NKX1-1

Summary

NKX1-1 (NK1 homeobox 1, HGNC:24975) is a protein-coding gene on chromosome 4p16.3, encoding NK1 transcription factor-related protein 1 (Q15270). May be required for the coordinated crosstalk of factors involved in the maintenance of energy homeostasis, possibly by regulating the transcription of specific factors involved in energy balance.

This gene encodes a transcription factor that belongs to NKX family of homeodomain-containing proteins which are critical regulators of organ development. In mice, the orthologous gene is expressed predominantly in the brainstem, in the vicinity of serotonergic neurons, and is required for the coordinated crosstalk of factors involved in the maintenance of energy homeostasis. Mice with a knockout of the orthologous gene lack subcutaneous fat and intra-abdominal epididymal and mesenteric white adipose tissue two weeks after birth, and die within three weeks after birth.

Source: NCBI Gene 54729 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_001290079

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24975
Approved symbol	NKX1-1
Name	NK1 homeobox 1
Location	4p16.3
Locus type	gene with protein product
Status	Approved
Aliases	HSPX153, SAX2
Ensembl gene	ENSG00000235608
Ensembl biotype	protein_coding
OMIM	617869
Entrez	54729

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000422806

RefSeq mRNA: 1 — MANE Select: NM_001290079 NM_001290079

CCDS: CCDS93464

Canonical transcript exons

ENST00000422806 — 2 exons

Exon	Start	End
ENSE00001722011	1402932	1403815
ENSE00001723973	1405980	1406442

Expression profiles

Bgee: expression breadth tissue_specific, 9 present calls, max score 53.09.

Top tissues by expression

244 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	53.09	gold quality
tendon of biceps brachii	UBERON:0008188	52.72	gold quality
middle temporal gyrus	UBERON:0002771	43.64	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
Brodmann (1909) area 23	UBERON:0013554	43.11	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
bone marrow cell	CL:0002092	41.95	gold quality
skin of hip	UBERON:0001554	41.55	silver quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
colonic epithelium	UBERON:0000397	41.17	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
jejunum	UBERON:0002115	40.18	gold quality
cartilage tissue	UBERON:0002418	40.06	gold quality
oviduct epithelium	UBERON:0004804	40.03	gold quality
mammary duct	UBERON:0001765	39.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	39.95	gold quality
deltoid	UBERON:0001476	39.83	gold quality
saphenous vein	UBERON:0007318	39.83	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.20

Regulation

Is transcription factor: no

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	nkx1.2lb	ENSDARG00000099427
mus_musculus	Nkx1-1	ENSMUSG00000029112
rattus_norvegicus	Nkx1-1	ENSRNOG00000005113
drosophila_melanogaster	NK7.1	FBGN0024321
drosophila_melanogaster	HGTX	FBGN0040318
drosophila_melanogaster	scro	FBGN0287186
caenorhabditis_elegans	ceh-9	WBGENE00000434
caenorhabditis_elegans		WBGENE00000447
caenorhabditis_elegans		WBGENE00000450
caenorhabditis_elegans		WBGENE00000584

Paralogs (13): NKX3-2 (ENSG00000109705), NKX2-3 (ENSG00000119919), NKX2-4 (ENSG00000125816), NKX2-2 (ENSG00000125820), NKX2-8 (ENSG00000136327), NKX2-1 (ENSG00000136352), NKX6-2 (ENSG00000148826), NKX6-1 (ENSG00000163623), NKX6-3 (ENSG00000165066), NKX3-1 (ENSG00000167034), NKX2-6 (ENSG00000180053), NKX2-5 (ENSG00000183072), NKX1-2 (ENSG00000229544)

Protein

Protein identifiers

NK1 transcription factor-related protein 1 — Q15270 (reviewed: Q15270)

Alternative names: Homeobox protein 153, Homeobox protein SAX-2, NKX-1.1

All UniProt accessions (1): Q15270

UniProt curated annotations — full annotation on UniProt →

Function. May be required for the coordinated crosstalk of factors involved in the maintenance of energy homeostasis, possibly by regulating the transcription of specific factors involved in energy balance.

Subcellular location. Nucleus.

Tissue specificity. Expressed in hemopoietic progenitor cells.

Similarity. Belongs to the NK-1 homeobox family.

RefSeq proteins (1): NP_001277008* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR020479	HD_metazoa	Domain
IPR050394	Homeobox_NK-like	Family

Pfam: PF00046

UniProt features (17 total): compositionally biased region 11, region of interest 3, chain 1, DNA-binding region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15270-F1	60.28	0.15

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 17 (showing top): chr4p16, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, STK33_SKM_DN, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, IGLV5_37_TARGET_GENES, HOFT_CD4_POSITIVE_ALPHA_BETA_MEMORY_T_CELL_BCG_VACCINE_AGE_18_45YO_7DY_DN, GSE18791_UNSTIM_VS_NEWCATSLE_VIRUS_DC_1H_UP, GOMF_DNA_BINDING_TRANSCRIPTION_FACTOR_ACTIVITY, GOMF_CIS_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, GSE2706_LPS_VS_R848_AND_LPS_2H_STIM_DC_UP, PULVER_FOREY_PERTURB_ACCUMULATION_S, GOMF_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, GOCC_CHROMATIN, GSE2770_IL12_ACT_VS_ACT_CD4_TCELL_6H_UP, GSE40274_CTRL_VS_FOXP3_AND_EOS_TRANSDUCED_ACTIVATED_CD4_TCELL_DN

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), cell differentiation (GO:0030154), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (3): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
cellular developmental process	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

414 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NKX1-1	M0QYG6	M0QYG6	541
NKX1-1	NKX6-3	A6NJ46	477
NKX1-1	INCA1	Q0VD86	430
NKX1-1	PXT1	Q8NFP0	417
NKX1-1	KASH5	Q8N6L0	402
NKX1-1	CCDC85B	Q15834	396
NKX1-1	SLC25A33	Q9BSK2	379
NKX1-1	FOXD4L5	Q5VV16	375
NKX1-1	DMC1	Q14565	367
NKX1-1	TTLL12	Q14166	358
NKX1-1	GLIS2	Q9BZE0	357
NKX1-1	POU5F2	Q8N7G0	353
NKX1-1	ASB9	Q96DX5	340
NKX1-1	ZNF541	Q9H0D2	301
NKX1-1	ZSWIM5	Q9P217	296

IntAct

2 interactions, top by confidence:

A	B	Type	Score
EIF3H		psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A2Z4LIS9, A6QPM6, A7X8B3, A7X8B5, A7X8B7, A7X8C4, A7X8C7, A7X8C9, A7XW16, A7XW20, A7XW25, O08664, O15054, O43151, O70218, O89113, P09066, P14652, P17542, P19419, P19622, P22091, P23683, P49640, P70061, P78412, P82976, P97503, Q00587, Q04890, Q05916, Q05917, Q12950, Q15270, Q17QW1, Q3U133, Q5JPB2, Q5NCY0, Q6ZW13, Q80WY3

Diamond homologs: A1YER7, A1YFD8, A1YFY3, A1YGA4, A2D4P8, A2D5I1, A2T6X6, A2T779, A5YC49, A6NJ46, A8XJD0, F1R2J1, G3UXB3, M0R6D8, O08686, O13074, O35137, O35762, O42230, O57601, O70218, O88181, P06798, P07548, P09016, P09017, P09089, P10284, P10628, P14840, P15142, P15858, P17277, P17278, P17483, P19601, P22544, P22574, P22807, P32443

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

427 predictions. Top by Δscore:

Variant	Effect	Δscore
4:1403811:GGCGT:G	acceptor_gain	1.0000
4:1403812:GCGT:G	acceptor_gain	1.0000
4:1403813:CGT:C	acceptor_gain	1.0000
4:1403813:CGTC:C	acceptor_gain	1.0000
4:1403814:GT:G	acceptor_gain	1.0000
4:1403816:C:CC	acceptor_gain	1.0000
4:1403816:CTG:C	acceptor_loss	1.0000
4:1403817:T:C	acceptor_loss	1.0000
4:1403820:G:T	acceptor_gain	0.9900
4:1404966:C:A	donor_gain	0.9900
4:1405978:A:AC	donor_gain	0.9900
4:1405979:C:CC	donor_gain	0.9900
4:1405979:CT:C	donor_gain	0.9900
4:1405979:CTCGG:C	donor_gain	0.9900
4:1406154:T:TA	donor_gain	0.9900
4:1404965:C:CA	donor_gain	0.9800
4:1405032:C:A	donor_gain	0.9800
4:1403812:GCGTC:G	acceptor_gain	0.9700
4:1403813:CGTCT:C	acceptor_gain	0.9700
4:1403814:GTCTG:G	acceptor_gain	0.9700
4:1403815:TCTGC:T	acceptor_gain	0.9700
4:1403832:C:CT	acceptor_gain	0.9700
4:1404004:C:A	donor_gain	0.9700
4:1404991:C:A	donor_gain	0.9700
4:1405090:AG:A	donor_gain	0.9700
4:1405974:A:AC	donor_gain	0.9700
4:1405975:C:CC	donor_gain	0.9700
4:1405031:C:CA	donor_gain	0.9600
4:1403816:CTGCG:C	acceptor_gain	0.9500
4:1403819:C:CT	acceptor_gain	0.9500

AlphaMissense

2816 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:1403223:C:A	K315N	1.000
4:1403223:C:G	K315N	1.000
4:1403226:C:A	W314C	1.000
4:1403226:C:G	W314C	1.000
4:1403228:A:G	W314R	1.000
4:1403228:A:T	W314R	1.000
4:1403229:C:A	K313N	1.000
4:1403229:C:G	K313N	1.000
4:1403231:T:C	K313E	1.000
4:1403236:C:G	R311P	1.000
4:1403237:G:C	R311G	1.000
4:1403239:C:G	R310P	1.000
4:1403240:G:C	R310G	1.000
4:1403240:G:T	R310S	1.000
4:1403241:G:C	N309K	1.000
4:1403241:G:T	N309K	1.000
4:1403242:T:A	N309I	1.000
4:1403242:T:C	N309S	1.000
4:1403242:T:G	N309T	1.000
4:1403243:T:C	N309D	1.000
4:1403243:T:G	N309H	1.000
4:1403244:C:A	Q308H	1.000
4:1403244:C:G	Q308H	1.000
4:1403245:T:G	Q308P	1.000
4:1403247:G:C	F307L	1.000
4:1403247:G:T	F307L	1.000
4:1403248:A:C	F307C	1.000
4:1403248:A:G	F307S	1.000
4:1403249:A:C	F307V	1.000
4:1403249:A:G	F307L	1.000

dbSNP variants (sampled 300 via entrez): RS1000186006 (4:1407067 C>A,T), RS1000586819 (4:1402959 C>A,T), RS1000950688 (4:1402574 C>A,T), RS1000960523 (4:1406302 A>G), RS1001637567 (4:1406321 C>T), RS1002375845 (4:1407377 G>A), RS1002415310 (4:1406999 G>A), RS1002428635 (4:1402896 C>A,T), RS1003639599 (4:1404943 C>G,T), RS1004184758 (4:1404693 C>G), RS1004216424 (4:1402677 C>T), RS1004372990 (4:1407337 C>A), RS1004422345 (4:1407123 C>A), RS1004769413 (4:1403641 GCCT>G), RS1006226817 (4:1402933 CAGAGGTGCGGCGCGT>C)

Disease associations

OMIM: gene MIM:617869 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

1 total (human), top 1 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.