Details of Disease

General Information of Disease (ID: DISB9AFI)

Disease Name Complex neurodevelopmental disorder
Synonyms complex neurodevelopmental disorder
Definition A disorder that involves more than one phenotype associated with the central nervous system, including but not limited to intellectual disability, autism, and seizures (epilepsy).
Disease Hierarchy
DIS372XH: Neurodevelopmental disorder
DISB9AFI: Complex neurodevelopmental disorder
Disease Identifiers
MONDO ID
MONDO_0100038
UMLS CUI
C5568766
MedGen ID
1800189
SNOMED CT ID
1187038009

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)
This Disease Is Related to 162 DOT Molecule(s)
Gene Name DOT ID Evidence Level Mode of Inheritance REF
TUBA3E OT707LNR Limited Autosomal recessive [1]
TUBAL3 OTONRBL7 Limited Autosomal recessive [1]
USP2 OTTUMGW7 Limited Autosomal recessive [1]
WAPL OT1BEQ78 Limited Autosomal dominant [1]
ZBTB47 OTFQDWJT Limited Autosomal dominant [1]
ZNF407 OT0SAIE9 Limited Autosomal recessive [1]
ZNF589 OTLO5JJ7 Limited Autosomal recessive [1]
ZNF804A OTHJCCUI Limited Autosomal dominant [1]
WDFY3 OTJAA5UZ Moderate Autosomal dominant [1]
YWHAZ OT2TKG9P Moderate Autosomal dominant [2]
UNC79 OT6FGTGJ Strong Autosomal dominant [1]
ZBTB7A OTQIVY9B Strong Autosomal dominant [1]
ZBTB18 OTOUVAG5 Definitive Autosomal dominant [3]
ZMIZ1 OT1Q9TX0 Definitive Autosomal dominant [3]
ZNF292 OT8X62ZC Definitive Autosomal dominant [3]
CLASP1 OTL04TBD No Known Autosomal dominant [8]
LMBRD2 OTD9C4IF No Known Autosomal dominant [3]
SPEN OT37A2MD No Known Autosomal dominant [3]
ALDH1B1 OTXW9TE2 Limited Autosomal dominant [1]
ALDOB OT7FR69A Limited Autosomal recessive [1]
ARHGAP33 OTIU622H Limited Autosomal recessive [1]
ARHGEF6 OTN1ABGL Limited Autosomal dominant [1]
ATG4D OTSWUO4R Limited Autosomal recessive [1]
ATP6V0A1 OT1IK0KA Limited Autosomal dominant [1]
B3GAT3 OTDSN5XF Limited Autosomal dominant [1]
BAZ2B OTB98CEY Limited Autosomal dominant [3]
BLOC1S1 OT123376 Limited Autosomal recessive [9]
BORCS5 OTAT6H8Q Limited Autosomal recessive [1]
CACNG2 OTETEMM0 Limited Autosomal dominant [3]
CAMK4 OT47RDGV Limited Autosomal dominant [10]
CAPZA2 OTHAO4V2 Limited Autosomal dominant [1]
CDK20 OTOLNN68 Limited Autosomal recessive [1]
CELF2 OTLJJ4VT Limited Autosomal dominant [1]
CHRNA7 OTBUSUTE Limited Autosomal dominant [1]
CNTN4 OTULXVE0 Limited Autosomal dominant [3]
CPNE6 OTW9DAG2 Limited Autosomal recessive [1]
CSNK1G1 OTCXB7BI Limited Autosomal dominant [1]
DMBX1 OT43YF6N Limited Autosomal recessive [1]
DNAJA1 OT38BZQQ Limited Autosomal recessive [1]
DNAJA3 OT61924T Limited Autosomal recessive [1]
DOCK8 OTNQLL21 Limited Autosomal dominant [1]
DRG1 OTIFYMI3 Limited Autosomal recessive [1]
EPB41L1 OT4CL5DC Limited Autosomal dominant [3]
