HMN2B
MCID: NRN041
MIFTS: 33

Neuronopathy, Distal Hereditary Motor, Type Iib (HMN2B)

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

Aliases & Classifications for Neuronopathy, Distal Hereditary Motor, Type Iib

MalaCards integrated aliases for Neuronopathy, Distal Hereditary Motor, Type Iib:

Name: Neuronopathy, Distal Hereditary Motor, Type Iib 57 70
Hmn Iib 57 12 72
Hmn2b 57 12 72
Neuropathy, Distal Hereditary Motor, Type Iib 57 13
Distal Hereditary Motor Neuronopathy Type 2b 29 6
Distal Hereditary Motor Neuropathy Type Iib 12 72
Distal Hereditary Motor Neuropathy Type 2b 12 15
Dhmn2b 57 72
Neuropathy, Distal Hereditary Motor, Type Iib; Dhmn2b 57
Neuropathy, Motor, Distal, Hereditary, Type 2b 39
Neuronopathy, Distal Hereditary Motor, 2b 72
Dhmn Ii 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

Miscellaneous:
slowly progressive
onset usually in adulthood although childhood onset has been reported
autosomal recessive inheritance has been reported in 1 family
allelic disorder to charcot-marie-tooth disease 2f (cmt2f, )
see also distal hmn2a


HPO:

31
neuronopathy, distal hereditary motor, type iib:
Inheritance autosomal dominant inheritance
Onset and clinical course adult onset slow progression


Classifications:



External Ids:

Disease Ontology 12 DOID:0111207
OMIM® 57 608634
MeSH 44 D009134
MedGen 41 C2608087
UMLS 70 C2608087

Summaries for Neuronopathy, Distal Hereditary Motor, Type Iib

UniProtKB/Swiss-Prot : 72 Neuronopathy, distal hereditary motor, 2B: A neuromuscular disorder. Distal hereditary motor neuronopathies constitute 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 : Neuronopathy, Distal Hereditary Motor, Type Iib, also known as hmn iib, is related to charcot-marie-tooth hereditary neuropathy and charcot-marie-tooth disease, axonal, type 2l. An important gene associated with Neuronopathy, Distal Hereditary Motor, Type Iib is HSPB1 (Heat Shock Protein Family B (Small) Member 1). Affiliated tissues include spinal cord, and related phenotypes are peripheral neuropathy and distal lower limb muscle weakness

Disease Ontology : 12 A distal hereditary motor neuropathy type 2 that has material basis in heterozygous mutation in HSPB1 on 7q11.23.

More information from OMIM: 608634

Related Diseases for Neuronopathy, Distal Hereditary Motor, Type Iib

Diseases in the Autosomal Dominant Distal Hereditary Motor Neuronopathy family:

Neuronopathy, Distal Hereditary Motor, Type Viia Neuronopathy, Distal Hereditary Motor, Type Iia
Neuronopathy, Distal Hereditary Motor, Type I Neuronopathy, Distal Hereditary Motor, Type Viii
Neuronopathy, Distal Hereditary Motor, Type Va Neuronopathy, Distal Hereditary Motor, Type Viib
Neuronopathy, Distal Hereditary Motor, Type Iib Neuronopathy, Distal Hereditary Motor, Type Iic
Neuronopathy, Distal Hereditary Motor, Type Vb Neuronopathy, Distal Hereditary Motor, Type Iid
Neuronopathy, Distal Hereditary Motor, Type Ix Neuronopathy, Distal Hereditary Motor, Type Vc
Autosomal Recessive Distal Hereditary Motor Neuronopathy Distal Hereditary Motor Neuronopathy Type 7
Distal Hereditary Motor Neuronopathy Type 2

