IVNS1ABP

Summary

IVNS1ABP (influenza virus NS1A binding protein, HGNC:16951) is a protein-coding gene on chromosome 1q25.3, encoding Influenza virus NS1A-binding protein (Q9Y6Y0). Involved in many cell functions, including pre-mRNA splicing, the aryl hydrocarbon receptor (AHR) pathway, F-actin organization and protein ubiquitination.

Predicted to enable ubiquitin-like ligase-substrate adaptor activity. Involved in RNA splicing; negative regulation of protein ubiquitination; and response to virus. Located in cytosol. Implicated in immunodeficiency 70.

Source: NCBI Gene 10625 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 70 (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 69 total — 3 pathogenic
• Phenotypes (HPO): 18
• MANE Select transcript: NM_006469

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16951
Approved symbol	IVNS1ABP
Name	influenza virus NS1A binding protein
Location	1q25.3
Locus type	gene with protein product
Status	Approved
Aliases	NS1-BP, HSPC068, NS-1, KIAA0850, ND1, KLHL39, ARA3
Ensembl gene	ENSG00000116679
Ensembl biotype	protein_coding
OMIM	609209
Entrez	10625

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 28 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000367497, ENST00000367498, ENST00000422754, ENST00000459929, ENST00000468217, ENST00000475046, ENST00000480769, ENST00000491112, ENST00000494880, ENST00000718429, ENST00000866810, ENST00000866811, ENST00000866812, ENST00000866813, ENST00000866814, ENST00000866815, ENST00000866816, ENST00000866817, ENST00000866818, ENST00000866819, ENST00000866820, ENST00000922269, ENST00000922270, ENST00000922271, ENST00000922272, ENST00000922273, ENST00000922274, ENST00000922275, ENST00000922276, ENST00000922277, ENST00000922278, ENST00000957477, ENST00000957478, ENST00000957479

RefSeq mRNA: 1 — MANE Select: NM_006469 NM_006469

CCDS: CCDS1368

Canonical transcript exons

ENST00000367498 — 15 exons

Exon	Start	End
ENSE00001030608	185316953	185317243
ENSE00001030613	185311095	185311322
ENSE00003459539	185300972	185301196
ENSE00003460963	185300217	185300343
ENSE00003504613	185309003	185309172
ENSE00003531299	185307014	185307139
ENSE00003555523	185307489	185307662
ENSE00003555996	185308800	185308875
ENSE00003565082	185300437	185300558
ENSE00003586409	185299710	185299883
ENSE00003624186	185309383	185309511
ENSE00003649901	185299999	185300130
ENSE00003662424	185301434	185301563
ENSE00003678304	185305536	185305643
ENSE00004035063	185296388	185298288

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 97.5418 / max 4829.4773, expressed in 1824 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16303	81.7933	1824
16305	7.0258	1103
16304	4.0345	1482
16302	3.2114	726
16299	0.3756	131
16295	0.3625	122
16296	0.3267	117
16298	0.2502	60
16297	0.1298	33
16294	0.0319	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	98.90	gold quality
metanephros cortex	UBERON:0010533	98.89	gold quality
tibia	UBERON:0000979	98.85	gold quality
minor salivary gland	UBERON:0001830	98.66	gold quality
ventricular zone	UBERON:0003053	98.39	gold quality
calcaneal tendon	UBERON:0003701	98.36	gold quality
skin of abdomen	UBERON:0001416	98.32	gold quality
embryo	UBERON:0000922	98.23	gold quality
bone marrow	UBERON:0002371	98.19	gold quality
mouth mucosa	UBERON:0003729	98.18	gold quality
cortical plate	UBERON:0005343	98.13	gold quality
rectum	UBERON:0001052	98.08	gold quality
skin of leg	UBERON:0001511	98.03	gold quality
bone marrow cell	CL:0002092	97.98	gold quality
granulocyte	CL:0000094	97.93	gold quality
tendon	UBERON:0000043	97.83	gold quality
omental fat pad	UBERON:0010414	97.79	gold quality
peritoneum	UBERON:0002358	97.78	gold quality
adult mammalian kidney	UBERON:0000082	97.68	gold quality
renal medulla	UBERON:0000362	97.64	gold quality
saliva-secreting gland	UBERON:0001044	97.58	gold quality
tendon of biceps brachii	UBERON:0008188	97.58	gold quality
zone of skin	UBERON:0000014	97.52	gold quality
adrenal tissue	UBERON:0018303	97.48	gold quality
vagina	UBERON:0000996	97.40	gold quality
sperm	CL:0000019	97.35	gold quality
gall bladder	UBERON:0002110	97.28	gold quality
upper lobe of left lung	UBERON:0008952	97.16	gold quality
monocyte	CL:0000576	97.10	gold quality
endometrium	UBERON:0001295	97.05	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	3939.99
E-MTAB-6108	yes	309.09
E-CURD-119	yes	54.91
E-GEOD-125970	yes	24.80
E-HCAD-10	yes	23.33
E-CURD-89	no	1010.85
E-GEOD-109979	no	871.09
E-MTAB-8271	no	245.33
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

142 targeting IVNS1ABP, 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-1252-5P	100.00	69.80	2774
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426

Literature-anchored findings (GeneRIF, showing 9)

• These findings further support the distinct roles of alpha-enolase and its MBP-1 variant in maintaining cell homeostasis. Moreover, these data suggest a novel function for NS1-BP in the control of cell proliferation. (PMID:17996313)
• NS1-BP-hnRNPK complex is a key mediator of influenza A virus gene expression. (PMID:23825951)
• This study provided evidence that miRNA-548an is involved in the regulation of NS1ABP. (PMID:24210102)
• Our study identifies KLHL39 as a negative regulator of Cul3-KLHL20 ubiquitin ligase and reveals a role of KLHL39-mediated PML and DAPK stabilization in colon cancer metastasis. (PMID:25619834)
• Comparison of the Kelch-domain structures of NS1-BP and its homologues showed that the Gly-Gly pair in beta-strand B and the hydrophobic Trp residue in beta-strand D are highly conserved, while the B-C loops in blades 2 and 6 are variable (PMID:29497022)
• In esophageal squamous cell carcinoma (ESCC) tissues, c-Myc expression was inversely correlated with NS1-binding protein (NS1-BP) levels, and was associated with a shorter disease-specific survival (DSS). (PMID:29871674)
• Data show that heterogeneous nuclear ribonucleoprotein K (hnRNP K) and influenza virus NS1A binding protein (NS1-BP) regulate host splicing events and that viral infection causes mis-splicing of some of these transcripts. (PMID:29921878)
• The central BACK domain of NS1-BP interacts directly with splicing factors such as hnRNP K and PTBP1 and with the viral NS1 protein. (PMID:30538201)
• Soluble NS1 Antagonizes IgG- and IgA- Mediated Monocytic Phagocytosis of DENV Infected Cells. (PMID:37103221)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ivns1abpb	ENSDARG00000013946
danio_rerio	ivns1abpa	ENSDARG00000031100
mus_musculus	Ivns1abp	ENSMUSG00000023150
rattus_norvegicus	Ivns1abp	ENSRNOG00000002618

Paralogs (54): KLHL13 (ENSG00000003096), KLHL20 (ENSG00000076321), KEAP1 (ENSG00000079999), KLHL42 (ENSG00000087448), KLHL22 (ENSG00000099910), KLHL4 (ENSG00000102271), KLHL2 (ENSG00000109466), KLHL5 (ENSG00000109790), BACH2 (ENSG00000112182), KLHL18 (ENSG00000114648), KLHL24 (ENSG00000114796), KLHL12 (ENSG00000117153), KLHL29 (ENSG00000119771), KBTBD7 (ENSG00000120696), KLHL7 (ENSG00000122550), KLHL31 (ENSG00000124743), KLHDC7B (ENSG00000130487), KLHL36 (ENSG00000135686), KLHL8 (ENSG00000145332), KLHL3 (ENSG00000146021), KLHL35 (ENSG00000149243), KLHL1 (ENSG00000150361), BACH1 (ENSG00000156273), KLHL40 (ENSG00000157119), KLHL10 (ENSG00000161594), KLHL21 (ENSG00000162413), KLHDC8A (ENSG00000162873), KBTBD8 (ENSG00000163376), KBTBD6 (ENSG00000165572), KLHL26 (ENSG00000167487), KLHL30 (ENSG00000168427), KBTBD2 (ENSG00000170852), KLHL6 (ENSG00000172578), KLHL15 (ENSG00000174010), KLHL38 (ENSG00000175946), KBTBD11 (ENSG00000176595), KLHDC7A (ENSG00000179023), KLHL28 (ENSG00000179454), KBTBD3 (ENSG00000182359), KLHL33 (ENSG00000185271)

Protein

Protein identifiers

Influenza virus NS1A-binding protein — Q9Y6Y0 (reviewed: Q9Y6Y0)

Alternative names: Aryl hydrocarbon receptor-associated protein 3, Kelch-like protein 39

All UniProt accessions (3): Q9Y6Y0, H0Y5Y2, X6R674

UniProt curated annotations — full annotation on UniProt →

Function. Involved in many cell functions, including pre-mRNA splicing, the aryl hydrocarbon receptor (AHR) pathway, F-actin organization and protein ubiquitination. Plays a role in the dynamic organization of the actin skeleton as a stabilizer of actin filaments by association with F-actin through Kelch repeats. Protects cells from cell death induced by actin destabilization. Functions as modifier of the AHR/Aryl hydrocarbon receptor pathway increasing the concentration of AHR available to activate transcription. In addition, functions as a negative regulator of BCR(KLHL20) E3 ubiquitin ligase complex to prevent ubiquitin-mediated proteolysis of PML and DAPK1, two tumor suppressors. Inhibits pre-mRNA splicing (in vitro). May play a role in mRNA nuclear export. (Microbial infection) Involved in the alternative splicing of influenza A virus M1 mRNA through interaction with HNRNPK, thereby facilitating the generation of viral M2 protein. The BTB and Kelch domains are required for splicing activity. Promotes export of viral M mRNA and RNP via its interaction with mRNA export factor ALYREF.

Subunit / interactions. Homodimer; through the BTB domain. Interacts with AHR/Aryl hydrocarbon receptor. Interacts (via BACK domain) with pre-mRNA-binding protein HNRNPK; the interaction is direct. Interacts (via BACK domain) with splicing factor PTBP1; the interaction is direct. Interacts (via Kelch repeats) with RNA polymerase POLR2A (via C-terminal domain). Interacts (via BACK domain) with splicing factor SNRPA; the interaction is indirect. Interacts (via Kelch repeats) with splicing factor SART1. Interacts (via BACK domain) with ALYREF; the interaction is indirect and likely plays a role in mRNA nuclear export. Interacts (via Kelch repeats) with KLHL20 (via Kelch repeats); this interaction blocks the assembly of Cul3-KLHL20 complex. (Microbial infection) Interacts (via BACK domain) with influenza A virus non-structural protein 1 (NS1); the interaction is direct and bridges the interaction between NS1 and HNRNPK.

Subcellular location. Cytoplasm. Cytoskeleton. Nucleus. Nucleoplasm.