EXOC2 OT5QG1WG Limited Autosomal recessive [3]
FEM1C OT4M4IBT Limited Autosomal dominant [11]
JMJD1C OTHAWK8C Limited Autosomal dominant [4]
KCND2 OTIFUVV7 Limited Autosomal dominant [12]
NTNG1 OTF48IID Limited Autosomal dominant [3]
OTUD7A OT3GCY98 Limited Autosomal recessive [3]
PRICKLE2 OTWBA48T Limited Autosomal dominant [3]
RALGAPA1 OTHT5DW0 Limited Autosomal dominant [1]
RALGAPB OTY8CGA3 Limited Autosomal dominant [1]
RALGDS OTG36NI7 Limited Autosomal recessive [1]
RARS2 OT3WLAD8 Limited Autosomal dominant [1]
RBL2 OTBQSOE6 Limited Autosomal recessive [1]
RFX3 OTE0EI8Z Limited Autosomal dominant [1]
RHEB OTFLTSEC Limited Autosomal dominant [1]
RING1 OTCWTAX0 Limited Unknown [13]
RSRC2 OTLE0KQM Limited Autosomal dominant [1]
SCHIP1 OTF3FR4A Limited Autosomal recessive [1]
SEMA6D OTU0UAZS Limited Autosomal dominant [1]
SLC7A5 OT2WPVXD Limited Autosomal recessive [1]
SLCO1C1 OTYRO19B Limited Autosomal recessive [1]
SMARCB1 OT2LP7LJ Limited Autosomal dominant [1]
SNRPA OT02TSQT Limited Autosomal recessive [1]
SORCS3 OT4VOMBC Limited Autosomal dominant [1]
SRPRA OT5NMYTY Limited Autosomal dominant [1]
TAF1C OTNV4CDH Limited Autosomal recessive [1]
TP53TG5 OTYRE3XO Limited Autosomal recessive [1]
TRAPPC6A OT0ZRV5C Limited Autosomal recessive [1]
TRERF1 OTA7UQF1 Limited Autosomal recessive [1]
TRIM23 OTVIGJ4T Limited Autosomal dominant [1]
CNTN6 OTXVGVOR Disputed Autosomal dominant [3]
DPP6 OTWW3H0K Disputed Autosomal dominant [3]
EN2 OT7EZCM2 Disputed Autosomal dominant [3]
EPHA4 OT3AMK0C Disputed Autosomal dominant [5]
KATNAL2 OTL33OIT Disputed Autosomal dominant [3]
KIRREL3 OTW7PENS Disputed Autosomal dominant [3]
LAMC3 OTKNAYJO Disputed Autosomal dominant [3]
MET OT7K55MU Disputed Autosomal dominant [3]
RELN OTLKMW1O Disputed Autosomal dominant [3]
ANKS1B OT26DGM9 Moderate Autosomal dominant [14]
CACNA1I OTRH8X8A Moderate Autosomal dominant [6]
CACNA2D2 OTFJXVQQ Moderate Autosomal recessive [3]
CDC42BPB OTO6NT7Q Moderate Autosomal dominant [1]
CEP55 OTGSG2PA Moderate Autosomal recessive [1]
EXOC7 OT4YA137 Moderate Autosomal recessive [3]
GABRD OTO38I2R Moderate Autosomal dominant [3]
PIP5K1C OT3LPG1R Moderate Autosomal dominant [1]
SCAMP5 OT9MXA2J Moderate Autosomal dominant [15]
SHMT2 OT5NCAZN Moderate Autosomal recessive [1]
SIAH1 OT29A838 Moderate Autosomal dominant [1]
ST3GAL3 OTOORKUE Moderate Autosomal recessive [3]
SUPT16H OT9XWMQZ Moderate Autosomal dominant [1]
TAOK1 OTFFLV6Q Moderate Autosomal dominant [1]
TFE3 OTM99ZWH Moderate Autosomal dominant [1]
TMEM147 OTMKZ4PV Moderate Autosomal recessive [1]
TRA2B OTZYQW52 Moderate Autosomal dominant [1]
AP1G1 OTEO6Y9H Strong Autosomal dominant [3]
ARF3 OTYYQX85 Strong Autosomal dominant [1]
CLCN3 OTEEXNMU Strong Autosomal dominant [7]
CTNND2 OTYKE30Y Strong Autosomal dominant [16]
DEAF1 OTCLX3ZW Strong Semidominant [17]
KDM4B OT5P1UPY Strong Autosomal dominant [18]
PSMC3 OTSKT0JI Strong Autosomal dominant [1]
RALA OT734R7X Strong Autosomal dominant [1]
SCAF4 OTFGHB1E Strong Autosomal dominant [19]
SIM1 OTYKFPKZ Strong Autosomal dominant [1]
SMARCA5 OT5GR4Z2 Strong Autosomal dominant [1]
TMEM63B OTQNB4KI Strong Autosomal dominant [1]
ANK2 OTWB4R1Y Definitive Autosomal dominant [3]
BRSK2 OT9YCPBU Definitive Autosomal dominant [3]
CC2D1A OTVPU04K Definitive Autosomal recessive [3]
CHAMP1 OTBGWU86 Definitive Autosomal dominant [3]
CHD2 OTRKL6YC Definitive Autosomal dominant [3]
CHD8 OTS7A6AF Definitive Autosomal dominant [3]
CNOT1 OTTEU05F Definitive Autosomal dominant [3]
CNOT3 OT4D5Z9L Definitive Autosomal dominant [3]
CNTN2 OTQG9W7C Definitive Autosomal recessive [3]
CNTNAP2 OT48T2ZP Definitive Autosomal recessive [3]
CSDE1 OT15D7GH Definitive Autosomal dominant [3]
CUL3 OTDNOAPM Definitive Autosomal dominant [3]
DLG4 OTD9E2LU Definitive Autosomal dominant [3]
DYRK1A OTPLXCDN Definitive Autosomal dominant [3]
EEF1A2 OT9Z23K5 Definitive Autosomal dominant [3]
GNAI1 OTE0KX9F Definitive Autosomal dominant [3]
GRIK2 OTQ41U3D Definitive Autosomal dominant [3]
GRIN1 OTZ5YBO8 Definitive Autosomal recessive [3]
GRIN2A OTTP0KN8 Definitive Autosomal dominant [3]
GRIN2B OT0GODXX Definitive Autosomal dominant [3]
GRIN2D OTTEKYKQ Definitive Autosomal dominant [3]
HECW2 OTP2IN12 Definitive Autosomal dominant [3]
HNRNPU OTLQN1E2 Definitive Autosomal dominant [3]
KCNB1 OTLCU4FR Definitive Autosomal dominant [3]
KCNC1 OTW9WF1J Definitive Autosomal dominant [3]
KCNQ2 OT3CXQJT Definitive Autosomal dominant [3]
KMT2E OTYOLNOG Definitive Autosomal dominant [3]
KMT5B OTOH7G8Q Definitive Autosomal dominant [3]
LINS1 OT1USO08 Definitive Autosomal recessive [3]
MBD5 OTFHT4MO Definitive Autosomal dominant [3]
MED13 OTP5LEJE Definitive Autosomal dominant [3]
MEF2C OTZGF1Y5 Definitive Autosomal dominant [3]
NBEA OTYLY5TY Definitive Autosomal dominant [3]
NCKAP1 OTEZQXXJ Definitive Autosomal dominant [3]
NR4A2 OT3F9IR2 Definitive Autosomal dominant [3]
NRXN1 OTJN1JQA Definitive Autosomal dominant [3]
PHF21A OTU3FFG4 Definitive Autosomal dominant [3]
PIGO OTGDOBO1 Definitive Autosomal recessive [3]
PPP2R1A OTYA3GB4 Definitive Autosomal dominant [3]
PURA OT975ELW Definitive Autosomal dominant [3]
RHOBTB2 OT2DATFX Definitive Autosomal dominant [3]
SCN2A OTUSYE4Z Definitive Autosomal dominant [3]
SCN8A OT0JGIZN Definitive Autosomal dominant [3]
SETBP1 OTKGCOSR Definitive Autosomal dominant [3]
SHANK2 OTSQTPFQ Definitive Autosomal dominant [3]
STAG1 OT564IX4 Definitive Autosomal dominant [3]
SYNGAP1 OT41HVYQ Definitive Autosomal dominant [3]
TBL1XR1 OTM3B3OA Definitive Autosomal dominant [3]
TBR1 OT14JQT8 Definitive Autosomal dominant [3]
TCF7L2 OTVWPZ8B Definitive Autosomal dominant [3]
TNRC6B OTGVT0SH Definitive Autosomal dominant [3]
TRIP12 OT2ORYIH Definitive Autosomal dominant [3]
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⏷ Show the Full List of 162 DOT(s)
This Disease Is Related to 31 DTT Molecule(s)
Gene Name DTT ID Evidence Level Mode of Inheritance REF
BAZ2B TT6K8YG Limited Autosomal dominant [3]
CHRNA7 TTLA931 Limited Autosomal dominant [1]
CSNK1G1 TTQR5YD Limited Autosomal dominant [1]
JMJD1C TTBISK4 Limited Autosomal dominant [4]
USP2 TTUEQ1W Limited Autosomal recessive [1]
EPHA4 TTG84D3 Disputed Autosomal dominant [5]
MET TTNDSF4 Disputed Autosomal dominant [3]
CACNA1I TTQZFTH Moderate Autosomal dominant [6]
CACNA2D2 TTU8P3M Moderate Autosomal recessive [3]
GABRD TTGXH6N Moderate Autosomal dominant [3]
TAOK1 TTQY9DH Moderate Autosomal dominant [1]
CLCN3 TT8XNZ7 Strong Autosomal dominant [7]
BRSK2 TTHZN4X Definitive Autosomal dominant [3]
CNTN2 TT2Z1WB Definitive Autosomal recessive [3]
CUL3 TTPCU0Q Definitive Autosomal dominant [3]
DLG4 TT9PB26 Definitive Autosomal dominant [3]
DYRK1A TTSBVFO Definitive Autosomal dominant [3]
GRIK2 TT0K5RG Definitive Autosomal dominant [3]
GRIN1 TTLD29N Definitive Autosomal recessive [3]
GRIN2A TTKJEMQ Definitive Autosomal dominant [3]
GRIN2B TTN9D8E Definitive Autosomal dominant [3]
GRIN2D TT5POTG Definitive Autosomal dominant [3]
KCNB1 TT5OEKU Definitive Autosomal dominant [3]
KCNC1 TTVUWHQ Definitive Autosomal dominant [3]
KCNQ2 TTPXI3S Definitive Autosomal dominant [3]
KMT5B TTJGV7F Definitive Autosomal dominant [3]
NR4A2 TT9HKN3 Definitive Autosomal dominant [3]
SCN2A TTLJTUF Definitive Autosomal dominant [3]
TBL1XR1 TTYXT16 Definitive Autosomal dominant [3]
TCF7L2 TT80QAL Definitive Autosomal dominant [3]
TRIP12 TTG2CRH Definitive Autosomal dominant [3]
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⏷ Show the Full List of 31 DTT(s)
This Disease Is Related to 4 DTP Molecule(s)
Gene Name DTP ID Evidence Level Mode of Inheritance REF
CACNG2 DTRL7OG Limited Autosomal dominant [3]
SLC7A5 DT48T0N Limited Autosomal recessive [1]
SLCO1C1 DTPYCQ4 Limited Autosomal recessive [1]
SCN8A DTIMSBJ Definitive Autosomal dominant [3]
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This Disease Is Related to 1 DME Molecule(s)
Gene Name DME ID Evidence Level Mode of Inheritance REF
ALDH1B1 DEXI4UQ Limited Autosomal dominant [1]
------------------------------------------------------------------------------------

References

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2 Neurodevelopmental and neuropsychiatric behaviour defects arise from 14-3-3 deficiency. Mol Psychiatry. 2012 Apr;17(4):451-66. doi: 10.1038/mp.2011.158. Epub 2011 Nov 29.
