RAX

Summary

RAX (retina and anterior neural fold homeobox, HGNC:18662) is a protein-coding gene on chromosome 18q21.32, encoding Retinal homeobox protein Rx (Q9Y2V3). Plays a critical role in eye formation by regulating the initial specification of retinal cells and/or their subsequent proliferation.

This gene encodes a homeobox-containing transcription factor that functions in eye development. The gene is expressed early in the eye primordia, and is required for retinal cell fate determination and also regulates stem cell proliferation. Mutations in this gene have been reported in patients with defects in ocular development, including microphthalmia, anophthalmia, and coloboma.

Source: NCBI Gene 30062 — RefSeq curated summary.

At a glance

• Gene–disease (curated): isolated microphthalmia 3 (Definitive, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 184 total — 6 pathogenic, 4 likely-pathogenic
• MANE Select transcript: NM_013435

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18662
Approved symbol	RAX
Name	retina and anterior neural fold homeobox
Location	18q21.32
Locus type	gene with protein product
Status	Approved
Aliases	RX, RAX1
Ensembl gene	ENSG00000134438
Ensembl biotype	protein_coding
OMIM	601881
Entrez	30062

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000256852, ENST00000334889, ENST00000555288, ENST00000591550

RefSeq mRNA: 1 — MANE Select: NM_013435 NM_013435

CCDS: CCDS11972

Canonical transcript exons

ENST00000334889 — 3 exons

Exon	Start	End
ENSE00000914716	59272361	59272614
ENSE00000914718	59272918	59273454
ENSE00003603449	59267038	59269501

Expression profiles

Bgee: expression breadth broad, 29 present calls, max score 75.47.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.2826 / max 123.4061, expressed in 163 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172186	0.9346	132
172187	0.3314	93
172188	0.0166	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	75.47	gold quality
nasal cavity epithelium	UBERON:0005384	74.17	gold quality
biceps brachii	UBERON:0001507	73.43	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	73.37	gold quality
heart right ventricle	UBERON:0002080	71.11	gold quality
myocardium	UBERON:0002349	71.06	gold quality
secondary oocyte	CL:0000655	67.24	gold quality
seminal vesicle	UBERON:0000998	67.14	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	66.91	gold quality
lateral nuclear group of thalamus	UBERON:0002736	66.77	gold quality
lateral globus pallidus	UBERON:0002476	66.35	gold quality
Brodmann (1909) area 46	UBERON:0006483	65.17	gold quality
deltoid	UBERON:0001476	65.09	gold quality
entorhinal cortex	UBERON:0002728	65.09	gold quality
postcentral gyrus	UBERON:0002581	64.46	gold quality
substantia nigra pars reticulata	UBERON:0001966	64.39	gold quality
vastus lateralis	UBERON:0001379	64.21	gold quality
quadriceps femoris	UBERON:0001377	64.04	gold quality
substantia nigra pars compacta	UBERON:0001965	63.58	gold quality
parietal lobe	UBERON:0001872	63.00	gold quality
neuron projection bundle connecting eye with brain	UBERON:0004904	62.49	silver quality
trabecular bone tissue	UBERON:0002483	62.47	gold quality
middle temporal gyrus	UBERON:0002771	62.15	gold quality
Brodmann (1909) area 23	UBERON:0013554	61.83	gold quality
vena cava	UBERON:0004087	61.59	gold quality
tendon of biceps brachii	UBERON:0008188	61.56	gold quality
subthalamic nucleus	UBERON:0001906	61.19	gold quality
dorsal plus ventral thalamus	UBERON:0001897	60.71	gold quality
endothelial cell	CL:0000115	60.30	gold quality
adenohypophysis	UBERON:0002196	59.48	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	37.33
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA0718.1	RAX	Paired-related HD factors
MA0718.2	RAX	Paired-related HD factors

JASPAR matrix evidence (PMIDs): PMID:18585360

miRNA regulators (miRDB)

38 targeting RAX, 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-5193	100.00	67.26	1744
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-3191-3P	99.45	63.94	356
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-3192-5P	96.98	65.76	1926
HSA-MIR-4793-5P	96.88	65.90	872
HSA-MIR-552-3P	96.68	64.12	1026
HSA-MIR-3139	96.68	66.77	652

Literature-anchored findings (GeneRIF, showing 7)

