Details of Disease

Disease Name

Intellectual disability, X-linked 1

X-linked intellectual disability 1/78; IQSEC2-related intellectual disability; IQSEC2-related epilepsy; IQSEC2; X-linked intellectual disability 1; X-linked intellectual disability 78; intellectual developmental disorder, X-linked 1, X-linked dominant; mental retardation, X-linked 1; mental retardation, X-linked 18; MRX1; mental retardation, X-linked 78; MRX; MRX78; mental retardation, X-linked type 1; intellectual disability, X-linked 1

Definition

An X-linked dominant condition caused by mutation(s) in the IQSEC2 gene, encoding IQ motif and SEC7 domain-containing protein 2. It is characterized by substantially impaired intellectual functioning and behavioral abnormalities.

Disease Hierarchy

DIS71AI3: Non-syndromic X-linked intellectual disability

DISET38E: Intellectual disability, X-linked 1

Disease Identifiers

MONDO ID

MONDO_0010656

MESH ID

C567906

UMLS CUI

C2931498

OMIM ID

309530

MedGen ID

444070

General Information of Disease (ID: DISET38E)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 7 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
MECP2	TTTAU9R	Limited	Genetic Variation	[1]
TSPAN7	TTMT6VE	Limited	GermlineCausalMutation	[2]
AGTR2	TTQVOEI	Strong	GermlineCausalMutation	[3]
DMD	TTWLFXU	Strong	GermlineCausalMutation	[4]
OPHN1	TTU7HRD	Strong	Genetic Variation	[5]
RPS6KA3	TTUM2ZR	Strong	GermlineCausalMutation	[6]
RPS6KA6	TT3KYWB	Strong	Biomarker	[7]
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⏷ Show the Full List of 7 DTT(s)

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC9A7	DTQPK6R	Strong	GermlineCausalMutation	[8]
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This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
ALAS2	DE437BY	Strong	Genetic Variation	[9]
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This Disease Is Related to 19 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
AFF2	OTMF1PZW	Limited	Biomarker	[10]
IL1RAPL1	OTW3T4B2	Limited	Biomarker	[11]
ALG13	OTOH9PMY	Strong	GermlineCausalMutation	[12]
ARHGEF6	OTN1ABGL	Strong	GermlineCausalMutation	[13]
CLCN4	OT4A2UWF	Strong	GermlineCausalMutation	[14]
CNKSR2	OTAGERJ2	Strong	GermlineCausalMutation	[14]
DLG3	OTH591WK	Strong	Biomarker	[15]
FRMPD4	OT60SNXQ	Strong	GermlineCausalMutation	[14]
FTSJ1	OTNE7W96	Strong	GermlineCausalMutation	[16]
GDI1	OTYM3928	Strong	GermlineCausalMutation	[17]
HCFC1	OT0UCK62	Strong	GermlineCausalMutation	[18]
PAK3	OT80M3BV	Strong	GermlineCausalMutation	[19]
POU3F4	OTKF5AF7	Strong	Genetic Variation	[7]
PTCHD1	OTFDLU5S	Strong	Genetic Variation	[20]
SERPINA4	OTBK0GG7	Strong	Genetic Variation	[21]
SYP	OTFJKMO4	Strong	GermlineCausalMutation	[22]
IQSEC2	OTYFRM4Q	Definitive	X-linked	[23]
MID2	OTAAQNZA	Definitive	GermlineCausalMutation	[24]
RAB39B	OTDCLLT0	Definitive	GermlineCausalMutation	[25]
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⏷ Show the Full List of 19 DOT(s)

References

1	MECP2 gene mutations in non-syndromic X-linked mental retardation: phenotype-genotype correlation.Am J Med Genet A. 2003 Dec 1;123A(2):129-39. doi: 10.1002/ajmg.a.20247.
2	A novel 2 bp deletion in the TM4SF2 gene is associated with MRX58.J Med Genet. 2002 Jun;39(6):430-3. doi: 10.1136/jmg.39.6.430.
3	Identification of two AGTR2 mutations in male patients with non-syndromic mental retardation. Hum Genet. 2004 Jan;114(2):211-3. doi: 10.1007/s00439-003-1048-8. Epub 2003 Nov 4.
4	A 3-base pair deletion, c.9711_9713del, in DMD results in intellectual disability without muscular dystrophy. Eur J Hum Genet. 2014 Apr;22(4):480-5. doi: 10.1038/ejhg.2013.169. Epub 2013 Jul 31.
5	Oligophrenin 1 mutations frequently cause X-linked mental retardation with cerebellar hypoplasia.Neurology. 2005 Nov 8;65(9):1364-9. doi: 10.1212/01.wnl.0000182813.94713.ee. Epub 2005 Oct 12.
6	Mutations in the RSK2(RPS6KA3) gene cause Coffin-Lowry syndrome and nonsyndromic X-linked mental retardation. Clin Genet. 2006 Dec;70(6):509-15. doi: 10.1111/j.1399-0004.2006.00723.x.
7	A novel ribosomal S6-kinase (RSK4; RPS6KA6) is commonly deleted in patients with complex X-linked mental retardation.Genomics. 1999 Dec 15;62(3):332-43. doi: 10.1006/geno.1999.6004.
8	A recurrent missense variant in SLC9A7 causes nonsyndromic X-linked intellectual disability with alteration of Golgi acidification and aberrant glycosylation. Hum Mol Genet. 2019 Feb 15;28(4):598-614. doi: 10.1093/hmg/ddy371.
9	X-linked mental retardation: a comprehensive molecular screen of 47 candidate genes from a 7.4 Mb interval in Xp11.Eur J Hum Genet. 2007 Jan;15(1):68-75. doi: 10.1038/sj.ejhg.5201714. Epub 2006 Sep 13.
10	Fragile XE-associated familial mental retardation protein 2 (FMR2) acts as a potent transcription activator.J Hum Genet. 2001;46(5):251-9. doi: 10.1007/s100380170074.
11	Novel mutation of IL1RAPL1 gene in a nonspecific X-linked mental retardation (MRX) family.Am J Med Genet A. 2008 Dec 15;146A(24):3167-72. doi: 10.1002/ajmg.a.32613.
12	X chromosome exome sequencing reveals a novel ALG13 mutation in a nonsyndromic intellectual disability family with multiple affected male siblings. Am J Med Genet A. 2014 Jan;164A(1):164-9. doi: 10.1002/ajmg.a.36233.
13	Mutations in ARHGEF6, encoding a guanine nucleotide exchange factor for Rho GTPases, in patients with X-linked mental retardation. Nat Genet. 2000 Oct;26(2):247-50. doi: 10.1038/80002.
14	X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes. Mol Psychiatry. 2016 Jan;21(1):133-48. doi: 10.1038/mp.2014.193. Epub 2015 Feb 3.
15	Altered thalamocortical development in the SAP102 knockout model of intellectual disability.Hum Mol Genet. 2016 Sep 15;25(18):4052-4061. doi: 10.1093/hmg/ddw244. Epub 2016 Jul 27.
16	A loss-of-function mutation in the FTSJ1 gene causes nonsyndromic X-linked mental retardation in a Japanese family. Am J Med Genet B Neuropsychiatr Genet. 2008 Jun 5;147B(4):479-84. doi: 10.1002/ajmg.b.30638.
17	Novel GDI1 mutation in a large family with nonsyndromic X-linked intellectual disability. Am J Med Genet A. 2011 Dec;155A(12):3067-70. doi: 10.1002/ajmg.a.34291. Epub 2011 Oct 14.
18	A noncoding, regulatory mutation implicates HCFC1 in nonsyndromic intellectual disability. Am J Hum Genet. 2012 Oct 5;91(4):694-702. doi: 10.1016/j.ajhg.2012.08.011. Epub 2012 Sep 20.
19	A novel splice mutation in PAK3 gene underlying mental retardation with neuropsychiatric features. Eur J Hum Genet. 2008 Nov;16(11):1358-63. doi: 10.1038/ejhg.2008.103. Epub 2008 Jun 4.
20	Deletion in Xp22.11: PTCHD1 is a candidate gene for X-linked intellectual disability with or without autism.Clin Genet. 2011 Jan;79(1):79-85. doi: 10.1111/j.1399-0004.2010.01590.x. Epub 2010 Nov 22.
21	Analysis of an interstitial deletion in a patient with Kallmann syndrome, X-linked ichthyosis and mental retardation.Clin Genet. 1998 Jul;54(1):45-51. doi: 10.1111/j.1399-0004.1998.tb03692.x.
22	A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. Nat Genet. 2009 May;41(5):535-43. doi: 10.1038/ng.367. Epub 2009 Apr 19.
23	Genotype-phenotype correlation: Inheritance and variant-type infer pathogenicity in IQSEC2 gene. Eur J Med Genet. 2020 Mar;63(3):103735. doi: 10.1016/j.ejmg.2019.103735. Epub 2019 Aug 12.
24	Targeted deep resequencing identifies MID2 mutation for X-linked intellectual disability with varied disease severity in a large kindred from India. Hum Mutat. 2014 Jan;35(1):41-4. doi: 10.1002/humu.22453. Epub 2013 Oct 21.
25	Mutations in the small GTPase gene RAB39B are responsible for X-linked mental retardation associated with autism, epilepsy, and macrocephaly. Am J Hum Genet. 2010 Feb 12;86(2):185-95. doi: 10.1016/j.ajhg.2010.01.011.