NOBOX (NOBOX oogenesis homeobox)

Gene

• Entrez ID: 135935
• Gene name: NOBOX oogenesis homeobox
• Gene symbol: NOBOX
• Synonyms (NCBI Gene): OG-2, OG2, OG2X, POF5, TCAG_12042
• Chromosome: 7
• Chromosome location: 7q35
• Summary: This homeobox gene encodes a transcription factor that is thought to play a role in oogenesis. In mice, it is essential for folliculogenesis and regulation of oocyte-specific genes. Defects in this gene result in premature ovarian failure type 5.[provided

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs7800847	G>A	Benign-likely-benign, likely-benign, pathogenic, benign	Coding sequence variant, missense variant
rs77587352	C>A	Benign, pathogenic-likely-pathogenic	Missense variant, coding sequence variant
rs193303102	G>A	Pathogenic	Coding sequence variant, stop gained
rs193303103	C>G	Pathogenic	Missense variant, coding sequence variant, intron variant
rs193303104	C>A	Pathogenic	Missense variant, coding sequence variant
rs201947677	C>G,T	Pathogenic	Missense variant, coding sequence variant
rs1218620893	G>A	Likely-pathogenic	Stop gained, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018764	hsa-miR-335-5p	Microarray	18185580

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	ISA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0003677	Function	DNA binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0005634	Component	Nucleus	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IDA	27798098
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IEA
GO:0030154	Process	Cell differentiation	IEA
GO:0043565	Function	Sequence-specific DNA binding	IDA	27798098
GO:0048477	Process	Oogenesis	IEA

Other IDs

• MIM: 610934
• HGNC: 22448
• e!Ensembl: ENSG00000106410

Protein

• UniProt ID: O60393
• Protein name: Homeobox protein NOBOX
• Protein function: Transcription factor which may play a role in oogenesis. Binds preferentially to the DNA sequences 5'-TAATTG-3', 5'-TAGTTG-3' and 5'-TAATTA-3'.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00046	Homeodomain	273 → 318	Homeodomain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in ovaries, testes and pancreas. Expressed within all stages of the adult female germline, from primordial follicles through to MII oocytes. {ECO:0000269|PubMed:16597639}.
• Sequence:

  MALLLTLTSPDLEGTWDTRDKDGFKAQEGPPLAVPEFPVCGLYRIYGVCGSFSSFFIIRC
  SLCALETLKSPQHDPLEIPEQSLKLIPLVSGKRELTRGQKAGEKPLAAGPGEEELLRGSA
  PHAQDTQSEELPPSCTISGEKKPPAVSGEATGADAGRLCPPPRSRAPHKDRTLARSRPQT
  QGEDCSLPVGEVKIGKRSYSPAPGKQKKPNAMGLAPTSSPGAPNSARATHNPVPCGSGRG
  PCHLANLLSTLAQSNQNRDHKQGPPEVTCQIRKKTRTLYRSDQLEELEKIFQEDHYPDSD
  KRREIAQTVGVTPQRIMVKGAGSLVAGWSGGGPTIETLELQSERSAVAWVWFQNRRAKWR
  KMEKLNGKESKDNPAAPGPASSQCSSAAEILPAVPMEPKPDPFPQESPLDTFPEPPMLLT
  SDQTLAPTQPSEGAQRVVTPPLFSPPPVRRADLPFPLGPVHTPQLMPLLMDVAGSDSSHK
  DGPCGSWGTSITLPPPCSYLEELEPQDYQQSNQPGPFQFSQAPQPPLFQSPQPKLPYLPT
  FPFSMPSSLTLPPPEDSLFMFPCGPSGGTSQGYCPGASSGQILMQPPAGNIGTASWSDPC
  LPELPFPGPFCPQALGHPPGGDGYFPDLFPTPCPQALGRQPSSALSWMPEGARPGTGPLL
  SKAKEEPPAASLDQPSALEEARGDDKNSHVP

• Sequence length: 691

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
Genetic non-acquired premature ovarian failure	Pathogenic; Likely pathogenic	rs1353957108, rs1476085935, rs2128861344, rs568492478, rs2128860927	RCV001661754 RCV001661773 RCV001663369 RCV001663374 RCV001663375	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NOBOX-related disorder	Likely pathogenic	rs991077121	RCV003402254	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Premature ovarian failure	Likely pathogenic	rs1006463439	RCV001270206	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Premature ovarian failure 5	Pathogenic; Likely pathogenic	rs193303102, rs193303103, rs193303104, rs1218620893	RCV000154189 RCV000154192 RCV000154193 RCV001002729	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Familial cancer of breast	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OVARIAN FAILURE, PREMATURE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Premature ovarian failure 1	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Amenorrhea	Amenorrhea	Pubtator	34480423	Associate	★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	BEFREE	18675947		★☆☆☆☆ Found in Text Mining only
Familial Testotoxicosis	Testotoxicosis	BEFREE	20593028		★☆☆☆☆ Found in Text Mining only
Gonadal Dysgenesis	Gonadal dysgenesis	Pubtator	33101191	Associate	★☆☆☆☆ Found in Text Mining only
NON RARE IN EUROPE: Primary ovarian failure	Ovarian Failure	Orphanet			★☆☆☆☆ Found in Text Mining only
Ovarian Dysgenesis 2	Ovarian dysgenesis	Pubtator	17701902, 18930203	Associate	★☆☆☆☆ Found in Text Mining only
Ovarian Failure, Premature	Ovarian Failure	BEFREE	15950662, 17701902, 18675947, 18689850, 25514101, 26848058, 27798098, 27836978, 28743298, 29067606		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian Failure, Premature	Ovarian Failure	LHGDN	15950662, 17701902		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian Failure, Premature	Ovarian Failure	GENOMICS_ENGLAND_DG	25514101		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Premature Menopause	Premature Menopause	BEFREE	15950662, 17701902, 18675947, 18689850, 25514101, 26848058, 27798098, 28743298		★☆☆☆☆ Found in Text Mining only
Premature Menopause	Premature Menopause	HPO_DG			★☆☆☆☆ Found in Text Mining only
Premature Ovarian Failure 5	Premature Ovarian Failure	UNIPROT_DG	17701902, 21837770, 25514101, 27798098		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Premature Ovarian Failure 5	Premature Ovarian Failure	GENOMICS_ENGLAND_DG	25514101		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Premature Ovarian Failure 5	Premature Ovarian Failure	CTD_human_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Premature Ovarian Failure 5	Premature Ovarian Failure	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Secondary physiologic amenorrhea	Secondary Physiologic Amenorrhea	HPO_DG			★☆☆☆☆ Found in Text Mining only