PKNOX1

protein-coding

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

Gene summary

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in angiogenesis and positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within camera-type eye development; hemopoiesis; and regulation of transcription by RNA polymerase II. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_004571.5

Inheritance

—

ClinVar variants

U:46

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr21:42,974,510-43,033,931

External References & Databases

Ensembl (ENSG00000160199)

Transcript & Mutation Effects

hg38 • Region Span ~59.4 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 PKNOX1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 38

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004571.5. 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			42 clinvar			42
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	46	0	0	46

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004571.5	RefSeq	NP_004562.2	10	MANE Select
ENST00000291547.10	Ensembl	ENSP00000291547.4	10	MANE Select
NM_001286258.2	RefSeq	NP_001273187.1	7	Standard
NM_001320694.2	RefSeq	NP_001307623.1	10	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
pknox1.2	Danio rerio	Structure: pharyngeal arch 3-7 Quality: physical object quality abnormal

Gene / Model

Organism

Observed Phenotype

pknox1.2

Danio rerio

Structure: pharyngeal arch 3-7

Quality: physical object quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways

Biological Process

angiogenesis
transcription by RNA polymerase II
T cell differentiation
erythrocyte differentiation
camera-type eye development

Molecular Function

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

Cellular Component

nucleus
transcription factor complex
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000291547
Coding exons: 10
Length: 59072
Individuals with no LoFs: 125675
Homozygous LoFs: 0
Heterozygous LoFs: 70
Defined: 125745
p: 0.000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.48	187	253	0.739	0.0000143	2865
Missense (PolyPhen)		51	97.938	0.52074		1135
Synonymous	-1.14	123	108	1.14	0.00000751	843
Loss of Function	4.17	2	24.0	0.0832	0.00000119	265

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000047	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0.0021	0.0021	notable
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Activates transcription in the presence of PBX1A and HOXA1. {ECO:0000250|UniProtKB:O70477}.;

Recessive Scores

pRec: 0.141

Intolerance Scores

RVIS EVS: -0.47
RVIS percentile EVS: 23.25

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.994

Gene Damage Prediction

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