PKNOX2

protein-coding

PBX/knotted 1 homeobox 2, the group of TALE class homeoboxes and pseudogenes

Gene summary

Homeodomain proteins are sequence-specific transcription factors that share a highly conserved DNA-binding domain and play fundamental roles in cell proliferation, differentiation, and death. PKNOX2 belongs to the TALE (3-amino acid loop extension) class of homeodomain proteins characterized by a 3-amino acid extension between alpha helices 1 and 2 within the homeodomain (Imoto et al., 2001 [PubMed 11549286]).[supplied by OMIM, Oct 2009]

MANE transcript

NM_001382323.2

Inheritance

—

ClinVar variants

U:40

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr11:125,164,687-125,433,389

External References & Databases

Ensembl (ENSG00000165495)

Transcript & Mutation Effects

hg38 • Region Span ~268.7 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 PKNOX2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 39

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001382323.2. 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						0
missense			39 clinvar			39
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	40	0	0	40

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001382323.2	RefSeq	NP_001369252.1	10	MANE Select
ENST00000298282.14	Ensembl	ENSP00000298282.8	10	MANE Select
NM_001382324.1	RefSeq	NP_001369253.1	10	Standard
NM_001382325.1	RefSeq	NP_001369254.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
actin monomer binding
actin filament binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
actin cytoskeleton
microtubule cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000298282
Coding exons: 10
Length: 268703
Individuals with no LoFs: 124793
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 124798
p: 0.0000200

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.63	198	274	0.722	0.0000148	3112
Missense (PolyPhen)		29	81.777	0.35463		938
Synonymous	-1.28	138	120	1.15	0.00000748	920
Loss of Function	4.08	2	23.2	0.0863	0.00000107	248

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000056	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.122

Intolerance Scores

LoFtool: 0.0732
RVIS EVS: -0.8
RVIS percentile EVS: 12.33

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

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