AGS3
MCID: ACR088
MIFTS: 37

Aicardi-Goutieres Syndrome 3 (AGS3)

Categories: Blood diseases, Bone diseases, Genetic diseases, Immune diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Aicardi-Goutieres Syndrome 3

MalaCards integrated aliases for Aicardi-Goutieres Syndrome 3:

Name: Aicardi-Goutieres Syndrome 3 58 76 13 74
Ags3 58 54 76
Aicardi Goutieres Syndrome 3 30 6
Pseudo-Torch Syndrome 76 74
Rnaseh2c -Related Aicardi-Goutieres Syndrome 54
Aicardi-Goutieres Syndrome, Type 3 41
Aicardi-Goutieres Syndrome Type 3 54
Aicardi-Goutieres Syndrome 1 74
Cree Encephalitis 76

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset in early infancy
one patient with normal psychomotor development has been reported


HPO:

33
aicardi-goutieres syndrome 3:
Clinical modifier death in childhood
Onset and clinical course progressive
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Aicardi-Goutieres Syndrome 3

NIH Rare Diseases : 54 Aicardi-Goutieres syndrome is an inherited disease that mainly affects the brain, immune system, and the skin. Loss of white matter in the brain (leukodystrophy) and abnormal deposits of calcium (calcification) in the brain leads to an early-onset severe brain dysfunction (encephalopathy) that usually results in severe intellectual and physical disability.  Additional symptoms may include epilepsy, painful, itchy skin lesion (chilblains), vision problems, and joint and muscle stiffness (spasticity), involuntary muscle twisting and contractions (dystonia), and weak muscle tone (hypotonia) in the torso. Other signs and symptoms may include a very small head (microcephaly), presence of white blood cells and other sign of inflammation in the  cerebrospinal fluid, which is the fluid that surrounds the brain and spinal cord (central nervous system). Symptoms usually progress over several months before the disease course stabilizes.  There are several types of Aicardi-Goutieres syndrome, depending on the gene that causes the condition: TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR and IFIH1, genes. Most cases are inherited in an autosomal recessive pattern, although rare autosomal dominant cases have been reported. Treatment is symptomatic and supportive. The prognosis depends mainly on the severity neurologic problems and in the age of onset of these problems.

MalaCards based summary : Aicardi-Goutieres Syndrome 3, also known as ags3, is related to aicardi-goutieres syndrome and pseudo-torch syndrome 1, and has symptoms including seizures, muscle spasticity and petechiae of skin. An important gene associated with Aicardi-Goutieres Syndrome 3 is RNASEH2C (Ribonuclease H2 Subunit C). Affiliated tissues include brain, skin and spinal cord, and related phenotypes are nystagmus and spasticity

OMIM : 58 Aicardi-Goutieres syndrome is an autosomal recessive disorder characterized by onset of encephalopathy in the first year of life following normal early development. Affected infants typically show extreme irritability, intermittent unexplained fever, chilblains, progressive microcephaly, spasticity, dystonia, and profound psychomotor retardation. Laboratory studies show lymphocytosis and raised titers of alpha-interferon in the cerebrospinal fluid. Brain imaging may show white matter abnormalities, intracerebral calcifications, and cerebral atrophy. Many patients die in childhood (summary by Vogt et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of Aicardi-Goutieres syndrome, see AGS1 (225750). (610329)

UniProtKB/Swiss-Prot : 76 Aicardi-Goutieres syndrome 3: A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood.

