MKX

Summary

MKX (mohawk homeobox, HGNC:23729) is a protein-coding gene on chromosome 10p12.1, encoding Homeobox protein Mohawk (Q8IYA7). May act as a morphogenetic regulator of cell adhesion.

The protein encoded by this gene is an IRX family-related homeobox protein that may play a role in cell adhesion. Studies in mice suggest that this protein may be a regulator of tendon development. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 283078 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 41 total
• MANE Select transcript: NM_173576

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23729
Approved symbol	MKX
Name	mohawk homeobox
Location	10p12.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC39616
Ensembl gene	ENSG00000150051
Ensembl biotype	protein_coding
OMIM	601332
Entrez	283078

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000375790, ENST00000419761, ENST00000460919, ENST00000561227, ENST00000881368, ENST00000881369, ENST00000881370, ENST00000969296

RefSeq mRNA: 2 — MANE Select: NM_173576 NM_001242702, NM_173576

CCDS: CCDS7156

Canonical transcript exons

ENST00000419761 — 7 exons

Exon	Start	End
ENSE00001649488	27743228	27743497
ENSE00001700604	27745707	27745819
ENSE00003841930	27672874	27675415
ENSE00003888782	27675521	27675554
ENSE00003889760	27741345	27741504
ENSE00003890433	27735221	27735374
ENSE00003893897	27734456	27734791

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 96.43.

FANTOM5 (CAGE): breadth broad, TPM avg 2.6373 / max 223.1898, expressed in 398 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108781	1.7032	251
108772	0.3991	210
108784	0.1794	90
108782	0.1301	69
108783	0.1107	56
108773	0.0753	36
108780	0.0395	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	96.43	gold quality
tendon	UBERON:0000043	86.46	gold quality
oviduct epithelium	UBERON:0004804	83.33	gold quality
endothelial cell	CL:0000115	82.08	silver quality
right coronary artery	UBERON:0001625	81.10	gold quality
prostate gland	UBERON:0002367	81.05	gold quality
popliteal artery	UBERON:0002250	78.33	gold quality
tibial artery	UBERON:0007610	78.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.15	gold quality
stromal cell of endometrium	CL:0002255	78.07	gold quality
adenohypophysis	UBERON:0002196	77.11	gold quality
left coronary artery	UBERON:0001626	76.94	gold quality
right ovary	UBERON:0002118	76.93	gold quality
left ovary	UBERON:0002119	76.36	gold quality
aorta	UBERON:0000947	76.33	gold quality
Brodmann (1909) area 23	UBERON:0013554	76.03	gold quality
lower esophagus muscularis layer	UBERON:0035833	76.01	gold quality
lower esophagus	UBERON:0013473	75.98	gold quality
pituitary gland	UBERON:0000007	75.76	gold quality
coronary artery	UBERON:0001621	75.29	gold quality
ascending aorta	UBERON:0001496	74.17	gold quality
ovary	UBERON:0000992	74.13	gold quality
tendon of biceps brachii	UBERON:0008188	74.05	silver quality
thoracic aorta	UBERON:0001515	73.98	gold quality
prefrontal cortex	UBERON:0000451	73.34	gold quality
mucosa of stomach	UBERON:0001199	73.08	gold quality
primary visual cortex	UBERON:0002436	72.58	gold quality
descending thoracic aorta	UBERON:0002345	72.48	gold quality
buccal mucosa cell	CL:0002336	72.46	gold quality
tibia	UBERON:0000979	71.98	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7037	yes	33.98
E-MTAB-7249	no	40.84
E-ANND-3	no	3.57

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
MYOD1
RUNX2	Activation
SCX	Activation
SOX5	Activation
SOX6	Activation
TGFB1	Activation
TGFB2	Activation

JASPAR motifs

Motif	Name	Family
MA2592.1	MKX	TALE-type HD

JASPAR matrix evidence (PMIDs): PMID:39605530

Upstream regulators (CollecTRI, top): TCF15

miRNA regulators (miRDB)

166 targeting MKX, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 7)

• In silico characterization of the C10orf48 sequence (PMID:16077953)
• Reduced expression of MKX is a feature of degenerated anterior cruciate ligament in osteoarthritis-affected joints. (PMID:23686683)
• Transcription factor Mohawk controls tenogenic differentiation of bone marrow mesenchymal stem cells in vitro and in vivo. (PMID:25312837)
• these data shed light on previously unrecognized roles of Mkx in tendinopathy, tenogenesis, and tendon repair as well as in regulating the TGFbeta pathway. (PMID:25332192)
• Data show that homeobox protein Mohawk (Mkx) is mainly expressed in the outer annulus fibrosus (OAF) of humans and mice. (PMID:27527664)
• Mohawk is a transcription factor that promotes meniscus cell phenotype and tissue repair and reduces osteoarthritis severity. (PMID:33115953)
• COBL, MKX and MYOC Are Potential Regulators of Brown Adipose Tissue Development Associated with Obesity-Related Metabolic Dysfunction in Children. (PMID:36834493)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mkxa	ENSDARG00000075450
mus_musculus	Mkx	ENSMUSG00000061013
rattus_norvegicus	Mkx	ENSRNOG00000018938
drosophila_melanogaster	CG11617	FBGN0031232

Paralogs (6): IRX4 (ENSG00000113430), IRX6 (ENSG00000159387), IRX1 (ENSG00000170549), IRX2 (ENSG00000170561), IRX5 (ENSG00000176842), IRX3 (ENSG00000177508)

Protein

Protein identifiers

Homeobox protein Mohawk — Q8IYA7 (reviewed: Q8IYA7)

All UniProt accessions (3): Q8IYA7, H0YKC7, H0YMU2

UniProt curated annotations — full annotation on UniProt →

Function. May act as a morphogenetic regulator of cell adhesion.

