NOBOX

protein-coding

NOBOX oogenesis homeobox, the group of PRD class homeoboxes and pseudogenes

Gene 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 by RefSeq, May 2011]

MANE transcript

N/A

Inheritance

AD, AR

ClinVar variants

P:7U:82B:21

Top phenotype

Premature ovarian failure 5

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr7:144,397,240-144,410,227

External References & Databases

Ensembl (ENSG00000106410)

Transcript & Mutation Effects

hg38 • Region Span ~13.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

premature ovarian failure 5STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0012689

Submitter: PanelApp Australia

premature ovarian failure 5STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012689

Submitter: PanelApp Australia

premature ovarian failure 5LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0012689

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Premature ovarian failure 5AD

Manifestation: Endocrine; Obstetric

Intervention: Obstetric

Rationale: Genetic knowledge may be beneficial to allow interventions such as preserving eggs in women with premature ovarian insufficiency

Refs: 17701902; 21837770; 25514101

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NOBOX variants in ClinVar

2 Conditions Cataloged

not providedTotal: 3

Premature ovarian failure 5Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript . Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	4 clinvar	3 clinvar	10
missense		1 clinvar	78 clinvar	5 clinvar	9 clinvar	93
nonsense	1 clinvar	1 clinvar	1 clinvar			3
start loss						0
frameshift	3 clinvar	1 clinvar				4
splice donor/acceptor (+/-2bp)						0
Total	4	3	82	9	12	110

Highest pathogenic variant AF is 0.00000656909

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
ENST00000467773.1	Ensembl	ENSP00000419457.1	10	MANE Select
ENST00000645489.3	Ensembl	ENSP00000496732.1	8	MANE Select
NM_001080413.3	RefSeq	NP_001073882.3	10	Standard
NM_001436401.1	RefSeq	NP_001423330.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
multicellular organism development
oogenesis

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
sequence-specific DNA binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000467773
Coding exons: 10
Length: 12988
Individuals with no LoFs: 124629
Homozygous LoFs: 0
Heterozygous LoFs: 21
Defined: 124650
p: 0.0000842

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.481	358	385	0.931	0.0000208	4370
Missense (PolyPhen)		87	91.165	0.95431		1080
Synonymous	0.869	144	158	0.912	0.00000899	1461
Loss of Function	2.49	12	25.6	0.468	0.00000133	292

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00017	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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'. {ECO:0000269|PubMed:25514101, ECO:0000269|PubMed:27798098}.;

Essentials

Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0290

Gene Damage Prediction

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