PAXIP1

PAX interacting protein 1

Basic information

Region (hg38): 7:154943687-155003124

Previous symbols: [ "PAXIP1L" ]

Links

ENSG00000157212 ∙ NCBI:22976 ∙ OMIM:608254 ∙ HGNC:8624 ∙ Uniprot:Q6ZW49 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PAXIP1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PAXIP1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2		2
missense			30	2		32
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	30	4	0

Variants in PAXIP1

This is a list of pathogenic ClinVar variants found in the PAXIP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-154946707-C-T		not specified	Uncertain significance (Oct 02, 2023)
7-154946725-G-T		not specified	Uncertain significance (Jan 24, 2024)
7-154946753-C-T		not specified	Uncertain significance (Jan 10, 2022)
7-154947989-T-C		not specified	Uncertain significance (Aug 20, 2024)
7-154954317-A-G		not specified	Uncertain significance (Dec 10, 2024)
7-154954414-T-C		not specified	Uncertain significance (Jan 25, 2023)
7-154955539-T-A		not specified	Uncertain significance (Nov 24, 2024)
7-154955624-C-T		not specified	Uncertain significance (Dec 16, 2022)
7-154957266-T-C		not specified	Uncertain significance (Dec 27, 2022)
7-154957286-T-A		not specified	Uncertain significance (Jun 16, 2024)
7-154960925-G-A		not specified	Uncertain significance (Dec 14, 2023)
7-154960970-A-C		not specified	Uncertain significance (Aug 13, 2021)
7-154961039-C-A		not specified	Uncertain significance (Jul 09, 2021)
7-154961072-G-A		not specified	Uncertain significance (Nov 12, 2021)
7-154962322-T-C		not specified	Uncertain significance (Jun 17, 2024)
7-154962384-C-T		not specified	Likely benign (Oct 04, 2024)
7-154963681-G-A		not specified	Likely benign (Apr 05, 2023)
7-154963683-G-A			Likely benign (Oct 01, 2024)
7-154968480-G-A		not specified	Uncertain significance (Dec 27, 2023)
7-154968513-G-A		not specified	Uncertain significance (Dec 19, 2022)
7-154968522-G-A		not specified	Uncertain significance (Jun 29, 2022)
7-154968556-T-C		not specified	Uncertain significance (Mar 29, 2022)
7-154969017-G-A		not specified	Uncertain significance (Aug 02, 2021)
7-154969059-T-C		not specified	Uncertain significance (Jun 05, 2023)
7-154969100-C-T			Likely benign (Nov 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PAXIP1	protein_coding	protein_coding	ENST00000404141	21	59398

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.33e-9	124650	0	4	124654	0.0000160

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.28	332	548	0.605	0.0000300	6969
Missense in Polyphen		61	101.82	0.59909		1244
Synonymous	1.29	190	214	0.888	0.0000127	1946
Loss of Function	7.15	2	63.5	0.0315	0.00000314	731

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000357	0.0000357
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000556	0.0000556
Finnish	0.00	0.00
European (Non-Finnish)	0.0000177	0.0000177
Middle Eastern	0.0000556	0.0000556
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:Q6NZQ4, ECO:0000269|PubMed:14576432, ECO:0000269|PubMed:15456759, ECO:0000269|PubMed:17690115, ECO:0000269|PubMed:17925232, ECO:0000269|PubMed:18353733, ECO:0000269|PubMed:20088963, ECO:0000269|PubMed:23727112}.
• Pathway: DNA Repair;Nonhomologous End-Joining (NHEJ);DNA Double-Strand Break Repair (Consensus)

Recessive Scores

• pRec: 0.119

Intolerance Scores

• loftool: 0.231
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.7

Haploinsufficiency Scores

• pHI: 0.899
• hipred: Y
• hipred_score: 0.825
• ghis: 0.603

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.584

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Paxip1
• Phenotype: embryo phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: positive regulation of histone H3-K36 methylation;vasculogenesis;double-strand break repair via nonhomologous end joining;DNA recombination;response to ionizing radiation;DNA damage response, signal transduction by p53 class mediator;positive regulation of protein ubiquitination;positive regulation of histone acetylation;endothelial cell migration;positive regulation of isotype switching;positive regulation of isotype switching to IgG isotypes;histone H3-K4 methylation;positive regulation of histone H3-K4 methylation;positive regulation of transcription initiation from RNA polymerase II promoter;adipose tissue development;chorion development;regulation of cell cycle G2/M phase transition;positive regulation of response to DNA damage stimulus
• Cellular component: nucleus;nucleoplasm;chromosome;nuclear matrix;histone methyltransferase complex;MLL3/4 complex
• Molecular function: protein binding