SMAX3
MCID: SPN188
MIFTS: 42

Spinal Muscular Atrophy, Distal, X-Linked 3 (SMAX3)

Categories: Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Spinal Muscular Atrophy, Distal, X-Linked 3

MalaCards integrated aliases for Spinal Muscular Atrophy, Distal, X-Linked 3:

Name: Spinal Muscular Atrophy, Distal, X-Linked 3 57 13 44 71
Smax3 57 12 58 73
Dsmax 57 12 58 73
X-Linked Distal Hereditary Motor Neuropathy Type 3 12 58
Distal Spinal Muscular Atrophy, X-Linked 3 29 6
X-Linked Distal Spinal Muscular Atrophy 3 12 15
Atp7a-Related Distal Motor Neuropathy 12 58
X-Linked Dhmn3 12 58
X-Linked Dsma3 12 58
Spinal Muscular Atrophy, Distal, X-Linked Recessive 57
Atrophy, Muscular, Spinal, Distal, X-Linked, Type 3 39
X-Linked Recessive Distal Spinal Muscular Atrophy 12
Spinal Muscular Atrophy Distal X-Linked Recessive 73
X-Linked Distal Spinal Muscular Atrophy Type 3 58
Distal Spinal Muscular Atrophy, X-Linked, 3 73
Dsmax3 73

Characteristics:

Orphanet epidemiological data:

58
x-linked distal spinal muscular atrophy type 3
Inheritance: X-linked recessive; Age of onset: Childhood;

OMIM®:

57 (Updated 05-Mar-2021)
Miscellaneous:
onset in first decade
slow disease progression
adult onset may also occur
affected individuals remain ambulatory in old age

Inheritance:
x-linked recessive


HPO:

31
spinal muscular atrophy, distal, x-linked 3:
Onset and clinical course juvenile onset slow progression
Inheritance x-linked recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0111196
OMIM® 57 300489
ICD10 via Orphanet 33 G12.2
UMLS via Orphanet 72 C1845359
Orphanet 58 ORPHA139557
MedGen 41 C1845359
UMLS 71 C1845359

Summaries for Spinal Muscular Atrophy, Distal, X-Linked 3

UniProtKB/Swiss-Prot : 73 Distal spinal muscular atrophy, X-linked, 3: A neuromuscular disorder. Distal spinal muscular atrophy, also known as distal hereditary motor neuronopathy, represents a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs.

MalaCards based summary : Spinal Muscular Atrophy, Distal, X-Linked 3, also known as smax3, is related to menkes disease and occipital horn syndrome. An important gene associated with Spinal Muscular Atrophy, Distal, X-Linked 3 is ATP7A (ATPase Copper Transporting Alpha), and among its related pathways/superpathways are Defensins and Mineral absorption. Affiliated tissues include spinal cord, and related phenotypes are distal sensory impairment and pes cavus

Disease Ontology : 12 A spinal muscular atrophy characterized by slowly progressive atrophy and weakness of distal muscles of hands and feet with absence of cognitive, pyramidal, or sensory impairment that has material basis in homozygous or hemizygous mutation in ATP7A on Xq21.1.

More information from OMIM: 300489

Related Diseases for Spinal Muscular Atrophy, Distal, X-Linked 3

Diseases related to Spinal Muscular Atrophy, Distal, X-Linked 3 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 32)
# Related Disease Score Top Affiliating Genes
1 menkes disease 29.3 PAM DBH CP COX17 ATP7B ATP7A
2 occipital horn syndrome 29.1 PAM DBH CP COX17 ATP7B ATP7A
3 amyotrophic lateral sclerosis 1 10.2
4 lateral sclerosis 10.2
5 motor neuron disease 10.2
6 myopathy 10.2
7 giant axonal neuropathy 10.2
8 disorder of copper metabolism 10.2 ATP7B ATP7A
9 spinal muscular atrophy 10.0
10 muscular atrophy 10.0
11 neuropathy 10.0
12 charcot-marie-tooth hereditary neuropathy 10.0
13 hypermanganesemia with dystonia 10.0 SLC33A1 AP1S1
14 bladder diverticulum 10.0 DBH CP ATP7A
15 hypermanganesemia with dystonia 2 10.0 SLC33A1 AP1S1
16 dopamine beta-hydroxylase deficiency 9.9 DBH ATP7A ATOX1
17 inherited metabolic disorder 9.9 CP ATP7B ATP7A
18 pettigrew syndrome 9.9 PAM AP1S1
19 hemochromatosis, type 5 9.9 SLC33A1 AP1S1
20 neuronopathy, distal hereditary motor, type i 9.9
21 charcot-marie-tooth disease, x-linked dominant, 1 9.9
22 charcot-marie-tooth disease, x-linked recessive, 3 9.9
23 sensory peripheral neuropathy 9.9
24 atp7a-related copper transport disorders 9.9
25 hereditary neuropathies 9.9
26 x-linked distal hereditary motor neuropathy 9.9
27 spinal muscular atrophy, distal, autosomal recessive, 3 9.9 C1orf87 ATP7A
28 mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma 9.7 SLC33A1 PAM ATP7B ATP7A AP1S1
29 wilson disease 9.6 DBH CP ATP7B ATP7A ATOX1
30 deficiency anemia 9.6 CP COX17 ATP7A ATOX1
31 metal metabolism disorder 9.6 CP COX17 ATP7B ATP7A ATOX1
32 aceruloplasminemia 9.5 SLC33A1 CP ATP7B ATP7A ATOX1