3 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
4 Mutations in JMJD1C are involved in Rett syndrome and intellectual disability. Genet Med. 2016 Apr;18(4):378-85. doi: 10.1038/gim.2015.100. Epub 2015 Jul 16.
5 DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources. Am J Hum Genet. 2009 Apr;84(4):524-33. doi: 10.1016/j.ajhg.2009.03.010. Epub 2009 Apr 2.
6 Whole exome sequencing of Rett syndrome-like patients reveals the mutational diversity of the clinical phenotype. Hum Genet. 2016 Dec;135(12):1343-1354. doi: 10.1007/s00439-016-1721-3. Epub 2016 Aug 19.
7 Unique variants in CLCN3, encoding an endosomal anion/proton exchanger, underlie a spectrum of neurodevelopmental disorders. Am J Hum Genet. 2021 Aug 5;108(8):1450-1465. doi: 10.1016/j.ajhg.2021.06.003. Epub 2021 Jun 28.
8 Prevalence and architecture of de novo mutations in developmental disorders. Nature. 2017 Feb 23;542(7642):433-438. doi: 10.1038/nature21062. Epub 2017 Jan 25.
9 Combining exome/genome sequencing with data repository analysis reveals novel gene-disease associations for a wide range of genetic disorders. Genet Med. 2021 Aug;23(8):1551-1568. doi: 10.1038/s41436-021-01159-0. Epub 2021 Apr 19.
10 A unique de novo gain-of-function variant in CAMK4 associated with intellectual disability and hyperkinetic movement disorder. Cold Spring Harb Mol Case Stud. 2018 Dec 17;4(6):a003293. doi: 10.1101/mcs.a003293. Print 2018 Dec.
11 Neurodevelopmental Disorders (NDD) Caused by Genomic Alterations of the Ubiquitin-Proteasome System (UPS): the Possible Contribution of Immune Dysregulation to Disease Pathogenesis. Front Mol Neurosci. 2021 Sep 8;14:733012. doi: 10.3389/fnmol.2021.733012. eCollection 2021.
12 Exome sequencing identifies de novo gain of function missense mutation in KCND2 in identical twins with autism and seizures that slows potassium channel inactivation. Hum Mol Genet. 2014 Jul 1;23(13):3481-9. doi: 10.1093/hmg/ddu056. Epub 2014 Feb 5.
13 De novo mutation in RING1 with epigenetic effects on neurodevelopment. Proc Natl Acad Sci U S A. 2018 Feb 13;115(7):1558-1563. doi: 10.1073/pnas.1721290115. Epub 2018 Jan 31.
14 Haploinsufficiency in the ANKS1B gene encoding AIDA-1 leads to a neurodevelopmental syndrome. Nat Commun. 2019 Aug 6;10(1):3529. doi: 10.1038/s41467-019-11437-w.
15 Novel SCAMPs lacking NPF repeats: ubiquitous and synaptic vesicle-specific forms implicate SCAMPs in multiple membrane-trafficking functions. J Neurosci. 2000 Nov 1;20(21):7941-50. doi: 10.1523/JNEUROSCI.20-21-07941.2000.
16 The clinical significance of small copy number variants in neurodevelopmental disorders. J Med Genet. 2014 Oct;51(10):677-88. doi: 10.1136/jmedgenet-2014-102588. Epub 2014 Aug 8.
17 Mutations affecting the SAND domain of DEAF1 cause intellectual disability with severe speech impairment and behavioral problems. Am J Hum Genet. 2014 May 1;94(5):649-61. doi: 10.1016/j.ajhg.2014.03.013. Epub 2014 Apr 10.
18 Heterozygous Variants in KDM4B Lead to Global Developmental Delay and Neuroanatomical Defects. Am J Hum Genet. 2020 Dec 3;107(6):1170-1177. doi: 10.1016/j.ajhg.2020.11.001. Epub 2020 Nov 23.
19 Variants in SCAF4 Cause a Neurodevelopmental Disorder and Are Associated with Impaired mRNA Processing. Am J Hum Genet. 2020 Sep 3;107(3):544-554. doi: 10.1016/j.ajhg.2020.06.019. Epub 2020 Jul 29.