NKX6-3

protein-coding

NK6 homeobox 3, the group of NKL subclass homeoboxes and pseudogenes

Gene summary

The NKX family of homeodomain proteins controls numerous developmental processes. Members of the NKX6 subfamily, including NKX6-3, are involved in development of the central nervous system (CNS), gastrointestinal tract, and pancreas (Alanentalo et al., 2006 [PubMed 16326147]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_001364841.2

Inheritance

—

ClinVar variants

U:19

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.64

Max pathogenic AF

—

Genomic locus

chr8:41,645,177-41,650,817

External References & Databases

Ensembl (ENSG00000165066)

Transcript & Mutation Effects

hg38 • Region Span ~5.6 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 NKX6-3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 26

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001364841.2. 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			19 clinvar			19
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	19	0	0	19

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001364841.2	RefSeq	NP_001351770.1	3	MANE Select
ENST00000518699.4	Ensembl	ENSP00000428361.2	3	MANE Select
NM_152568.3	RefSeq	NP_689781.1	2	Standard
ENST00000524115.2	Ensembl	ENSP00000429553.2	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell differentiation
positive regulation of transcription by RNA polymerase II

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
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

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000524115
Coding exons: 2
Length: 6159
Individuals with no LoFs: 124898
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 124904
p: 0.0000240

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.112	75	72.3	1.04	0.00000351	829
Missense (PolyPhen)		28	21.365	1.3105		213
Synonymous	-0.103	36	35.2	1.02	0.00000201	290
Loss of Function	0.715	3	4.67	0.643	2.01e-7	54

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	0.0	absent
European (Non-Finnish)	0.0000089	0.0000089	rare
South Asian	0.00014	0.00013	rare
Other	0.00018	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Putative transcription factor, which may be involved in patterning of central nervous system and pancreas. {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.206
RVIS EVS: 0.46
RVIS percentile EVS: 78.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.141

Gene Damage Prediction

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