OTX1

protein-coding

orthodenticle homeobox 1, the group of PRD class homeoboxes and pseudogenes

Gene summary

This gene encodes a member of the bicoid sub-family of homeodomain-containing transcription factors. The encoded protein acts as a transcription factor and may play a role in brain and sensory organ development. A similar protein in mouse is required for proper brain and sensory organ development and can cause epilepsy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

MANE transcript

NM_014562.4

Inheritance

—

ClinVar variants

U:36B:2

Top phenotype

OTX1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr2:63,050,057-63,057,836

External References & Databases

Ensembl (ENSG00000115507)

Transcript & Mutation Effects

hg38 • Region Span ~7.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to OTX1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 33

not providedTotal: 2

OTX1-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014562.4. 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			1 clinvar		1 clinvar	2
missense			34 clinvar		1 clinvar	35
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	36	0	2	38

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014562.4	RefSeq	NP_055377.1	3	MANE Select
ENST00000282549.7	Ensembl	ENSP00000282549.2	3	MANE Select
NM_001199770.2	RefSeq	NP_001186699.1	3	Standard
ENST00000366671.7	Ensembl	ENSP00000355631.3	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
otx1	Danio rerio	Structure: whole organism Quality: unbalanced abnormal

Gene / Model

Organism

Observed Phenotype

otx1

Danio rerio

Structure: whole organism

Quality: unbalanced

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human)

Biological Process

anterior/posterior pattern specification
metencephalon development
midbrain development
inner ear morphogenesis
positive regulation of transcription by RNA polymerase II

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription activator activity, RNA polymerase II-specific
protein binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000282549
Coding exons: 3
Length: 7780
Individuals with no LoFs: 125275
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125276
p: 0.00000399

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.39	156	213	0.733	0.0000104	2265
Missense (PolyPhen)		20	43.144	0.46356		463
Synonymous	0.937	88	99.9	0.881	0.00000549	758
Loss of Function	2.75	1	10.7	0.0933	4.60e-7	119

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probably plays a role in the development of the brain and the sense organs. Can bind to the BCD target sequence (BTS): 5'-TCTAATCCC-3'.;

Recessive Scores

pRec: 0.277

Intolerance Scores

LoFtool: 0.0413
RVIS EVS: -0.1
RVIS percentile EVS: 46.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.429

Gene Damage Prediction

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