Diseases related to Neuronopathy, Distal Hereditary Motor, Type Iib via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 22)
# Related Disease Score Top Affiliating Genes
1 charcot-marie-tooth hereditary neuropathy 10.0 IGHMBP2 GARS1
2 charcot-marie-tooth disease, axonal, type 2l 10.0 HSPB1 GARS1
3 spinal muscular atrophy with lower extremity predominance 10.0 IGHMBP2 GARS1
4 charcot-marie-tooth disease, axonal, type 2f 10.0 HSPB1 GARS1
5 scapuloperoneal spinal muscular atrophy 9.9 IGHMBP2 GARS1
6 brown-vialetto-van laere syndrome 9.9 MORC2 IGHMBP2
7 neuronopathy, distal hereditary motor, type va 9.9 IGHMBP2 GARS1
8 autosomal dominant distal hereditary motor neuronopathy 9.8 IGHMBP2 HSPB1 GARS1
9 distal hereditary motor neuronopathy type 2 9.8 IGHMBP2 HSPB1 GARS1
10 motor peripheral neuropathy 9.8 IGHMBP2 GARS1
11 autosomal recessive distal hereditary motor neuronopathy 9.8 MORC2 IGHMBP2 GARS1
12 spinal muscular atrophy, distal, autosomal recessive, 1 9.7 MORC2 IGHMBP2 GARS1
13 spinal muscular atrophy 9.7 MORC2 IGHMBP2 GARS1
14 muscular atrophy 9.7 MORC2 IGHMBP2 GARS1
15 axonal neuropathy 9.7 MORC2 GARS1 COA7
16 neuropathy, congenital hypomyelinating, 1, autosomal recessive 9.6 HSPB1 GARS1 DRP2
17 hypertrophic neuropathy of dejerine-sottas 9.6 GARS1 DRP2
18 neuropathy 9.3 MORC2 IGHMBP2 HSPB1 GARS1 COA7
19 neuromuscular disease 9.2 MORC2 IGHMBP2 HSPB1 GARS1 DRP2
20 tooth disease 9.1 MORC2 IGHMBP2 HSPB1 GARS1 DHTKD1
21 charcot-marie-tooth disease, axonal, type 2e 8.8 MORC2 IGHMBP2 HSPB1 GARS1 DRP2 DHTKD1
22 charcot-marie-tooth disease 8.8 MORC2 IGHMBP2 HSPB1 GARS1 DRP2 DHTKD1

Graphical network of the top 20 diseases related to Neuronopathy, Distal Hereditary Motor, Type Iib:



Diseases related to Neuronopathy, Distal Hereditary Motor, Type Iib

Symptoms & Phenotypes for Neuronopathy, Distal Hereditary Motor, Type Iib

Human phenotypes related to Neuronopathy, Distal Hereditary Motor, Type Iib:

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 peripheral neuropathy 31 HP:0009830
2 distal lower limb muscle weakness 31 HP:0009053
3 difficulty walking 31 HP:0002355
4 paralysis 31 HP:0003470
5 areflexia of lower limbs 31 HP:0002522
6 emg: neuropathic changes 31 HP:0003445
7 hyporeflexia of lower limbs 31 HP:0002600
8 paresis of extensor muscles of the big toe 31 HP:0002601

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Peripheral Nervous System:
difficulty walking
areflexia of lower limbs
hyporeflexia of lower limbs
muscle weakness, distal (lower limbs more affected than upper limbs), due to motor neuronopathy
emg shows neurogenic abnormalities
more

Clinical features from OMIM®:

608634 (Updated 20-May-2021)

GenomeRNAi Phenotypes related to Neuronopathy, Distal Hereditary Motor, Type Iib according to GeneCards Suite gene sharing:

26 (show all 14)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-105 9.47 GARS1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-132 9.47 GARS1
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-157 9.47 GARS1
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-160 9.47 DRP2
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-177 9.47 GARS1
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-186 9.47 DRP2
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-199 9.47 GARS1
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-214 9.47 GARS1
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-38 9.47 DRP2
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-41 9.47 GARS1
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-67 9.47 GARS1
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-84 9.47 DRP2
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-87 9.47 GARS1
14 Decreased shRNA abundance (Z-score < -2) GR00366-A-91 9.47 DRP2

MGI Mouse Phenotypes related to Neuronopathy, Distal Hereditary Motor, Type Iib:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 muscle MP:0005369 8.92 DHTKD1 GARS1 IGHMBP2 MORC2

Drugs & Therapeutics for Neuronopathy, Distal Hereditary Motor, Type Iib

Search Clinical Trials , NIH Clinical Center for Neuronopathy, Distal Hereditary Motor, Type Iib

Genetic Tests for Neuronopathy, Distal Hereditary Motor, Type Iib

Genetic tests related to Neuronopathy, Distal Hereditary Motor, Type Iib:

# Genetic test Affiliating Genes
1 Distal Hereditary Motor Neuronopathy Type 2b 29 HSPB1

Anatomical Context for Neuronopathy, Distal Hereditary Motor, Type Iib

MalaCards organs/tissues related to Neuronopathy, Distal Hereditary Motor, Type Iib:

40
Spinal Cord

Publications for Neuronopathy, Distal Hereditary Motor, Type Iib

Articles related to Neuronopathy, Distal Hereditary Motor, Type Iib:

# Title Authors PMID Year
1
Mutations in the HSP27 (HSPB1) gene cause dominant, recessive, and sporadic distal HMN/CMT type 2. 57 6
18832141 2008
2
Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy. 57 6
15122254 2004
3
HDAC6 inhibitors reverse axonal loss in a mouse model of mutant HSPB1-induced Charcot-Marie-Tooth disease. 57
21785432 2011
4
Disruption of neurofilament network with aggregation of light neurofilament protein: a common pathway leading to motor neuron degeneration due to Charcot-Marie-Tooth disease-linked mutations in NFL and HSPB1. 6
17881652 2007
5
A mutation in the small heat-shock protein HSPB1 leading to distal hereditary motor neuronopathy disrupts neurofilament assembly and the axonal transport of specific cellular cargoes. 6
16368711 2006
6
Mutation analysis of the small heat shock protein 27 gene in chinese patients with Charcot-Marie-Tooth disease. 6
16087758 2005
7
Small heat shock protein 27 mutation in a Japanese patient with distal hereditary motor neuropathy. 6
16155736 2005
8
A new locus for autosomal dominant Charcot-Marie-Tooth disease type 2 (CMT2F) maps to chromosome 7q11-q21. 6
11528513 2001
9
Characterization of New Transgenic Mouse Models for Two Charcot-Marie-Tooth-Causing HspB1 Mutations using the Rosa26 Locus. 61
27854215 2016

Variations for Neuronopathy, Distal Hereditary Motor, Type Iib

ClinVar genetic disease variations for Neuronopathy, Distal Hereditary Motor, Type Iib:

