PAXIP1

Summary

PAXIP1 (PAX interacting protein 1, HGNC:8624) is a protein-coding gene on chromosome 7q36.2, encoding PAX-interacting protein 1 (Q6ZW49). Involved in DNA damage response and in transcriptional regulation through histone methyltransferase (HMT) complexes. It is a selective cancer dependency (DepMap: 22.9% of cell lines).

This gene is a member of the paired box (PAX) gene family and encodes a nuclear protein with six BRCT (breast cancer carboxy-terminal) domains. This protein plays a critical role in maintaining genome stability, condensation of chromatin and progression through mitosis.

Source: NCBI Gene 22976 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 103 total
• Cancer dependency (DepMap): dependent in 22.9% of screened cell lines
• MANE Select transcript: NM_007349

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8624
Approved symbol	PAXIP1
Name	PAX interacting protein 1
Location	7q36.2
Locus type	gene with protein product
Status	Approved
Aliases	CAGF29, CAGF28, TNRC2, PTIP
Ensembl gene	ENSG00000157212
Ensembl biotype	protein_coding
OMIM	608254
Entrez	22976

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 3 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000404141, ENST00000419436, ENST00000457196, ENST00000464717, ENST00000473219, ENST00000475066, ENST00000485730, ENST00000494182, ENST00000919354

RefSeq mRNA: 1 — MANE Select: NM_007349 NM_007349

CCDS: CCDS47753

Canonical transcript exons

ENST00000404141 — 21 exons

Exon	Start	End
ENSE00003483411	154955529	154955631
ENSE00003490259	154947903	154948003
ENSE00003494420	154967816	154967910
ENSE00003502483	154946679	154946813
ENSE00003511982	154975696	154976331
ENSE00003550966	154954255	154954423
ENSE00003568862	154943690	154944164
ENSE00003579839	154946365	154946425
ENSE00003586330	154962321	154962458
ENSE00003612298	154983219	154983332
ENSE00003616447	154961527	154961648
ENSE00003619613	154993726	154993769
ENSE00003624492	154991006	154991069
ENSE00003647262	154968403	154969126
ENSE00003651193	154963671	154963766
ENSE00003667854	154960893	154961077
ENSE00003670642	154959890	154959933
ENSE00003678769	154957224	154957294
ENSE00003682654	154998650	154998784
ENSE00003694441	154946512	154946587
ENSE00003893224	155002849	155003124

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 98.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.7818 / max 46.6123, expressed in 1511 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86996	1.5767	926
86998	1.5322	1005
86997	0.6728	402

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.88	gold quality
oocyte	CL:0000023	98.78	gold quality
cerebellar hemisphere	UBERON:0002245	91.29	gold quality
cerebellar cortex	UBERON:0002129	91.27	gold quality
cerebellum	UBERON:0002037	91.11	gold quality
ventricular zone	UBERON:0003053	91.03	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.72	gold quality
corpus epididymis	UBERON:0004359	87.10	gold quality
thymus	UBERON:0002370	87.00	gold quality
cerebellar vermis	UBERON:0004720	85.57	gold quality
cartilage tissue	UBERON:0002418	84.19	gold quality
embryo	UBERON:0000922	84.12	gold quality
ganglionic eminence	UBERON:0004023	83.34	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.11	gold quality
caput epididymis	UBERON:0004358	83.03	gold quality
palpebral conjunctiva	UBERON:0001812	82.45	gold quality
endothelial cell	CL:0000115	81.93	silver quality
trabecular bone tissue	UBERON:0002483	81.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.81	gold quality
placenta	UBERON:0001987	81.17	gold quality
adult organism	UBERON:0007023	80.75	gold quality
oral cavity	UBERON:0000167	80.72	gold quality
skin of hip	UBERON:0001554	80.71	gold quality
mucosa of sigmoid colon	UBERON:0004993	80.47	gold quality
bone marrow	UBERON:0002371	80.26	gold quality
colonic mucosa	UBERON:0000317	80.11	gold quality
testis	UBERON:0000473	79.89	gold quality
cauda epididymis	UBERON:0004360	79.89	gold quality
colonic epithelium	UBERON:0000397	79.76	gold quality
right testis	UBERON:0004534	79.63	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

58 targeting PAXIP1, 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-3163	100.00	77.23	8605
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-570-3P	99.96	72.41	4910
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-548D-3P	99.87	70.67	4362
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-1303	99.65	69.77	1662

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 22.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 21)

• PTIP (PAXIP1) is a strong inhibitor of the trans-activation activities of Pax2A and Pax2B on the glucagon gene promoter and p8 binding to PTIP prevents inhibition of this promoter. (PMID:11940591)
• identified tandem BRCT (BRCA1 carboxyl-terminal) domains in PTIP and in BRCA1 as phosphoserine- or phosphothreonine-specific binding modules that recognize substrates phosphorylated by the kinases ATM and ATR in response to gamma-irradiation (PMID:14576432)
• hPTIP (PAXIP1) shows increased association with 53BP1 in response to ionizing radiation but not in response to other DNA-damaging agents. (PMID:15456759)
• Without DNA damage agent treatment, endogenous PTIP associates with MLL3- and MLL4-containing histone H3 K4 methyltransferase complex that also contains ASH2L, RBBP5, WDR5, hDPY-30, NCOA6, PA1 and JmjC domain-containing putative histone demethylase UTX. (PMID:17500065)
• Determination of a single ATM-phosphorylated residue in 53BP1–Ser25–that is required for binding of 53BP1 to hPTIP. (PMID:17690115)
• PTIP depletion from mammalian cells by RNAi reduced PCNA ubiquitination in response to DNA damage, and also decreased the recruitment to chromatin of polymerase eta and the recombination protein Rad51 (PMID:18353733)
• subset of PTIP.PA1 complex is recruited to DNA damage sites via the RNF8-dependent pathway and is required for cell survival in response to DNA damage. (PMID:19124460)
• PTIP regulates 53BP1-dependent signaling pathway following DNA damage (PMID:19414588)
• PTIP controls expression of PPARgamma and C/EBPalpha, the two principal adipogenic transcription factors, and is therefore required for adipogenesis. (PMID:19583951)
• PTIP promotes double-strand break repair through a direct role in homologous recombination. (PMID:20088963)
• a new clue to identify the role of PTIP in DNA damage pathway (PMID:22064073)
• Polyglutamine expansion AR sequesters PTIP to attenuate DNA repair and increase genomic instability. (PMID:22736030)
• PITX2 and PTIP co-occupy the promoter of the PITX2’s transcriptional target. (PMID:24486544)
• uncovered a nuclease, Artemis, as a PTIP-binding protein (PMID:25512557)
• PPM1B can dephosphorylate the Pax2 activation domain and displace the adaptor protein PTIP, thus inhibiting H3K4 methylation and gene activation. (PMID:25631048)
• PAXIP1 is involved in sensitizing lung cancer cells to the WEE1 inhibitor AZD1775 in combination with platinum-based treatment. (PMID:27196765)
• PAXIP1 and 53BP1 protein levels followed gene expression results, i.e., are intrinsically correlated, and also reduced in more advanced breast cancer tumors. (PMID:28475402)
• PTIP governs NAD(+) metabolism by regulating CD38 expression to drive macrophage inflammation. (PMID:35354042)
• Polymorphisms in the HSF2, LRRC6, MEIG1 and PTIP genes correlate with sperm motility in idiopathic infertility. (PMID:35768906)
• Longitudinal profiling identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1 and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer. (PMID:38244928)
• PTIP epigenetically regulates DNA damage-induced cell cycle arrest by upregulating PRDM1. (PMID:39097652)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	paxip1	ENSDARG00000005606
mus_musculus	Paxip1	ENSMUSG00000002221
rattus_norvegicus	Paxip1	ENSRNOG00000007131
caenorhabditis_elegans		WBGENE00004031

Paralogs (1): MDC1 (ENSG00000137337)

Protein

Protein identifiers

PAX-interacting protein 1 — Q6ZW49 (reviewed: Q6ZW49)

Alternative names: PAX transactivation activation domain-interacting protein

All UniProt accessions (3): Q6ZW49, F8WC23, H7BZI8

UniProt curated annotations — full annotation on UniProt →

Function. Involved in DNA damage response and in transcriptional regulation through histone methyltransferase (HMT) complexes. Plays a role in early development. In DNA damage response is required for cell survival after ionizing radiation. In vitro shown to be involved in the homologous recombination mechanism for the repair of double-strand breaks (DSBs). Its localization to DNA damage foci requires RNF8 and UBE2N. Recruits TP53BP1 to DNA damage foci and, at least in particular repair processes, effective DNA damage response appears to require the association with TP53BP1 phosphorylated by ATM at ‘Ser-25’. Together with TP53BP1 regulates ATM association. Proposed to recruit PAGR1 to sites of DNA damage and the PAGR1:PAXIP1 complex is required for cell survival in response to DNA damage; the function is probably independent of MLL-containing histone methyltransferase (HMT) complexes. However, this function has been questioned. Promotes ubiquitination of PCNA following UV irradiation and may regulate recruitment of polymerase eta and RAD51 to chromatin after DNA damage. Proposed to be involved in transcriptional regulation by linking MLL-containing histone methyltransferase (HMT) complexes to gene promoters by interacting with promoter-bound transcription factors such as PAX2. Associates with gene promoters that are known to be regulated by KMT2D/MLL2. During immunoglobulin class switching in activated B-cells is involved in trimethylation of histone H3 at ‘Lys-4’ and in transcription initiation of downstream switch regions at the immunoglobulin heavy-chain (Igh) locus; this function appears to involve the recruitment of MLL-containing HMT complexes. Conflictingly, its function in transcriptional regulation during immunoglobulin class switching is reported to be independent of the MLL2/MLL3 complex.

Subunit / interactions. Interacts with the C-terminal transactivation domain of PAX2. Forms a constitutive complex with PAGR1 independently of the MLL2/MLL3 complex. Interacts with TP53BP1 (when phosphorylated at the N-terminus by ATM). Interacts with HLTF. Component of the KMT2 family MLL2/MLL3 complex (also named ASCOM complex), at least composed of the HMTs KMT2D and/or KMT2C, the common subunits ASH2L, RBBP5, WDR5 and DPY30, and the complex type-specific subunits PAXIP1/PTIP, PAGR1, NCOA6 and KDM6A; required for the association of PAGR1 with the MLL2/MLL3 complex. Interacts with NUPR1; this interaction prevents PAXIP1 inhibition of PAX2 transcription factor activity.

Subcellular location. Nucleus matrix. Chromosome.

Domain organisation. The BRCT 1 and 2 domains mediate the interaction with PAGR1A. The BRCT 5 and 6 domains mediate the association with the MLL2/MLL3 complex. The BRCT 5 and 6 domains function as a single module and are necessary and sufficient for in vitro phospho-specific binding (substrates phosphorylated by the kinases ataxia telangiectasia-mutated (ATM), ataxia telangiectasia and RAD3-related (ATR) in response to gamma irradiation). In contrast, in vivo two pairs of BRCT domains (3-6) bind to phosphorylated TP53BP1 much more efficiently.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6ZW49-6	1	yes
Q6ZW49-1	2
Q6ZW49-2	3

RefSeq proteins (1): NP_031375* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001357	BRCT_dom	Domain
IPR036420	BRCT_dom_sf	Homologous_superfamily
IPR051579	DDR_Transcriptional_Reg	Family

Pfam: PF00533, PF12738, PF16589, PF16770

UniProt features (58 total): helix 13, sequence conflict 8, compositionally biased region 7, domain 6, strand 6, region of interest 5, mutagenesis site 3, turn 3, modified residue 2, splice variant 2, chain 1, short sequence motif 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3SQD	X-RAY DIFFRACTION	2.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZW49-F1	69.24	0.43

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): 227, 235

Mutagenesis-validated functional residues (3):

Position	Phenotype
676	abolishes interaction with tp53bp1; prevents recruitment to dna damage foci.
910	abolishes interaction with tp53bp1; impairs intact cellular response to dna damage.
929	abolishes interaction with tp53bp1; prevents recruitment to dna damage foci.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-5693571	Nonhomologous End-Joining (NHEJ)
R-HSA-9772755	Formation of WDR5-containing histone-modifying complexes
R-HSA-9818564	Epigenetic regulation of gene expression by MLL3 and MLL4 complexes
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis

MSigDB gene sets: 278 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_RESPONSE_TO_IONIZING_RADIATION, MORF_FLT1, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, MORF_MSH3, GOBP_B_CELL_ACTIVATION, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, MORF_BRCA1, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, MORF_ATRX, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN

GO Biological Process (16): vasculogenesis (GO:0001570), DNA repair (GO:0006281), DNA recombination (GO:0006310), chromatin remodeling (GO:0006338), response to ionizing radiation (GO:0010212), DNA damage response, signal transduction by p53 class mediator (GO:0030330), positive regulation of protein ubiquitination (GO:0031398), obsolete negative regulation of DNA-binding transcription factor activity (GO:0043433), endothelial cell migration (GO:0043542), positive regulation of isotype switching (GO:0045830), positive regulation of isotype switching to IgG isotypes (GO:0048304), positive regulation of transcription initiation by RNA polymerase II (GO:0060261), adipose tissue development (GO:0060612), chorion development (GO:0060717), regulation of cell cycle G2/M phase transition (GO:1902749), DNA damage response (GO:0006974)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), nuclear matrix (GO:0016363), histone methyltransferase complex (GO:0035097), MLL3/4 complex (GO:0044666)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Epigenetic regulation by WDR5-containing histone modifying complexes	2
Activation of HOX genes during differentiation	1
DNA Double-Strand Break Repair	1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	2
nuclear lumen	2
cellular anatomical structure	2
cell differentiation	1
blood vessel morphogenesis	1
DNA damage response	1
chromatin organization	1
response to radiation	1
signal transduction in response to DNA damage	1
signal transduction by p53 class mediator	1
protein ubiquitination	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
cell migration	1
positive regulation of immunoglobulin production	1
positive regulation of immunoglobulin mediated immune response	1
isotype switching	1
regulation of isotype switching	1
positive regulation of DNA recombination	1
positive regulation of B cell activation	1
positive regulation of developmental process	1
positive regulation of isotype switching	1
isotype switching to IgG isotypes	1
regulation of isotype switching to IgG isotypes	1
transcription initiation at RNA polymerase II promoter	1
positive regulation of transcription by RNA polymerase II	1
regulation of transcription initiation by RNA polymerase II	1
positive regulation of DNA-templated transcription initiation	1
animal organ development	1
connective tissue development	1
extraembryonic membrane development	1
cell cycle G2/M phase transition	1
regulation of cell cycle phase transition	1
cellular response to stress	1
binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
nucleoplasm	1
methyltransferase complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

2224 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PAXIP1	KMT2C	Q8NEZ4	998
PAXIP1	NCOA6	Q14686	997
PAXIP1	KDM6A	O15550	995
PAXIP1	TP53BP1	Q12888	994
PAXIP1	PAGR1	Q9BTK6	984
PAXIP1	PAX2	Q02962	974
PAXIP1	ASH2L	Q9UBL3	973
PAXIP1	WDR5	P61964	965
PAXIP1	RBBP5	Q15291	955
PAXIP1	MAD2L2	Q9UI95	930
PAXIP1	DPY30	Q9C005	924
PAXIP1	ATM	Q13315	900
PAXIP1	KMT2D	O14686	885
PAXIP1	SETD1A	O15047	857
PAXIP1	PAX5	Q02548	763

IntAct

146 interactions, top by confidence:

A	B	Type	Score
WDR5	RBBP5	psi-mi:“MI:0914”(association)	0.960
RBBP5	WDR5	psi-mi:“MI:0914”(association)	0.960
ASH2L	WDR5	psi-mi:“MI:0914”(association)	0.950
ASH2L	NCOA6	psi-mi:“MI:0914”(association)	0.930
NCOA6	WDR5	psi-mi:“MI:0914”(association)	0.920
KMT2D	WDR5	psi-mi:“MI:0914”(association)	0.910
WDR5	KMT2D	psi-mi:“MI:0914”(association)	0.910
PAXIP1	WDR5	psi-mi:“MI:0915”(physical association)	0.900
PAXIP1	WDR5	psi-mi:“MI:0914”(association)	0.900
RBBP5	NCOA6	psi-mi:“MI:0914”(association)	0.890
NCOA6	RBBP5	psi-mi:“MI:0914”(association)	0.890
ASH2L	KMT2D	psi-mi:“MI:0403”(colocalization)	0.890
ASH2L	KMT2D	psi-mi:“MI:0914”(association)	0.890
PAXIP1	ASH2L	psi-mi:“MI:0915”(physical association)	0.840
KMT2D	RBBP5	psi-mi:“MI:0914”(association)	0.840
RBBP5	KMT2D	psi-mi:“MI:0914”(association)	0.840
PAXIP1	NCOA6	psi-mi:“MI:0914”(association)	0.790
KDM6A	RBBP5	psi-mi:“MI:0914”(association)	0.790
PAGR1	PAXIP1	psi-mi:“MI:0915”(physical association)	0.790
PAXIP1	PAGR1	psi-mi:“MI:0915”(physical association)	0.790
PAXIP1	PAGR1	psi-mi:“MI:0914”(association)	0.790
KMT2C	WDR5	psi-mi:“MI:0914”(association)	0.770
PAXIP1	RBBP5	psi-mi:“MI:0915”(physical association)	0.770
MED23	MED19	psi-mi:“MI:2364”(proximity)	0.770

BioGRID (485): PAXIP1 (Two-hybrid), PAXIP1 (Two-hybrid), NXT1 (Two-hybrid), PAXIP1 (Affinity Capture-MS), PAXIP1 (Co-fractionation), PAXIP1 (Proximity Label-MS), PAXIP1 (Affinity Capture-MS), PAXIP1 (Affinity Capture-MS), PAXIP1 (Affinity Capture-MS), PAXIP1 (Affinity Capture-MS), PAXIP1 (Affinity Capture-MS), PAXIP1 (Affinity Capture-MS), ZBTB8A (Two-hybrid), PAXIP1 (Affinity Capture-MS), PAXIP1 (Affinity Capture-MS)

ESM2 similar proteins: A0JNA8, A2AFR3, A2AWP8, F1LXF1, O15034, O94844, O94967, O95267, P11274, P28028, Q01826, Q08BT5, Q14161, Q14CM0, Q15139, Q3UGM2, Q3UHE1, Q4R4I0, Q5R5M3, Q5VUG0, Q5XIS9, Q60611, Q62101, Q66H91, Q68FF6, Q6NZQ4, Q6PAJ1, Q6PB44, Q6ZW49, Q6ZWH5, Q80U28, Q8BWW9, Q8BZ03, Q8CGF6, Q8TCU6, Q8VDD9, Q8VI24, Q96GD3, Q9BZ71, Q9BZL6

Diamond homologs: A0JNA8, Q14676, Q5PSV9, Q5TM68, Q5U2M8, Q5XIY8, Q6NZQ4, Q6ZQF0, Q6ZW49, Q767L8, Q7YR40, Q7ZZY3, Q800K6, Q90WJ3, Q92547, Q10337, Q07139, Q9H8V3, P32372

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PAXIP1	“up-regulates activity”	PAX2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 116 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
Formation of WDR5-containing histone-modifying complexes	11	34.0×	5e-12
Deactivation of the beta-catenin transactivating complex	11	29.8×	1e-11
Activation of HOX genes during differentiation	5	25.5×	4e-05
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	11	25.2×	7e-11
Gastrulation	6	18.1×	3e-05
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	7	17.5×	6e-06
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	10	17.0×	2e-08
Epigenetic regulation by WDR5-containing histone modifying complexes	8	14.4×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
neuron fate specification	5	32.5×	4e-05
positive regulation of miRNA transcription	11	29.6×	2e-11
transcription initiation-coupled chromatin remodeling	7	24.8×	2e-06
somatic stem cell population maintenance	7	16.1×	3e-05
positive regulation of transcription initiation by RNA polymerase II	6	15.1×	2e-04
inner ear morphogenesis	5	13.9×	1e-03
cell fate commitment	5	13.7×	1e-03
anatomical structure morphogenesis	10	12.9×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3936 predictions. Top by Δscore:

Variant	Effect	Δscore
7:154946809:TTTGC:T	acceptor_gain	1.0000
7:154946810:TTGC:T	acceptor_gain	1.0000
7:154946812:GCCTA:G	acceptor_loss	1.0000
7:154946813:CCTA:C	acceptor_loss	1.0000
7:154946814:C:A	acceptor_loss	1.0000
7:154946814:C:CC	acceptor_gain	1.0000
7:154946815:T:A	acceptor_loss	1.0000
7:154954252:T:TG	donor_loss	1.0000
7:154954253:A:AC	donor_gain	1.0000
7:154954253:A:AG	donor_loss	1.0000
7:154954254:C:CC	donor_gain	1.0000
7:154954254:CCA:C	donor_gain	1.0000
7:154954421:CTT:C	acceptor_gain	1.0000
7:154954422:TT:T	acceptor_gain	1.0000
7:154954424:C:CC	acceptor_gain	1.0000
7:154954432:C:CT	acceptor_gain	1.0000
7:154955497:AAAAT:A	donor_gain	1.0000
7:154955525:TCAC:T	donor_loss	1.0000
7:154955527:ACCT:A	donor_loss	1.0000
7:154955528:C:G	donor_loss	1.0000
7:154955627:CAATT:C	acceptor_gain	1.0000
7:154955628:AATT:A	acceptor_gain	1.0000
7:154955629:ATT:A	acceptor_gain	1.0000
7:154955629:ATTCT:A	acceptor_loss	1.0000
7:154955630:TT:T	acceptor_gain	1.0000
7:154955631:TCT:T	acceptor_loss	1.0000
7:154955632:C:CC	acceptor_gain	1.0000
7:154955632:CT:C	acceptor_loss	1.0000
7:154955634:G:C	acceptor_gain	1.0000
7:154961082:T:C	acceptor_gain	1.0000

AlphaMissense

7037 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:154946389:A:G	L1057P	1.000
7:154946401:A:G	L1053P	1.000
7:154954348:G:T	R910S	1.000
7:154954368:A:G	L903P	1.000
7:154959928:A:G	W814R	1.000
7:154959928:A:T	W814R	1.000
7:154961016:A:G	W771R	1.000
7:154961016:A:T	W771R	1.000
7:154961043:A:G	W762R	1.000
7:154961043:A:T	W762R	1.000
7:154961051:G:T	A759D	1.000
7:154961539:A:G	L746P	1.000
7:154962422:A:G	W676R	1.000
7:154962422:A:T	W676R	1.000
7:154963708:A:G	L651P	1.000
7:154993763:A:G	W75R	1.000
7:154993763:A:T	W75R	1.000
7:154998717:A:T	I50N	1.000
7:154946389:A:T	L1057H	0.999
7:154946395:C:T	G1055E	0.999
7:154946396:C:G	G1055R	0.999
7:154946396:C:T	G1055R	0.999
7:154946404:A:T	V1052D	0.999
7:154946422:A:T	V1046D	0.999
7:154946565:A:T	I1027K	0.999
7:154946779:G:T	P986Q	0.999
7:154954291:A:G	W929R	0.999
7:154954291:A:T	W929R	0.999
7:154954332:A:G	L915P	0.999
7:154954348:G:C	R910G	0.999

dbSNP variants (sampled 300 via entrez): RS1000183092 (7:155002983 G>A,C,T), RS1000211148 (7:154949168 T>C), RS1000242832 (7:154994695 A>T), RS1000247032 (7:155000556 G>A), RS1000314965 (7:154948801 A>T), RS1000411079 (7:155004216 C>T), RS1000468400 (7:154956201 A>G,T), RS1000497758 (7:154958168 C>A,G), RS1000524156 (7:155002310 C>T), RS1000537843 (7:154969809 G>C,T), RS1000577897 (7:155002064 A>C,G), RS1000613946 (7:154951123 T>C), RS1000683481 (7:155000055 T>G), RS1000742558 (7:154957896 A>G,T), RS1000763710 (7:154996332 C>T)

Disease associations

OMIM: gene MIM:608254 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002397_2	Bladder cancer (smoking interaction)	2.000000e-06
GCST009391_440	Metabolite levels	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010385	phosphatidylcholine 38:3 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	increases abundance, decreases expression, affects cotreatment	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Cyclosporine	decreases expression, increases methylation	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
methylselenic acid	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
NSC 689534	affects binding, decreases 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
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Arsenic	increases abundance, affects cotreatment, decreases expression	1
Copper	affects binding, decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Formaldehyde	decreases expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Ozone	affects expression, increases abundance	1
Piroxicam	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	increases methylation	1
Asbestos, Serpentine	affects methylation	1
Copper Sulfate	decreases expression	1
tert-Butylhydroperoxide	decreases expression	1
Vitamin K 3	affects expression	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_TC32	HAP1 PAXIP1 (-) 1	Cancer cell line	Male
CVCL_TC33	HAP1 PAXIP1 (-) 2	Cancer cell line	Male
CVCL_UM28	TUSMi008-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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