ESX1

protein-coding

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

Gene summary

This gene encodes a dual-function 65 kDa protein that undergoes proteolytic cleavage to produce a 45 kDa N-terminal fragment with a paired-like homeodomain and a 20 kDa C-terminal fragment with a proline-rich domain. The C-terminal fragment localizes to the cytoplasm while the N-terminal fragment localizes exclusively to the nucleus. In contrast to human, the mouse homolog has a novel PN/PF motif in the C-terminus and is paternally imprinted in placental tissue. This gene likely plays a role in placental development and spermatogenesis. [provided by RefSeq, Jan 2010]

Previous symbols:

ESX1L

MANE transcript

NM_153448.4

Inheritance

—

ClinVar variants

P:1U:58B:15

Top phenotype

ESX1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chrX:104,250,038-104,254,933

External References & Databases

Ensembl (ENSG00000123576)

Transcript & Mutation Effects

hg38 • Region Span ~4.9 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 ESX1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 65

not providedTotal: 15

ESX1-related disorderTotal: 1

Male infertility with azoospermia or oligozoospermia due to single gene mutationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_153448.4. 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	5 clinvar		6
missense		1 clinvar	56 clinvar	10 clinvar		67
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	1	58	15	0	74

Highest pathogenic variant AF is 0.000020967685

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_153448.4	RefSeq	NP_703149.1	4	MANE Select
ENST00000372588.4	Ensembl	ENSP00000361669.4	4	MANE Select

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

negative regulation of transcription by RNA polymerase II
negative regulation of transcription, DNA-templated
regulation of cell cycle

Molecular Function

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

Cellular Component

nucleus
cytoplasm
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372588
Coding exons: 4
Length: 4896
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0380	157	156	1.01	0.0000116	2580
Missense (PolyPhen)		15	16.932	0.88589		254
Synonymous	-2.80	95	66.1	1.44	0.00000541	897
Loss of Function	1.96	1	6.33	0.158	4.04e-7	102

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	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May coordinately regulate cell cycle progression and transcription during spermatogenesis. Inhibits degradation of polyubiquitinated cyclin A and cyclin B1 and thereby arrests the cell cycle at early M phase. ESXR1-N acts as a transcriptional repressor. Binds to the sequence 5'-TAATGTTATTA-3' which is present within the first intron of the KRAS gene and inhibits its expression. ESXR1-C has the ability to inhibit cyclin turnover. {ECO:0000269|PubMed:15235584, ECO:0000269|PubMed:15897875}.;

Recessive Scores

pRec: 0.0957

Intolerance Scores

LoFtool: 0.249
RVIS EVS: 0.04
RVIS percentile EVS: 57.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.00000366

Gene Damage Prediction

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