.0000
2:191681945:GGTA:G	acceptor_gain	1.0000
2:191681945:GGTAT:G	acceptor_gain	1.0000
2:191682013:GGGGA:G	donor_gain	1.0000
2:191682014:GGGA:G	donor_gain	1.0000
2:191682014:GGGAG:G	donor_gain	1.0000
2:191682015:G:GT	donor_gain	1.0000
2:191682015:G:T	donor_gain	1.0000
2:191682015:GGA:G	donor_gain	1.0000
2:191682015:GGAGT:G	donor_loss	1.0000
2:191682016:GA:G	donor_gain	1.0000
2:191682016:GAG:G	donor_gain	1.0000
2:191682017:AG:A	donor_loss	1.0000
2:191682018:G:A	donor_loss	1.0000
2:191682018:G:GG	donor_gain	1.0000
2:191682019:TAAG:T	donor_loss	1.0000
2:191682586:GGGGT:G	donor_gain	1.0000
2:191682587:GGGTG:G	donor_gain	1.0000

AlphaMissense

1344 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:191679053:G:A	G52D	1.000
2:191679073:T:A	W59R	1.000
2:191679073:T:C	W59R	1.000
2:191679075:G:C	W59C	1.000
2:191679075:G:T	W59C	1.000
2:191678694:T:A	V27D	0.999
2:191679040:G:C	A48P	0.999
2:191679041:C:A	A48E	0.999
2:191679043:G:C	D49H	0.999
2:191679052:G:C	G52R	0.999
2:191679074:G:C	W59S	0.999
2:191681963:A:T	K83I	0.999
2:191681978:T:A	L88H	0.999
2:191681978:T:C	L88P	0.999
2:191683730:T:C	F102L	0.999
2:191683732:T:A	F102L	0.999
2:191683732:T:G	F102L	0.999
2:191683763:A:C	S113R	0.999
2:191683765:T:A	S113R	0.999
2:191683765:T:G	S113R	0.999
2:191678691:T:A	I26N	0.998
2:191678697:T:C	L28P	0.998
2:191679023:T:A	V42E	0.998
2:191679031:T:C	C45R	0.998
2:191679038:T:A	V47E	0.998
2:191679044:A:T	D49V	0.998
2:191679053:G:T	G52V	0.998
2:191679071:T:A	V58E	0.998
2:191679076:G:C	D60H	0.998
2:191679077:A:T	D60V	0.998

dbSNP variants (sampled 300 via entrez): RS1000267654 (2:191682565 C>T), RS1000273384 (2:191682284 G>A), RS1000325953 (2:191681899 A>G), RS1000504882 (2:191676965 C>T), RS1000596631 (2:191676677 A>G), RS1000610877 (2:191684363 C>T), RS1000659895 (2:191683974 A>G), RS1001327923 (2:191680422 GAC>G), RS1001671044 (2:191680829 A>G), RS1001953587 (2:191686831 A>G), RS1002004329 (2:191686528 G>T), RS1002131992 (2:191678201 G>A,C,T), RS1002267447 (2:191678010 G>A,T), RS1002693482 (2:191686009 G>C,T), RS1003011019 (2:191685136 C>T)

Disease associations

OMIM: gene MIM:612103 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

36 total (30 of 36 shown, HPO-id order):

HPO	Term
HP:0000212	Gingival overgrowth
HP:0000225	Gingival bleeding
HP:0000421	Epistaxis
HP:0000790	Hematuria
HP:0000967	Petechiae
HP:0000978	Bruising susceptibility
HP:0000979	Purpura
HP:0001324	Muscle weakness
HP:0001824	Weight loss
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001876	Pancytopenia
HP:0001882	Decreased total leukocyte count
HP:0001892	Abnormal bleeding
HP:0001903	Anemia
HP:0001945	Fever
HP:0001974	Increased total leukocyte count
HP:0002027	Abdominal pain
HP:0002039	Anorexia
HP:0002321	Vertigo
HP:0002653	Bone pain
HP:0002716	Lymphadenopathy
HP:0002875	Exertional dyspnea
HP:0005521	Disseminated intravascular coagulation
HP:0010280	Stomatitis
HP:0011900	Hypofibrinogenemia
HP:0012378	Fatigue
HP:0025420	Diffuse alveolar hemorrhage
HP:0030140	Oral cavity bleeding
HP:0030955	Addictive alcohol use

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001787_6	Colorectal cancer	4.000000e-08
GCST001997_4	Adverse response to chemotherapy (neutropenia/leucopenia) (5-fluorouracil)	9.000000e-06
GCST009391_1601	Metabolite levels	3.000000e-06
GCST009391_1835	Metabolite levels	7.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010377	phosphatidylcholine 34:3 measurement
EFO:0010412	triacylglycerol 50:5 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, decreases methylation	9
Benzo(a)pyrene	decreases expression, increases expression	6
sodium arsenite	increases expression, affects expression, affects cotreatment, increases abundance	5
Cyclosporine	decreases expression, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Acetaminophen	decreases expression, increases expression	3
Air Pollutants	affects cotreatment, decreases expression, increases abundance, affects expression	3
Aflatoxin B1	affects expression, decreases methylation, increases expression	3
mercuric bromide	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Dexamethasone	increases expression, affects cotreatment, decreases expression	2
Indomethacin	increases expression, affects cotreatment, decreases expression	2
Nickel	increases expression	2
Ozone	decreases expression, increases abundance, affects expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8R0	Ubigene HCT 116 NABP1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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