Details of Disease

General Information of Disease (ID: DISD6L06)

• Disease Name: Autosomal dominant non-syndromic intellectual disability
• Synonyms: autosomal dominant mental retardation; non-syndromic intellectual disability, autosomal dominant; autosomal dominant non-syndromic mental retardation; autosomal dominant non-syndromic intellectual disability
• Definition: Autosomal dominant form of non-syndromic intellectual disability.|Editor note: wrongly classified in ORDO, see https://github.com/monarch-initiative/monarch-disease-ontology/issues/407 - check also Koolen-de vries
• Disease Hierarchy:
  DIS1I87P: Intellectual disability, autosomal dominant
  DISTFIZ6: Non-syndromic intellectual disability
  DISD6L06: Autosomal dominant non-syndromic intellectual disability
• Disease Identifiers:
  MONDO ID: MONDO_0015802
  UMLS CUI: C5680502
  MedGen ID: 1826082
  Orphanet ID: 178469

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 34 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ZMYND11	OT2A1WLT	Supportive	Autosomal dominant	[1]
ASH1L	OTUT5NLJ	Supportive	Autosomal dominant	[10]
BRSK2	OT9YCPBU	Supportive	Autosomal dominant	[2]
CACNG2	OTETEMM0	Supportive	Autosomal dominant	[4]
CAMK2A	OTJGX19T	Supportive	Autosomal dominant	[11]
CAMK2B	OTS9YK3E	Supportive	Autosomal dominant	[11]
CDH15	OTJ1TO02	Supportive	Autosomal dominant	[12]
CHAMP1	OTBGWU86	Supportive	Autosomal dominant	[13]
CIC	OTFXCHNZ	Supportive	Autosomal dominant	[14]
CLTC	OTBFASMA	Supportive	Autosomal dominant	[15]
CSNK2B	OT2WW7R1	Supportive	Autosomal dominant	[16]
CUX1	OTU1LCNJ	Supportive	Autosomal dominant	[17]
DEAF1	OTCLX3ZW	Supportive	Autosomal dominant	[18]
DLL1	OTCKXBQR	Supportive	Autosomal dominant	[3]
DOCK8	OTNQLL21	Supportive	Autosomal dominant	[19]
DYNC1H1	OTD1KRKO	Supportive	Autosomal dominant	[20]
EEF1A2	OT9Z23K5	Supportive	Autosomal dominant	[21]
EPB41L1	OT4CL5DC	Supportive	Autosomal dominant	[4]
GRIN1	OTZ5YBO8	Supportive	Autosomal dominant	[4]
GRIN2B	OT0GODXX	Supportive	Autosomal dominant	[5]
HIVEP2	OTVOMCW4	Supportive	Autosomal dominant	[22]
KCNQ5	OTMED202	Supportive	Autosomal dominant	[6]
KIF1A	OT3JVEGV	Supportive	Autosomal dominant	[4]
KIRREL3	OTW7PENS	Supportive	Autosomal dominant	[12]
MBD5	OTFHT4MO	Supportive	Autosomal dominant	[23]
MED12L	OTT0HR5M	Supportive	Autosomal dominant	[24]
PPP3CA	OT58PUEN	Supportive	Autosomal dominant	[7]
RAB11A	OTC4FW0J	Supportive	Autosomal dominant	[15]
SET	OTGYYQJO	Supportive	Autosomal dominant	[25]
STXBP1	OTRYA8C3	Supportive	Autosomal dominant	[26]
SYNGAP1	OT41HVYQ	Supportive	Autosomal dominant	[27]
TAOK1	OTFFLV6Q	Supportive	Autosomal dominant	[8]
TCF4	OTB9ASTK	Supportive	Autosomal dominant	[28]
TRPM3	OTE4CDOQ	Supportive	Autosomal dominant	[9]

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
BRSK2	TTHZN4X	Supportive	Autosomal dominant	[2]
DLL1	TT9CFQD	Supportive	Autosomal dominant	[3]
GRIN1	TTLD29N	Supportive	Autosomal dominant	[4]
GRIN2B	TTN9D8E	Supportive	Autosomal dominant	[5]
KCNQ5	TTWVL5Q	Supportive	Autosomal dominant	[6]
PPP3CA	TTA4LDE	Supportive	Autosomal dominant	[7]
TAOK1	TTQY9DH	Supportive	Autosomal dominant	[8]
TRPM3	TTO3TD8	Supportive	Autosomal dominant	[9]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
CACNG2	DTRL7OG	Supportive	Autosomal dominant	[4]

References

• [1] Refining analyses of copy number variation identifies specific genes associated with developmental delay. Nat Genet. 2014 Oct;46(10):1063-71. doi: 10.1038/ng.3092. Epub 2014 Sep 14.
• [2] Deleterious Variation in BRSK2 Associates with a Neurodevelopmental Disorder. Am J Hum Genet. 2019 Apr 4;104(4):701-708. doi: 10.1016/j.ajhg.2019.02.002. Epub 2019 Mar 14.
• [3] Haploinsufficiency of the Notch Ligand DLL1 Causes Variable Neurodevelopmental Disorders. Am J Hum Genet. 2019 Sep 5;105(3):631-639. doi: 10.1016/j.ajhg.2019.07.002. Epub 2019 Jul 25.
• [4] Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability. Am J Hum Genet. 2011 Mar 11;88(3):306-16. doi: 10.1016/j.ajhg.2011.02.001. Epub 2011 Mar 3.
• [5] Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes. Nat Genet. 2010 Nov;42(11):1021-6. doi: 10.1038/ng.677. Epub 2010 Oct 3.
• [6] Loss-of-Function and Gain-of-Function Mutations in KCNQ5 Cause Intellectual Disability or Epileptic Encephalopathy. Am J Hum Genet. 2017 Jul 6;101(1):65-74. doi: 10.1016/j.ajhg.2017.05.016. Epub 2017 Jun 29.
• [7] De Novo Mutations in PPP3CA Cause Severe Neurodevelopmental Disease with Seizures. Am J Hum Genet. 2017 Oct 5;101(4):516-524. doi: 10.1016/j.ajhg.2017.08.013. Epub 2017 Sep 21.
• [8] De Novo Variants in TAOK1 Cause Neurodevelopmental Disorders. Am J Hum Genet. 2019 Jul 3;105(1):213-220. doi: 10.1016/j.ajhg.2019.05.005. Epub 2019 Jun 20.
• [9] De novo substitutions of TRPM3 cause intellectual disability and epilepsy. Eur J Hum Genet. 2019 Oct;27(10):1611-1618. doi: 10.1038/s41431-019-0462-x. Epub 2019 Jul 5.
• [10] Diagnostic exome sequencing in persons with severe intellectual disability. N Engl J Med. 2012 Nov 15;367(20):1921-9. doi: 10.1056/NEJMoa1206524. Epub 2012 Oct 3.
• [11] De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability. Am J Hum Genet. 2017 Nov 2;101(5):768-788. doi: 10.1016/j.ajhg.2017.10.003.
• [12] Alterations in CDH15 and KIRREL3 in patients with mild to severe intellectual disability. Am J Hum Genet. 2008 Dec;83(6):703-13. doi: 10.1016/j.ajhg.2008.10.020. Epub 2008 Nov 13.
• [13] De Novo Mutations in CHAMP1 Cause Intellectual Disability with Severe Speech Impairment. Am J Hum Genet. 2015 Sep 3;97(3):493-500. doi: 10.1016/j.ajhg.2015.08.003.
• [14] Disruption of the ATXN1-CIC complex causes a spectrum of neurobehavioral phenotypes in mice and humans. Nat Genet. 2017 Apr;49(4):527-536. doi: 10.1038/ng.3808. Epub 2017 Mar 13.
• [15] High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies. Am J Hum Genet. 2017 Nov 2;101(5):664-685. doi: 10.1016/j.ajhg.2017.09.008.
• [16] CSNK2B splice site mutations in patients cause intellectual disability with or without myoclonic epilepsy. Hum Mutat. 2017 Aug;38(8):932-941. doi: 10.1002/humu.23270. Epub 2017 Jun 19.
• [17] Haploinsufficiency of CUX1 Causes Nonsyndromic Global Developmental Delay With Possible Catch-up Development. Ann Neurol. 2018 Aug;84(2):200-207. doi: 10.1002/ana.25278. Epub 2018 Aug 31.
• [18] 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.
• [19] Dedicator of cytokinesis 8 is disrupted in two patients with mental retardation and developmental disabilities. Genomics. 2008 Feb;91(2):195-202. doi: 10.1016/j.ygeno.2007.10.011. Epub 2007 Dec 3.
• [20] Mutations in DYNC1H1 cause severe intellectual disability with neuronal migration defects. J Med Genet. 2012 Mar;49(3):179-83. doi: 10.1136/jmedgenet-2011-100542.
• [21] De novo EEF1A2 mutations in patients with characteristic facial features, intellectual disability, autistic behaviors and epilepsy. Clin Genet. 2015 Apr;87(4):356-61. doi: 10.1111/cge.12394. Epub 2014 Apr 29.
• [22] Loss-of-function variants in HIVEP2 are a cause of intellectual disability. Eur J Hum Genet. 2016 Apr;24(4):556-61. doi: 10.1038/ejhg.2015.151. Epub 2015 Jul 8.
• [23] Extended spectrum of MBD5 mutations in neurodevelopmental disorders. Eur J Hum Genet. 2013 Dec;21(12):1457-61. doi: 10.1038/ejhg.2013.22. Epub 2013 Feb 20.
• [24] Variants in MED12L, encoding a subunit of the mediator kinase module, are responsible for intellectual disability associated with transcriptional defect. Genet Med. 2019 Dec;21(12):2713-2722. doi: 10.1038/s41436-019-0557-3. Epub 2019 Jun 3.
• [25] De novo mutations in the SET nuclear proto-oncogene, encoding a component of the inhibitor of histone acetyltransferases (INHAT) complex in patients with nonsyndromic intellectual disability. Hum Mutat. 2018 Jul;39(7):1014-1023. doi: 10.1002/humu.23541. Epub 2018 May 10.
• [26] STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy. Neurology. 2016 Mar 8;86(10):954-62. doi: 10.1212/WNL.0000000000002457. Epub 2016 Feb 10.
• [27] Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency. Hum Mutat. 2013 Feb;34(2):385-94. doi: 10.1002/humu.22248. Epub 2012 Dec 12.
• [28] Parent-child exome sequencing identifies a de novo truncating mutation in TCF4 in non-syndromic intellectual disability. Clin Genet. 2013 Feb;83(2):198-200. doi: 10.1111/j.1399-0004.2012.01890.x. Epub 2012 Jun 4.