PADI6 (peptidyl arginine deiminase 6)

Gene

• Entrez ID: 353238
• Gene name: Peptidyl arginine deiminase 6
• Gene symbol: PADI6
• Synonyms (NCBI Gene): OZEMA16, PREMBL2, hPADVI
• Chromosome: 1
• Chromosome location: 1p36.13
• Summary: This gene encodes a member of the peptidyl arginine deiminase family of enzymes, which catalyze the post-translational deimination of proteins by converting arginine residues into citrullines in the presence of calcium ions. The family members have distin

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs775156958	T>A	Pathogenic	Coding sequence variant, missense variant
rs1057517681	C>G,T	Pathogenic	Stop gained, missense variant, coding sequence variant
rs1057517682	AG>-	Pathogenic	Coding sequence variant, frameshift variant
rs1057517683	C>T	Pathogenic	Stop gained, coding sequence variant
rs1057517684	G>A	Pathogenic	Missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1210220	hsa-miR-3918	CLIP-seq
MIRT1210221	hsa-miR-4487	CLIP-seq
MIRT1210222	hsa-miR-4512	CLIP-seq
MIRT1210223	hsa-miR-4660	CLIP-seq
MIRT1210224	hsa-miR-4685-5p	CLIP-seq
MIRT1210225	hsa-miR-486-3p	CLIP-seq
MIRT1210226	hsa-miR-885-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001701	Process	In utero embryonic development	IEA
GO:0004668	Function	Protein-arginine deiminase activity	IBA
GO:0004668	Function	Protein-arginine deiminase activity	IDA	38656308, 39286527
GO:0005509	Function	Calcium ion binding	IEA
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IDA	27545678
GO:0005737	Component	Cytoplasm	IEA
GO:0007010	Process	Cytoskeleton organization	IEA
GO:0007028	Process	Cytoplasm organization	IEA
GO:0008104	Process	Intracellular protein localization	IEA
GO:0015631	Function	Tubulin binding	IEA
GO:0015631	Function	Tubulin binding	ISS
GO:0031410	Component	Cytoplasmic vesicle	IEA
GO:0040016	Process	Embryonic cleavage	IEA
GO:0040016	Process	Embryonic cleavage	ISS
GO:0042802	Function	Identical protein binding	IDA	38656308, 39286527
GO:0043143	Process	Regulation of translation by machinery localization	IEA
GO:0044725	Process	Epigenetic programming in the zygotic pronuclei	IEA
GO:0044725	Process	Epigenetic programming in the zygotic pronuclei	ISS
GO:0045111	Component	Intermediate filament cytoskeleton	IEA
GO:0060473	Component	Cortical granule	IEA
GO:0060473	Component	Cortical granule	ISS
GO:0140089	Process	Protein storage	IDA	37922900
GO:0140089	Process	Protein storage	IEA
GO:0140094	Function	Structural constituent of cytoplasmic lattice	IDA	37922900
GO:0140094	Function	Structural constituent of cytoplasmic lattice	IEA
GO:0140095	Component	Cytoplasmic lattice	IDA	37922900
GO:0140095	Component	Cytoplasmic lattice	IEA
GO:1990917	Component	Ooplasm	IEA

Other IDs

• MIM: 610363
• HGNC: 20449
• e!Ensembl: ENSG00000276747

Protein

• UniProt ID: Q6TGC4
• Protein name: Inactive protein-arginine deiminase type-6 (Peptidyl arginine deiminase-like protein) (Peptidylarginine deiminase VI) (hPADVI) (Protein-arginine deiminase type VI) (Protein-arginine deiminase type-6)
• Protein function: Structural constituent of cytoplasmic lattices, which plays a key role in early embryonic development (PubMed:37922900). Cytoplasmic lattices consist in fibrous structures found in the cytoplasm of oocytes and preimplantation embryos (PubMed:379
• PDB: 4DAT, 4DAU, 8QL0, 9FMN
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF08526	PAD_N	9 → 120	Protein-arginine deiminase (PAD) N-terminal domain	Domain
  PF08527	PAD_M	122 → 281	Protein-arginine deiminase (PAD) middle domain	Domain
  PF03068	PAD	292 → 691	Protein-arginine deiminase (PAD)	Family

• Tissue specificity: TISSUE SPECIFICITY: Highly expressed in oocytes and weakly expressed in other somatic tissues. {ECO:0000269|PubMed:15625577, ECO:0000269|PubMed:27545678}.
• Sequence:

  MVSVEGRAMSFQSIIHLSLDSPVHAVCVLGTEICLDLSGCAPQKCQCFTIHGSGRVLIDV
  ANTVISEKEDATIWWPLSDPTYATVKMTSPSPSVDADKVSVTYYGPNEDAPVGTAVLYLT
  GIEVSLEVDIYRNGQVEMSSDKQAKKKWIWGPSGWGAILLVNCNPADVGQQLEDKKTKKV
  IFSEEITNLSQMTLNVQGPSCILKKYRLVLHTSKEESKKARVYWPQKDNSSTFELVLGPD
  QHAYTLALLGNHLKETFYVEAIAFPSAEFSGLISYSVSLVEESQDPSIPETVLYKDTVVF
  RVAPCVFIPCTQVPLEVYLCRELQLQGFVDTVTKLSEKSNSQVASVYEDPNRLGRWLQDE
  MAFCYTQAPHKTTSLILDTPQAADLDEFPMKYSLSPGIGYMIQDTEDHKVASMDSIGNLM
  VSPPVKVQGKEYPLGRVLIGSSFYPSAEGRAMSKTLRDFLYAQQVQAPVELYSDWLMTGH
  VDEFMCFIPTDDKNEGKKGFLLLLASPSACYKLFREKQKEGYGDALLFDELRADQLLSNG
  REAKTIDQLLADESLKKQNEYVEKCIHLNRDILKTELGLVEQDIIEIPQLFCLEKLTNIP
  SDQQPKRSFARPYFPDLLRMIVMGKNLGIPKPFGPQIKGTCCLEEKICCLLEPLGFKCTF
  INDFDCYLTEVGDICACANIRRVPFAFKWWKMVP

• Sequence length: 694

Pathways

Reactome:

Chromatin modifying enzymes

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
PADI6-related disorder	Likely pathogenic	rs1275178104	RCV003400019	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Preimplantation embryonic lethality 2	Likely pathogenic; Pathogenic	rs766402946, rs1464076815, rs2100297230, rs2100316317, rs755260464, rs1275059440, rs2100280270, rs2100332594, rs1048529437, rs1057517681, rs1057517682, rs775156958, rs1057517683, rs1057517684	RCV001814586 RCV001814587 RCV001814588 RCV001814589 RCV001814591 RCV001814593 RCV001814597 RCV001814598 RCV004018313 RCV000412544 RCV000412605 RCV000412664 RCV000412549 RCV000412606	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
BASAL CELL CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BILIARY TRACT CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CERVICAL CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLORECTAL CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ENDOMETRIAL CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EPILEPSY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ESOPHAGEAL CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ESTROGEN-RECEPTOR NEGATIVE BREAST CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GASTRIC CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GENERALISED EPILEPSY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEPATOCELLULAR CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG ADENOCARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-HODGKINS LYMPHOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OOCYTE/ZYGOTE/EMBRYO MATURATION ARREST 16	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OVARIAN CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OVARIAN CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OVARIAN ENDOMETRIOID CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OVARIAN FAILURE, PREMATURE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OVARIAN SEROUS CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PANCREATIC CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Premature ovarian failure	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SQUAMOUS CELL LUNG CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Arthritis	Arthritis	BEFREE	17968929		★☆☆☆☆ Found in Text Mining only
Basal Cell Cancer	Basal Cell Neoplasm	GWASCAT_DG	18849993, 24403052, 25855136		★☆☆☆☆ Found in Text Mining only
Basal cell carcinoma	Carcinoma	GWASCAT_DG	18849993, 24403052, 25855136		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Basal Cell Neoplasm	Basal Cell Neoplasm	GWASCAT_DG	18849993, 24403052, 25855136		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	GWASCAT_DG	29059683		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Carcinoma Embryonal	Embryonal carcinoma	Pubtator	29693651, 31664658, 34036456, 35946397	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma, Basal Cell	Carcinoma	GWASDB_DG	18849993, 24403052		★☆☆☆☆ Found in Text Mining only
Carcinoma, Basal Cell	Carcinoma	BEFREE	25227856		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	BEFREE	17968929		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	35946397	Associate	★☆☆☆☆ Found in Text Mining only
Epilepsy Generalized	Generalized epilepsy	Pubtator	34573423	Associate	★☆☆☆☆ Found in Text Mining only
Hydatidiform Mole	Hydatidiform Mole	BEFREE	29693651		★☆☆☆☆ Found in Text Mining only
Hydatidiform Mole	Hydatidiform mole	Pubtator	29693651, 32592075, 32928291	Associate	★☆☆☆☆ Found in Text Mining only
Infertility	Infertility	Pubtator	29693651, 32928291, 34036456, 36088419	Associate	★☆☆☆☆ Found in Text Mining only
Infertility Female	Female infertility	Pubtator	32928291, 34036456	Associate	★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	24188633	Associate	★☆☆☆☆ Found in Text Mining only
Nasopharyngeal carcinoma	Nasopharyngeal Carcinoma	GWASDB_DG	20512145		★☆☆☆☆ Found in Text Mining only
Paroxysmal ventricular fibrillation	Paroxysmal ventricular fibrillation	Pubtator	29693651	Associate	★☆☆☆☆ Found in Text Mining only
PREIMPLANTATION EMBRYONIC LETHALITY 2	Preimplantation Embryonic Lethality	UNIPROT_DG	27545678		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
PREIMPLANTATION EMBRYONIC LETHALITY 2	Preimplantation Embryonic Lethality	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
PREIMPLANTATION EMBRYONIC LETHALITY 2	Preimplantation Embryonic Lethality	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Rheumatoid Arthritis	Rheumatoid arthritis	BEFREE	17968929		★☆☆☆☆ Found in Text Mining only