NKX3-2
protein-codingNK3 homeobox 2, the group of NKL subclass homeoboxes and pseudogenes
Gene summary
Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in cell differentiation; negative regulation of chondrocyte differentiation; and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including intestinal epithelial cell development; middle ear morphogenesis; and skeletal system development. Predicted to be located in chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]
- BAPX1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0013228
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0013228
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0013228
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0013228
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0013228
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to NKX3-2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001189.4. 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 | 2 | 59 | 3 | 64 | ||
| missense | 107 | 12 | 1 | 120 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 5 | 2 | 7 | |||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 7 | 2 | 109 | 71 | 4 | 193 |
Highest pathogenic variant AF is 0.0000021009757
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001180.1 | 2 | MANE Select | |
| Ensembl | ENSP00000371875.5 | 2 | MANE Select | |
| Ensembl | ENSP00000811322.1 | 2 | Standard | |
| RefSeq | XP_047272005.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| nkx3.2 | Danio rerio | Structure: pharyngeal arch 1 Quality: absent abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endochondral Ossification
- Transcriptional regulation by RUNX2
- Gene expression (Transcription)
- Generic Transcription Pathway
- RNA Polymerase II Transcription
Biological Process
- negative regulation of transcription by RNA polymerase II
- skeletal system development
- transcription by RNA polymerase II
- determination of left/right symmetry
- cell differentiation
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- sequence-specific DNA binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000382438
- Coding exons
- 2
- Length
- 4221
- Individuals with no LoFs
- 123278
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 123280
- p
- 0.00000811
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.596 | 193 | 171 | 1.13 | 0.00000790 | 2017 |
| Missense (PolyPhen) | 54 | 58.171 | 0.92829 | 710 | ||
| Synonymous | -1.71 | 98 | 78.7 | 1.25 | 0.00000400 | 724 |
| Loss of Function | 2.20 | 1 | 7.52 | 0.133 | 3.21e-7 | 101 |
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 | 0.00014 | 0.000047 | rare |
| European (Non-Finnish) | 0.0000097 | 0.0000090 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional repressor that acts as a negative regulator of chondrocyte maturation. PLays a role in distal stomach development; required for proper antral-pyloric morphogenesis and development of antral-type epithelium. In concert with GSC, defines the structural components of the middle ear; required for tympanic ring and gonium development and in the regulation of the width of the malleus (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.141
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.925
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |