LBX1

Summary

LBX1 (ladybird homeobox 1, HGNC:16960) is a protein-coding gene on chromosome 10q24.32, encoding Transcription factor LBX1 (P52954). Transcription factor required for the development of GABAergic interneurons in the dorsal horn of the spinal cord and migration and further development of hypaxial muscle precursor cells for limb muscles, diaphragm and hypoglossal cord.

This gene and the orthologous mouse gene were found by their homology to the Drosophila lady bird early and late homeobox genes. In the mouse, this gene is a key regulator of muscle precursor cell migration and is required for the acquisition of dorsal identities of forelimb muscles.

Source: NCBI Gene 10660 — RefSeq curated summary.

At a glance

• Gene–disease (curated): central hypoventilation syndrome, congenital, 3 (Moderate, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 32 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 20
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_006562

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16960
Approved symbol	LBX1
Name	ladybird homeobox 1
Location	10q24.32
Locus type	gene with protein product
Status	Approved
Aliases	LBX1H, HPX6
Ensembl gene	ENSG00000138136
Ensembl biotype	protein_coding
OMIM	604255
Entrez	10660

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000370193, ENST00000945825, ENST00000945826

RefSeq mRNA: 1 — MANE Select: NM_006562 NM_006562

CCDS: CCDS31270

Canonical transcript exons

ENST00000370193 — 2 exons

Exon	Start	End
ENSE00001137900	101226994	101227790
ENSE00001452039	101228491	101229463

Expression profiles

Bgee: expression breadth broad, 28 present calls, max score 81.50.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	81.50	gold quality
muscle of leg	UBERON:0001383	80.21	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.07	silver quality
skeletal muscle tissue	UBERON:0001134	61.88	gold quality
muscle tissue	UBERON:0002385	57.47	gold quality
frontal pole	UBERON:0002795	56.98	gold quality
right hemisphere of cerebellum	UBERON:0014890	56.62	gold quality
cerebellar cortex	UBERON:0002129	56.29	gold quality
cerebellar hemisphere	UBERON:0002245	56.06	gold quality
metanephric glomerulus	UBERON:0004736	55.97	gold quality
buccal mucosa cell	CL:0002336	55.56	gold quality
cerebellum	UBERON:0002037	55.42	gold quality
endometrium epithelium	UBERON:0004811	52.17	gold quality
parotid gland	UBERON:0001831	51.70	gold quality
biceps brachii	UBERON:0001507	50.83	gold quality
quadriceps femoris	UBERON:0001377	50.66	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
vastus lateralis	UBERON:0001379	50.14	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	46.22	gold quality
spinal cord	UBERON:0002240	45.68	gold quality
colonic epithelium	UBERON:0000397	45.34	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	44.19	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
amniotic fluid	UBERON:0000173	42.96	gold quality
thymus	UBERON:0002370	42.72	gold quality
secondary oocyte	CL:0000655	42.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.65

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
LBX1
SNAI1	Activation
SST	Unknown
ZEB1	Activation

JASPAR motifs

Motif	Name	Family
MA0618.1	LBX1	NK
MA0618.2	LBX1	NK

JASPAR matrix evidence (PMIDs): PMID:23332764

Upstream regulators (CollecTRI, top): CTNNB1, LBX1, PAX3

miRNA regulators (miRDB)

12 targeting LBX1, 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-137-3P	99.87	74.74	2401
HSA-MIR-3960	99.41	66.11	96
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-8072	98.27	66.24	83
HSA-MIR-3977	98.00	68.17	1500
HSA-MIR-219B-3P	97.31	66.96	672
HSA-MIR-10400-5P	96.91	66.00	56
HSA-MIR-4467	96.51	64.44	69
HSA-MIR-3177-3P	92.33	62.02	156
HSA-MIR-4497	92.25	64.06	134
HSA-MIR-6089	89.72	61.35	324
HSA-MIR-6784-5P	84.56	60.91	126

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 21)

• Ladybird homeobox 1 (LBX1), a developmentally regulated homeobox gene, directs expression of the known EMT inducers ZEB1, ZEB2, Snail1, and transforming growth factor beta2 (TGFB2). (PMID:19651985)
• A genome-wide association study identifies common variants near LBX1 associated with adolescent idiopathic scoliosis (PMID:22019779)
• Single nucleotide polymorphism near LBX1 is significantly associated with adolescent idiopathic scoliosis in southern Chinese. (PMID:22301463)
• The SNP rs11190870 near LBX1 is associated with both susceptibility and curve progression of adolescent idiopathic scoliosis in Han Chinese adolescents. (PMID:23096252)
• This study shows that the genetic variants near the LBX1 gene are associated with adolescent idiopathic scoliosis susceptibility in Chinese Han population. (PMID:23308168)
• Performed a meta-analysis of the LBX1 locus in six Asian and three non-Asian cohorts of adolescent idiopathic scoliosis (AIS) and found significant evidence for association of this locus with AIS susceptibility in all nine cohorts. (PMID:24721834)
• Based on meta-analysis rs11190870 near LBX1 is likely a susceptibility variant for adolescent idiopathic scoliosis in East Asians. (PMID:24878781)
• Our results identify two clinically relevant haplotypes in the LBX1-region with opposite effects on AIS risk. (PMID:25675428)
• LBX1 is a susceptibility gene for idiopathic scoliosis in a Scandinavian population. (PMID:25987191)
• In embryos overexpressing lbx1b, wnt5b, a ligand of the non-canonical Wnt/planar cell polarity (PCP) pathway, was significantly downregulated. (PMID:26820155)
• Meta-analysis provides evidence that rs111090870, rs678741 and rs625039 polymorphisms near LBX1 gene are associated with adolescent idiopathic scoliosis susceptibility in some populations.[meta-analysis] (PMID:27450593)
• Two single nucleotide polymorphisms around LBX1 are associated with adolescent idiopathic scoliosis in a Northern Chinese Han population. (PMID:28187071)
• We have replicated the association of the LBX1 locus with AIS in French-Canadian population, a novel European descent cohort, which is known for its unique genetic architecture. (PMID:28604496)
• Genome-wide association study on the etiology of adolescent idiopathic scoliosis using samples from more than 5 000 patients and 6 000 normal controls showed two genes: LBX1-AS1 on 10q24.32 and TNIK on 3q26.2 highly related to AIS initiation and progression [review] (PMID:30107698)
• Homozygous LBX1 Frameshift Mutation Causes Recessive Congenital Central Hypoventilation Syndrome. (PMID:30487221)
• The pooled results showed a statistically significant association between LBX1 gene polymorphisms and adolescent idiopathic scoliosis (for rs11190870, T vs C, OR = 1.54, 95% CI = 1.48-1.61, P < .00001; for rs625039, G vs A, OR = 1.50, 95% CI: 1.38-1.62; P < .00001; for rs678741, G vs A, OR = 0.74, 95% CI: 0.63-0.86; P < .0001; for rs11598564, G vs A, OR = 1.41, 95% CI: 1.31-1.51; P < .0001) Meta-Analysis) (PMID:31277174)
• A LBX1 single nucleotide polymorphism, rs11190870, was associated with a strong susceptibility for adult spinal deformity. (PMID:31365516)
• Role of differentially expressed LBX1 in Adolescent Idiopathic Scoliosis (AIS) paraspinal muscle phenotypes and muscle-bone crosstalk through modulating myoblasts. (PMID:34190053)
• LBX1 may play a role in the development of AIS via regulating the proliferation and differentiation of myosatellite cells. (PMID:34190099)
• Biological effect of dysregulated LBX1 on adolescent idiopathic scoliosis through modulating muscle carbohydrate metabolism. (PMID:35460899)
• Association of LBX1 Gene Methylation Level with Disease Severity in Patients with Idiopathic Scoliosis: Study on Deep Paravertebral Muscles. (PMID:36140724)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	lbx1a	ENSDARG00000018321
danio_rerio	lbx1b	ENSDARG00000018611
mus_musculus	Lbx1	ENSMUSG00000025216
rattus_norvegicus	Lbx1	ENSRNOG00000025520
drosophila_melanogaster	lbl	FBGN0008651
drosophila_melanogaster	lbe	FBGN0011278

Paralogs (1): LBX2 (ENSG00000179528)

Protein

Protein identifiers

Transcription factor LBX1 — P52954 (reviewed: P52954)

Alternative names: Ladybird homeobox protein homolog 1

All UniProt accessions (1): P52954

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor required for the development of GABAergic interneurons in the dorsal horn of the spinal cord and migration and further development of hypaxial muscle precursor cells for limb muscles, diaphragm and hypoglossal cord.

Subunit / interactions. Interacts with SKOR1 which acts as a transcriptional corepressor.

Subcellular location. Nucleus.

Disease relevance. Central hypoventilation syndrome, congenital, 3 (CCHS3) [MIM:619483] A form of congenital central hypoventilation syndrome, a rare disorder characterized by abnormal control of respiration in the absence of neuromuscular, lung or cardiac disease, or an identifiable brainstem lesion. CCHS3 is an autosomal recessive, neonatal form characterized by slow and shallow breathing due to a deficiency in autonomic control of respiration. Affected individuals present with respiratory insufficiency and absence of the hypercapnic reflex that stimulates breathing. Additional features include gastrointestinal problems, poor heat tolerance and paroxysmal hypertension. The disease may be caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_006553* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000047	HTH_motif	Conserved_site
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR051892	LBX_TF	Family

Pfam: PF00046

UniProt features (12 total): sequence conflict 5, compositionally biased region 3, region of interest 2, chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52954-F1	68.61	0.26

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 197 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, MYAATNNNNNNNGGC_UNKNOWN, AAGCAAT_MIR137, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, BENPORATH_ES_WITH_H3K27ME3, PAX4_01, MAZ_Q6, AP4_Q6, GOBP_NEUROGENESIS, MEF2_02, AP2_Q3, LHX3_01, CHX10_01

GO Biological Process (15): heart looping (GO:0001947), regulation of transcription by RNA polymerase II (GO:0006357), muscle organ development (GO:0007517), cell population proliferation (GO:0008283), negative regulation of cell population proliferation (GO:0008285), anatomical structure morphogenesis (GO:0009653), spinal cord association neuron specification (GO:0021519), spinal cord motor neuron differentiation (GO:0021522), neuron fate determination (GO:0048664), negative regulation of glutamatergic neuron differentiation (GO:0120007), glutamatergic neuron differentiation (GO:1905962), regulation of DNA-templated transcription (GO:0006355), nervous system development (GO:0007399), cell differentiation (GO:0030154), neuron fate commitment (GO:0048663)

GO Molecular Function (5): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), transcription regulator complex (GO:0005667)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
neuron differentiation	2
embryonic heart tube morphogenesis	1
determination of heart left/right asymmetry	1
transcription by RNA polymerase II	1
animal organ development	1
muscle structure development	1
cellular process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
developmental process	1
anatomical structure development	1
spinal cord association neuron differentiation	1
neuron fate specification	1
cell differentiation in spinal cord	1
ventral spinal cord development	1
central nervous system neuron differentiation	1
cell fate determination	1
neuron fate commitment	1
negative regulation of neuron differentiation	1
regulation of glutamatergic neuron differentiation	1
glutamatergic neuron differentiation	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
system development	1
cellular developmental process	1
cell fate commitment	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
binding	1
chromosome	1

Protein interactions and networks

STRING

646 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LBX1	FBXW4	P57775	894
LBX1	POLL	Q9UGP5	814
LBX1	SIX4	Q9UIU6	746
LBX1	SIX1	Q15475	704
LBX1	DUX4L2	P0CJ85	690
LBX1	SEBOX	Q9HB31	675
LBX1	SIX6	O95475	669
LBX1	SIX2	Q9NPC8	646
LBX1	BTRC	Q9Y297	619
LBX1	SUFU	Q9UMX1	572
LBX1	NOBOX	O60393	561
LBX1	SIX3	O95343	528
LBX1	TPRX1	Q8N7U7	527
LBX1	ADGRG6	Q86SQ4	526
LBX1	TLE1	Q04724	520

IntAct

76 interactions, top by confidence:

A	B	Type	Score
LBX1	TMEM252	psi-mi:“MI:0915”(physical association)	0.560
LBX1	KANK2	psi-mi:“MI:0915”(physical association)	0.560
LBX1	ZNF483	psi-mi:“MI:0915”(physical association)	0.560
LBX1	WNK3	psi-mi:“MI:0915”(physical association)	0.560
LBX1	FAM9B	psi-mi:“MI:0915”(physical association)	0.560
IQGAP1	LBX1	psi-mi:“MI:0915”(physical association)	0.560
LBX1	TBCEL	psi-mi:“MI:0915”(physical association)	0.560
EFEMP2	LBX1	psi-mi:“MI:0915”(physical association)	0.560
LBX1	TSSK3	psi-mi:“MI:0915”(physical association)	0.560
LBX1	KRTAP5-6	psi-mi:“MI:0915”(physical association)	0.560
LBX1	PRPF31	psi-mi:“MI:0915”(physical association)	0.560
UBTFL1	LBX1	psi-mi:“MI:0915”(physical association)	0.560
LBX1	QRICH1	psi-mi:“MI:0915”(physical association)	0.560
LBX1	AIPL1	psi-mi:“MI:0915”(physical association)	0.560
DES	LBX1	psi-mi:“MI:0915”(physical association)	0.560
PHF1	LBX1	psi-mi:“MI:0915”(physical association)	0.560
LBX1	MAB21L3	psi-mi:“MI:0915”(physical association)	0.560
LBX1	KIFC3	psi-mi:“MI:0915”(physical association)	0.560
LBX1	EIF5A	psi-mi:“MI:0915”(physical association)	0.560
FAM221B	LBX1	psi-mi:“MI:0915”(physical association)	0.560
LBX1	KRTAP9-2	psi-mi:“MI:0915”(physical association)	0.560
KIF5B	LBX1	psi-mi:“MI:0915”(physical association)	0.560
rep	LBX1	psi-mi:“MI:0915”(physical association)	0.560
	LBX1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (28): LBX1 (Two-hybrid), LBX1 (Two-hybrid), LBX1 (Two-hybrid), LBX1 (Two-hybrid), IQGAP1 (Two-hybrid), KIFC3 (Two-hybrid), TBCEL (Two-hybrid), TSSK3 (Two-hybrid), KIF5B (Two-hybrid), EFEMP2 (Two-hybrid), MAB21L3 (Two-hybrid), ZNF483 (Two-hybrid), DES (Two-hybrid), FAM9B (Two-hybrid), TMEM252 (Two-hybrid)

ESM2 similar proteins: A0A1W2PRP0, A6NCS4, A7Y7W2, O14512, O43638, O57601, O70220, O96004, P07812, P09023, P10085, P10284, P17483, P22091, P24899, P50548, P52954, P52955, P55318, P57100, P63156, P63157, P70447, P79772, P97832, Q02346, Q05917, Q0VCE2, Q12952, Q1XID0, Q28555, Q3I5G5, Q3Y598, Q60688, Q61660, Q63244, Q63250, Q64279, Q64305, Q64731

Diamond homologs: A0JPN1, A1YG85, A5PKG8, A6NJ46, A6NMT0, A7MB54, A9L937, B0VXK3, D2KQB0, E7FDX5, M0R6D8, O08686, O13023, O35762, O42365, O43364, O43711, O55144, O88181, O93366, O93367, O93590, P0C1T1, P10035, P14652, P14837, P20009, P28468, P31245, P31246, P31261, P31314, P42583, P42584, P43120, P43345, P43688, P50219, P52945, P52950

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SKOR1	“down-regulates activity”	LBX1	binding
LBX1	“up-regulates quantity by expression”	SNAI1	“transcriptional regulation”
LBX1	“up-regulates quantity by expression”	ZEB1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	26
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1283920	LBX1, 1-BP DEL, 697T	Pathogenic
4532288	NM_006562.5(LBX1):c.707del (p.Val236fs)	Likely pathogenic

SpliceAI

198 predictions. Top by Δscore:

Variant	Effect	Δscore
10:101227787:CGGC:C	acceptor_gain	1.0000
10:101227788:GGC:G	acceptor_gain	1.0000
10:101227788:GGCCT:G	acceptor_loss	1.0000
10:101227789:GC:G	acceptor_gain	1.0000
10:101227789:GCCTG:G	acceptor_loss	1.0000
10:101227790:CC:C	acceptor_gain	1.0000
10:101227791:C:CC	acceptor_gain	1.0000
10:101227791:C:T	acceptor_gain	1.0000
10:101227791:CTGGG:C	acceptor_loss	1.0000
10:101227792:T:G	acceptor_loss	1.0000
10:101227786:GCGGC:G	acceptor_gain	0.9900
10:101227787:CGGCC:C	acceptor_gain	0.9900
10:101228486:CCTAC:C	donor_loss	0.9900
10:101228487:CTA:C	donor_loss	0.9900
10:101228488:TA:T	donor_loss	0.9900
10:101228489:A:T	donor_loss	0.9900
10:101229702:G:C	donor_gain	0.9900
10:101228489:A:AC	donor_gain	0.9800
10:101228490:C:CC	donor_gain	0.9800
10:101228490:CCTT:C	donor_gain	0.9700
10:101228533:T:TA	donor_gain	0.9600
10:101228356:C:CA	donor_gain	0.9500
10:101228513:G:T	donor_gain	0.9400
10:101228517:T:TA	donor_gain	0.9000
10:101228669:T:TA	donor_gain	0.9000
10:101228486:CCTA:C	donor_gain	0.8700
10:101228487:CTAC:C	donor_gain	0.8700
10:101228489:A:AT	donor_gain	0.8700
10:101228348:T:C	donor_gain	0.8600
10:101228488:TACC:T	donor_gain	0.8600