• Mutations associated with recessive anophthalmos and sclerocornea. (PMID:14662654)
• A missense mutation in RX was observed in a patient with a small, typical chorioretinal coloboma, and postulate that the mutation is responsible for the patient’s phenotype. (PMID:19158959)
• Mutations in the newly identified RAX regulatory sequence are not a frequent cause of micro/anophthalmia. (PMID:19397404)
• Photosensitive photoreceptor cells can be generated by combinations of transcription factors. The combination of CRX and RX generate immature photoreceptors: and additional NEUROD promotes maturation. (PMID:22558175)
• The three consanguineous Egyptian anophthalmia patients carry a novel homozygous c.543+3A>G mutation (IVS2+3A>G) in RAX. (PMID:22736936)
• combination of WES and homozygosity mapping identified a novel homozygous RAX mutation in a consanguineous family segregating with rarely reported asymmetrical coloboma. Clinical findings and genetic results support that RAX mutation is responsible for eye malformations. (PMID:28831107)
• Construction and characterization of EGFP reporter plasmid harboring putative human RAX promoter for in vitro monitoring of retinal progenitor cells identity. (PMID:34348662)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rax	ENSMUSG00000024518
rattus_norvegicus	Rax	ENSRNOG00000016944

Paralogs (50): ARX (ENSG00000004848), PAX6 (ENSG00000007372), PAX7 (ENSG00000009709), ALX4 (ENSG00000052850), GSC2 (ENSG00000063515), PITX1 (ENSG00000069011), PAX2 (ENSG00000075891), RHOXF1 (ENSG00000101883), CRX (ENSG00000105392), EVX1 (ENSG00000106038), PAX4 (ENSG00000106331), NOBOX (ENSG00000106410), PITX3 (ENSG00000107859), PHOX2B (ENSG00000109132), OTX1 (ENSG00000115507), PRRX1 (ENSG00000116132), VSX2 (ENSG00000119614), ESX1 (ENSG00000123576), PAX8 (ENSG00000125618), PAX1 (ENSG00000125813), RHOXF2 (ENSG00000131721), GSC (ENSG00000133937), PAX3 (ENSG00000135903), ALX3 (ENSG00000156150), HESX1 (ENSG00000163666), PITX2 (ENSG00000164093), UNCX (ENSG00000164853), PHOX2A (ENSG00000165462), OTX2 (ENSG00000165588), DRGX (ENSG00000165606), PRRX2 (ENSG00000167157), SHOX2 (ENSG00000168779), OTP (ENSG00000171540), RAX2 (ENSG00000173976), EVX2 (ENSG00000174279), PROP1 (ENSG00000175325), ISX (ENSG00000175329), ALX1 (ENSG00000180318), MIXL1 (ENSG00000185155), SHOX (ENSG00000185960)

Protein

Protein identifiers

Retinal homeobox protein Rx — Q9Y2V3 (reviewed: Q9Y2V3)

Alternative names: Retina and anterior neural fold homeobox protein

All UniProt accessions (2): Q9Y2V3, G3V2C8

UniProt curated annotations — full annotation on UniProt →

Function. Plays a critical role in eye formation by regulating the initial specification of retinal cells and/or their subsequent proliferation. Binds to the photoreceptor conserved element-I (PCE-1/Ret 1) in the photoreceptor cell-specific arrestin promoter.

Subcellular location. Nucleus.

Tissue specificity. Expressed in the developing eye and weakly expressed in the adult retina.

Disease relevance. Microphthalmia, syndromic 16 (MCOPS16) [MIM:611038] An autosomal recessive disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Some patients exhibit developmental delay and intellectual disability or autism. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the paired homeobox family. Bicoid subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y2V3-1	1	yes
Q9Y2V3-2	2

RefSeq proteins (1): NP_038463* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR003654	OAR_dom	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR043562	RAX/RAX2	Family

Pfam: PF00046, PF03826

UniProt features (21 total): compositionally biased region 6, sequence variant 5, short sequence motif 3, splice variant 2, region of interest 2, chain 1, DNA-binding region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2V3-F1	65.10	0.19

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 87 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, BENPORATH_ES_WITH_H3K27ME3, LHX3_01, GOBP_FOREBRAIN_DEVELOPMENT, SHEPARD_BMYB_MORPHOLINO_DN, GOBP_HYPOTHALAMUS_DEVELOPMENT, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_APPENDAGE_DEVELOPMENT, GOBP_HEAD_DEVELOPMENT, LYF1_01, GOBP_DIENCEPHALON_DEVELOPMENT, GOBP_SENSORY_PERCEPTION, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_LIMBIC_SYSTEM_DEVELOPMENT, PITX2_Q2

GO Biological Process (9): regulation of transcription by RNA polymerase II (GO:0006357), pattern specification process (GO:0007389), visual perception (GO:0007601), hypothalamus development (GO:0021854), camera-type eye development (GO:0043010), positive regulation of transcription by RNA polymerase II (GO:0045944), limb development (GO:0060173), regulation of DNA-templated transcription (GO:0006355), brain development (GO:0007420)

GO Molecular Function (5): 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), sequence-specific double-stranded DNA binding (GO:1990837), 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	3
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
regulation of DNA-templated transcription	1
multicellular organism development	1
multicellular organismal process	1
sensory perception of light stimulus	1
diencephalon development	1
limbic system development	1
anatomical structure development	1
eye development	1
positive regulation of DNA-templated transcription	1
appendage development	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
central nervous system development	1
animal organ development	1
head development	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
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

420 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAX	TTC4	O95801	665
RAX	SOX2	P48431	631
RAX	FIZ1	Q96SL8	528
RAX	SIX3	O95343	504
RAX	NRL	P54845	435
RAX	SIX6	O95475	422
RAX	GPR50	Q13585	397
RAX	SH3BP1	Q9Y3L3	396
RAX	SLCO6A1	Q86UG4	392
RAX	OTX2	P32243	353
RAX	FOXE3	Q13461	342
RAX	RPE65	Q16518	296
RAX	SHH	Q15465	296
RAX	LMAN1L	Q9HAT1	294
RAX	RHO	P08100	289
RAX	CPLX4	Q7Z7G2	289

IntAct

1 interactions, top by confidence:

A	B	Type	Score
RAX	SIRT6	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (4): RAX (Phenotypic Enhancement), RAX (Reconstituted Complex), RAX (Affinity Capture-Western), SIRT6 (Affinity Capture-MS)

ESM2 similar proteins: A0A1W2PQ73, A1YF16, A1YG93, A2RU54, A5PKG8, O02786, O14813, O15353, O35602, O43638, O57601, P13297, P19419, P28360, P35548, P41969, P42580, P43687, P49640, P50223, P50548, P52946, P52950, P63156, P63157, P70459, P78413, Q03358, Q14549, Q2VL78, Q2VL79, Q2VL82, Q2VL83, Q2VL84, Q2VL85, Q2VL86, Q2VL87, Q2VL88, Q5NSW5, Q61575

Diamond homologs: A0A1W2PPK0, A0A1W2PPM1, A1A546, A1YEY5, A1YFI3, A1YG57, A1YGA2, A2T733, A2T777, A2T7P4, A6NFQ7, G5EC89, L8E946, O14813, O15499, O35690, O42250, O42356, O42357, O42477, O70137, O73917, O75360, O95076, O97670, P0DMV5, P26367, P26630, P29454, P41935, P47237, P47238, P53544, P53545, P53546, P54366, P55813, P55864, P56915, P56916

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	4
Uncertain significance	116
Likely benign	34
Benign	14

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
1723189	NM_013435.3(RAX):c.560G>A (p.Arg187Gln)	Pathogenic
1723190	NM_013435.3(RAX):c.266del (p.Pro89fs)	Pathogenic
1879402	NM_013435.3(RAX):c.499G>T (p.Glu167Ter)	Pathogenic
7635	NM_013435.3(RAX):c.439C>T (p.Gln147Ter)	Pathogenic
7636	NM_013435.3(RAX):c.575G>A (p.Arg192Gln)	Pathogenic
7638	NM_013435.3(RAX):c.909C>G (p.Tyr303Ter)	Pathogenic
1723188	NM_013435.3(RAX):c.543+3A>G	Likely pathogenic
3583379	NM_013435.3(RAX):c.50_53dup (p.Gly19fs)	Likely pathogenic
504029	NM_013435.3(RAX):c.262_263delinsA (p.Ala88fs)	Likely pathogenic
932556	NM_013435.3(RAX):c.106G>T (p.Glu36Ter)	Likely pathogenic

SpliceAI

377 predictions. Top by Δscore:

Variant	Effect	Δscore
18:59272362:TGG:T	donor_gain	1.0000
18:59272358:TA:T	donor_loss	0.9900
18:59272359:A:C	donor_loss	0.9900
18:59272360:CCTGG:C	donor_loss	0.9900
18:59269499:CAC:C	acceptor_gain	0.9800
18:59269500:ACCT:A	acceptor_loss	0.9800
18:59269502:C:T	acceptor_loss	0.9800
18:59269503:T:C	acceptor_loss	0.9800
18:59270370:G:C	donor_gain	0.9800
18:59272384:TG:T	donor_gain	0.9800
18:59272913:CTCA:C	donor_loss	0.9800
18:59272914:TCAC:T	donor_loss	0.9800
18:59272915:CAC:C	donor_loss	0.9800
18:59272916:A:AT	donor_loss	0.9800
18:59272917:C:A	donor_loss	0.9800
18:59269497:CACAC:C	acceptor_gain	0.9700
18:59269452:T:TA	donor_gain	0.9600
18:59269502:C:CC	acceptor_gain	0.9600
18:59270359:CTAAG:C	donor_gain	0.9600
18:59270621:TGCA:T	donor_gain	0.9600
18:59270624:A:AT	donor_gain	0.9600
18:59272385:G:T	donor_gain	0.9600
18:59272391:G:A	donor_gain	0.9600
18:59272912:ACTC:A	donor_loss	0.9600
18:59272911:CACT:C	donor_loss	0.9500
18:59270360:TAAG:T	donor_gain	0.9400
18:59270361:AAGA:A	donor_gain	0.9400
18:59272383:TTG:T	donor_gain	0.9400
18:59270358:CCTAA:C	donor_gain	0.9000
18:59272361:CTG:C	donor_gain	0.9000

AlphaMissense

2188 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:59269050:G:T	A332D	1.000
18:59269062:A:G	L328P	1.000
18:59269062:A:T	L328Q	1.000
18:59269071:A:T	I325N	1.000
18:59269467:C:G	R193P	1.000
18:59269470:C:G	R192P	1.000
18:59269472:C:A	W191C	1.000
18:59269472:C:G	W191C	1.000
18:59269474:A:G	W191R	1.000
18:59269474:A:T	W191R	1.000
18:59269475:C:A	K190N	1.000
18:59269475:C:G	K190N	1.000
18:59269476:T:A	K190M	1.000
18:59269477:T:C	K190E	1.000
18:59269477:T:G	K190Q	1.000
18:59269479:G:A	A189V	1.000
18:59269479:G:T	A189D	1.000
18:59269480:C:G	A189P	1.000
18:59269482:C:G	R188P	1.000
18:59269482:C:T	R188Q	1.000
18:59269483:G:A	R188W	1.000
18:59269483:G:C	R188G	1.000
18:59269485:C:A	R187L	1.000
18:59269485:C:G	R187P	1.000
18:59269486:G:C	R187G	1.000
18:59269487:G:C	N186K	1.000
18:59269487:G:T	N186K	1.000
18:59269488:T:A	N186I	1.000
18:59269488:T:C	N186S	1.000
18:59269488:T:G	N186T	1.000

dbSNP variants (sampled 300 via entrez): RS1000290359 (18:59271777 T>A), RS1000590358 (18:59271385 C>A), RS1001130280 (18:59266933 C>A,T), RS1001616686 (18:59267637 C>A,T), RS1001627554 (18:59272686 G>A,T), RS1001773725 (18:59267390 G>A,C), RS1002379426 (18:59270298 G>T), RS1002522362 (18:59267015 A>G,T), RS1002534016 (18:59271262 T>C), RS1002583129 (18:59273432 G>A), RS1002747109 (18:59273243 G>A,C,T), RS1003538642 (18:59269941 C>A,G,T), RS1003667904 (18:59269691 C>T), RS1003942307 (18:59268237 G>A), RS1004149963 (18:59268914 G>A,T)

Disease associations

OMIM: gene MIM:601881 | disease phenotypes: MIM:611038

GenCC curated gene-disease

Disease	Classification	Inheritance
isolated microphthalmia 3	Definitive	Autosomal recessive
isolated anophthalmia-microphthalmia syndrome	Supportive	Autosomal dominant
coloboma	Limited	Autosomal recessive

Mondo (3): isolated microphthalmia 3 (MONDO:0012604), isolated anophthalmia-microphthalmia syndrome (MONDO:0016764), coloboma (MONDO:0001476)

Orphanet (1): Isolated microphthalmia-anophthalmia-coloboma (Orphanet:2542)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003103	Coloboma	C11.250.110; C11.270.147; C16.131.384.282
C567025	Microphthalmia, Isolated 3 (supp.)

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
Valproic Acid	affects cotreatment, decreases expression, decreases methylation	5
trichostatin A	affects cotreatment, decreases expression	3
entinostat	decreases expression, affects cotreatment	2
belinostat	affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression, increases expression	2
methylmercuric chloride	decreases expression	1
propionaldehyde	decreases expression	1
bisphenol A	decreases methylation	1
arsenite	increases methylation	1
sodium arsenite	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
MT19c compound	decreases expression	1
Vorinostat	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Diazinon	increases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00368004	Not specified	TERMINATED	Family Studies of Uveal Coloboma
NCT01778543	Not specified	RECRUITING	Pathogenesis and Genetics of Microphthalmia, Anophthalmia and Uveal Coloboma (MAC)
NCT04833361	Not specified	COMPLETED	Potential Environmental Causes of Uveal Coloboma
NCT06293560	Not specified	RECRUITING	Microphthalmia, Anophthalmia, and Coloboma Genetic Epidemiology in Children