LINGO4

Summary

LINGO4 (leucine rich repeat and Ig domain containing 4, HGNC:31814) is a protein-coding gene on chromosome 1q21.3, encoding Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 4 (Q6UY18).

Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be located in membrane. Predicted to be active in extracellular matrix and extracellular space.

Source: NCBI Gene 339398 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 101 total
• MANE Select transcript: NM_001004432

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31814
Approved symbol	LINGO4
Name	leucine rich repeat and Ig domain containing 4
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000213171
Ensembl biotype	protein_coding
OMIM	609794
Entrez	339398

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000368820

RefSeq mRNA: 1 — MANE Select: NM_001004432 NM_001004432

CCDS: CCDS30855

Canonical transcript exons

ENST00000368820 — 2 exons

Exon	Start	End
ENSE00001448024	151800264	151802717
ENSE00001448025	151805230	151805419

Expression profiles

Bgee: expression breadth broad, 87 present calls, max score 90.13.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.13	gold quality
gastrocnemius	UBERON:0001388	86.71	gold quality
muscle of leg	UBERON:0001383	84.11	gold quality
skeletal muscle tissue	UBERON:0001134	80.56	gold quality
hindlimb stylopod muscle	UBERON:0004252	79.92	gold quality
right hemisphere of cerebellum	UBERON:0014890	71.39	gold quality
cerebellum	UBERON:0002037	71.13	gold quality
cerebellar cortex	UBERON:0002129	70.97	gold quality
cerebellar hemisphere	UBERON:0002245	70.90	gold quality
muscle tissue	UBERON:0002385	69.52	gold quality
right uterine tube	UBERON:0001302	67.84	gold quality
pituitary gland	UBERON:0000007	57.47	gold quality
islet of Langerhans	UBERON:0000006	57.17	gold quality
apex of heart	UBERON:0002098	57.07	gold quality
heart left ventricle	UBERON:0002084	57.00	gold quality
liver	UBERON:0002107	55.98	gold quality
right lobe of liver	UBERON:0001114	55.90	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	55.12	gold quality
adenohypophysis	UBERON:0002196	53.44	gold quality
skin of leg	UBERON:0001511	51.60	gold quality
pancreas	UBERON:0001264	51.22	gold quality
prostate gland	UBERON:0002367	50.92	gold quality
lymph node	UBERON:0000029	49.44	gold quality
thyroid gland	UBERON:0002046	49.37	gold quality
saliva-secreting gland	UBERON:0001044	49.32	gold quality
zone of skin	UBERON:0000014	49.10	gold quality
tonsil	UBERON:0002372	48.88	silver quality
heart	UBERON:0000948	48.79	gold quality
left lobe of thyroid gland	UBERON:0001120	48.74	gold quality
minor salivary gland	UBERON:0001830	48.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting LINGO4, 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-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-657	99.48	66.02	848
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-143-5P	98.98	68.87	946
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-487A-5P	98.85	69.37	993
HSA-MIR-487B-5P	98.85	69.48	987
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-4490	98.51	68.47	943
HSA-MIR-4722-5P	98.46	66.34	1611

Literature-anchored findings (GeneRIF, showing 1)

• variants in coding region of the LINGO4 gene may play little or no role in the risk of Essential tremor susceptibility (PMID:22104011)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrtm2b	ENSDARG00000045811
danio_rerio	lingo3a	ENSDARG00000061970
danio_rerio		ENSDARG00000067815
danio_rerio	si:dkey-182i3.11	ENSDARG00000069270
danio_rerio	si:dkey-1j5.4	ENSDARG00000073747
danio_rerio	wu:fc23c09	ENSDARG00000088002
mus_musculus	Lingo4	ENSMUSG00000044505
rattus_norvegicus	Lingo4	ENSRNOG00000022863
drosophila_melanogaster	CG5819	FBGN0034717
drosophila_melanogaster	CG4781	FBGN0035043
caenorhabditis_elegans		WBGENE00006366

Paralogs (10): EPYC (ENSG00000083782), OGN (ENSG00000106809), ECM2 (ENSG00000106823), FMOD (ENSG00000122176), OMG (ENSG00000126861), OMD (ENSG00000127083), LUM (ENSG00000139329), KERA (ENSG00000139330), PRELP (ENSG00000188783), LINGO3 (ENSG00000220008)