Graphical network of the top 20 diseases related to Spinal Muscular Atrophy, Distal, X-Linked 3:



Diseases related to Spinal Muscular Atrophy, Distal, X-Linked 3

Symptoms & Phenotypes for Spinal Muscular Atrophy, Distal, X-Linked 3

Human phenotypes related to Spinal Muscular Atrophy, Distal, X-Linked 3:

31 (show all 9)
# Description HPO Frequency HPO Source Accession
1 distal sensory impairment 31 occasional (7.5%) HP:0002936
2 pes cavus 31 HP:0001761
3 hyporeflexia 31 HP:0001265
4 unsteady gait 31 HP:0002317
5 distal amyotrophy 31 HP:0003693
6 distal muscle weakness 31 HP:0002460
7 emg: neuropathic changes 31 HP:0003445
8 spinal muscular atrophy 31 HP:0007269
9 abnormal peripheral nervous system morphology 31 HP:0000759

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Skeletal Feet:
pes cavus
pes varus

Neurologic Peripheral Nervous System:
peripheral nerve biopsy is normal
mild distal sensory impairment (in some)

Neurologic Central Nervous System:
hyporeflexia
muscle weakness, distal
gait instability
muscle atrophy, distal
lower limbs affected before upper limbs
more

Clinical features from OMIM®:

300489 (Updated 05-Mar-2021)

MGI Mouse Phenotypes related to Spinal Muscular Atrophy, Distal, X-Linked 3:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 pigmentation MP:0001186 8.92 ATOX1 ATP7A ATP7B CP

Drugs & Therapeutics for Spinal Muscular Atrophy, Distal, X-Linked 3

Search Clinical Trials , NIH Clinical Center for Spinal Muscular Atrophy, Distal, X-Linked 3

Cochrane evidence based reviews: spinal muscular atrophy, distal, x-linked 3

Genetic Tests for Spinal Muscular Atrophy, Distal, X-Linked 3

Genetic tests related to Spinal Muscular Atrophy, Distal, X-Linked 3:

# Genetic test Affiliating Genes
1 Distal Spinal Muscular Atrophy, X-Linked 3 29 ATP7A

Anatomical Context for Spinal Muscular Atrophy, Distal, X-Linked 3

MalaCards organs/tissues related to Spinal Muscular Atrophy, Distal, X-Linked 3:

40
Spinal Cord

Publications for Spinal Muscular Atrophy, Distal, X-Linked 3

Articles related to Spinal Muscular Atrophy, Distal, X-Linked 3:

# Title Authors PMID Year
1
Missense mutations in the copper transporter gene ATP7A cause X-linked distal hereditary motor neuropathy. 6 57
20170900 2010
2
X-linked distal hereditary motor neuropathy maps to the DSMAX locus on chromosome Xq13.1-q21. 57 6
19153371 2009
3
A new locus for recessive distal spinal muscular atrophy at Xq13.1-q21. 57 6
14985388 2004
4
ATP7A mutation with occipital horns and distal motor neuropathy: A continuum. 61
33137485 2020
5
Report of a novel ATP7A mutation causing distal motor neuropathy. 61
31558336 2019
6
X-linked spinal muscular atrophy in mice caused by autonomous loss of ATP7A in the motor neuron. 61
25639447 2015
7
Conditional knockout of the Menkes disease copper transporter demonstrates its critical role in embryogenesis. 61
22900086 2012