Related Diseases for Aicardi-Goutieres Syndrome 3

Graphical network of the top 20 diseases related to Aicardi-Goutieres Syndrome 3:



Diseases related to Aicardi-Goutieres Syndrome 3

Symptoms & Phenotypes for Aicardi-Goutieres Syndrome 3

Human phenotypes related to Aicardi-Goutieres Syndrome 3:

33 (show all 15)
# Description HPO Frequency HPO Source Accession
1 nystagmus 33 HP:0000639
2 spasticity 33 HP:0001257
3 hyperreflexia 33 HP:0001347
4 cerebral calcification 33 HP:0002514
5 severe global developmental delay 33 HP:0011344
6 elevated hepatic transaminase 33 HP:0002910
7 dystonia 33 HP:0001332
8 thrombocytopenia 33 HP:0001873
9 generalized hypotonia 33 HP:0001290
10 encephalopathy 33 HP:0001298
11 hypoplasia of the corpus callosum 33 HP:0002079
12 hepatosplenomegaly 33 HP:0001433
13 progressive microcephaly 33 HP:0000253
14 delayed myelination 33 HP:0012448
15 csf lymphocytic pleiocytosis 33 HP:0200149

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
nystagmus
roving eye movements
visual inattention

Head And Neck Head:
microcephaly

Skin Nails Hair Skin:
chilblains

Neurologic Central Nervous System:
hyperreflexia
encephalopathy
delayed myelination
intracranial calcifications
thin corpus callosum
more
Muscle Soft Tissue:
hypotonia

Laboratory Abnormalities:
increased csf alpha-interferon
csf lymphocytosis
increased serum alpha-interferon

Clinical features from OMIM:

610329

UMLS symptoms related to Aicardi-Goutieres Syndrome 3:


seizures, muscle spasticity, petechiae of skin

GenomeRNAi Phenotypes related to Aicardi-Goutieres Syndrome 3 according to GeneCards Suite gene sharing:

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased homologous recombination repair frequency GR00236-A-1 9.56 KAT5 RNASEH2C
2 Decreased homologous recombination repair frequency GR00236-A-2 9.56 KAT5 RNASEH2C
3 Increased viability with MLN4924 (a NAE inhibitor) GR00250-A-3 8.62 KAT5 RNASEH2C

Drugs & Therapeutics for Aicardi-Goutieres Syndrome 3

Search Clinical Trials , NIH Clinical Center for Aicardi-Goutieres Syndrome 3

Genetic Tests for Aicardi-Goutieres Syndrome 3

Genetic tests related to Aicardi-Goutieres Syndrome 3:

# Genetic test Affiliating Genes
1 Aicardi Goutieres Syndrome 3 30 RNASEH2C

Anatomical Context for Aicardi-Goutieres Syndrome 3

MalaCards organs/tissues related to Aicardi-Goutieres Syndrome 3:

42
Brain, Skin, Spinal Cord, Eye, Lung, Heart, Cortex

Publications for Aicardi-Goutieres Syndrome 3

Articles related to Aicardi-Goutieres Syndrome 3:

(show all 42)
# Title Authors Year
1
Role of G-proteins and phosphorylation in the distribution of AGS3 to cell puncta. ( 30404823 )
2018
2
Extensive intracranial calcification of pseudo-TORCH syndrome with features of Dandy-Walker malformation. ( 28761539 )
2017
3
Loss of the canonical spindle orientation function in the Pins/LGN homolog AGS3. ( 28684399 )
2017
4
Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome. ( 27325888 )
2016
5
Regulation of Airway Inflammation by G-protein Regulatory Motif Peptides of AGS3 protein. ( 27270970 )
2016
6
AGS3 is involved in TNF-α medicated osteogenic differentiation of human dental pulp stem cells. ( 26143356 )
2015
7
A role for activator of G-protein signaling 3 (AGS3) in multiple myeloma. ( 24307516 )
2014
8
Defective chemokine signal integration in leukocytes lacking activator of G protein signaling 3 (AGS3). ( 24573680 )
2014
9
Striking intrafamilial phenotypic variability in Aicardi-Goutières syndrome associated with the recurrent Asian founder mutation in RNASEH2C. ( 23322642 )
2013
10
Anaesthetic Management of a Patient with Pseudo-TORCH Syndrome. ( 25207129 )
2013
11
Increased expression of AGS3 in rat brain cortex after traumatic brain injury. ( 23404409 )
2013
12
Differential effects of AGS3 expression on D(2L) dopamine receptor-mediated adenylyl cyclase signaling. ( 23504261 )
2013
13
Normal autophagic activity in macrophages from mice lacking Gαi3, AGS3, or RGS19. ( 24312373 )
2013
14
A GDI (AGS3) and a GEF (GIV) regulate autophagy by balancing G protein activity and growth factor signals. ( 21209316 )
2011
15
Distribution of activator of G-protein signaling 3 within the aggresomal pathway: role of specific residues in the tetratricopeptide repeat domain and differential regulation by the AGS3 binding partners Gi(alpha) and mammalian inscuteable. ( 20065032 )
2010
16
An inhibitory role of the G-protein regulator AGS3 in mTOR-dependent macroautophagy. ( 20126274 )
2010
17
Identification of a deubiquitinating enzyme as a novel AGS3-interacting protein. ( 20305814 )
2010
18
Regulation of the AGS3·G{alpha}i signaling complex by a seven-transmembrane span receptor. ( 20716524 )
2010
19
Up-regulation of AGS3 during morphine withdrawal promotes cAMP superactivation via adenylyl cyclase 5 and 7 in rat nucleus accumbens/striatal neurons. ( 19549762 )
2009
20
Ric-8A catalyzes guanine nucleotide exchange on G alphai1 bound to the GPR/GoLoco exchange inhibitor AGS3. ( 18541531 )
2008
21
Nucleus accumbens AGS3 expression drives ethanol seeking through G betagamma. ( 18719114 )
2008
22
Clinical and molecular phenotype of Aicardi-Goutieres syndrome. ( 17846997 )
2007
23
A specific role of AGS3 in the surface expression of plasma membrane proteins. ( 17991770 )
2007
24
Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutières syndrome and mimic congenital viral brain infection. ( 16845400 )
2006
25
Two forms of human Inscuteable-related protein that links Par3 to the Pins homologues LGN and AGS3. ( 16458856 )
2006
26
AGS3, an alpha(1-3)glucan synthase gene family member of Aspergillus fumigatus, modulates mycelium growth in the lung of experimentally infected mice. ( 16531086 )
2006
27
G protein betagamma subunits and AGS3 control spindle orientation and asymmetric cell fate of cerebral cortical progenitors. ( 16009138 )
2005
28
AGS3 and signal integration by Galpha(s)- and Galpha(i)-coupled receptors: AGS3 blocks the sensitization of adenylyl cyclase following prolonged stimulation of a Galpha(i)-coupled receptor by influencing processing of Galpha(i). ( 14726514 )
2004
29
Asymmetric localization of LGN but not AGS3, two homologs of Drosophila pins, in dividing human neural progenitor cells. ( 14994339 )
2004
30
Two brothers with findings resembling congenital intrauterine infection-like syndrome (pseudo-TORCH syndrome). ( 12833411 )
2003
31
The G-protein regulator AGS3 controls an early event during macroautophagy in human intestinal HT-29 cells. ( 12642577 )
2003
32
Interaction of activator of G-protein signaling 3 (AGS3) with LKB1, a serine/threonine kinase involved in cell polarity and cell cycle progression: phosphorylation of the G-protein regulatory (GPR) motif as a regulatory mechanism for the interaction of GPR motifs with Gi alpha. ( 12719437 )
2003
33
Asymmetrically distributed C. elegans homologs of AGS3/PINS control spindle position in the early embryo. ( 12814548 )
2003
34
Influence of cytosolic AGS3 on receptor--G protein coupling. ( 12834360 )
2003
35
Thermodynamic characterization of the binding of activator of G protein signaling 3 (AGS3) and peptides derived from AGS3 with G alpha i1. ( 14530282 )
2003
36
AGS3: a G-Protein regulator of addiction-associated behaviors. ( 14684460 )
2003
37
Expression analysis and subcellular distribution of the two G-protein regulators AGS3 and LGN indicate distinct functionality. Localization of LGN to the midbody during cytokinesis. ( 11832491 )
2002
38
Pseudo-TORCH syndrome or Baraitser-Reardon syndrome: diagnostic criteria. ( 11226724 )
2001
39
Selective interaction of AGS3 with G-proteins and the influence of AGS3 on the activation state of G-proteins. ( 11042168 )
2001
40
Identification of a truncated form of the G-protein regulator AGS3 in heart that lacks the tetratricopeptide repeat domains. ( 11278352 )
2001
41
Stabilization of the GDP-bound conformation of Gialpha by a peptide derived from the G-protein regulatory motif of AGS3. ( 10969064 )
2000
42
AGS3 inhibits GDP dissociation from galpha subunits of the Gi family and rhodopsin-dependent activation of transducin. ( 11024022 )
2000

