CDC45 (cell division cycle 45)

Gene

• Entrez ID: 8318
• Gene name: Cell division cycle 45
• Gene symbol: CDC45
• Synonyms (NCBI Gene): CDC45L, CDC45L2, MGORS7, PORC-PI-1
• Chromosome: 22
• Chromosome location: 22q11.21
• Summary: The protein encoded by this gene was identified by its strong similarity with Saccharomyces cerevisiae Cdc45, an essential protein required to the initiation of DNA replication. Cdc45 is a member of the highly conserved multiprotein complex including Cdc6

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs146559223	C>A,T	Likely-pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs540217942	C>T	Likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant, genic upstream transcript variant
rs540900837	C>T	Likely-pathogenic	Non coding transcript variant, missense variant, coding sequence variant
rs745800041	C>T	Pathogenic	Synonymous variant, non coding transcript variant, intron variant, genic upstream transcript variant, coding sequence variant
rs748749078	C>T	Pathogenic	Synonymous variant, non coding transcript variant, intron variant, genic upstream transcript variant, coding sequence variant
rs752023208	->TATA	Pathogenic	Non coding transcript variant, intron variant, frameshift variant, genic upstream transcript variant, coding sequence variant
rs754080445	A>G	Likely-pathogenic	Intron variant, missense variant, coding sequence variant, non coding transcript variant
rs778665661	C>T	Uncertain-significance, likely-pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs879255632	A>C	Likely-pathogenic	Non coding transcript variant, intron variant, missense variant, coding sequence variant, genic upstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT037897	hsa-miR-455-3p	CLASH	23622248
MIRT054111	hsa-miR-575	Microarray	22995316
MIRT1960434	hsa-miR-4762-5p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000076	Process	DNA replication checkpoint signaling	TAS	9660782
GO:0000727	Process	Double-strand break repair via break-induced replication	IBA
GO:0003682	Function	Chromatin binding	IBA
GO:0003688	Function	DNA replication origin binding	IBA
GO:0003697	Function	Single-stranded DNA binding	IBA
GO:0005515	Function	Protein binding	IPI	10518787, 15232106, 17887956, 19805216, 23910567, 25241761, 25416956, 26167883, 31515488, 32296183, 33961781, 39009827
GO:0005634	Component	Nucleus	IDA	21383955, 22474384
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	TAS	9660782
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005694	Component	Chromosome	IEA
GO:0005813	Component	Centrosome	IDA
GO:0006260	Process	DNA replication	IDA	22474384
GO:0006260	Process	DNA replication	IEA
GO:0006270	Process	DNA replication initiation	IBA
GO:0006270	Process	DNA replication initiation	IEA
GO:0006270	Process	DNA replication initiation	TAS	9660782
GO:0031261	Component	DNA replication preinitiation complex	IBA
GO:0036064	Component	Ciliary basal body	IDA	29257953
GO:0071162	Component	CMG complex	IPI	22474384
GO:1902977	Process	Mitotic DNA replication preinitiation complex assembly	IBA

Other IDs

• MIM: 603465
• HGNC: 1739
• e!Ensembl: ENSG00000093009

Protein

• UniProt ID: O75419
• Protein name: Cell division control protein 45 homolog (PORC-PI-1)
• Protein function: Required for initiation of chromosomal DNA replication. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built. {ECO:0000269|PubMed:32453425, E
• PDB: 5DGO, 6XTX, 6XTY, 7PFO, 7PLO
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02724	CDC45	19 → 163	CDC45-like protein	Family
  PF02724	CDC45	131 → 563	CDC45-like protein	Family

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed, highest levels are found in adult testis and thymus and in fetal liver.
• Sequence:

  MFVSDFRKEFYEVVQSQRVLLFVASDVDALCACKILQALFQCDHVQYTLVPVSGWQELET
  AFLEHKEQFHYFILINCGANVDLLDILQPDEDTIFFVCDTHRPVNVVNVYNDTQIKLLIK
  QDDDLEVPAYEDIFRDEEEDEEHSGNDSDGSEPSEKRTRLEEEIVEQTMRRRQRREWEAR
  RRDILFDYEQYEYHGTSSAMVMFELAWMLSKDLNDMLWWAIVGLTDQWVQDKITQMKYVT
  DVGVLQRHVSRHNHRNEDEENTLSVDCTRISFEYDLRLVLYQHWSLHDSLCNTSYTAARF
  KLWSVHGQKRLQEFLADMGLPLKQVKQKFQAMDISLKENLREMIEESANKFGMKDMRVQT
  FSIHFGFKHKFLASDVVFATMSLMESPEKDGSGTDHFIQALDSLSRSNLDKLYHGLELAK
  KQLRATQQTIASCLCTNLVISQGPFLYCSLMEGTPDVMLFSRPASLSLLSKHLLKSFVCS
  TKNRRCKLLPLVMAAPLSMEHGTVTVVGIPPETDSSDRKNFFGRAFEKAAESTSSRMLHN
  HFDLSVIELKAEDRSKFLDALISLLS

• Sequence length: 566

Pathways

KEGG:

Cell cycle

Reactome:

Activation of ATR in response to replication stress
Activation of the pre-replicative complex
G1/S-Specific Transcription

