NKX2-2

NK2 homeobox 2, the group of NKL subclass homeoboxes and pseudogenes

Basic information

Region (hg38): 20:21511017-21514064

Previous symbols: [ "NKX2B" ]

Links

ENSG00000125820 ∙ NCBI:4821 ∙ OMIM:604612 ∙ HGNC:7835 ∙ Uniprot:O95096 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neonatal diabetes mellitus (Strong), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NKX2-2 gene.

• not_provided (32 variants)
• NKX2-2-related_disorder (5 variants)
• Inborn_genetic_diseases (5 variants)
• not_specified (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NKX2-2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002509.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	19	1	21
missense			10	3	2	15
nonsense			1			1
start loss						0
frameshift		1				1
splice donor/acceptor (+/-2bp)						0
Total	0	1	12	22	3

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NKX2-2	protein_coding	protein_coding	ENST00000377142	2	3017

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.414	0.579	125711	0	4	125715	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.00371	161	161	0.999	0.00000724	1734
Missense in Polyphen		29	53.303	0.54406		556
Synonymous	-2.38	100	73.9	1.35	0.00000349	568
Loss of Function	2.25	2	9.47	0.211	4.11e-7	101

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000550	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000274	0.0000264
Middle Eastern	0.0000550	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional activator involved in the development of insulin-producting beta cells in the endocrine pancreas (By similarity). May also be involved in specifying diencephalic neuromeric boundaries, and in controlling the expression of genes that play a role in axonal guidance. Binds to elements within the NEUROD1 promoter (By similarity). {ECO:0000250|UniProtKB:P42586}.
• Pathway: Maturity onset diabetes of the young - Homo sapiens (human);Dopaminergic Neurogenesis;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways (Consensus)

Recessive Scores

• pRec: 0.250

Intolerance Scores

• loftool: 0.199
• rvis_EVS: 0.51
• rvis_percentile_EVS: 80.01

Haploinsufficiency Scores

• pHI: 0.481
• hipred: Y
• hipred_score: 0.736
• ghis: 0.412

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.942

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nkx2-2
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; embryo phenotype

Zebrafish Information Network

• Gene name: nkx2.2a
• Affected structure: myelinating Schwann cell
• Phenotype tag: abnormal
• Phenotype quality: mislocalised

Gene ontology

• Biological process: type B pancreatic cell development;pancreatic A cell fate commitment;type B pancreatic cell fate commitment;pancreatic PP cell fate commitment;smoothened signaling pathway;brain development;response to glucose;oligodendrocyte development;spinal cord motor neuron differentiation;spinal cord oligodendrocyte cell fate specification;optic nerve development;cell differentiation;endocrine pancreas development;response to progesterone;negative regulation of neuron differentiation;positive regulation of neuron differentiation;positive regulation of transcription by RNA polymerase II;digestive tract development;neuron fate specification;astrocyte differentiation;positive regulation of oligodendrocyte differentiation;positive regulation of DNA-binding transcription factor activity;ventral spinal cord interneuron fate determination
• Cellular component: nucleus;nucleoplasm
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;proximal promoter sequence-specific DNA binding;chromatin binding;DNA-binding transcription factor activity;transcription coactivator activity;transcription factor binding;sequence-specific DNA binding