Variations for Aicardi-Goutieres Syndrome 3

UniProtKB/Swiss-Prot genetic disease variations for Aicardi-Goutieres Syndrome 3:

76
# Symbol AA change Variation ID SNP ID
1 RNASEH2C p.Arg69Trp VAR_027287 rs78635798
2 RNASEH2C p.Lys143Ile VAR_027288 rs75146158
3 RNASEH2C p.Arg13His VAR_070618 rs75328625
4 RNASEH2C p.Asp39Tyr VAR_070619 rs773527127
5 RNASEH2C p.Pro76Leu VAR_070620 rs76091978
6 RNASEH2C p.Pro138Leu VAR_070621
7 RNASEH2C p.Pro151Ser VAR_070622 rs78464826

ClinVar genetic disease variations for Aicardi-Goutieres Syndrome 3:

6 (show all 28)
# Gene Variation Type Significance SNP ID Assembly Location
1 RNASEH2C NM_032193.3(RNASEH2C): c.205C> T (p.Arg69Trp) single nucleotide variant Pathogenic/Likely pathogenic rs78635798 GRCh37 Chromosome 11, 65487856: 65487856
2 RNASEH2C NM_032193.3(RNASEH2C): c.205C> T (p.Arg69Trp) single nucleotide variant Pathogenic/Likely pathogenic rs78635798 GRCh38 Chromosome 11, 65720385: 65720385
3 RNASEH2C NM_032193.3(RNASEH2C): c.428A> T (p.Lys143Ile) single nucleotide variant Pathogenic rs75146158 GRCh37 Chromosome 11, 65487556: 65487556
4 RNASEH2C NM_032193.3(RNASEH2C): c.428A> T (p.Lys143Ile) single nucleotide variant Pathogenic rs75146158 GRCh38 Chromosome 11, 65720085: 65720085
5 RNASEH2C NM_032193.3(RNASEH2C): c.434G> C (p.Arg145Pro) single nucleotide variant Uncertain significance rs774773395 GRCh38 Chromosome 11, 65720079: 65720079
6 RNASEH2C NM_032193.3(RNASEH2C): c.434G> C (p.Arg145Pro) single nucleotide variant Uncertain significance rs774773395 GRCh37 Chromosome 11, 65487550: 65487550
7 RNASEH2C NM_032193.3(RNASEH2C): c.178dup (p.Glu60Glyfs) duplication Likely pathogenic rs772940104 GRCh38 Chromosome 11, 65720412: 65720412
8 RNASEH2C NM_032193.3(RNASEH2C): c.178dup (p.Glu60Glyfs) duplication Likely pathogenic rs772940104 GRCh37 Chromosome 11, 65487883: 65487883
9 RNASEH2C NM_032193.3(RNASEH2C): c.-10A> G single nucleotide variant Benign/Likely benign rs77371161 GRCh37 Chromosome 11, 65488239: 65488239
10 RNASEH2C NM_032193.3(RNASEH2C): c.-10A> G single nucleotide variant Benign/Likely benign rs77371161 GRCh38 Chromosome 11, 65720768: 65720768
11 RNASEH2C NM_032193.3(RNASEH2C): c.468+13G> A single nucleotide variant Conflicting interpretations of pathogenicity rs182000627 GRCh37 Chromosome 11, 65487503: 65487503
12 RNASEH2C NM_032193.3(RNASEH2C): c.468+13G> A single nucleotide variant Conflicting interpretations of pathogenicity rs182000627 GRCh38 Chromosome 11, 65720032: 65720032
13 RNASEH2C NM_032193.3(RNASEH2C): c.417C> G (p.Gly139=) single nucleotide variant Conflicting interpretations of pathogenicity rs147021687 GRCh37 Chromosome 11, 65487567: 65487567
