INIP

Summary

INIP (INTS3 and NABP interacting protein, HGNC:24994) is a protein-coding gene on chromosome 9q32, encoding SOSS complex subunit C (Q9NRY2). Component of the SOSS complex, a multiprotein complex that functions downstream of the MRN complex to promote DNA repair and G2/M checkpoint.

The protein encoded by this gene is a subunit of single-stranded DNA binding complexes that are important for maintaining genome stability. These complexes are involved in G2/M checkpoint control and homologous recombination repair.

Source: NCBI Gene 58493 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 12 total
• MANE Select transcript: NM_021218

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24994
Approved symbol	INIP
Name	INTS3 and NABP interacting protein
Location	9q32
Locus type	gene with protein product
Status	Approved
Aliases	HSPC043, hSSBIP1, SOSS-C, MISE
Ensembl gene	ENSG00000148153
Ensembl biotype	protein_coding
OMIM	613273
Entrez	58493

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000374234, ENST00000374236, ENST00000374242, ENST00000476599, ENST00000481146, ENST00000497712, ENST00000901038, ENST00000939313, ENST00000939314

RefSeq mRNA: 7 — MANE Select: NM_021218 NM_001329585, NM_001329586, NM_001329587, NM_001329588, NM_001329589, NM_001329590, NM_021218

CCDS: CCDS6785, CCDS87676

Canonical transcript exons

ENST00000374242 — 5 exons

Exon	Start	End
ENSE00001758595	112683926	112687633
ENSE00001947697	112717987	112718117
ENSE00003493224	112694131	112694233
ENSE00003593261	112689527	112689617
ENSE00003671055	112716461	112716541

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 95.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.2430 / max 221.5980, expressed in 1776 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102071	12.2430	1776

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	95.00	gold quality
kidney epithelium	UBERON:0004819	94.49	gold quality
pons	UBERON:0000988	93.19	gold quality
inferior vagus X ganglion	UBERON:0005363	91.72	gold quality
endothelial cell	CL:0000115	91.65	gold quality
jejunal mucosa	UBERON:0000399	91.63	gold quality
entorhinal cortex	UBERON:0002728	91.60	gold quality
corpus callosum	UBERON:0002336	91.42	gold quality
subthalamic nucleus	UBERON:0001906	91.41	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.09	gold quality
colonic mucosa	UBERON:0000317	91.05	gold quality
lateral globus pallidus	UBERON:0002476	91.00	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.92	gold quality
postcentral gyrus	UBERON:0002581	90.63	gold quality
parietal lobe	UBERON:0001872	90.62	gold quality
corpus epididymis	UBERON:0004359	90.57	gold quality
monocyte	CL:0000576	90.54	gold quality
dorsal plus ventral thalamus	UBERON:0001897	90.52	gold quality
leukocyte	CL:0000738	90.23	gold quality
superior vestibular nucleus	UBERON:0007227	90.12	gold quality
adult organism	UBERON:0007023	89.86	gold quality
superficial temporal artery	UBERON:0001614	89.83	gold quality
globus pallidus	UBERON:0001875	89.71	gold quality
medulla oblongata	UBERON:0001896	89.68	gold quality
upper arm skin	UBERON:0004263	89.68	gold quality
lower lobe of lung	UBERON:0008949	89.66	gold quality
superior frontal gyrus	UBERON:0002661	89.47	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.33	gold quality
medial globus pallidus	UBERON:0002477	89.31	gold quality
caput epididymis	UBERON:0004358	89.31	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.43

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting INIP, 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-3613-3P	100.00	76.36	7965
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-153-5P	99.89	73.86	6317
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-4694-3P	99.79	69.53	2640
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626

Literature-anchored findings (GeneRIF, showing 4)

