NKX6-2

NK6 homeobox 2, the group of NKL subclass homeoboxes and pseudogenes

Basic information

Region (hg38): 10:132783179-132786147

Links

ENSG00000148826 ∙ NCBI:84504 ∙ OMIM:605955 ∙ HGNC:19321 ∙ Uniprot:Q9C056 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy (Strong), mode of inheritance: AR
• spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy (Supportive), mode of inheritance: AR
• spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy	AR	General	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	Neurologic	28575651

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NKX6-2 gene.

• Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NKX6-2 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	35		36
missense	2		69	2	1	74
nonsense	2	2				4
start loss						0
frameshift	1	3	2			6
inframe indel				1		1
splice donor/acceptor (+/-2bp)		1				1
splice region			2	1		3
non coding				2	4	6
Total	5	6	72	40	5

Variants in NKX6-2

This is a list of pathogenic ClinVar variants found in the NKX6-2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-132784926-T-C			Uncertain significance (Jan 06, 2022)
10-132784939-C-G		Inborn genetic diseases	Uncertain significance (May 09, 2023)
10-132784957-G-C		Inborn genetic diseases	Uncertain significance (Jan 24, 2023)
10-132784961-C-T			Likely benign (Aug 22, 2022)
10-132784970-G-A			Likely benign (Aug 10, 2023)
10-132784972-G-A			Uncertain significance (Apr 27, 2022)
10-132784976-G-A			Likely benign (Jul 17, 2023)
10-132784999-T-G			Uncertain significance (Jun 09, 2022)
10-132785002-T-C		Inborn genetic diseases	Uncertain significance (Mar 28, 2022)
10-132785005-C-T		Inborn genetic diseases	Uncertain significance (Oct 03, 2022)
10-132785013-G-A			Uncertain significance (Jun 13, 2022)
10-132785016-T-C			Uncertain significance (Jun 03, 2022)
10-132785028-G-A			Uncertain significance (May 17, 2022)
10-132785028-G-C			Uncertain significance (Aug 23, 2022)
10-132785029-G-A		Inborn genetic diseases	Uncertain significance (Jun 29, 2021)
10-132785032-G-A		Inborn genetic diseases	Uncertain significance (Dec 06, 2021)
10-132785061-G-A		Inborn genetic diseases	Uncertain significance (Sep 28, 2022)
10-132785066-G-T			Likely benign (Aug 09, 2022)
10-132785068-C-T		Inborn genetic diseases	Uncertain significance (Feb 14, 2024)
10-132785084-G-A			Likely benign (Oct 03, 2023)
10-132785091-G-C			Uncertain significance (Feb 18, 2022)
10-132785093-G-A			Likely benign (Aug 01, 2023)
10-132785093-G-C			Uncertain significance (Dec 02, 2021)
10-132785104-TC-T			Uncertain significance (Sep 06, 2022)
10-132785115-G-A			Uncertain significance (Dec 02, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NKX6-2	protein_coding	protein_coding	ENST00000368592	3	1260

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0289	0.815	124947	0	7	124954	0.0000280

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.139	120	116	1.04	0.00000549	1710
Missense in Polyphen		53	48.578	1.091		575
Synonymous	-0.196	57	55.1	1.03	0.00000278	593
Loss of Function	1.09	3	5.85	0.513	2.50e-7	86

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000868	0.0000868
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000277	0.0000267
Middle Eastern	0.00	0.00
South Asian	0.0000338	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor with repressor activity involved in the regulation of axon-glial interactions at myelin paranodes in oligodendrocytes. Binds to the consensus DNA sequence 5'- (A/T)TTAATGA-3'. In oligodendrocytes, binds to MBP and PLP1 promoter regions. {ECO:0000250|UniProtKB:D3Z4R4}.

Recessive Scores

• pRec: 0.168

Haploinsufficiency Scores

• pHI: 0.334
• hipred: Y
• hipred_score: 0.752
• ghis: 0.514

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.282

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nkx6-2
• Phenotype: normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); vision/eye 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); cellular phenotype

Zebrafish Information Network

• Gene name: nkx6.2
• Affected structure: primary motor neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;regulation of transcription, DNA-templated;negative regulation of cell fate commitment;positive regulation of cell fate commitment;regulation of transcription from RNA polymerase II promoter involved in spinal cord motor neuron fate specification;regulation of transcription from RNA polymerase II promoter involved in ventral spinal cord interneuron specification;central nervous system myelination;cell differentiation;endocrine pancreas development;regulation of myelination;negative regulation of glial cell differentiation;positive regulation of glial cell differentiation;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;neuromuscular process controlling balance
• Cellular component: nucleus
• 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;DNA-binding transcription factor activity;sequence-specific DNA binding