PADI4

peptidyl arginine deiminase 4, the group of Peptidyl arginine deiminases

Basic information

Region (hg38): 1:17308195-17364004

Previous symbols: [ "PADI5" ]

Links

ENSG00000159339 ∙ NCBI:23569 ∙ OMIM:605347 ∙ HGNC:18368 ∙ Uniprot:Q9UM07 ∙ 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 PADI4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PADI4 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				5	4	9
missense			31	4	11	46
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	31	9	15

Variants in PADI4

This is a list of pathogenic ClinVar variants found in the PADI4 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-17308245-G-A		PADI4-related disorder	Benign (Jun 26, 2018)
1-17308269-A-G		not specified	Uncertain significance (Aug 08, 2022)
1-17308274-G-A		not specified	Uncertain significance (Feb 05, 2024)
1-17331024-G-A		not specified	Uncertain significance (Jan 10, 2023)
1-17331039-G-A		Rheumatoid arthritis;Abnormal pulmonary interstitial morphology • PADI4-related disorder	Benign; association (Feb 01, 2020)
1-17331096-G-T		not specified	Likely benign (Aug 30, 2021)
1-17331097-T-C			Benign (Jun 18, 2018)
1-17331112-C-G		PADI4-related disorder	Benign (Dec 06, 2019)
1-17331112-C-T			Benign (Jun 26, 2018)
1-17331121-T-C		Rheumatoid arthritis;Abnormal pulmonary interstitial morphology • PADI4-related disorder	Benign; association (Feb 01, 2020)
1-17333961-G-A		not specified	Uncertain significance (Dec 06, 2021)
1-17333979-G-A		not specified	Uncertain significance (Aug 30, 2021)
1-17333991-C-G		not specified	Uncertain significance (Apr 08, 2024)
1-17333995-A-G		not specified	Uncertain significance (Jun 21, 2021)
1-17334002-C-T		PADI4-related disorder	Likely benign (Feb 19, 2019)
1-17334004-G-C		Rheumatoid arthritis;Abnormal pulmonary interstitial morphology • PADI4-related disorder	Benign; association (Feb 01, 2020)
1-17336144-T-C		Rheumatoid arthritis	association (-)
1-17336167-T-C		Rheumatoid arthritis;Abnormal pulmonary interstitial morphology • PADI4-related disorder	Benign; association (Feb 01, 2020)
1-17336168-T-C		not specified	Uncertain significance (May 28, 2024)
1-17336176-G-A		not specified	Uncertain significance (Mar 01, 2023)
1-17336189-C-A		not specified	Uncertain significance (May 25, 2022)
1-17336213-C-T		not specified	Uncertain significance (Aug 22, 2023)
1-17338068-G-A		not specified	Uncertain significance (Aug 10, 2021)
1-17338085-G-T		PADI4-related disorder	Likely benign (Feb 21, 2019)
1-17338120-T-C		PADI4-related disorder	Benign (Jun 05, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PADI4	protein_coding	protein_coding	ENST00000375448	16	55810

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.60e-16	0.0852	125564	1	183	125748	0.000732

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0775	396	392	1.01	0.0000222	4358
Missense in Polyphen		182	169.89	1.0713		1867
Synonymous	0.565	165	175	0.946	0.0000117	1294
Loss of Function	0.933	27	32.8	0.824	0.00000156	373

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00558	0.00552
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000501	0.000489
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000208	0.000202
Middle Eastern	0.000501	0.000489
South Asian	0.000880	0.000850
Other	0.000342	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the citrullination/deimination of arginine residues of proteins such as histones, thereby playing a key role in histone code and regulation of stem cell maintenance. Citrullinates histone H1 at 'Arg-54' (to form H1R54ci), histone H3 at 'Arg-2', 'Arg-8', 'Arg-17' and/or 'Arg-26' (to form H3R2ci, H3R8ci, H3R17ci, H3R26ci, respectively) and histone H4 at 'Arg-3' (to form H4R3ci). Acts as a key regulator of stem cell maintenance by mediating citrullination of histone H1: citrullination of 'Arg- 54' of histone H1 (H1R54ci) results in H1 displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance. Promotes profound chromatin decondensation during the innate immune response to infection in neutrophils by mediating formation of H1R54ci. Citrullination of histone H3 prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1. {ECO:0000269|PubMed:15339660, ECO:0000269|PubMed:15345777, ECO:0000269|PubMed:15731352, ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:18209087, ECO:0000269|PubMed:21245532}.
• Disease: DISEASE: Rheumatoid arthritis (RA) [MIM:180300]: An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. {ECO:0000269|PubMed:12833157}. Note=The gene represented in this entry may be involved in disease pathogenesis. The association to rheumatoid arthritis was initially thought to result from increased citrullination of target proteins (PubMed:12833157). However, variants that have been associated to rheumatoid arthritis (Ser-55, Ala-82 and Ala-112) do not affect the catalytic activity or the citrullination activity of PADI4, suggesting that these variants may affect the mRNA stability rather than the protein (PubMed:21245532). {ECO:0000269|PubMed:12833157, ECO:0000269|PubMed:21245532}.
• Pathway: Chromatin modifying enzymes;Chromatin organization;protein citrullination (Consensus)

Intolerance Scores

• loftool: 0.911
• rvis_EVS: 2.23
• rvis_percentile_EVS: 98.17

Haploinsufficiency Scores

• pHI: 0.0813
• hipred: N
• hipred_score: 0.341
• ghis: 0.409

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.732

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Padi4
• Phenotype: immune system 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); growth/size/body region phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: chromatin organization;nucleosome assembly;chromatin remodeling;cellular protein modification process;protein citrullination;arginine deiminase pathway;stem cell population maintenance;histone H3-R26 citrullination;histone citrullination;innate immune response
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;protein-containing complex
• Molecular function: protein-arginine deiminase activity;calcium ion binding;protein binding;arginine deiminase activity;arginine binding;protein homodimerization activity