MEOX2

Summary

MEOX2 (mesenchyme homeobox 2, HGNC:7014) is a protein-coding gene on chromosome 7p21.2, encoding Homeobox protein MOX-2 (P50222). Mesodermal transcription factor that plays a key role in somitogenesis and somitogenesis and limb muscle differentiation.

This gene encodes a member of a subfamily of non-clustered, diverged, antennapedia-like homeobox-containing genes. The encoded protein may play a role in the regulation of vertebrate limb myogenesis. Mutations in the related mouse protein may be associated with craniofacial and/or skeletal abnormalities, in addition to neurovascular dysfunction observed in Alzheimer’s disease.

Source: NCBI Gene 4223 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 53 total
• MANE Select transcript: NM_005924

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7014
Approved symbol	MEOX2
Name	mesenchyme homeobox 2
Location	7p21.2
Locus type	gene with protein product
Status	Approved
Aliases	MOX2
Ensembl gene	ENSG00000106511
Ensembl biotype	protein_coding
OMIM	600535
Entrez	4223

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000262041, ENST00000904167

RefSeq mRNA: 1 — MANE Select: NM_005924 NM_005924

CCDS: CCDS34605

Canonical transcript exons

ENST00000262041 — 3 exons

Exon	Start	End
ENSE00000672103	15626746	15626918
ENSE00001141562	15685886	15686683
ENSE00001157422	15611212	15612611

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 98.16.

FANTOM5 (CAGE): breadth broad, TPM avg 4.6407 / max 1683.2972, expressed in 468 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82880	1.9937	280
82879	1.2130	273
82876	0.2949	98
82878	0.2943	122
82871	0.2566	119
82877	0.1691	81
82873	0.1373	56
82875	0.0926	41
82872	0.0587	23
82870	0.0564	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.16	gold quality
parietal pleura	UBERON:0002400	95.40	gold quality
tendon	UBERON:0000043	95.38	gold quality
dorsal root ganglion	UBERON:0000044	95.08	gold quality
tibial nerve	UBERON:0001323	93.34	gold quality
synovial joint	UBERON:0002217	92.36	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.43	gold quality
pleura	UBERON:0000977	91.20	gold quality
tendon of biceps brachii	UBERON:0008188	90.85	gold quality
saphenous vein	UBERON:0007318	90.75	gold quality
sural nerve	UBERON:0015488	90.54	gold quality
trigeminal ganglion	UBERON:0001675	90.31	gold quality
vena cava	UBERON:0004087	90.20	gold quality
pericardium	UBERON:0002407	90.10	gold quality
adipose tissue	UBERON:0001013	89.94	gold quality
connective tissue	UBERON:0002384	89.53	gold quality
popliteal artery	UBERON:0002250	89.36	gold quality
tibial artery	UBERON:0007610	89.36	gold quality
right lung	UBERON:0002167	87.93	gold quality
adipose tissue of abdominal region	UBERON:0007808	87.93	gold quality
omental fat pad	UBERON:0010414	87.84	gold quality
peritoneum	UBERON:0002358	87.77	gold quality
placenta	UBERON:0001987	86.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.89	gold quality
lower lobe of lung	UBERON:0008949	85.58	gold quality
thoracic mammary gland	UBERON:0005200	85.25	gold quality
mammary gland	UBERON:0001911	85.06	gold quality
aorta	UBERON:0000947	84.46	gold quality
visceral pleura	UBERON:0002401	84.36	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	84.14	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	12.57
E-ANND-3	yes	5.83

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
BAX	Activation
BCL2	Repression
CDKN1A	Activation
CDKN2A
MYF5	Unknown
NKX3-2
RNF10

Upstream regulators (CollecTRI, top): CTNNB1, MEF2A, ZEB2

miRNA regulators (miRDB)

161 targeting MEOX2, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-454-3P	99.91	74.01	1925

Literature-anchored findings (GeneRIF, showing 27)