• hSSBIP1 forms complexes with INTS3/hSSB1 and INTS3/hSSB2 and participates in the DNA damage response (PMID:19605351)
• SOSS-C is part of an ssDNA-binding heterotrimeric complex, SOSS which is involved in the maintenance of genome stability. (PMID:19683501)
• MISE is part of the INTS3/MISE/hSSB1 (IMS1) complex, which controls the DNA damage response (PMID:19786574)
• INTS3, but not C9ORF80, affects the nucleic acid-binding ability of hNABP1 and hNABP2, indicating that INTS3 might regulate hNABP1/hNABP2 biological function, while the role of C9ORF80 remains unknown. (PMID:29150435)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	inip	ENSDARG00000028523
mus_musculus	Inip	ENSMUSG00000038544
rattus_norvegicus	Inip	ENSRNOG00000069187
drosophila_melanogaster	CG42374	FBGN0259720

Protein

Protein identifiers

SOSS complex subunit C — Q9NRY2 (reviewed: Q9NRY2)

Alternative names: INTS3- and NABP-interacting protein, Sensor of single-strand DNA complex subunit C, Sensor of ssDNA subunit C, Single-stranded DNA-binding protein-interacting protein 1

All UniProt accessions (3): Q9NRY2, Q5VWJ6, X6R8P6

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. The SOSS complex associates with single-stranded DNA at 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. Interacts with INTS3; the interaction is direct.

Subcellular location. Nucleus.

Similarity. Belongs to the SOSS-C family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NRY2-1	1	yes
Q9NRY2-2	2

RefSeq proteins (7): NP_001316514, NP_001316515, NP_001316516, NP_001316517, NP_001316518, NP_001316519, NP_067041* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031821	SOSSC	Family

Pfam: PF15925

UniProt features (10 total): strand 3, modified residue 2, splice variant 2, initiator methionine 1, chain 1, helix 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4OWT	X-RAY DIFFRACTION	2
4OWW	X-RAY DIFFRACTION	2.3
8RBZ	ELECTRON MICROSCOPY	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRY2-F1	76.79	0.29

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 (2): 2, 50

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 122 (showing top): GOBP_RESPONSE_TO_IONIZING_RADIATION, MODULE_255, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_CELL_CYCLE_PHASE_TRANSITION, MODULE_317, GOBP_MITOTIC_G2_M_TRANSITION_CHECKPOINT, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GROSS_HYPOXIA_VIA_ELK3_UP, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_NEGATIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_DNA_DAMAGE_RESPONSE, GOBP_RESPONSE_TO_RADIATION, GARCIA_TARGETS_OF_FLI1_AND_DAX1_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 (1): protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), site of double-strand break (GO:0035861), SOSS complex (GO:0070876)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
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
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
site of DNA damage	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

576 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INIP	INTS3	Q68E01	999
INIP	SSBP2	P81877	890
INIP	SSBP1	Q04837	876
INIP	NABP2	Q9BQ15	867
INIP	RBBP8	Q99708	831
INIP	NBN	O60934	763
INIP	NABP1	Q96AH0	762
INIP	INTS11	Q5TA45	729
INIP	INTS6	Q9UL03	564
INIP	SSBP4	Q9BWG4	470
INIP	SSBP3	Q9BWW4	470
INIP	C1orf116	Q9BW04	460
INIP	POMK	Q9H5K3	459
INIP	MGAT4B	Q9UQ53	459
INIP	TRIM7	Q9C029	458

IntAct

70 interactions, top by confidence:

A	B	Type	Score
NABP2	INTS3	psi-mi:“MI:0914”(association)	0.810
INTS3	NABP2	psi-mi:“MI:0915”(physical association)	0.810
RBPMS	INIP	psi-mi:“MI:0915”(physical association)	0.670
INIP	RBPMS	psi-mi:“MI:0915”(physical association)	0.670
INIP	INTS3	psi-mi:“MI:0914”(association)	0.630
INTS3	INIP	psi-mi:“MI:0915”(physical association)	0.630
INTS3	INIP	psi-mi:“MI:0407”(direct interaction)	0.630
INTS3	NABP1	psi-mi:“MI:0914”(association)	0.620
NABP1	INTS3	psi-mi:“MI:0914”(association)	0.620
DGCR6L	INIP	psi-mi:“MI:0915”(physical association)	0.600
INIP	DGCR6L	psi-mi:“MI:0915”(physical association)	0.600
KRT34	INIP	psi-mi:“MI:0915”(physical association)	0.560
BPIFA1	INIP	psi-mi:“MI:0915”(physical association)	0.560
ARID5A	INIP	psi-mi:“MI:0915”(physical association)	0.560
DGCR6	INIP	psi-mi:“MI:0915”(physical association)	0.560
COMTD1	IFRD1	psi-mi:“MI:0914”(association)	0.530
SUPT5H	POLR2D	psi-mi:“MI:0914”(association)	0.530
CFTR	INIP	psi-mi:“MI:0915”(physical association)	0.370
Mad2l1	MAD1L1	psi-mi:“MI:0914”(association)	0.350
CHAMP1	GTPBP1	psi-mi:“MI:0914”(association)	0.350
NABP1	XPO1	psi-mi:“MI:0914”(association)	0.350
NABP2	LUC7L3	psi-mi:“MI:0914”(association)	0.350
NABP2	DBT	psi-mi:“MI:0914”(association)	0.350
NABP1	DBT	psi-mi:“MI:0914”(association)	0.350
DLD	NFKBIE	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
SIGLECL1	KIAA1324L	psi-mi:“MI:0914”(association)	0.350

BioGRID (83): INIP (Two-hybrid), INIP (Affinity Capture-MS), INIP (Affinity Capture-MS), INIP (Co-fractionation), INIP (Co-fractionation), INIP (Affinity Capture-MS), INIP (Affinity Capture-MS), INIP (Affinity Capture-MS), INIP (Affinity Capture-MS), INIP (Affinity Capture-MS), INIP (Affinity Capture-MS), INIP (Affinity Capture-MS), INIP (Affinity Capture-MS), INIP (Affinity Capture-MS), RBPMS (Two-hybrid)

ESM2 similar proteins: A6ZVF4, A7RTB3, B5KFM4, B9EQ30, G5EEG1, O42470, O70437, O94900, P03634, P05549, P09414, P17923, P20486, P21999, P25046, P34428, P34708, P40473, P48437, P55924, P58197, P63002, P63003, P97471, Q08117, Q12857, Q13485, Q196U8, Q1HE26, Q2NKT2, Q32NJ6, Q3TXT3, Q58CN7, Q5ZJ32, Q66652, Q66JW3, Q6FK59, Q75BW4, Q7ZV26, Q7ZY13

Diamond homologs: A7RTB3, B4J184, B4KZN6, B5KFM4, B9EQ30, Q2NKT2, Q3TXT3, Q5ZJ32, Q7ZV26, Q8AVV6, Q9NRY2, B3M7M6, B3NDY8, B4H957, B4IG10, B4MHR1, B4MXH8, B4QQE2, B5DRT7, B7Z073

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 63 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
FGFR2 mutant receptor activation	5	92.8×	4e-08
Signaling by FGFR2 IIIa TM	5	73.3×	1e-07
Abortive elongation of HIV-1 transcript in the absence of Tat	6	72.7×	8e-09
Pausing and recovery of Tat-mediated HIV elongation	7	62.9×	2e-09
Tat-mediated HIV elongation arrest and recovery	7	62.9×	2e-09
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	6	59.7×	2e-08
RNA Pol II CTD phosphorylation and interaction with CE	6	59.7×	2e-08
HIV elongation arrest and recovery	7	59.1×	2e-09

GO biological processes:

GO term	Partners	Fold	FDR
double-strand break repair via homologous recombination	5	14.2×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

870 predictions. Top by Δscore:

Variant	Effect	Δscore
9:112687507:CAAAG:C	donor_gain	1.0000
9:112694133:AGCT:A	donor_gain	1.0000
9:112694134:G:C	donor_gain	1.0000
9:112687503:A:AC	donor_gain	0.9900
9:112687511:G:C	donor_gain	0.9900
9:112687630:CATG:C	acceptor_gain	0.9900
9:112687632:TG:T	acceptor_gain	0.9900
9:112687633:GC:G	acceptor_loss	0.9900
9:112687634:C:CC	acceptor_gain	0.9900
9:112687634:C:CG	acceptor_loss	0.9900
9:112687644:T:TC	acceptor_gain	0.9900
9:112689618:C:CC	acceptor_gain	0.9900
9:112694125:CAATA:C	donor_loss	0.9900
9:112694130:CCTAG:C	donor_gain	0.9900
9:112694133:AG:A	donor_gain	0.9900
9:112694133:AGCTC:A	donor_gain	0.9900
9:112694233:CCTA:C	acceptor_loss	0.9900
9:112694234:C:CC	acceptor_gain	0.9900
9:112694235:T:A	acceptor_loss	0.9900
9:112717984:TA:T	donor_loss	0.9900
9:112717985:A:AC	donor_gain	0.9900
9:112717985:ACCT:A	donor_loss	0.9900
9:112717986:C:CC	donor_gain	0.9900
9:112687629:GCATG:G	acceptor_gain	0.9800
9:112687630:CATGC:C	acceptor_gain	0.9800
9:112689613:CAATG:C	acceptor_gain	0.9800
9:112689616:TG:T	acceptor_gain	0.9800
9:112687519:T:A	donor_gain	0.9700
9:112687631:A:C	acceptor_gain	0.9700
9:112694230:AAAC:A	acceptor_gain	0.9700

AlphaMissense

678 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:112687563:A:T	V97D	1.000
9:112687566:G:C	P96R	1.000
9:112687566:G:T	P96H	1.000
9:112687569:A:G	L95P	1.000
9:112687569:A:T	L95H	1.000
9:112687572:A:C	I94S	1.000
9:112687572:A:G	I94T	1.000
9:112687572:A:T	I94N	1.000
9:112687575:A:G	L93P	1.000
9:112687577:G:C	N92K	1.000
9:112687577:G:T	N92K	1.000
9:112687578:T:A	N92I	1.000
9:112687581:C:A	G91V	1.000
9:112687581:C:G	G91A	1.000
9:112687581:C:T	G91E	1.000
9:112687582:C:A	G91W	1.000
9:112687582:C:G	G91R	1.000
9:112687582:C:T	G91R	1.000
9:112687583:A:C	F90L	1.000
9:112687583:A:T	F90L	1.000
9:112687585:A:G	F90L	1.000
9:112687585:A:T	F90I	1.000
9:112687590:G:A	S88F	1.000
9:112687590:G:T	S88Y	1.000
9:112687591:A:G	S88P	1.000
9:112687602:A:T	I84N	1.000
9:112687604:G:C	F83L	1.000
9:112687604:G:T	F83L	1.000
9:112687605:A:C	F83C	1.000
9:112687605:A:G	F83S	1.000

dbSNP variants (sampled 300 via entrez): RS1000080128 (9:112695753 G>A), RS1000193803 (9:112716923 C>A,T), RS1000287330 (9:112702567 T>A), RS1000415113 (9:112688277 T>C), RS1000455886 (9:112702524 G>C), RS1000463695 (9:112709896 A>C,T), RS1000649037 (9:112717236 C>G), RS1000687879 (9:112711802 A>G), RS1001002834 (9:112698297 CTG>C), RS1001070654 (9:112696834 A>G,T), RS1001111774 (9:112691231 A>C), RS1001192766 (9:112704021 G>C), RS1001241093 (9:112713808 T>G), RS1001322552 (9:112720111 G>T), RS1001348675 (9:112690368 T>A,C)

Disease associations

OMIM: gene MIM:613273 | 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
GCST004402_4	Reading disability or specific language impairment adjusted for intelligence quotient (pleiotropy)	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence

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
Tobacco Smoke Pollution	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
ginger extract	decreases expression, decreases reaction, increases abundance	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases reaction, increases abundance, decreases expression	1
trichostatin A	affects expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	increases 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	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Air Pollutants, Occupational	decreases expression	1
Ethanol	affects cotreatment, decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Atrazine	decreases expression	1
Doxorubicin	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Hydrogen Peroxide	affects cotreatment, decreases expression	1
Lead	affects splicing	1
Nickel	decreases expression	1
Oils, Volatile	decreases expression, decreases reaction, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Polycyclic Aromatic Hydrocarbons	increases abundance, affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Testosterone	decreases expression	1
Theophylline	affects cotreatment, decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1

Clinical trials (associated diseases)

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