MRXSH
MCID: MNT192
MIFTS: 40

Mental Retardation, X-Linked, Syndromic, Hedera Type (MRXSH)

Categories: Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Mental Retardation, X-Linked, Syndromic, Hedera Type

MalaCards integrated aliases for Mental Retardation, X-Linked, Syndromic, Hedera Type:

Name: Mental Retardation, X-Linked, Syndromic, Hedera Type 56 12 29 6 39
Mental Retardation, X-Linked, with Epilepsy 73 13 71
Mrxsh 56 12 58
Mrxe 56 12 73
Syndromic X-Linked Intellectual Disability Hedera Type 12 15
Mental Retardation, X-Linked, with Epilepsy; Mrxe 56
X-Linked Intellectual Disability, Hedera Type 58

Characteristics:

Orphanet epidemiological data:

58
x-linked intellectual disability, hedera type
Inheritance: X-linked recessive; Age of onset: Infancy;

OMIM:

56
Miscellaneous:
neurodegeneration
variable expressivity
onset in infancy
progressive disorder
three unrelated families have been reported (last curated april 2020)

Inheritance:
x-linked recessive


HPO:

31
mental retardation, x-linked, syndromic, hedera type:
Onset and clinical course variable expressivity infantile onset
Inheritance x-linked recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases


Summaries for Mental Retardation, X-Linked, Syndromic, Hedera Type

OMIM : 56 The Hedera type of X-linked syndromic mental retardation (MRXSH) is characterized by global developmental delay apparent from infancy and progressive neurologic decline with abnormal movements, spasticity, and seizures. Brain imaging shows volume loss of cortical white and gray matter, thin corpus callosum, and myelination defects, consistent with a neurodegenerative process. Only males are affected (summary by Hirose et al., 2019). (300423)

MalaCards based summary : Mental Retardation, X-Linked, Syndromic, Hedera Type, also known as mental retardation, x-linked, with epilepsy, is related to electroclinical syndrome and infancy electroclinical syndrome, and has symptoms including drop attack An important gene associated with Mental Retardation, X-Linked, Syndromic, Hedera Type is ATP6AP2 (ATPase H+ Transporting Accessory Protein 2), and among its related pathways/superpathways are Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. and Insulin receptor recycling. Affiliated tissues include brain, and related phenotypes are intellectual disability and bilateral tonic-clonic seizure

Disease Ontology : 12 A syndromic X-linked intellectual disability characterized by mild to moderate mental retardation and epilepsy that has material basis in mutation in the ATP6AP2 gene on chromosome Xp11.

UniProtKB/Swiss-Prot : 73 Mental retardation, X-linked, with epilepsy: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXE patients manifest mild to moderate mental retardation associated with epilepsy, delays in motor milestones and speech acquisition in infancy.

Related Diseases for Mental Retardation, X-Linked, Syndromic, Hedera Type

Graphical network of the top 20 diseases related to Mental Retardation, X-Linked, Syndromic, Hedera Type:



Diseases related to Mental Retardation, X-Linked, Syndromic, Hedera Type

Symptoms & Phenotypes for Mental Retardation, X-Linked, Syndromic, Hedera Type

Human phenotypes related to Mental Retardation, X-Linked, Syndromic, Hedera Type:

58 31 (show all 36)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 bilateral tonic-clonic seizure 31 hallmark (90%) HP:0002069
3 delayed speech and language development 58 31 frequent (33%) Frequent (79-30%) HP:0000750
4 motor delay 58 31 frequent (33%) Frequent (79-30%) HP:0001270
5 unsteady gait 58 31 frequent (33%) Frequent (79-30%) HP:0002317
6 extrapyramidal muscular rigidity 58 31 frequent (33%) Frequent (79-30%) HP:0007076
7 atonic seizure 58 31 frequent (33%) Frequent (79-30%) HP:0010819
8 hyporeflexia of lower limbs 58 31 frequent (33%) Frequent (79-30%) HP:0002600
9 hyporeflexia of upper limbs 58 31 frequent (33%) Frequent (79-30%) HP:0012391
10 scoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002650
11 pes planus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001763
12 slurred speech 58 31 occasional (7.5%) Occasional (29-5%) HP:0001350
13 obesity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001513
14 left ventricular hypertrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001712
15 dysmetria 58 31 occasional (7.5%) Occasional (29-5%) HP:0001310
16 weak voice 58 31 occasional (7.5%) Occasional (29-5%) HP:0001621
17 babinski sign 58 31 occasional (7.5%) Occasional (29-5%) HP:0003487
18 cerebellar atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001272
19 hypoplasia of the corpus callosum 58 31 occasional (7.5%) Occasional (29-5%) HP:0002079
20 frequent falls 58 31 occasional (7.5%) Occasional (29-5%) HP:0002359
21 echolalia 58 31 occasional (7.5%) Occasional (29-5%) HP:0010529
22 inability to walk 58 31 occasional (7.5%) Occasional (29-5%) HP:0002540
23 drooling 58 31 occasional (7.5%) Occasional (29-5%) HP:0002307
24 apraxia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002186
25 absent achilles reflex 58 31 occasional (7.5%) Occasional (29-5%) HP:0003438
26 hypomimic face 58 31 occasional (7.5%) Occasional (29-5%) HP:0000338
27 action tremor 58 31 occasional (7.5%) Occasional (29-5%) HP:0002345
28 calcaneovalgus deformity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001848
29 astereognosia 58 31 occasional (7.5%) Occasional (29-5%) HP:0010527
30 agraphesthesia 58 31 occasional (7.5%) Occasional (29-5%) HP:0011812
31 gait disturbance 58 31 Occasional (29-5%) HP:0001288
32 hyporeflexia 31 HP:0001265
33 generalized tonic-clonic seizures 58 Very frequent (99-80%)
34 cerebral atrophy 31 HP:0002059
35 parkinsonism 31 HP:0001300
36 bradykinesia 31 HP:0002067

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
spasticity
cerebellar atrophy
cerebral atrophy
abnormal myelination
delayed motor development
more
Neurologic Peripheral Nervous System:
hyporeflexia (family a)

Clinical features from OMIM:

300423

UMLS symptoms related to Mental Retardation, X-Linked, Syndromic, Hedera Type:


drop attack

Drugs & Therapeutics for Mental Retardation, X-Linked, Syndromic, Hedera Type

Search Clinical Trials , NIH Clinical Center for Mental Retardation, X-Linked, Syndromic, Hedera Type

Genetic Tests for Mental Retardation, X-Linked, Syndromic, Hedera Type

Genetic tests related to Mental Retardation, X-Linked, Syndromic, Hedera Type:

# Genetic test Affiliating Genes
1 Mental Retardation, X-Linked, Syndromic, Hedera Type 29 ATP6AP2

Anatomical Context for Mental Retardation, X-Linked, Syndromic, Hedera Type

MalaCards organs/tissues related to Mental Retardation, X-Linked, Syndromic, Hedera Type:

40
Brain

Publications for Mental Retardation, X-Linked, Syndromic, Hedera Type

Articles related to Mental Retardation, X-Linked, Syndromic, Hedera Type:

# Title Authors PMID Year
1
ATP6AP2 variant impairs CNS development and neuronal survival to cause fulminant neurodegeneration. 6 56
30985297 2019
2
A splice site mutation in ATP6AP2 causes X-linked intellectual disability, epilepsy, and parkinsonism. 56 6
26467484 2015
3
A unique exonic splice enhancer mutation in a family with X-linked mental retardation and epilepsy points to a novel role of the renin receptor. 6 56
15746149 2005
4
Novel mental retardation-epilepsy syndrome linked to Xp21.1-p11.4. 6 56
11782983 2002
5
Altered splicing of ATP6AP2 causes X-linked parkinsonism with spasticity (XPDS). 61
23595882 2013
6
The role of individual domains and the significance of shedding of ATP6AP2/(pro)renin receptor in vacuolar H(+)-ATPase biogenesis. 61
24223829 2013

Variations for Mental Retardation, X-Linked, Syndromic, Hedera Type

ClinVar genetic disease variations for Mental Retardation, X-Linked, Syndromic, Hedera Type:

6 (show all 25) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ATP6AP2 NM_005765.3(ATP6AP2):c.301-11_301-10deldeletion Pathogenic 869368 X:40456490-40456491 X:40597238-40597239
2 ATP6AP2 NM_005765.3(ATP6AP2):c.321C>T (p.Asp107=)SNV Pathogenic 10801 rs121918521 X:40456521-40456521 X:40597269-40597269
3 ATP6AP2 NM_005765.3(ATP6AP2):c.168+6T>ASNV Pathogenic 375269 rs1057519331 X:40448374-40448374 X:40589122-40589122
4 ATP6AP2 NM_005765.3(ATP6AP2):c.490G>A (p.Val164Ile)SNV Conflicting interpretations of pathogenicity 204912 rs142013283 X:40456872-40456872 X:40597620-40597620
5 ATP6AP2 NM_005765.3(ATP6AP2):c.922A>C (p.Asn308His)SNV Conflicting interpretations of pathogenicity 380358 rs756836341 X:40464876-40464876 X:40605624-40605624
6 ATP6AP2 NM_005765.3(ATP6AP2):c.408G>A (p.Met136Ile)SNV Uncertain significance 465129 rs1555977799 X:40456790-40456790 X:40597538-40597538
7 ATP6AP2 NM_005765.3(ATP6AP2):c.953C>A (p.Ala318Asp)SNV Uncertain significance 465132 rs1555978614 X:40464907-40464907 X:40605655-40605655
8 ATP6AP2 NM_005765.3(ATP6AP2):c.840C>G (p.Ile280Met)SNV Uncertain significance 465131 rs1555978066 X:40460115-40460115 X:40600863-40600863
9 subset of 11 genes: BCOR , CASK , DDX3X , NYX , USP9X NC_000023.10:g.(?_39911342)_(41782261_?)dupduplication Uncertain significance 533692 X:39911342-41782261
10 ATP6AP2 NM_005765.3(ATP6AP2):c.858G>A (p.Ala286=)SNV Uncertain significance 533691 rs1555978069 X:40460133-40460133 X:40600881-40600881
11 ATP6AP2 NC_000023.11:g.(?_40581046)_(40605775_?)dupduplication Uncertain significance 832810 X:40440298-40465027
12 ATP6AP2 NM_005765.3(ATP6AP2):c.50A>G (p.Asn17Ser)SNV Uncertain significance 862603 X:40448250-40448250 X:40588998-40588998
13 ATP6AP2 NM_005765.3(ATP6AP2):c.160G>T (p.Val54Leu)SNV Uncertain significance 852040 X:40448360-40448360 X:40589108-40589108
14 ATP6AP2 NM_005765.3(ATP6AP2):c.218G>A (p.Arg73Gln)SNV Uncertain significance 861472 X:40450535-40450535 X:40591283-40591283
15 ATP6AP2 NM_005765.3(ATP6AP2):c.1015A>G (p.Ile339Val)SNV Uncertain significance 854936 X:40464969-40464969 X:40605717-40605717
16 ATP6AP2 NM_005765.3(ATP6AP2):c.315T>G (p.Ser105Arg)SNV Uncertain significance 204917 rs745748841 X:40456515-40456515 X:40597263-40597263
17 ATP6AP2 NM_005765.3(ATP6AP2):c.463C>T (p.Arg155Cys)SNV Uncertain significance 204911 rs146371390 X:40456845-40456845 X:40597593-40597593
18 ATP6AP2 NM_005765.3(ATP6AP2):c.596G>A (p.Arg199His)SNV Uncertain significance 204918 rs751433380 X:40458851-40458851 X:40599599-40599599
19 ATP6AP2 NM_005765.3(ATP6AP2):c.516T>C (p.Ser172=)SNV Likely benign 759346 X:40456898-40456898 X:40597646-40597646
20 ATP6AP2 NM_005765.3(ATP6AP2):c.189C>T (p.Leu63=)SNV Benign/Likely benign 136463 rs150392503 X:40450506-40450506 X:40591254-40591254
21 ATP6AP2 NM_005765.3(ATP6AP2):c.38-5T>CSNV Benign 136465 rs190477001 X:40448233-40448233 X:40588981-40588981
22 ATP6AP2 NM_005765.3(ATP6AP2):c.1050T>C (p.Asp350=)SNV Benign 199113 rs79790275 X:40465004-40465004 X:40605752-40605752
23 ATP6AP2 NM_005765.3(ATP6AP2):c.268C>G (p.Pro90Ala)SNV Benign 95311 rs9014 X:40450585-40450585 X:40591333-40591333
24 ATP6AP2 NM_005765.3(ATP6AP2):c.285G>A (p.Ser95=)SNV Benign 128486 rs34217273 X:40450602-40450602 X:40591350-40591350
25 ATP6AP2 NM_005765.3(ATP6AP2):c.868G>C (p.Ala290Pro)SNV Benign 128487 rs35798522 X:40464822-40464822 X:40605570-40605570