• homeobox protein Gax is expressed in vascular endothelium and strongly inhibits endothelial cell activation in response to growth factors and tube formation in vitro (PMID:12842453)
• The link of MEOX2 to neurovascular dysfunction in Alzheimer disease provides new mechanistic and therapeutic insights into this illness. (PMID:16116430)
• MEOX2 binding to RNF10 protein, human, was characterized. (PMID:16335786)
• GAX activates p21WAF1/CIP1 expression in vascular endothelial cells through direct interaction with upstream AT-rich sequences (PMID:17074759)
• miR-130a is a regulator of the angiogenic phenotype of vascular endothelial cells largely through its ability to modulate the expression of GAX and HOXA5 (PMID:17957028)
• MEOX2-induced senescence is dependent upon INK4a activity, and chromatin immunoprecipitation studies indicate that MEOX2 directly binds the INK4a promoter (PMID:19340300)
• ectopic Meox2 suppressed epithelial cell proliferation in cooperation with TGF-beta1, and mediated induction of the cell cycle inhibitor gene p21. (PMID:19383287)
• Loss of MEOX2 gene is associated with Wilms tumor. (PMID:19760604)
• Report of an interaction between a homeobox protein and IkappaBbeta in endothelial cells and suggest that MEOX2 modulates the activity of the RelA complex through direct interaction with its components. (PMID:20421348)
• MEOX1 and MEOX2 activate p16(INK4a) in a DNA binding dependent manner, whereas they induce p21(CIP1/WAF1) in a DNA binding independent manner. (PMID:22206000)
• downregulated expression of GAX is an independent prognostic factor and is correlated with poor survival in hepatocellular carcinoma patients (PMID:22644917)
• MEOX2 participates in chemoresistance irrespective of high CNV, but it is significantly dependent upon H3K27me3 enrichment probably associated with aggressiveness and chemotherapy failure in NSCLC patients (PMID:25460568)
• Microarray profiling on freshly isolated ECs had a genetic signature for microvascular heart ECs and identified Meox2/Tcf15 heterodimers as novel transcriptional determinants. This signature was similar in skeletal muscle and adipose tissue endothelium. (PMID:25561514)
• 3D topography transiently induces concomitant upregulation of IL-1beta and MAPK ERK1/2 through nuclear factor-kappaB-dependent signaling pathway. (PMID:26041434)
• Genetic variation in MEOX2, but not TCF15, is a strong predictor of CHD. Further experimental studies should elucidate the underlying molecular mechanisms. (PMID:26428460)
• MEOX2 may serve a protective role, enabling increased vessel formation despite exposure to a diabetes mellitus intrauterine environment. (PMID:27966787)
• MEOX2 polymorphism is associated with nonsyndromic cleft palate. (PMID:29030958)
• Over-expression of MEOX2 in laryngeal cancer cells inhibited cell viability and promoted apoptosis, via regulating apoptosis and PI3K/Akt pathway related factors. (PMID:29940775)
• our results may be the first to provide insight into the clinical significance of MEOX2 in gliomas (PMID:30659268)
• Facilitation of Bone Healing Processes Based on the Developmental Function of Meox2 in Tooth Loss Lesion. (PMID:33218046)
• Tumor-derived exosomal miRNA-141 promote angiogenesis and malignant progression of lung cancer by targeting growth arrest-specific homeobox gene (GAX). (PMID:33627047)
• Exosomal circular RNA circ_0074673 regulates the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells via the microRNA-1200/MEOX2 axis. (PMID:34516311)
• Identification of Diagnostic Signatures and Immune Cell Infiltration Characteristics in Rheumatoid Arthritis by Integrating Bioinformatic Analysis and Machine-Learning Strategies. (PMID:34691030)
• Mesenchyme homeobox 2 has a cancer-inhibiting function in breast carcinoma via affection of the PI3K/AKT/mTOR and ERK1/2 pathways. (PMID:35051778)
• MEOX2-mediated regulation of Cathepsin S promotes cell proliferation and motility in glioma. (PMID:35436995)
• MEOX2 homeobox gene promotes growth of malignant gliomas. (PMID:35468210)
• Low expression of MEOX2 is associated with poor survival in patients with breast cancer. (PMID:36625258)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	meox2a	ENSDARG00000040911
mus_musculus	Meox2	ENSMUSG00000036144
rattus_norvegicus	Meox2	ENSRNOG00000006588
drosophila_melanogaster	btn	FBGN0014949

Paralogs (1): MEOX1 (ENSG00000005102)

Protein

Protein identifiers

Homeobox protein MOX-2 — P50222 (reviewed: P50222)

Alternative names: Growth arrest-specific homeobox, Mesenchyme homeobox 2

All UniProt accessions (1): P50222

UniProt curated annotations — full annotation on UniProt →

Function. Mesodermal transcription factor that plays a key role in somitogenesis and somitogenesis and limb muscle differentiation. Required during limb development for normal appendicular muscle formation and for the normal regulation of myogenic genes. May have a regulatory role when quiescent vascular smooth muscle cells reenter the cell cycle. Also acts as a negative regulator of angiogenesis. Activates expression of CDKN1A and CDKN2A in endothelial cells, acting as a regulator of vascular cell proliferation. While it activates CDKN1A in a DNA-dependent manner, it activates CDKN2A in a DNA-independent manner. Together with TCF15, regulates transcription in heart endothelial cells to regulate fatty acid transport across heart endothelial cells.

Subunit / interactions. Interacts with RNF10. Interacts with TCF15.

Subcellular location. Nucleus. Nucleus speckle.

Domain organisation. The polyhistidine repeat may act as a targeting signal to nuclear speckles.

Induction. Expression is repressed by ZEB2.

Polymorphism. The poly-His region of MEOX2 is polymorphic and the number of His varies in the population.

RefSeq proteins (1): NP_005915* (*=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
IPR042634	MOX-1/MOX-2	Family

Pfam: PF00046

UniProt features (13 total): compositionally biased region 5, sequence variant 3, chain 1, DNA-binding region 1, mutagenesis site 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50222-F1	61.92	0.20

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (1):

Position	Phenotype
236	abolishes dna-binding. does not affect ability to activate expression of cdkn2a.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 233 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_NEGATIVE_REGULATION_OF_BLOOD_VESSEL_ENDOTHELIAL_CELL_MIGRATION, GOBP_CELL_MIGRATION_INVOLVED_IN_SPROUTING_ANGIOGENESIS, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, MAHADEVAN_IMATINIB_RESISTANCE_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, MEF2_02, GGGTGGRR_PAX4_03, GOBP_BLOOD_VESSEL_ENDOTHELIAL_CELL_MIGRATION, CEBP_Q2

GO Biological Process (10): angiogenesis (GO:0001525), somite specification (GO:0001757), regulation of transcription by RNA polymerase II (GO:0006357), skeletal muscle tissue development (GO:0007519), positive regulation of transcription by RNA polymerase II (GO:0045944), roof of mouth development (GO:0060021), limb development (GO:0060173), somite development (GO:0061053), negative regulation of cell migration involved in sprouting angiogenesis (GO:0090051), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (8): 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 transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), cytoplasm (GO:0005737), nuclear speck (GO:0016607)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
somitogenesis	1
segment specification	1
embryonic pattern specification	1
striated muscle tissue development	1
skeletal muscle organ development	1
positive regulation of DNA-templated transcription	1
anatomical structure development	1
appendage development	1
embryo development	1
epithelium development	1
cell migration involved in sprouting angiogenesis	1
negative regulation of blood vessel endothelial cell migration	1
regulation of cell migration involved in sprouting angiogenesis	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
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
DNA binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

1368 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MEOX2	TCF15	Q12870	829
MEOX2	MYF5	P13349	643
MEOX2	MYOD1	P15172	605
MEOX2	SIX1	Q15475	583
MEOX2	MAFB	Q9Y5Q3	570
MEOX2	ZEB2	O60315	566
MEOX2	LRP1	Q07954	552
MEOX2	EYA2	O00167	546
MEOX2	PAX9	P55771	543
MEOX2	TBX22	Q9Y458	519
MEOX2	PAX1	P15863	498
MEOX2	SHH	Q15465	483
MEOX2	MYOG	P15173	462
MEOX2	CAV1	Q03135	442
MEOX2	MDFI	Q99750	433
MEOX2	PXYLP1	Q8TE99	433

IntAct

639 interactions, top by confidence:

A	B	Type	Score
MEOX2	CSF2	psi-mi:“MI:0915”(physical association)	0.720
SMAD3	MEOX2	psi-mi:“MI:0915”(physical association)	0.720
MEOX2	PGBD1	psi-mi:“MI:0915”(physical association)	0.720
MEOX2	SPRY1	psi-mi:“MI:0915”(physical association)	0.670
MEOX2	KRTAP12-1	psi-mi:“MI:0915”(physical association)	0.670
FUCA2	MEOX2	psi-mi:“MI:0915”(physical association)	0.670
MEOX2	CRCT1	psi-mi:“MI:0915”(physical association)	0.670
KRTAP10-9	MEOX2	psi-mi:“MI:0915”(physical association)	0.600
MEOX2	MT1DP	psi-mi:“MI:0915”(physical association)	0.560
POM121C	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	LAMTOR5	psi-mi:“MI:0915”(physical association)	0.560
MEOX2		psi-mi:“MI:0915”(physical association)	0.560
MEOX2	TCL6	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	PRR19	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	ATG5	psi-mi:“MI:0915”(physical association)	0.560
SIRPB1	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	PSMD14	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	STX16	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	HAT1	psi-mi:“MI:0915”(physical association)	0.560
XRCC2	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	SPRY2	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	NCK2	psi-mi:“MI:0915”(physical association)	0.560
ITM2A	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	PRKAB2	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	KRT86	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (772): MEOX2 (Two-hybrid), MEOX2 (Two-hybrid), MEOX2 (Two-hybrid), MEOX2 (Two-hybrid), MEOX2 (Two-hybrid), MEOX2 (Two-hybrid), MEOX2 (Two-hybrid), MEOX2 (Two-hybrid), MEOX2 (Two-hybrid), MEOX2 (Two-hybrid), MEOX2 (Two-hybrid), MEOX2 (Two-hybrid), MEOX2 (Two-hybrid), MEOX2 (Two-hybrid), MEOX2 (Two-hybrid)

ESM2 similar proteins: A0A8V0YY16, A0JPN1, A7MB54, A8MTJ6, O35762, O42115, O57601, O88181, O95096, P09065, P23683, P28356, P31311, P31315, P32443, P39020, P42581, P42586, P43697, P48031, P49640, P50222, P50476, P52951, P52954, P52955, P78426, P81067, P81068, P97334, Q14549, Q14774, Q1KKY1, Q1XID0, Q2NKI2, Q2VL76, Q2VL80, Q4V5A3, Q5SQQ9, Q60554

Diamond homologs: A1YER7, A1YF08, A1YFD8, A1YFY3, A1YG85, A1YGA4, A2D4P8, A2D5I1, A2D5K9, A2D5Y4, A2T6X6, A2T756, A2T779, A2T7T2, F1Q4R9, M0R6D8, O13074, O42230, O42365, O42367, O42506, O57374, P06798, P07548, P09016, P09017, P09019, P09020, P09021, P09067, P09070, P09074, P0C1T1, P10178, P10284, P10628, P14652, P14837, P14838, P14840

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
ZEB2	“down-regulates quantity by repression”	MEOX2	“transcriptional regulation”
RNF10	“up-regulates activity”	MEOX2	binding
miR221	“down-regulates quantity”	MEOX2
PAX1	“up-regulates activity”	MEOX2	binding
PAX3	“up-regulates activity”	MEOX2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 171 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Keratinization	18	10.1×	8e-11

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1211 predictions. Top by Δscore:

Variant	Effect	Δscore
7:15626740:CTTTA:C	donor_loss	1.0000
7:15626741:TTTAC:T	donor_loss	1.0000
7:15626742:TTACC:T	donor_loss	1.0000
7:15626743:TACC:T	donor_loss	1.0000
7:15626745:C:A	donor_loss	1.0000
7:15626745:CCTGT:C	donor_gain	1.0000
7:15626914:GGAGT:G	acceptor_gain	1.0000
7:15626915:GAGT:G	acceptor_gain	1.0000
7:15626916:AGT:A	acceptor_gain	1.0000
7:15626917:GT:G	acceptor_gain	1.0000
7:15626919:C:CC	acceptor_gain	1.0000
7:15685883:TA:T	donor_loss	1.0000
7:15685884:ACCT:A	donor_loss	1.0000
7:15612619:C:CT	acceptor_gain	0.9900
7:15612620:A:T	acceptor_gain	0.9900
7:15620962:C:CT	donor_gain	0.9900
7:15626915:GAGTC:G	acceptor_gain	0.9900
7:15626916:AGTC:A	acceptor_gain	0.9900
7:15626917:GTCTG:G	acceptor_gain	0.9900
7:15626918:TC:T	acceptor_gain	0.9900
7:15626919:CTGAA:C	acceptor_gain	0.9900
7:15626920:T:C	acceptor_gain	0.9900
7:15685884:A:AC	donor_gain	0.9900
7:15685885:C:CC	donor_gain	0.9900
7:15620967:T:TA	donor_gain	0.9800
7:15626744:A:AC	donor_gain	0.9800
7:15626745:C:CC	donor_gain	0.9800
7:15612616:A:T	acceptor_gain	0.9700
7:15637852:T:TC	acceptor_gain	0.9700
7:15637855:T:TC	acceptor_gain	0.9700