Disease relevance. Immunodeficiency 70 (IMD70) [MIM:618969] A primary immunodeficiency clinically characterized by human papillomavirus-associated warts on the hands, feet and face, recurrent bacterial infections, and autoinflammatory features, such as colitis, celiac disease, and retinal vasculitis. Immunologic workup shows decreased CD4+ T cells, decreased CD19+ B cells, and hypogammaglobulinemia. IMD70 inheritance is autosomal dominant with incomplete penetrance. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. When the BTB domain is lacking, AHR signaling induction promoted by IVNS1ABP is massively increased; Thus, the BTB domain inhibits AHR signaling induced by IVNS1ABP. Dimerization is necessary for proper splicing activity of IVNS1ABP and this is mediated by the BTB domain. The BACK domain is necessary for proper viral M mRNA export.

Similarity. Belongs to the BTB-kelch protein family.

RefSeq proteins (1): NP_006460* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR006652	Kelch_1	Repeat
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR011705	BACK	Domain
IPR015915	Kelch-typ_b-propeller	Homologous_superfamily
IPR017096	BTB-kelch_protein	Family

Pfam: PF00651, PF01344, PF07707, PF24681

UniProt features (76 total): strand 34, helix 8, sequence conflict 6, repeat 6, turn 6, modified residue 5, mutagenesis site 3, domain 2, region of interest 2, sequence variant 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5YY8	X-RAY DIFFRACTION	1.98
6N3H	X-RAY DIFFRACTION	2.6
6N34	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6Y0-F1	84.95	0.67

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 (5): 246, 277, 322, 336, 338

Mutagenesis-validated functional residues (3):

Position	Phenotype
1–12	destabilises dimer and impairs splicing of viral m1 mrna.
198	significant inhibition of interaction with ahr; partial decrease of ahr signaling induced by ivns1abp.
288	significant inhibition of interaction with ahr; partial decrease of ahr signaling induced by ivns1abp.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 372 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, RORA1_01, FISCHER_G1_S_CELL_CYCLE, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, ATGCAGT_MIR217, USF_C, TANG_SENESCENCE_TP53_TARGETS_UP, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, GOBP_APOPTOTIC_SIGNALING_PATHWAY

GO Biological Process (8): transcription by RNA polymerase III (GO:0006383), mRNA processing (GO:0006397), RNA splicing (GO:0008380), response to virus (GO:0009615), negative regulation of protein ubiquitination (GO:0031397), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), intrinsic apoptotic signaling pathway (GO:0097193), negative regulation of intrinsic apoptotic signaling pathway (GO:2001243)

GO Molecular Function (5): ubiquitin-like ligase-substrate adaptor activity (GO:1990756), DNA binding (GO:0003677), protein binding (GO:0005515), zinc ion binding (GO:0008270), metal ion binding (GO:0046872)

GO Cellular Component (8): nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), spliceosomal complex (GO:0005681), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), Cul3-RING ubiquitin ligase complex (GO:0031463), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
RNA processing	2
DNA-templated transcription	1
mRNA metabolic process	1
response to other organism	1
protein ubiquitination	1
regulation of protein ubiquitination	1
negative regulation of protein modification by small protein conjugation or removal	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
intracellular signal transduction	1
apoptotic signaling pathway	1
intrinsic apoptotic signaling pathway	1
negative regulation of intracellular signal transduction	1
negative regulation of apoptotic signaling pathway	1
regulation of intrinsic apoptotic signaling pathway	1
enzyme-substrate adaptor activity	1
nucleic acid binding	1
binding	1
transition metal ion binding	1
cation binding	1
nuclear lumen	1
protein-containing complex	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membraneless organelle	1
cullin-RING ubiquitin ligase complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