AlphaMissense

1809 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:101227565:A:G	L184P	1.000
10:101227568:T:C	D183G	1.000
10:101227571:C:G	R182P	1.000
10:101227573:C:A	K181N	1.000
10:101227573:C:G	K181N	1.000
10:101227575:T:C	K181E	1.000
10:101227577:A:G	L180P	1.000
10:101227579:C:A	K179N	1.000
10:101227579:C:G	K179N	1.000
10:101227580:T:A	K179M	1.000
10:101227581:T:C	K179E	1.000
10:101227583:G:T	A178D	1.000
10:101227584:C:G	A178P	1.000
10:101227586:C:A	R177L	1.000
10:101227586:C:G	R177P	1.000
10:101227586:C:T	R177H	1.000
10:101227587:G:A	R177C	1.000
10:101227587:G:C	R177G	1.000
10:101227587:G:T	R177S	1.000
10:101227589:C:A	R176L	1.000
10:101227589:C:G	R176P	1.000
10:101227590:G:A	R176W	1.000
10:101227590:G:C	R176G	1.000
10:101227591:A:C	N175K	1.000
10:101227591:A:T	N175K	1.000
10:101227592:T:A	N175I	1.000
10:101227592:T:C	N175S	1.000
10:101227592:T:G	N175T	1.000
10:101227593:T:C	N175D	1.000
10:101227593:T:G	N175H	1.000

dbSNP variants (sampled 300 via entrez): RS1000058435 (10:101229405 T>C), RS1000898245 (10:101228212 G>A), RS1001503173 (10:101226739 G>C,T), RS1002679155 (10:101231387 G>A), RS1003677739 (10:101229956 T>C), RS1003784796 (10:101229022 C>T), RS1003954903 (10:101229301 TTCTC>T), RS1003970116 (10:101229255 C>T), RS1004792213 (10:101231416 C>T), RS1006054385 (10:101230674 T>C), RS1006205585 (10:101230041 C>T), RS1006688734 (10:101230432 C>G), RS1006789896 (10:101228594 C>A,G), RS1007251530 (10:101229061 C>T), RS1008208013 (10:101227143 G>A,C)

Disease associations

OMIM: gene MIM:604255 | disease phenotypes: MIM:619483

GenCC curated gene-disease

Disease	Classification	Inheritance
central hypoventilation syndrome, congenital, 3	Moderate	Autosomal recessive

Mondo (1): central hypoventilation syndrome, congenital, 3 (MONDO:0030539)

Orphanet (0):

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000875	Episodic hypertension
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0002046	Heat intolerance
HP:0002093	Respiratory insufficiency
HP:0002104	Apnea
HP:0002251	Aganglionic megacolon
HP:0002270	Abnormality of the autonomic nervous system
HP:0002572	Episodic vomiting
HP:0002878	Respiratory failure
HP:0003005	Ganglioneuroma
HP:0003006	Neuroblastoma
HP:0003623	Neonatal onset
HP:0006747	Ganglioneuroblastoma
HP:0007110	Central hypoventilation
HP:0011968	Feeding difficulties
HP:0012450	Chronic constipation
HP:0100006	Neoplasm of the central nervous system
HP:0100543	Cognitive impairment

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001293_1	Scoliosis	1.000000e-19
GCST003052_2	Adolescent idiopathic scoliosis	5.000000e-39
GCST006902_1	Adolescent idiopathic scoliosis	2.000000e-55
GCST008789_15	Adolescent idiopathic scoliosis	2.000000e-82
GCST009391_763	Metabolite levels	8.000000e-06
GCST010002_298	Refractive error	3.000000e-22
GCST90026414_3	Severe insulin-resistant type 2 diabetes	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010391	sphingomyelin 16:0 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
arsenite	increases methylation	1
CGP 52608	affects binding, increases reaction	1
MT19c compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Plant Extracts	decreases expression, affects cotreatment	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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