AlphaMissense

2009 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:15612570:C:A	R244S	1.000
7:15612570:C:G	R244S	1.000
7:15612571:C:A	R244M	1.000
7:15612571:C:G	R244T	1.000
7:15612573:C:A	K243N	1.000
7:15612573:C:G	K243N	1.000
7:15612574:T:A	K243M	1.000
7:15612574:T:G	K243T	1.000
7:15612575:T:C	K243E	1.000
7:15612578:A:G	W242R	1.000
7:15612578:A:T	W242R	1.000
7:15612579:C:A	K241N	1.000
7:15612579:C:G	K241N	1.000
7:15612580:T:A	K241M	1.000
7:15612580:T:G	K241T	1.000
7:15612581:T:C	K241E	1.000
7:15612581:T:G	K241Q	1.000
7:15612582:C:A	M240I	1.000
7:15612582:C:G	M240I	1.000
7:15612582:C:T	M240I	1.000
7:15612583:A:C	M240R	1.000
7:15612583:A:G	M240T	1.000
7:15612583:A:T	M240K	1.000
7:15612586:C:G	R239P	1.000
7:15612586:C:T	R239Q	1.000
7:15612587:G:A	R239W	1.000
7:15612587:G:C	R239G	1.000
7:15612588:C:A	R238S	1.000
7:15612588:C:G	R238S	1.000
7:15612589:C:A	R238M	1.000

dbSNP variants (sampled 300 via entrez): RS1000010593 (7:15630812 T>C), RS1000029939 (7:15625542 A>G), RS1000070240 (7:15672878 C>A,T), RS1000134234 (7:15616352 A>G), RS1000187451 (7:15684804 C>T), RS1000193728 (7:15645266 G>A,C), RS1000206584 (7:15616580 G>A), RS1000224635 (7:15645462 TAC>T), RS1000252914 (7:15649876 G>A,C), RS1000258076 (7:15679301 C>T), RS1000337522 (7:15684014 T>A), RS1000362666 (7:15611676 C>G), RS1000376126 (7:15640259 T>C), RS1000396378 (7:15675037 A>G,T), RS1000485723 (7:15615350 G>A)

Disease associations

OMIM: gene MIM:600535 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST002040_7	Blood trace element (Zn levels)	7.000000e-07
GCST002720_3	Kidney function decline traits	4.000000e-07
GCST006138_23	Resting-state electroencephalogram vigilance	3.000000e-06
GCST006288_142	Heel bone mineral density	7.000000e-07
GCST006288_584	Heel bone mineral density	2.000000e-17
GCST006288_742	Heel bone mineral density	2.000000e-11
GCST006979_326	Heel bone mineral density	1.000000e-25
GCST006979_725	Heel bone mineral density	1.000000e-14
GCST008789_13	Adolescent idiopathic scoliosis	4.000000e-08
GCST009204_6	Total intracranial volume	5.000000e-06
GCST010242_250	HDL cholesterol levels	1.000000e-08
GCST010244_285	Triglyceride levels	1.000000e-15
GCST010572_8	Sweet taste preference	3.000000e-06
GCST010724_13	HOMA-B (corrected for HOMA-IR)	6.000000e-08

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0006836	rapid kidney function decline
EFO:0004357	electroencephalogram measurement
EFO:0009270	heel bone mineral density
EFO:0004886	intracranial volume measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0010156	sweet liking measurement
EFO:0004469	HOMA-B

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
bisphenol A	decreases methylation	1
beta-lapachone	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
rofecoxib	decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
bisphenol S	increases methylation	1
Acetaminophen	decreases expression	1
Estradiol	increases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Melphalan	decreases expression	1
Mercury	increases expression	1
Oxygen	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tetradecanoylphorbol Acetate	affects cotreatment, affects expression	1
Tretinoin	increases expression	1
Zinc	affects cotreatment, affects expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_UL87	ZZUi013-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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