Variations for Spinal Muscular Atrophy, Distal, X-Linked 3

ClinVar genetic disease variations for Spinal Muscular Atrophy, Distal, X-Linked 3:

6 (show top 50) (show all 223)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ATP7A NM_000052.7(ATP7A):c.2981C>T (p.Thr994Ile) SNV Pathogenic 11794 rs267606673 X:77284811-77284811 X:78029314-78029314
2 ATP7A NM_000052.7(ATP7A):c.4156C>T (p.Pro1386Ser) SNV Pathogenic 11795 rs267606672 X:77300999-77300999 X:78045502-78045502
3 ATP7A NM_000052.7(ATP7A):c.3473C>A (p.Ser1158Ter) SNV Pathogenic 459840 rs1557237451 X:77289281-77289281 X:78033783-78033783
4 ATP7A NC_000023.10:g.(?_77271231)_(77271398_?)del Deletion Pathogenic 533690 X:77271231-77271398
5 ATP7A NM_000052.7(ATP7A):c.2467del (p.Ile822_Val823insTer) Deletion Pathogenic 571199 rs1569549974 X:77270219-77270219 X:78014722-78014722
6 ATP7A NM_000052.7(ATP7A):c.453del (p.Thr152fs) Deletion Pathogenic 642741 rs1603381331 X:77244068-77244068 X:77988572-77988572
7 ATP7A NM_000052.7(ATP7A):c.3294+1G>A SNV Pathogenic 648378 rs797045374 X:77287081-77287081 X:78031583-78031583
8 ATP7A NM_000052.7(ATP7A):c.1537G>T (p.Glu513Ter) SNV Pathogenic 581017 rs1569549699 X:77254175-77254175 X:77998678-77998678
9 ATP7A NM_000052.7(ATP7A):c.420_421AG[1] (p.Glu141fs) Microsatellite Pathogenic 210474 rs797045397 X:77244037-77244038 X:77988541-77988542
10 ATP7A NM_000052.7(ATP7A):c.3868C>T (p.Gln1290Ter) SNV Pathogenic 657355 rs1603391120 X:77298149-77298149 X:78042651-78042651
11 ATP7A NM_000052.7(ATP7A):c.3250dup (p.Ser1084fs) Duplication Pathogenic 651544 rs1603389393 X:77287035-77287036 X:78031537-78031538
12 ATP7A NM_000052.7(ATP7A):c.4027del (p.Ala1343fs) Deletion Pathogenic 846390 X:77298835-77298835 X:78043337-78043337
13 ATP7A NM_000052.7(ATP7A):c.2576A>G (p.Asp859Gly) SNV Pathogenic 929465 X:77271328-77271328 X:78015831-78015831
14 ATP7A NM_000052.7(ATP7A):c.3526C>T (p.Gln1176Ter) SNV Pathogenic 945136 X:77294348-77294348 X:78038850-78038850
15 ATP7A NM_000052.7(ATP7A):c.462dup (p.Lys155fs) Duplication Pathogenic 964347 X:77244078-77244079 X:77988582-77988583
16 ATP7A NM_000052.7(ATP7A):c.1933C>T (p.Arg645Ter) SNV Pathogenic 210404 rs72554640 X:77266736-77266736 X:78011239-78011239
17 ATP7A NM_000052.7(ATP7A):c.2383C>T (p.Arg795Ter) SNV Pathogenic 210425 rs72554645 X:77268586-77268586 X:78013089-78013089
18 ATP7A NM_000052.7(ATP7A):c.4156C>T (p.Pro1386Ser) SNV Pathogenic 11795 rs267606672 X:77300999-77300999 X:78045502-78045502
19 ATP7A NM_000052.7(ATP7A):c.601C>T (p.Arg201Ter) SNV Pathogenic 11793 rs151340633 X:77244218-77244218 X:77988722-77988722
20 ATP7A NM_000052.7(ATP7A):c.2663del (p.Thr888fs) Deletion Pathogenic 963560 X:77275777-77275777 X:78020280-78020280
21 ATP7A NM_000052.7(ATP7A):c.1639C>T (p.Arg547Ter) SNV Pathogenic 210395 rs797045332 X:77258665-77258665 X:78003168-78003168
22 ATP7A NM_000052.7(ATP7A):c.1273del (p.Leu424_Leu425insTer) Deletion Pathogenic 971523 X:77245391-77245391 X:77989895-77989895
23 ATP7A NM_000052.7(ATP7A):c.2172+5G>C SNV Likely pathogenic 210415 rs797045347 X:77267176-77267176 X:78011679-78011679
24 ATP7A NM_000052.7(ATP7A):c.2972C>A (p.Ala991Asp) SNV Likely pathogenic 549669 rs1557236729 X:77284802-77284802 X:78029305-78029305
25 ATP7A NM_000052.7(ATP7A):c.4006-1G>A SNV Likely pathogenic 465121 rs1557238665 X:77298814-77298814 X:78043316-78043316