956 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IVNS1ABP	HNRNPK	P61978	836
IVNS1ABP	TLX2	O43763	825
IVNS1ABP	PRODH	O43272	717
IVNS1ABP	SRSF2	Q01130	702
IVNS1ABP	PRPSAP1	Q14558	579
IVNS1ABP	SART1	O43290	571
IVNS1ABP	SWT1	Q5T5J6	532
IVNS1ABP	NUCLEOLIN	P19338	485
IVNS1ABP	SRSF6	Q13247	482
IVNS1ABP	TRMT1L	Q7Z2T5	459
IVNS1ABP	SYNCRIP	O60506	421
IVNS1ABP	FBF1	Q8TES7	402
IVNS1ABP	SERPINB10	P48595	400
IVNS1ABP	ERVMER34-1	Q9H9K5	394
IVNS1ABP	PDLIM2	Q96JY6	393

IntAct

101 interactions, top by confidence:

A	B	Type	Score
KLHL20	CUL3	psi-mi:“MI:0914”(association)	0.920
CUL3	KLHL20	psi-mi:“MI:0914”(association)	0.920
KLHL20	PML	psi-mi:“MI:0914”(association)	0.810
PLK1	SPAG9	psi-mi:“MI:0914”(association)	0.790
KLHL20	DAPK1	psi-mi:“MI:0914”(association)	0.780
PRPSAP1	PRPSAP2	psi-mi:“MI:0914”(association)	0.740
NCK1	NCK2	psi-mi:“MI:0914”(association)	0.730
DDX6	RPS3	psi-mi:“MI:0915”(physical association)	0.690
KLHL20	PML	psi-mi:“MI:0914”(association)	0.660
KLHL20	IVNS1ABP	psi-mi:“MI:0915”(physical association)	0.650
KLHL20	IVNS1ABP	psi-mi:“MI:0407”(direct interaction)	0.650
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
SH3KBP1	USP27X	psi-mi:“MI:0914”(association)	0.640
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
PRPS1	NMT2	psi-mi:“MI:0914”(association)	0.640
DDX6	RPLP0	psi-mi:“MI:0915”(physical association)	0.620
PRPSAP1	PRPSAP2	psi-mi:“MI:0914”(association)	0.610
GSK3B	UBR5	psi-mi:“MI:0915”(physical association)	0.610
PRPSAP2	CCNB1	psi-mi:“MI:0914”(association)	0.530
CRK	ARHGAP42	psi-mi:“MI:0914”(association)	0.530
YWHAB	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAE	SHTN1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	SHTN1	psi-mi:“MI:0914”(association)	0.530
CUL3	IVNS1ABP	psi-mi:“MI:0915”(physical association)	0.500
IVNS1ABP	CCT3	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (192): IVNS1ABP (Affinity Capture-MS), IVNS1ABP (Affinity Capture-MS), IVNS1ABP (Affinity Capture-MS), IVNS1ABP (Affinity Capture-MS), IVNS1ABP (Affinity Capture-MS), IVNS1ABP (Affinity Capture-MS), IVNS1ABP (Affinity Capture-MS), IVNS1ABP (Affinity Capture-MS), IVNS1ABP (Affinity Capture-MS), IVNS1ABP (Affinity Capture-MS), IVNS1ABP (Affinity Capture-MS), KLHL20 (Affinity Capture-Western), IVNS1ABP (Affinity Capture-Western), IVNS1ABP (Reconstituted Complex), DAPK1 (Affinity Capture-Western)

ESM2 similar proteins: A0A1B8YAB1, B1H285, B3DIV9, E9QIN8, E9QJ30, F1QEG2, O88879, Q08CL3, Q08CY1, Q0D2A9, Q13939, Q28068, Q3UQV5, Q3ZCT8, Q503R4, Q5F3N5, Q5R4S6, Q5R663, Q5RG82, Q5XHZ6, Q5XI58, Q5ZI33, Q69ZK5, Q6DFF7, Q6DFU2, Q6Q7X9, Q6V595, Q7ZVQ8, Q86V97, Q8BHI4, Q8BUL5, Q8BWA5, Q8CA72, Q8CDE2, Q8CE33, Q8IXQ5, Q8NAB2, Q8NFY9, Q8R179, Q8WVZ9

Diamond homologs: B1WBS3, B1WBU4, B2RXF5, D3ZUU2, E1B932, G5E8B9, O14682, O15060, O15062, O15209, O35709, O43298, O88282, O95625, P10074, P41182, P41183, P59280, P97303, Q05516, Q0D2A9, Q0D2K2, Q13105, Q1H9T6, Q1L8W0, Q2WGJ6, Q3B7M1, Q3B7N9, Q3ZB90, Q4KLM4, Q4VBD9, Q503R4, Q52KB5, Q53G59, Q562B4, Q5BK60, Q5EXX3, Q5R5N5, Q5R633, Q5RG82

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 113 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	46.3×	2e-07
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	46.3×	2e-07
Activation of BAD and translocation to mitochondria	5	43.8×	4e-06
Activation of BH3-only proteins	5	28.5×	3e-05
RHO GTPases activate PKNs	6	21.9×	1e-05
Intrinsic Pathway for Apoptosis	6	20.2×	2e-05
Parasite infection	5	19.9×	1e-04
Leishmania phagocytosis	5	19.9×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	6	20.4×	5e-04
protein targeting	5	18.1×	2e-03
positive regulation of actin filament polymerization	5	16.4×	2e-03
negative regulation of translation	5	9.7×	8e-03
endocytosis	8	7.5×	2e-03
intracellular protein localization	7	7.2×	4e-03
protein phosphorylation	9	6.1×	2e-03
cell migration	9	5.5×	4e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	42
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
974682	NC_000001.10:g.185276239_185287961del	Pathogenic
974683	NM_006469.5(IVNS1ABP):c.1072C>T (p.Arg358Ter)	Pathogenic
974684	NM_006469.5(IVNS1ABP):c.1899G>A (p.Trp633Ter)	Pathogenic

SpliceAI

2012 predictions. Top by Δscore:

Variant	Effect	Δscore
1:185298284:TTTTC:T	acceptor_gain	1.0000
1:185298285:TTTC:T	acceptor_gain	1.0000
1:185298286:TTC:T	acceptor_gain	1.0000
1:185298286:TTCC:T	acceptor_loss	1.0000
1:185298287:TC:T	acceptor_gain	1.0000
1:185298288:CC:C	acceptor_gain	1.0000
1:185298288:CCTA:C	acceptor_loss	1.0000
1:185298289:C:CC	acceptor_gain	1.0000
1:185298290:T:C	acceptor_loss	1.0000
1:185299705:CTCA:C	donor_loss	1.0000
1:185299706:TCAC:T	donor_loss	1.0000
1:185299707:CAC:C	donor_loss	1.0000
1:185299708:A:AC	donor_gain	1.0000
1:185299708:AC:A	donor_gain	1.0000
1:185299708:ACC:A	donor_loss	1.0000
1:185299709:C:CC	donor_gain	1.0000
1:185299709:CC:C	donor_gain	1.0000
1:185299880:CTCC:C	acceptor_gain	1.0000
1:185299881:TCC:T	acceptor_gain	1.0000
1:185299881:TCCC:T	acceptor_loss	1.0000
1:185299882:CC:C	acceptor_gain	1.0000
1:185299882:CCC:C	acceptor_gain	1.0000
1:185299882:CCCTA:C	acceptor_loss	1.0000
1:185299883:CC:C	acceptor_gain	1.0000
1:185299884:C:CC	acceptor_gain	1.0000
1:185299992:AACTT:A	donor_loss	1.0000
1:185299993:ACTTA:A	donor_loss	1.0000
1:185299994:CTTA:C	donor_loss	1.0000
1:185299995:TTA:T	donor_loss	1.0000
1:185299996:TACG:T	donor_loss	1.0000

AlphaMissense

4261 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:185298107:A:C	F619L	1.000
1:185298107:A:T	F619L	1.000
1:185298109:A:G	F619L	1.000
1:185298122:G:C	F614L	1.000
1:185298122:G:T	F614L	1.000
1:185298124:A:G	F614L	1.000
1:185298126:C:T	G613E	1.000
1:185298129:C:T	G612E	1.000
1:185298208:A:G	W586R	1.000
1:185298208:A:T	W586R	1.000
1:185299770:A:G	W539R	1.000
1:185299770:A:T	W539R	1.000
1:185299818:A:G	W523R	1.000
1:185299818:A:T	W523R	1.000
1:185299832:C:T	G518E	1.000
1:185300026:A:G	W492R	1.000
1:185300026:A:T	W492R	1.000
1:185300257:C:A	W443C	1.000
1:185300257:C:G	W443C	1.000
1:185300259:A:G	W443R	1.000
1:185300259:A:T	W443R	1.000
1:185300321:C:T	G422E	1.000
1:185300464:T:A	R405S	1.000
1:185300464:T:G	R405S	1.000
1:185300496:A:G	W395R	1.000
1:185300496:A:T	W395R	1.000
1:185300538:A:G	C381R	1.000
1:185300555:C:T	G375D	1.000
1:185300556:C:G	G375R	1.000
1:185300558:C:T	G374D	1.000

dbSNP variants (sampled 300 via entrez): RS1000379743 (1:185313993 TA>T), RS1000578356 (1:185314776 C>T), RS1000642384 (1:185315347 A>G,T), RS1000652694 (1:185319220 C>T), RS1000715301 (1:185315640 A>T), RS1000871876 (1:185307956 T>C), RS1000999866 (1:185300817 T>C,G), RS1001070049 (1:185307849 T>C,G), RS1001156305 (1:185301191 T>A,C), RS1001488078 (1:185302704 T>A,G), RS1001576150 (1:185311968 A>G), RS1001600464 (1:185310001 C>T), RS1001682900 (1:185317825 G>C), RS1001744840 (1:185318137 T>G), RS1002180635 (1:185313628 A>G)

Disease associations

OMIM: gene MIM:609209 | disease phenotypes: MIM:618969

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 70	Strong	Autosomal dominant

Mondo (1): immunodeficiency 70 (MONDO:0033542)

Orphanet (0):

HPO phenotypes

18 total (18 of 18 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0002571	Achalasia
HP:0002583	Colitis
HP:0002608	Celiac disease
HP:0002721	Immunodeficiency
HP:0002850	Decreased circulating total IgM
HP:0003460	Decreased circulating total IgA
HP:0004313	Decreased circulating immunoglobulin concentration
HP:0010976	Decreased total B cell count
HP:0011108	Recurrent sinusitis
HP:0012432	Chronic fatigue
HP:0020083	Furuncle
HP:0025188	Retinal vasculitis
HP:0032132	Decreased circulating total IgG concentration
HP:0032218	Decreased CD4+ T cell proportion
HP:0033004	Palmar warts
HP:0033005	Plantar warts
HP:0200043	Verrucae

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002935_15	Lead levels	5.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	5
Benzo(a)pyrene	decreases expression, decreases methylation	4
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
trichostatin A	affects cotreatment, increases expression	2
sodium arsenite	decreases expression, increases abundance	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Tetrachlorodibenzodioxin	decreases expression	2
Tretinoin	increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
beta-lapachone	decreases expression	1
cobaltous chloride	decreases expression	1
nickel sulfate	decreases expression	1
coumarin	increases phosphorylation	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants, Occupational	affects expression	1

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1UX	Abcam HeLa IVNS1ABP KO	Cancer cell line	Female
CVCL_ST65	HAP1 IVNS1ABP (-) 1	Cancer cell line	Male
CVCL_ST66	HAP1 IVNS1ABP (-) 2	Cancer cell line	Male
CVCL_ST67	HAP1 IVNS1ABP (-) 3	Cancer cell line	Male
CVCL_ST68	HAP1 IVNS1ABP (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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