14 RNASEH2C NM_032193.3(RNASEH2C): c.417C> G (p.Gly139=) single nucleotide variant Conflicting interpretations of pathogenicity rs147021687 GRCh38 Chromosome 11, 65720096: 65720096
15 RNASEH2C NM_032193.3(RNASEH2C): c.268_270delAAG (p.Lys90del) deletion Benign/Likely benign rs141875736 GRCh37 Chromosome 11, 65487791: 65487793
16 RNASEH2C NM_032193.3(RNASEH2C): c.268_270delAAG (p.Lys90del) deletion Benign/Likely benign rs141875736 GRCh38 Chromosome 11, 65720320: 65720322
17 RNASEH2C NM_032193.3(RNASEH2C): c.61T> C (p.Leu21=) single nucleotide variant Conflicting interpretations of pathogenicity rs376140250 GRCh37 Chromosome 11, 65488169: 65488169
18 RNASEH2C NM_032193.3(RNASEH2C): c.61T> C (p.Leu21=) single nucleotide variant Conflicting interpretations of pathogenicity rs376140250 GRCh38 Chromosome 11, 65720698: 65720698
19 RNASEH2C NM_032193.3(RNASEH2C): c.468G> T (p.Ala156=) single nucleotide variant Conflicting interpretations of pathogenicity rs61736590 GRCh37 Chromosome 11, 65487516: 65487516
20 RNASEH2C NM_032193.3(RNASEH2C): c.468G> T (p.Ala156=) single nucleotide variant Conflicting interpretations of pathogenicity rs61736590 GRCh38 Chromosome 11, 65720045: 65720045
21 RNASEH2C NM_032193.3(RNASEH2C): c.115G> T (p.Asp39Tyr) single nucleotide variant Uncertain significance rs773527127 GRCh37 Chromosome 11, 65488115: 65488115
22 RNASEH2C NM_032193.3(RNASEH2C): c.115G> T (p.Asp39Tyr) single nucleotide variant Uncertain significance rs773527127 GRCh38 Chromosome 11, 65720644: 65720644
23 RNASEH2C NM_032193.3(RNASEH2C): c.268_269delAAinsGT (p.Lys90Val) indel Uncertain significance GRCh38 Chromosome 11, 65720321: 65720322
24 RNASEH2C NM_032193.3(RNASEH2C): c.268_269delAAinsGT (p.Lys90Val) indel Uncertain significance GRCh37 Chromosome 11, 65487792: 65487793
25 RNASEH2C NM_032193.3(RNASEH2C): c.260A> G (p.Glu87Gly) single nucleotide variant Uncertain significance GRCh37 Chromosome 11, 65487801: 65487801
26 RNASEH2C NM_032193.3(RNASEH2C): c.260A> G (p.Glu87Gly) single nucleotide variant Uncertain significance GRCh38 Chromosome 11, 65720330: 65720330
27 RNASEH2C NM_032193.3(RNASEH2C): c.56C> G (p.Ala19Gly) single nucleotide variant Uncertain significance GRCh37 Chromosome 11, 65488174: 65488174
28 RNASEH2C NM_032193.3(RNASEH2C): c.56C> G (p.Ala19Gly) single nucleotide variant Uncertain significance GRCh38 Chromosome 11, 65720703: 65720703

Expression for Aicardi-Goutieres Syndrome 3

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Pathways for Aicardi-Goutieres Syndrome 3

GO Terms for Aicardi-Goutieres Syndrome 3

Sources for Aicardi-Goutieres Syndrome 3

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