26 ATP7A NM_000052.7(ATP7A):c.2071G>A (p.Glu691Lys) SNV Uncertain significance 465109 rs944415019 X:77267070-77267070 X:78011573-78011573
27 ATP7A NM_000052.7(ATP7A):c.3476C>T (p.Thr1159Ile) SNV Uncertain significance 465119 rs1557237452 X:77289284-77289284 X:78033786-78033786
28 ATP7A NM_000052.7(ATP7A):c.1814A>G (p.His605Arg) SNV Uncertain significance 465107 rs1020034878 X:77264705-77264705 X:78009208-78009208
29 ATP7A NM_000052.7(ATP7A):c.2458G>C (p.Ala820Pro) SNV Uncertain significance 465111 rs1557234938 X:77270210-77270210 X:78014713-78014713
30 ATP7A NM_000052.7(ATP7A):c.278C>T (p.Thr93Met) SNV Uncertain significance 372700 rs539177302 X:77243895-77243895 X:77988399-77988399
31 ATP7A NM_000052.7(ATP7A):c.3002C>T (p.Pro1001Leu) SNV Uncertain significance 210439 rs797045365 X:77284832-77284832 X:78029335-78029335
32 ATP7A NM_000052.7(ATP7A):c.4445C>G (p.Pro1482Arg) SNV Uncertain significance 465126 rs1557239147 X:77302009-77302009 X:78046512-78046512
33 ATP7A NC_000023.10:g.(?_77266653)_(77268629_?)dup Duplication Uncertain significance 465103 X:77266653-77268629
34 ATP7A NM_000052.7(ATP7A):c.3028_3030delinsGTG (p.Thr1010Val) Indel Uncertain significance 465115 rs1557236745 X:77284858-77284860 X:78029361-78029363
35 ATP7A NM_000052.7(ATP7A):c.2725G>A (p.Ala909Thr) SNV Uncertain significance 533670 rs146119866 X:77275839-77275839 X:78020342-78020342
36 ATP7A NM_000052.7(ATP7A):c.3289A>C (p.Lys1097Gln) SNV Uncertain significance 533672 rs1557237081 X:77287075-77287075 X:78031577-78031577
37 ATP7A NM_000052.7(ATP7A):c.2353C>A (p.Pro785Thr) SNV Uncertain significance 389710 rs1057523512 X:77268556-77268556 X:78013059-78013059
38 ATP7A NM_000052.7(ATP7A):c.1385C>T (p.Pro462Leu) SNV Uncertain significance 533673 rs201999500 X:77254023-77254023 X:77998526-77998526
39 ATP7A NM_000052.7(ATP7A):c.1597A>G (p.Asn533Asp) SNV Uncertain significance 392357 rs1057524455 X:77258623-77258623 X:78003126-78003126
40 ATP7A NM_000052.7(ATP7A):c.4244A>G (p.Tyr1415Cys) SNV Uncertain significance 533674 rs1280037924 X:77301808-77301808 X:78046311-78046311
41 ATP7A NM_000052.7(ATP7A):c.4490A>G (p.Asp1497Gly) SNV Uncertain significance 533675 rs1557239152 X:77302054-77302054 X:78046557-78046557
42 ATP7A NM_000052.7(ATP7A):c.3553C>T (p.Arg1185Trp) SNV Uncertain significance 533676 rs781907456 X:77294375-77294375 X:78038877-78038877
43 ATP7A NM_000052.7(ATP7A):c.3245G>A (p.Ser1082Asn) SNV Uncertain significance 651307 rs1603389390 X:77287031-77287031 X:78031533-78031533
44 ATP7A NM_000052.7(ATP7A):c.4356G>C (p.Leu1452Phe) SNV Uncertain significance 639627 rs782364202 X:77301920-77301920 X:78046423-78046423
45 ATP7A NM_000052.7(ATP7A):c.2513A>G (p.Asp838Gly) SNV Uncertain significance 642511 rs1603386154 X:77271265-77271265 X:78015768-78015768
46 ATP7A NM_000052.7(ATP7A):c.112C>T (p.His38Tyr) SNV Uncertain significance 648639 rs1603378831 X:77227250-77227250 X:77971753-77971753
47 ATP7A NM_000052.7(ATP7A):c.368G>A (p.Arg123Lys) SNV Uncertain significance 648905 rs782664232 X:77243985-77243985 X:77988489-77988489
48 ATP7A NM_000052.7(ATP7A):c.1558C>T (p.Leu520Phe) SNV Uncertain significance 649439 rs1331470313 X:77258584-77258584 X:78003087-78003087
49 ATP7A NM_000052.7(ATP7A):c.3701C>G (p.Pro1234Arg) SNV Uncertain significance 650145 rs1557238254 X:77296131-77296131 X:78040633-78040633
50 ATP7A NM_000052.7(ATP7A):c.2039C>T (p.Thr680Ile) SNV Uncertain significance 643466 rs782455461 X:77267038-77267038 X:78011541-78011541

