EVX2

protein-coding

even-skipped homeobox 2, the group of HOXL subclass homeoboxes

Gene summary

This gene is located at the 5' end of the HOXD gene cluster on chromosome 2. The encoded protein is a homeobox transcription factor that is related to the protein encoded by the Drosophila even-skipped (eve) gene, a member of the pair-rule class of segmentation genes. A 117 kb microdeletion at the 5' end of the HOXD gene cluster, which includes this gene and the HOXD9-HOXD13 genes, causes synpolydactyly, a dominantly inherited disease resulting in limb malformation. [provided by RefSeq, Sep 2009]

MANE transcript

NM_001080458.2

Inheritance

—

ClinVar variants

U:97B:6

Top phenotype

EVX2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr2:176,077,472-176,083,962

External References & Databases

Ensembl (ENSG00000174279)

Transcript & Mutation Effects

hg38 • Region Span ~6.5 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 EVX2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 97

not providedTotal: 4

EVX2-related disorderTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001080458.2. 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	1 clinvar	4
missense			97 clinvar	2 clinvar		99
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	97	5	1	103

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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_001080458.2	RefSeq	NP_001073927.1	3	MANE Select
ENST00000308618.5	Ensembl	ENSP00000312385.4	3	MANE Select

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
evx2	Danio rerio	Structure: spinal cord Quality: has extra parts of type abnormal

Gene / Model

Organism

Observed Phenotype

evx2

Danio rerio

Structure: spinal cord

Quality: has extra parts of type

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
biological_process
limb morphogenesis

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: ENST00000308618
Coding exons: 3
Length: 6442
Individuals with no LoFs: 121578
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 121580
p: 0.00000823

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.151	208	214	0.971	0.0000102	2936
Missense (PolyPhen)		38	57.001	0.66665		832
Synonymous	-0.513	103	96.6	1.07	0.00000502	1057
Loss of Function	2.22	2	9.32	0.215	4.00e-7	130

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000030	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000097	0.0000091	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.131

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.905

Gene Damage Prediction

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