Expression for Mental Retardation, X-Linked, Syndromic, Hedera Type

Search GEO for disease gene expression data for Mental Retardation, X-Linked, Syndromic, Hedera Type.

Pathways for Mental Retardation, X-Linked, Syndromic, Hedera Type

GO Terms for Mental Retardation, X-Linked, Syndromic, Hedera Type

Cellular components related to Mental Retardation, X-Linked, Syndromic, Hedera Type according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lysosomal membrane GO:0005765 9.5 TCIRG1 ATP6V0A1 ATP6AP2
2 phagocytic vesicle membrane GO:0030670 9.37 TCIRG1 ATP6V0A1
3 ficolin-1-rich granule membrane GO:0101003 9.33 TCIRG1 ATP6V0A1 ATP6AP2
4 proton-transporting V-type ATPase, V0 domain GO:0033179 9.26 TCIRG1 ATP6V0A1
5 vacuolar proton-transporting V-type ATPase, V0 domain GO:0000220 8.96 TCIRG1 ATP6V0A1
6 vacuolar proton-transporting V-type ATPase complex GO:0016471 8.8 TCIRG1 ATP6V0A1 ATP6AP2

Biological processes related to Mental Retardation, X-Linked, Syndromic, Hedera Type according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ion transmembrane transport GO:0034220 9.56 TCIRG1 GABRA1 ATP6V1E2 ATP6V0A1
2 ion transport GO:0006811 9.55 TCIRG1 MT-ATP6 GABRA1 ATP6V1E2 ATP6V0A1
3 proton transmembrane transport GO:1902600 9.54 TCIRG1 ATP6V1E2 ATP6V0A1
4 insulin receptor signaling pathway GO:0008286 9.5 TCIRG1 ATP6V1E2 ATP6V0A1
5 regulation of macroautophagy GO:0016241 9.43 ATP6V1E2 ATP6V0A1
6 vacuolar acidification GO:0007035 9.4 TCIRG1 ATP6V0A1
7 transferrin transport GO:0033572 9.13 TCIRG1 ATP6V1E2 ATP6V0A1
8 phagosome acidification GO:0090383 8.8 TCIRG1 ATP6V1E2 ATP6V0A1

Molecular functions related to Mental Retardation, X-Linked, Syndromic, Hedera Type according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATPase binding GO:0051117 9.16 TCIRG1 ATP6V0A1
2 proton transmembrane transporter activity GO:0015078 9.13 TCIRG1 MT-ATP6 ATP6V0A1
3 proton-transporting ATPase activity, rotational mechanism GO:0046961 8.8 TCIRG1 ATP6V1E2 ATP6V0A1

Sources for Mental Retardation, X-Linked, Syndromic, Hedera Type

3 CDC
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10 dbSNP
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17 EFO
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56 OMIM
57 OMIM via Orphanet
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68 SNOMED-CT via HPO
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72 UMLS via Orphanet
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