6 (show all 44)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 HSPB1 NM_001540.5(HSPB1):c.560C>T (p.Ser187Leu) SNV Pathogenic 560409 rs774585320 GRCh37: 7:75933432-75933432
GRCh38: 7:76304115-76304115
2 HSPB1 NM_001540.5(HSPB1):c.404C>T (p.Ser135Phe) SNV Pathogenic 7478 rs28939680 GRCh37: 7:75933158-75933158
GRCh38: 7:76303841-76303841
3 HSPB1 NM_001540.5(HSPB1):c.379C>T (p.Arg127Trp) SNV Pathogenic 7479 rs29001571 GRCh37: 7:75933133-75933133
GRCh38: 7:76303816-76303816
4 HSPB1 NM_001540.5(HSPB1):c.452C>T (p.Thr151Ile) SNV Pathogenic 7480 rs28937568 GRCh37: 7:75933324-75933324
GRCh38: 7:76304007-76304007
5 HSPB1 NM_001540.5(HSPB1):c.544C>T (p.Pro182Ser) SNV Pathogenic 7483 rs104894020 GRCh37: 7:75933416-75933416
GRCh38: 7:76304099-76304099
6 HSPB1 NM_001540.5(HSPB1):c.418C>G (p.Arg140Gly) SNV Pathogenic 7484 rs121909112 GRCh37: 7:75933172-75933172
GRCh38: 7:76303855-76303855
7 HSPB1 NM_001540.5(HSPB1):c.545C>T (p.Pro182Leu) SNV Pathogenic 7481 rs28937569 GRCh37: 7:75933417-75933417
GRCh38: 7:76304100-76304100
8 HSPB1 NM_001540.5(HSPB1):c.116C>T (p.Pro39Leu) SNV Pathogenic 533814 rs557327165 GRCh37: 7:75932145-75932145
GRCh38: 7:76302828-76302828
9 HSPB1 NM_001540.5(HSPB1):c.510del (p.Lys171fs) Deletion Likely pathogenic 954704 GRCh37: 7:75933380-75933380
GRCh38: 7:76304063-76304063
10 HSPB1 NM_001540.5(HSPB1):c.404C>G (p.Ser135Cys) SNV Likely pathogenic 637060 rs28939680 GRCh37: 7:75933158-75933158
GRCh38: 7:76303841-76303841
11 HSPB1 NM_001540.5(HSPB1):c.19C>T (p.Pro7Ser) SNV Likely pathogenic 560407 rs1563651698 GRCh37: 7:75932048-75932048
GRCh38: 7:76302731-76302731
12 HSPB1 NM_001540.5(HSPB1):c.295C>A (p.Leu99Met) SNV Likely pathogenic 7485 rs121909113 GRCh37: 7:75932324-75932324
GRCh38: 7:76303007-76303007
13 HSPB1 NM_001540.5(HSPB1):c.415A>G (p.Thr139Ala) SNV Likely pathogenic 549674 rs1554614648 GRCh37: 7:75933169-75933169
GRCh38: 7:76303852-76303852
14 HSPB1 NM_001540.5(HSPB1):c.158G>A (p.Gly53Asp) SNV Likely pathogenic 560408 rs375244209 GRCh37: 7:75932187-75932187
GRCh38: 7:76302870-76302870
15 HSPB1 NM_001540.5(HSPB1):c.180dup (p.Ala61fs) Duplication Likely pathogenic 423339 rs1064796370 GRCh37: 7:75932203-75932204
GRCh38: 7:76302886-76302887
16 HSPB1 NM_001540.5(HSPB1):c.383A>G (p.Gln128Arg) SNV Conflicting interpretations of pathogenicity 360738 rs558882005 GRCh37: 7:75933137-75933137
GRCh38: 7:76303820-76303820
17 HSPB1 NM_001540.5(HSPB1):c.610G>A (p.Ala204Thr) SNV Uncertain significance 216545 rs367857772 GRCh37: 7:75933482-75933482
GRCh38: 7:76304165-76304165
18 HSPB1 NM_001540.4(HSPB1):c.-122G>T SNV Uncertain significance 360734 rs553127513 GRCh37: 7:75931908-75931908
GRCh38: 7:76302591-76302591
19 HSPB1 NM_001540.5(HSPB1):c.216C>T (p.Ala72=) SNV Uncertain significance 360737 rs11547168 GRCh37: 7:75932245-75932245
GRCh38: 7:76302928-76302928
20 HSPB1 NM_001540.5(HSPB1):c.60C>T (p.Arg20=) SNV Uncertain significance 908808 GRCh37: 7:75932089-75932089
GRCh38: 7:76302772-76302772
21 HSPB1 NM_001540.4(HSPB1):c.-129G>T SNV Uncertain significance 360733 rs886062446 GRCh37: 7:75931901-75931901
GRCh38: 7:76302584-76302584
22 HSPB1 NM_001540.5(HSPB1):c.615G>A (p.Lys205=) SNV Uncertain significance 908866 GRCh37: 7:75933487-75933487
GRCh38: 7:76304170-76304170
23 HSPB1 NM_001540.5(HSPB1):c.*116C>T SNV Uncertain significance 909722 GRCh37: 7:75933606-75933606
GRCh38: 7:76304289-76304289
24 HSPB1 NM_001540.5(HSPB1):c.236G>C (p.Arg79Pro) SNV Uncertain significance 910589 GRCh37: 7:75932265-75932265
GRCh38: 7:76302948-76302948
25 HSPB1 NM_001540.5(HSPB1):c.305A>T (p.Asn102Ile) SNV Uncertain significance 447528 rs765142574 GRCh37: 7:75932334-75932334
GRCh38: 7:76303017-76303017
26 HSPB1 NM_001540.5(HSPB1):c.364+6C>G SNV Uncertain significance 447529 rs753061670 GRCh37: 7:75932399-75932399
GRCh38: 7:76303082-76303082
27 HSPB1 NM_001540.5(HSPB1):c.210G>A (p.Ala70=) SNV Uncertain significance 681059 rs749963653 GRCh37: 7:75932239-75932239
GRCh38: 7:76302922-76302922
28 HSPB1 NM_001540.5(HSPB1):c.498G>A (p.Glu166=) SNV Likely benign 698878 rs148357753 GRCh37: 7:75933370-75933370
GRCh38: 7:76304053-76304053
29 HSPB1 NM_001540.5(HSPB1):c.9G>A (p.Glu3=) SNV Likely benign 193215 rs77586767 GRCh37: 7:75932038-75932038
GRCh38: 7:76302721-76302721
30 HSPB1 NM_001540.5(HSPB1):c.36G>T (p.Arg12=) SNV Benign 377969 rs145369859 GRCh37: 7:75932065-75932065
GRCh38: 7:76302748-76302748
31 HSPB1 NM_001540.5(HSPB1):c.-4C>T SNV Benign 360736 rs372833436 GRCh37: 7:75932026-75932026
GRCh38: 7:76302709-76302709
32 HSPB1 NM_001540.5(HSPB1):c.-19C>T SNV Benign 258165 rs199602956 GRCh37: 7:75932011-75932011
GRCh38: 7:76302694-76302694
33 HSPB1 NM_001540.4(HSPB1):c.-46C>T SNV Benign 360735 rs35907174 GRCh37: 7:75931984-75931984
GRCh38: 7:76302667-76302667
34 HSPB1 NM_001540.5(HSPB1):c.501C>T (p.Ala167=) SNV Benign 381272 rs529095936 GRCh37: 7:75933373-75933373
GRCh38: 7:76304056-76304056
35 HSPB1 NM_001540.5(HSPB1):c.610G>A (p.Ala204Thr) SNV Benign 216545 rs367857772 GRCh37: 7:75933482-75933482
GRCh38: 7:76304165-76304165
36 HSPB1 NM_001540.5(HSPB1):c.108C>G (p.Pro36=) SNV Benign 909658 GRCh37: 7:75932137-75932137
GRCh38: 7:76302820-76302820
37 HSPB1 NM_001540.5(HSPB1):c.178C>T (p.Pro60Ser) SNV Benign 239028 rs61751217 GRCh37: 7:75932207-75932207
GRCh38: 7:76302890-76302890
38 HSPB1 NM_001540.5(HSPB1):c.*11C>T SNV Benign 258164 rs1058872 GRCh37: 7:75933501-75933501
GRCh38: 7:76304184-76304184
39 HSPB1 NM_001540.5(HSPB1):c.24C>T (p.Phe8=) SNV Benign 258166 rs201769668 GRCh37: 7:75932053-75932053
GRCh38: 7:76302736-76302736
40 HSPB1 NM_001540.5(HSPB1):c.365-7C>T SNV Benign 910590 GRCh37: 7:75933112-75933112
GRCh38: 7:76303795-76303795
41 HSPB1 NC_000007.14:g.76302657C>T SNV Benign 911771 GRCh37: 7:75931974-75931974
GRCh38: 7:76302657-76302657
42 HSPB1 NM_001540.5(HSPB1):c.365-6C>G SNV Benign 533816 rs200902768 GRCh37: 7:75933113-75933113
GRCh38: 7:76303796-76303796
43 HSPB1 NM_001540.5(HSPB1):c.399C>T (p.Tyr133=) SNV Benign 911820 GRCh37: 7:75933153-75933153
GRCh38: 7:76303836-76303836
44 HSPB1 NM_001540.5(HSPB1):c.*22C>T SNV Benign 909721 GRCh37: 7:75933512-75933512
GRCh38: 7:76304195-76304195