Subcellular location. Nucleus.

Similarity. Belongs to the TALE/IRO homeobox family.

RefSeq proteins (2): NP_001229631, NP_775847* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR008422	KN_HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site

Pfam: PF05920

UniProt features (7 total): region of interest 3, chain 1, DNA-binding region 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYA7-F1	63.88	0.21

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 119 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, BENPORATH_ES_WITH_H3K27ME3, PEREZ_TP63_TARGETS, TATTATA_MIR374, CTATGCA_MIR153, GTGCCTT_MIR506, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, FREAC3_01, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, PU1_Q6, LINDVALL_IMMORTALIZED_BY_TERT_UP, LIU_SMARCA4_TARGETS

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), muscle organ development (GO:0007517), cell development (GO:0048468), 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
animal organ development	1
muscle structure development	1
cell differentiation	1
anatomical structure development	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

964 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MKX	TNMD	Q9H2S6	856
MKX	TCF15	Q12870	795
MKX	SCX	Q7RTU7	749
MKX	FMOD	Q06828	634
MKX	DCN	P07585	622
MKX	COL1A1	P02452	589
MKX	BGN	P13247	531
MKX	EGR1	P18146	523
MKX	SMAD3	P84022	511
MKX	THBS4	P35443	495
MKX	GDF7	Q7Z4P5	494
MKX	COL3A1	P02461	494
MKX	SOX9	P48436	483
MKX	ACAN	P16112	440
MKX	GDF6	Q6KF10	435

IntAct

5 interactions, top by confidence:

A	B	Type	Score
MKX	RAB34	psi-mi:“MI:0915”(physical association)	0.400
HSP90AB1	MKX	psi-mi:“MI:0915”(physical association)	0.400
MKX	TBL1X	psi-mi:“MI:0914”(association)	0.350

BioGRID (55): TBL1X (Affinity Capture-MS), TBL1XR1 (Affinity Capture-MS), MKX (Affinity Capture-RNA), CNP (Affinity Capture-MS), HSH2D (Affinity Capture-MS), RAB34 (Proximity Label-MS), TBL1X (Affinity Capture-MS), TBL1XR1 (Affinity Capture-MS), MKX (Affinity Capture-MS), MKX (Cross-Linking-MS (XL-MS)), AMPD2 (Affinity Capture-MS), CHD4 (Affinity Capture-MS), ERCC3 (Affinity Capture-MS), GPS2 (Affinity Capture-MS), HDAC1 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LFM6, A0A1B0GVH6, A0A2K1J5A5, A0A2K1JJ00, A4IGV6, B3DHS1, C5DZR8, C8ZEW0, F1QPR4, F1QR98, O35413, P05432, P0CAX8, P32845, P34469, P48437, P97440, Q04438, Q06616, Q1RMQ5, Q3UTJ2, Q3ZBS1, Q5RDK8, Q5ZM13, Q62417, Q69Z38, Q6DFB0, Q6P9N1, Q6PKN7, Q8BIA3, Q8BLN6, Q8IYA7, Q8N2C7, Q8N9R6, Q8VEB3, Q91018, Q92786, Q96GV9, Q96GY3, Q96L14

Diamond homologs: A1YGI6, A6NDR6, A8K0S8, A8WL06, B7ZRT8, O00470, O04136, O14770, O22300, O42261, O46339, O65685, O70477, P41779, P41817, P46606, P48000, P48001, P48002, P48731, P53147, P54269, P55347, P56659, P56660, P56664, P56665, P56669, P70284, P78412, P78413, P78414, P78415, P79937, P81067, P81068, P97367, P97368, Q0E3C3, Q0J6N4

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
MKX	“up-regulates quantity by expression”	SCX	“transcriptional regulation”
MKX	“up-regulates quantity by expression”	SOX5	“transcriptional regulation”
MKX	“up-regulates quantity by expression”	RUNX2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1791 predictions. Top by Δscore:

Variant	Effect	Δscore
10:27734451:CTTA:C	donor_loss	1.0000
10:27734452:TTACC:T	donor_loss	1.0000
10:27734453:TACCT:T	donor_loss	1.0000
10:27734454:A:AC	donor_gain	1.0000
10:27734454:A:C	donor_loss	1.0000
10:27734455:C:A	donor_loss	1.0000
10:27734455:C:CC	donor_gain	1.0000
10:27734792:C:CC	acceptor_gain	1.0000
10:27741512:A:C	acceptor_gain	1.0000
10:27675411:CTGCG:C	acceptor_gain	0.9900
10:27675416:C:CC	acceptor_gain	0.9900
10:27675551:GTGT:G	acceptor_gain	0.9900
10:27675551:GTGTC:G	acceptor_loss	0.9900
10:27675552:TGT:T	acceptor_gain	0.9900
10:27675553:GT:G	acceptor_gain	0.9900
10:27675553:GTCT:G	acceptor_loss	0.9900
10:27675554:TC:T	acceptor_loss	0.9900
10:27675555:C:CC	acceptor_gain	0.9900
10:27675556:T:G	acceptor_loss	0.9900
10:27699478:T:A	donor_gain	0.9900
10:27718535:AGCT:A	donor_gain	0.9900
10:27734455:CCT:C	donor_gain	0.9900
10:27734788:CCAT:C	acceptor_gain	0.9900
10:27734789:CAT:C	acceptor_gain	0.9900
10:27734789:CATC:C	acceptor_gain	0.9900
10:27734791:TCT:T	acceptor_loss	0.9900
10:27734792:C:CA	acceptor_loss	0.9900
10:27734793:T:C	acceptor_loss	0.9900
10:27735217:AAAC:A	donor_loss	0.9900
10:27735218:AAC:A	donor_loss	0.9900

AlphaMissense

2304 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:27735287:A:C	Y146D	1.000
10:27735295:A:G	I143T	1.000
10:27735295:A:T	I143K	1.000
10:27735297:T:A	R142S	1.000
10:27735297:T:G	R142S	1.000
10:27735306:C:A	W139C	1.000
10:27735306:C:G	W139C	1.000
10:27735307:C:G	W139S	1.000
10:27735308:A:G	W139R	1.000
10:27735308:A:T	W139R	1.000
10:27735328:A:T	V132D	1.000
10:27735336:C:A	K129N	1.000
10:27735336:C:G	K129N	1.000
10:27735338:T:C	K129E	1.000
10:27735340:A:C	L128R	1.000
10:27735340:A:G	L128P	1.000
10:27735340:A:T	L128H	1.000
10:27735344:G:C	R127G	1.000
10:27735346:C:G	R126P	1.000
10:27735347:G:A	R126C	1.000
10:27735347:G:C	R126G	1.000
10:27735347:G:T	R126S	1.000
10:27735348:T:A	R125S	1.000
10:27735348:T:G	R125S	1.000
10:27735349:C:A	R125I	1.000
10:27735349:C:G	R125T	1.000
10:27735350:T:C	R125G	1.000
10:27735353:C:G	A124P	1.000
10:27735354:A:C	N123K	1.000
10:27735354:A:T	N123K	1.000

dbSNP variants (sampled 300 via entrez): RS1000009169 (10:27685827 A>C,G), RS1000072147 (10:27729080 A>C), RS1000098702 (10:27711115 A>G), RS1000137441 (10:27722740 A>C), RS1000151138 (10:27710791 G>A), RS1000160085 (10:27712267 A>G), RS1000188506 (10:27722494 A>G), RS1000190909 (10:27680492 A>C), RS1000194021 (10:27730931 G>A), RS1000238449 (10:27717660 G>A), RS1000255162 (10:27738175 T>C), RS1000278003 (10:27735551 C>A,G,T), RS1000317557 (10:27724624 T>G), RS1000327299 (10:27724307 C>G), RS1000378848 (10:27681498 A>G)

Disease associations

OMIM: gene MIM:601332 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001491_34	Immune response to smallpox vaccine (IL-6)	1.000000e-10
GCST002875_97	Diisocyanate-induced asthma	2.000000e-06
GCST003991_3	Childhood ear infection	5.000000e-16
GCST005013_11	Childhood ear infection	5.000000e-16
GCST006979_566	Heel bone mineral density	1.000000e-13
GCST008154_22	Trunk fat mass	3.000000e-06
GCST008163_559	Height	2.000000e-06
GCST008839_31	Height	2.000000e-12
GCST009959_8	Retinal detachment or retinal break	5.000000e-06
GCST012227_605	Hip circumference adjusted for BMI	4.000000e-11
GCST012227_606	Hip circumference adjusted for BMI	2.000000e-13

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0006995	response to diisocyanate
EFO:0007904	susceptibility to childhood ear infection measurement
EFO:0009270	heel bone mineral density
EFO:0010698	retinal break
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects splicing, decreases expression, affects cotreatment, increases abundance	2
potassium chromate(VI)	increases expression, affects cotreatment, decreases expression	2
(+)-JQ1 compound	decreases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Valproic Acid	decreases methylation, increases expression	2
Cyclosporine	increases expression	2
GSK-J4	increases expression	1
TAK-243	increases sumoylation	1
bisphenol A	decreases expression	1
trichostatin A	increases expression	1
arsenite	increases methylation	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
nickel sulfate	increases expression	1
stearic acid	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	affects expression	1
perfluoro-n-nonanoic acid	increases expression	1
bisphenol S	affects methylation	1
NSC668394	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Irinotecan	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Fluorouracil	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Nickel	decreases expression	1
Phthalic Acids	decreases methylation	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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