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
Meier-Gorlin syndrome 7	Pathogenic; Likely pathogenic	rs1933800287, rs754080445, rs879255632, rs879255633, rs146559223, rs2517554532, rs751663397, rs752023208	RCV001507095 RCV000239518 RCV000239492 RCV000239478 RCV000239581 RCV003992106 RCV000755754 RCV000850142	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Androgen resistance syndrome	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANDROGEN-INSENSITIVITY SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARCINOMA, HEPATOCELLULAR	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CDC45-related disorder	Likely benign; Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEMENTIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EAR, PATELLA, SHORT STATURE SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EAR-PATELLA-SHORT STATURE SYNDROME	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MEIER-GORLIN SYNDROME	—	CTD, GWAS catalog CTD, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microcephaly	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
2-3 toe syndactyly	Syndactyly Of The Toes	HPO_DG			★☆☆☆☆ Found in Text Mining only
Anus, Imperforate	Imperforate anus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Arnold-Chiari Malformation, Type I	Arnold-Chiari malformation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ataxia Telangiectasia	Ataxia telangiectasia	Pubtator	23910567	Associate	★☆☆☆☆ Found in Text Mining only
Atrial Septal Defects	Atrial Septal Defect	HPO_DG			★☆☆☆☆ Found in Text Mining only
Atrioventricular Septal Defect	Atrioventricular septal defect	HPO_DG			★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	32932728	Associate	★☆☆☆☆ Found in Text Mining only
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	33622998	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	29962817, 31011256, 32393195, 33622998, 37985379, 40255404	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	21231984		★☆☆☆☆ Found in Text Mining only
Choanal Atresia	Choanal Atresia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Chromosomal Instability	Chromosomal instability	Pubtator	36516748	Associate	★☆☆☆☆ Found in Text Mining only
Clinodactyly of the 5th finger	Camptodactyly of fingers	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	31477839		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	29197895	Associate	★☆☆☆☆ Found in Text Mining only
Congenital Abnormalities	Congenital abnormalities	Pubtator	9660782	Associate	★☆☆☆☆ Found in Text Mining only
Congenital absence of breast	Breast aplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital absence of external ear	Anotia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital absence of mandible	Mandibular aplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of lung	Pulmonary hypoplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of penis	Congenital Hypoplasia Of Penis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital small ears	Microtia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Conotruncal cardiac defects	Conotruncal cardiac defect	Pubtator	22185286	Associate	★☆☆☆☆ Found in Text Mining only
Craniosynostoses	Craniosynostosis	Pubtator	27374770, 27884935, 31474763, 34353863	Associate	★☆☆☆☆ Found in Text Mining only
Craniosynostosis	Craniosynostosis	BEFREE	27374770, 30986546, 31474763		★☆☆☆☆ Found in Text Mining only
Craniosynostosis	Craniosynostosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Craniosynostosis radial aplasia syndrome	Craniosynostosis	Pubtator	31474763	Associate	★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
DiGeorge Syndrome	DiGeorge Syndrome	BEFREE	10390621, 9660782		★☆☆☆☆ Found in Text Mining only
DiGeorge Syndrome	Digeorge syndrome	Pubtator	22185286	Inhibit	★☆☆☆☆ Found in Text Mining only
DiGeorge Syndrome	Digeorge syndrome	Pubtator	27846841, 31474763, 34971493, 9660782	Associate	★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
EAR, PATELLA, SHORT STATURE SYNDROME	Ear Diseases	ORPHANET_DG	27374770		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EAR, PATELLA, SHORT STATURE SYNDROME	Ear Diseases	BEFREE	30595439, 30986546		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EAR, PATELLA, SHORT STATURE SYNDROME	Ear Diseases	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ear-patella-short stature syndrome	Ear-Patella-Short Stature Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Epispadias	Epispadias	HPO_DG			★☆☆☆☆ Found in Text Mining only
Exophthalmos	Proptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Fanconi Anemia	Fanconi anemia	Pubtator	34404366	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	31407396		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	34353863	Associate	★☆☆☆☆ Found in Text Mining only
Hypertrophy of clitoris	Hypertrophy Of Clitoris	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoplasia of the maxilla	Hypoplasia of the maxilla	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypospadias	Hypospadias	HPO_DG			★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	GWASCAT_DG	26252872		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	CTD_human_DG	28284560		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	21231984		★☆☆☆☆ Found in Text Mining only
Megalencephaly cutis marmorata telangiectatica congenita	Megalencephaly Cutis Marmorata Telangiectatica Congenita	BEFREE	31014174		★☆☆☆☆ Found in Text Mining only
MEIER-GORLIN SYNDROME 7	Meier-Gorlin Syndrome	GENOMICS_ENGLAND_DG	25985138, 27374770		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MEIER-GORLIN SYNDROME 7	Meier-Gorlin Syndrome	UNIPROT_DG	27374770		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MEIER-GORLIN SYNDROME 7	Meier-Gorlin Syndrome	CLINVAR_DG	27374770		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Microcephaly	Microcephaly	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Microstomia	Microstomia	HPO_DG			★☆☆☆☆ Found in Text Mining only
MUNGAN SYNDROME	MUNGAN SYNDROME	BEFREE	27374770, 29036220, 30986546		★☆☆☆☆ Found in Text Mining only
Myopia	Myopia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Nasopharyngeal Carcinoma	Nasopharyngeal carcinoma	Pubtator	34664875	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	31407396		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	30887286		★☆☆☆☆ Found in Text Mining only
Papillary thyroid carcinoma	Papillary thyroid carcinoma	BEFREE	28474999		★☆☆☆☆ Found in Text Mining only
Penis agenesis	Penis Agenesis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Posteriorly rotated ear	Posteriorly Rotated Ear	HPO_DG			★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	32953881, 34497666	Associate	★☆☆☆☆ Found in Text Mining only
Radial polydactyly	Radial Polydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Respiratory Failure	Respiratory Failure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Rothmund-Thomson syndrome	Rothmund-Thomson Syndrome	BEFREE	15960976		★☆☆☆☆ Found in Text Mining only
Sagittal craniosynostosis	Sagittal craniosynostosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Shprintzen-Goldberg syndrome	Shprintzen-Goldberg Syndrome	BEFREE	10390621, 9660782		★☆☆☆☆ Found in Text Mining only
Specific learning disability	Specific Learning Disorder	HPO_DG			★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	33315534, 33982750	Associate	★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of tongue	Tongue carcinoma	BEFREE	19116018		★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Submucous cleft of hard palate	Submucosal cleft palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Thyroid Neoplasms	Thyroid cancer	Pubtator	37864896	Associate	★☆☆☆☆ Found in Text Mining only
Uterine Cervical Dysplasia	Uterine disease	Pubtator	34404366	Associate	★☆☆☆☆ Found in Text Mining only
Uterine Cervical Neoplasms	Uterine neoplasm	Pubtator	27034707, 33302814, 34404366	Associate	★☆☆☆☆ Found in Text Mining only
Ventricular Septal Defects	Ventricular septal defect	HPO_DG			★☆☆☆☆ Found in Text Mining only
Vesico-Ureteral Reflux	Vesicoureteral Reflux	HPO_DG			★☆☆☆☆ Found in Text Mining only