UniProtKB/Swiss-Prot genetic disease variations for Neuronopathy, Distal Hereditary Motor, Type Iib:

72 (show all 15)
# Symbol AA change Variation ID SNP ID
1 HSPB1 p.Arg127Trp VAR_018506 rs29001571
2 HSPB1 p.Ser135Phe VAR_018507 rs28939680
3 HSPB1 p.Thr151Ile VAR_018509 rs28937568
4 HSPB1 p.Pro182Leu VAR_018510 rs28937569
5 HSPB1 p.Gly34Arg VAR_077483 rs155461443
6 HSPB1 p.Pro39Leu VAR_077484 rs557327165
7 HSPB1 p.Glu41Lys VAR_077485 rs139340497
8 HSPB1 p.Gly84Arg VAR_077486 rs770272088
9 HSPB1 p.Leu99Met VAR_077487 rs121909113
10 HSPB1 p.Arg136Leu VAR_077488 rs863225022
11 HSPB1 p.Arg140Gly VAR_077489 rs121909112
12 HSPB1 p.Lys141Gln VAR_077490 rs155461465
13 HSPB1 p.Pro7Ser VAR_078128 rs156365169
14 HSPB1 p.Gly53Asp VAR_078129 rs375244209
15 HSPB1 p.Ser187Leu VAR_078132 rs774585320

Expression for Neuronopathy, Distal Hereditary Motor, Type Iib

Search GEO for disease gene expression data for Neuronopathy, Distal Hereditary Motor, Type Iib.

Pathways for Neuronopathy, Distal Hereditary Motor, Type Iib

GO Terms for Neuronopathy, Distal Hereditary Motor, Type Iib

Sources for Neuronopathy, Distal Hereditary Motor, Type Iib

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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....