UniProtKB/Swiss-Prot genetic disease variations for Spinal Muscular Atrophy, Distal, X-Linked 3:

73
# Symbol AA change Variation ID SNP ID
1 ATP7A p.Thr994Ile VAR_063882 rs267606673
2 ATP7A p.Pro1386Ser VAR_063884 rs267606672

Expression for Spinal Muscular Atrophy, Distal, X-Linked 3

Search GEO for disease gene expression data for Spinal Muscular Atrophy, Distal, X-Linked 3.

Pathways for Spinal Muscular Atrophy, Distal, X-Linked 3

Pathways related to Spinal Muscular Atrophy, Distal, X-Linked 3 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.77 DEFB110 ATP7A ATOX1
2 10.9 ATP7B ATP7A ATOX1
3 10.75 COX17 COX11 ATP7B ATP7A ATOX1
4 10.62 ATP7B ATP7A

GO Terms for Spinal Muscular Atrophy, Distal, X-Linked 3

Cellular components related to Spinal Muscular Atrophy, Distal, X-Linked 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transport vesicle membrane GO:0030658 8.96 PAM DBH
2 trans-Golgi network GO:0005802 8.8 PAM ATP7B ATP7A

Biological processes related to Spinal Muscular Atrophy, Distal, X-Linked 3 according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 metal ion transport GO:0030001 9.5 ATP7B ATP7A ATOX1
2 lactation GO:0007595 9.49 PAM ATP7A
3 blood vessel remodeling GO:0001974 9.48 DBH ATP7A
4 response to zinc ion GO:0010043 9.46 PAM ATP7A
5 inorganic cation transmembrane transport GO:0098662 9.43 ATP7B ATP7A
6 response to copper ion GO:0046688 9.43 PAM ATP7B ATP7A
7 copper ion import GO:0015677 9.4 ATP7B ATP7A
8 divalent inorganic cation transport GO:0072511 9.37 ATP7B ATP7A
9 cellular copper ion homeostasis GO:0006878 9.33 ATP7B ATP7A ATOX1
10 copper ion export GO:0060003 9.13 ATP7B ATP7A ATOX1
11 copper ion transport GO:0006825 9.02 CP COX17 ATP7B ATP7A ATOX1

Molecular functions related to Spinal Muscular Atrophy, Distal, X-Linked 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 L-ascorbic acid binding GO:0031418 9.46 PAM DBH
2 cation-transporting ATPase activity GO:0019829 9.43 ATP7B ATP7A
3 cuprous ion binding GO:1903136 9.4 COX17 ATP7A
4 copper ion transmembrane transporter activity GO:0005375 9.37 ATP7B ATP7A
5 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced ascorbate as one donor, and incorporation of one atom of oxygen GO:0016715 9.32 PAM DBH
6 copper chaperone activity GO:0016531 9.26 COX17 ATOX1
7 copper ion binding GO:0005507 9.23 PAM DBH CP COX17 COX11 ATP7B
8 copper-dependent protein binding GO:0032767 9.16 ATP7A ATOX1
9 copper-transporting ATPase activity GO:0043682 8.96 ATP7B ATP7A

Sources for Spinal Muscular Atrophy, Distal, X-Linked 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....