Protein

Protein identifiers

Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 4 — Q6UY18 (reviewed: Q6UY18)

Alternative names: Leucine-rich repeat neuronal protein 6D

All UniProt accessions (1): Q6UY18

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (1): NP_001004432* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000372	LRRNT	Domain
IPR000483	Cys-rich_flank_reg_C	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050467	LRFN	Family

Pfam: PF07679, PF13855

UniProt features (26 total): repeat 11, glycosylation site 6, domain 3, topological domain 2, signal peptide 1, chain 1, disulfide bond 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UY18-F1	85.70	0.70

Functional residue map

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

Disulfide bonds (1): 435–484

Glycosylation sites (6): 191, 253, 263, 492, 508, 515

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 33 (showing top): GOBP_SYNAPSE_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_REGULATION_OF_SYNAPSE_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_SYNAPSE_STRUCTURE_OR_ACTIVITY, GOBP_CELL_JUNCTION_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_POSITIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, chr1q21

GO Biological Process (1): positive regulation of synapse assembly (GO:0051965)

GO Molecular Function (2): signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
synapse assembly	1
positive regulation of nervous system development	1
regulation of synapse assembly	1
positive regulation of cell junction assembly	1
molecular transducer activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

544 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LINGO4	THEM5	Q8N1Q8	495
LINGO4	HS1BP3	Q53T59	452
LINGO4	CRCT1	Q9UGL9	440
LINGO4	TCHHL1	Q5QJ38	405
LINGO4	CENPP	Q6IPU0	373
LINGO4	STK32B	Q9NY57	365
LINGO4	CRNN	Q9UBG3	348
LINGO4	RPTN	Q6XPR3	341
LINGO4	INTS3	Q68E01	333
LINGO4	PGLYRP4	Q96LB8	331
LINGO4	BNIPL	Q7Z465	328
LINGO4	GIGYF1	O75420	323
LINGO4	RIT2	Q99578	306
LINGO4	ADAT3	Q96EY9	305
LINGO4	OGN	P20774	302

IntAct

2 interactions, top by confidence:

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

BioGRID (2): LINGO4 (Proximity Label-MS), LINGO4 (Proximity Label-MS)

ESM2 similar proteins: A1A4H9, A2ARI4, A2VDH3, A6H793, D4A6D8, E9Q7T7, F1MLX5, F1MT22, O75325, P59034, P59035, Q13641, Q149C3, Q3URE9, Q3UVD5, Q3UY51, Q4KLL3, Q4R8Y9, Q50LG9, Q5M8M9, Q5PQV5, Q5R6B1, Q5RDJ4, Q5VT99, Q6GQU6, Q6UY18, Q6ZSA7, Q7M6Z0, Q7TQ62, Q80WD1, Q86UE6, Q86UN2, Q86UN3, Q86WK6, Q8BHA1, Q8K0S5, Q8K377, Q8N7C0, Q91ZV8, Q96FE5

Diamond homologs: A0N0X6, A1KZ92, A2A8L5, A3KNN3, A4IFW2, A4IGL7, A4IIW9, A6H793, A7MBJ4, A8WGA3, B0BNK7, B0V2N1, B3MH43, B3NS99, B4GBH0, B4HNW4, B4KPU0, B4MR28, B4P5Q9, B4QC63, D2HFT7, D3YXG0, D4A1J9, D4ABX8, E9Q7T7, F1MLX5, F1NWE3, F1NY98, O55005, O60469, O75325, O89026, O94779, O95428, P0C6S8, P0C7J6, P10586, P16621, P59034, P59035

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	96
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

294 predictions. Top by Δscore:

Variant	Effect	Δscore
1:151805223:CACTT:C	donor_loss	0.9800
1:151805224:ACTTA:A	donor_loss	0.9800
1:151805225:CTTA:C	donor_loss	0.9800
1:151805226:TTA:T	donor_loss	0.9800
1:151805227:TACCG:T	donor_loss	0.9800
1:151805228:A:AC	donor_gain	0.9800
1:151805228:A:AT	donor_loss	0.9800
1:151805229:C:CC	donor_gain	0.9800
1:151802793:T:C	acceptor_gain	0.9300
1:151805229:CCG:C	donor_gain	0.8700
1:151805228:AC:A	donor_gain	0.8500
1:151805229:CC:C	donor_gain	0.8500
1:151805222:GCACT:G	donor_loss	0.8300
1:151805229:CCGGA:C	donor_gain	0.7900
1:151802785:GGCCC:G	acceptor_gain	0.7600
1:151802787:CCCTT:C	acceptor_gain	0.7300
1:151802788:CCTTC:C	acceptor_gain	0.7300
1:151805229:CCGG:C	donor_gain	0.7300
1:151802793:T:TC	acceptor_gain	0.7100
1:151802793:T:TG	acceptor_gain	0.7100
1:151802585:C:A	acceptor_gain	0.7000
1:151802630:TCCAG:T	acceptor_gain	0.7000
1:151802442:T:TA	donor_gain	0.6700
1:151802789:CTTCT:C	acceptor_gain	0.6600
1:151802790:TTCTT:T	acceptor_gain	0.6600
1:151802565:C:A	acceptor_gain	0.6300
1:151802789:CTT:C	acceptor_gain	0.6300
1:151805326:C:A	donor_gain	0.6200
1:151802819:T:A	acceptor_gain	0.6000
1:151802791:T:G	acceptor_gain	0.5900

AlphaMissense

3784 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:151801364:C:A	W447C	0.998
1:151801364:C:G	W447C	0.998
1:151801254:C:G	C484S	0.996
1:151801255:A:T	C484S	0.996
1:151801241:A:C	N488K	0.995
1:151801241:A:T	N488K	0.995
1:151801253:A:C	C484W	0.994
1:151801255:A:G	C484R	0.994
1:151801254:C:T	C484Y	0.993
1:151801631:G:C	N358K	0.993
1:151801631:G:T	N358K	0.993
1:151801703:G:C	N334K	0.993
1:151801703:G:T	N334K	0.993
1:151802280:T:A	N142I	0.993
1:151801209:A:G	L499P	0.992
1:151801847:A:C	N286K	0.992
1:151801847:A:T	N286K	0.992
1:151802423:G:C	N94K	0.992
1:151802423:G:T	N94K	0.992
1:151801242:T:A	N488I	0.991
1:151801261:A:C	Y482D	0.991
1:151801299:A:G	L469P	0.991
1:151801366:A:G	W447R	0.991
1:151801366:A:T	W447R	0.991
1:151801401:C:G	C435S	0.991
1:151801402:A:T	C435S	0.991
1:151801704:T:A	N334I	0.991
1:151801857:A:G	L283P	0.991
1:151802424:T:A	N94I	0.991
1:151801791:A:G	L305P	0.990

dbSNP variants (sampled 300 via entrez): RS1001398538 (1:151805067 T>A), RS1001899209 (1:151800404 T>C), RS1002271177 (1:151804374 G>A,C,T), RS1002353033 (1:151799998 G>A), RS1002436952 (1:151806300 T>C), RS1004887199 (1:151799877 C>A), RS1005006403 (1:151806400 G>A,C,T), RS1005802102 (1:151803178 A>G), RS1005999733 (1:151804812 G>C), RS1006073054 (1:151803591 T>G), RS1007818480 (1:151805342 C>A,G), RS1008099961 (1:151805740 C>T), RS1008966534 (1:151806698 G>A), RS1009071032 (1:151800135 C>T), RS1009094370 (1:151800725 C>T)

Disease associations

OMIM: gene MIM:609794 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal recessive

Mondo (2): polymicrogyria (MONDO:0000087), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): Polymicrogyria (Orphanet:35981)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005195_138	Coronary artery disease	3.000000e-11
GCST008916_130	Asthma	1.000000e-12
GCST008916_88	Asthma	1.000000e-25
GCST010866_19	Coronary artery disease	5.000000e-12
GCST90002383_333	Hematocrit	7.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004348	hematocrit

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
D065706	Polymicrogyria	C10.500.507.500.500; C16.131.666.507.500.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Rosiglitazone	decreases expression	1
Leflunomide	increases expression	1
Vehicle Emissions	decreases methylation	1
N-Nitrosopyrrolidine	decreases expression	1
Valproic Acid	decreases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice