NEM8
MCID: NML025
MIFTS: 35

Nemaline Myopathy 8 (NEM8)

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

Aliases & Classifications for Nemaline Myopathy 8

MalaCards integrated aliases for Nemaline Myopathy 8:

Name: Nemaline Myopathy 8 56 12 73 29 6 15 71
Nemaline Myopathy 8, Autosomal Recessive 56 12 73 29
Nem8 56 12 73
Myopathy, Nemaline, Type 8 39

Characteristics:

HPO:

31
nemaline myopathy 8:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0110930
OMIM 56 615348
OMIM Phenotypic Series 56 PS161800
MeSH 43 D017696
UMLS 71 C3809209

Summaries for Nemaline Myopathy 8

UniProtKB/Swiss-Prot : 73 Nemaline myopathy 8: A severe form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. NEM8 is characterized by fetal akinesia or hypokinesia, followed by contractures, fractures, respiratory failure, and swallowing difficulties apparent at birth. Most patients die in infancy. Skeletal muscle biopsy shows numerous small nemaline bodies, often with no normal myofibrils.

MalaCards based summary : Nemaline Myopathy 8, also known as nemaline myopathy 8, autosomal recessive, is related to typical congenital nemaline myopathy and childhood-onset nemaline myopathy. An important gene associated with Nemaline Myopathy 8 is KLHL40 (Kelch Like Family Member 40). Affiliated tissues include skeletal muscle and bone, and related phenotypes are dysphagia and facial palsy

Disease Ontology : 12 A nemaline myopathy characterized by fetal akinesia or hypokinesia, followed by contractures, fractures, respiratory failure, and swallowing difficulties apparent at birth that has material basis in homozygous or compound heterozygous mutation in the KLHL40 gene on chromosome 3p22.

OMIM : 56 Nemaline myopathy-8 is a severe autosomal recessive muscle disorder characterized by fetal akinesia or hypokinesia, followed by contractures, fractures, respiratory failure, and swallowing difficulties apparent at birth. Most patients die in infancy. Skeletal muscle biopsy shows numerous small nemaline bodies, often with no normal myofibrils (summary by Ravenscroft et al., 2013). For a discussion of genetic heterogeneity of nemaline myopathy, see NEM3 (161800). (615348)

Related Diseases for Nemaline Myopathy 8

Graphical network of the top 20 diseases related to Nemaline Myopathy 8:



Diseases related to Nemaline Myopathy 8

Symptoms & Phenotypes for Nemaline Myopathy 8

Human phenotypes related to Nemaline Myopathy 8:

31 (show all 9)
# Description HPO Frequency HPO Source Accession
1 dysphagia 31 HP:0002015
2 facial palsy 31 HP:0010628
3 flexion contracture 31 HP:0001371
4 abnormality of the thorax 31 HP:0000765
5 nemaline bodies 31 HP:0003798
6 fetal akinesia sequence 31 HP:0001989
7 respiratory failure 31 HP:0002878
8 hypokinesia 31 HP:0002375
9 myofibrillar myopathy 31 HP:0003715

Clinical features from OMIM:

615348

Drugs & Therapeutics for Nemaline Myopathy 8

Search Clinical Trials , NIH Clinical Center for Nemaline Myopathy 8

Genetic Tests for Nemaline Myopathy 8

Genetic tests related to Nemaline Myopathy 8:

# Genetic test Affiliating Genes
1 Nemaline Myopathy 8 29 KLHL40
2 Nemaline Myopathy 8, Autosomal Recessive 29

Anatomical Context for Nemaline Myopathy 8

MalaCards organs/tissues related to Nemaline Myopathy 8:

40
Skeletal Muscle, Bone

Publications for Nemaline Myopathy 8

Articles related to Nemaline Myopathy 8:

# Title Authors PMID Year
1
Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy. 56 6
23746549 2013
2
KLHL40 deficiency destabilizes thin filament proteins and promotes nemaline myopathy. 56
24960163 2014
3
Nemaline Myopathy 6
20301465 2002

Variations for Nemaline Myopathy 8

ClinVar genetic disease variations for Nemaline Myopathy 8:

6 (show top 50) (show all 79) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 KLHL40 NM_152393.4(KLHL40):c.1582G>A (p.Glu528Lys)SNV Pathogenic 60512 rs397509419 3:42730521-42730521 3:42689029-42689029
2 KLHL40 NM_152393.4(KLHL40):c.1405G>T (p.Gly469Cys)SNV Pathogenic 60513 rs367579275 3:42730193-42730193 3:42688701-42688701
3 KLHL40 NM_152393.4(KLHL40):c.602G>T (p.Trp201Leu)SNV Pathogenic 60514 rs397509420 3:42727712-42727712 3:42686220-42686220
4 KLHL40 NM_152393.4(KLHL40):c.1612G>C (p.Ala538Pro)SNV Pathogenic 60515 rs397509421 3:42732355-42732355 3:42690863-42690863
5 KLHL40 NM_152393.4(KLHL40):c.602G>A (p.Trp201Ter)SNV Pathogenic 60516 rs397509420 3:42727712-42727712 3:42686220-42686220
6 KLHL40 NM_152393.4(KLHL40):c.1395C>A (p.Tyr465Ter)SNV Pathogenic 541327 rs139588377 3:42730183-42730183 3:42688691-42688691
7 KLHL40 NM_152393.4(KLHL40):c.631del (p.Ala211fs)deletion Pathogenic 658674 3:42727740-42727740 3:42686248-42686248
8 KLHL40 NM_152393.4(KLHL40):c.818dup (p.Lys275fs)duplication Pathogenic 650910 3:42727926-42727927 3:42686434-42686435
9 KLHL40 NM_152393.4(KLHL40):c.1498C>T (p.Arg500Cys)SNV Pathogenic/Likely pathogenic 423767 rs758188096 3:42730437-42730437 3:42688945-42688945
10 KLHL40 NM_152393.4(KLHL40):c.1153-2A>TSNV Likely pathogenic 541330 rs752493018 3:42729632-42729632 3:42688140-42688140
11 KLHL40 NM_152393.4(KLHL40):c.1152+2T>ASNV Likely pathogenic 653053 3:42728264-42728264 3:42686772-42686772
12 KLHL40 NM_152393.4(KLHL40):c.25G>T (p.Glu9Ter)SNV Likely pathogenic 804436 3:42727135-42727135 3:42685643-42685643
13 KLHL40 NM_152393.4(KLHL40):c.176G>C (p.Arg59Pro)SNV Likely pathogenic 807621 3:42727286-42727286 3:42685794-42685794
14 KLHL40 NM_152393.4(KLHL40):c.1421+1G>TSNV Likely pathogenic 571143 rs1186218257 3:42730210-42730210 3:42688718-42688718
15 KLHL40 NM_152393.4(KLHL40):c.100G>C (p.Asp34His)SNV Conflicting interpretations of pathogenicity 640377 3:42727210-42727210 3:42685718-42685718
16 KLHL40 NM_152393.4(KLHL40):c.864C>T (p.Ser288=)SNV Conflicting interpretations of pathogenicity 651780 3:42727974-42727974 3:42686482-42686482
17 KLHL40 NM_152393.4(KLHL40):c.931C>A (p.Arg311Ser)SNV Conflicting interpretations of pathogenicity 474339 rs763283033 3:42728041-42728041 3:42686549-42686549
18 KLHL40 NM_152393.4(KLHL40):c.1204C>T (p.Arg402Cys)SNV Uncertain significance 474323 rs149076152 3:42729685-42729685 3:42688193-42688193
19 KLHL40 NM_152393.4(KLHL40):c.1477C>G (p.Leu493Val)SNV Uncertain significance 474329 rs375270697 3:42730416-42730416 3:42688924-42688924
20 KLHL40 NM_152393.4(KLHL40):c.1345C>T (p.Pro449Ser)SNV Uncertain significance 541328 rs1194342086 3:42730133-42730133 3:42688641-42688641
21 KLHL40 NM_152393.4(KLHL40):c.197C>G (p.Pro66Arg)SNV Uncertain significance 541332 rs200810691 3:42727307-42727307 3:42685815-42685815
22 KLHL40 NM_152393.4(KLHL40):c.1709C>T (p.Thr570Met)SNV Uncertain significance 541331 rs139268932 3:42732452-42732452 3:42690960-42690960
23 KLHL40 NM_152393.4(KLHL40):c.1381A>G (p.Met461Val)SNV Uncertain significance 546303 rs776547008 3:42730169-42730169 3:42688677-42688677
24 KLHL40 NM_152393.4(KLHL40):c.88G>A (p.Gly30Ser)SNV Uncertain significance 578842 rs140056720 3:42727198-42727198 3:42685706-42685706
25 KLHL40 NM_152393.4(KLHL40):c.752T>A (p.Leu251Gln)SNV Uncertain significance 581235 rs928500134 3:42727862-42727862 3:42686370-42686370
26 KLHL40 NM_152393.4(KLHL40):c.1153-3C>ASNV Uncertain significance 578779 rs767265252 3:42729631-42729631 3:42688139-42688139
27 KLHL40 NM_152393.4(KLHL40):c.1504C>A (p.Leu502Ile)SNV Uncertain significance 578731 rs766195312 3:42730443-42730443 3:42688951-42688951
28 KLHL40 NM_152393.4(KLHL40):c.1761C>G (p.Asn587Lys)SNV Uncertain significance 574846 rs34020089 3:42733380-42733380 3:42691888-42691888
29 KLHL40 NM_152393.4(KLHL40):c.764A>G (p.Gln255Arg)SNV Uncertain significance 575376 rs139088361 3:42727874-42727874 3:42686382-42686382
30 KLHL40 NM_152393.4(KLHL40):c.395A>G (p.Asn132Ser)SNV Uncertain significance 579724 rs767039942 3:42727505-42727505 3:42686013-42686013
31 KLHL40 NM_152393.4(KLHL40):c.1053C>A (p.His351Gln)SNV Uncertain significance 574271 rs61736693 3:42728163-42728163 3:42686671-42686671
32 KLHL40 NM_152393.4(KLHL40):c.1493C>G (p.Thr498Ser)SNV Uncertain significance 577365 rs761479692 3:42730432-42730432 3:42688940-42688940
33 KLHL40 NM_152393.4(KLHL40):c.1595T>C (p.Ile532Thr)SNV Uncertain significance 577617 rs368161576 3:42730534-42730534 3:42689042-42689042
34 KLHL40 NM_152393.4(KLHL40):c.1793G>A (p.Arg598Gln)SNV Uncertain significance 568454 rs775821505 3:42733412-42733412 3:42691920-42691920
35 KLHL40 NM_152393.4(KLHL40):c.1383G>C (p.Met461Ile)SNV Uncertain significance 574408 rs762113138 3:42730171-42730171 3:42688679-42688679
36 KLHL40 NM_152393.4(KLHL40):c.1090G>C (p.Ala364Pro)SNV Uncertain significance 569209 rs1559613938 3:42728200-42728200 3:42686708-42686708
37 KLHL40 NM_152393.4(KLHL40):c.1746C>A (p.Asp582Glu)SNV Uncertain significance 420929 rs202096553 3:42732489-42732489 3:42690997-42690997
38 KLHL40 NM_152393.4(KLHL40):c.1355T>C (p.Val452Ala)SNV Uncertain significance 447661 rs140389534 3:42730143-42730143 3:42688651-42688651
39 KLHL40 NM_152393.4(KLHL40):c.643C>T (p.Arg215Cys)SNV Uncertain significance 474337 rs376618797 3:42727753-42727753 3:42686261-42686261
40 KLHL40 NM_152393.4(KLHL40):c.1306G>A (p.Asp436Asn)SNV Uncertain significance 474327 rs372145157 3:42729787-42729787 3:42688295-42688295
41 KLHL40 NM_152393.4(KLHL40):c.1621G>A (p.Glu541Lys)SNV Uncertain significance 474332 rs142761414 3:42732364-42732364 3:42690872-42690872
42 KLHL40 NM_152393.4(KLHL40):c.968T>G (p.Ile323Ser)SNV Uncertain significance 279825 rs146161469 3:42728078-42728078 3:42686586-42686586
43 KLHL40 NM_152393.4(KLHL40):c.1372_1383del (p.Leu458_Met461del)deletion Uncertain significance 474328 rs1553680747 3:42730158-42730169 3:42688666-42688677
44 KLHL40 NM_152393.4(KLHL40):c.887_889AGG[1] (p.Glu297del)short repeat Uncertain significance 641052 3:42727996-42727998 3:42686504-42686506
45 KLHL40 NM_152393.4(KLHL40):c.1019G>C (p.Cys340Ser)SNV Uncertain significance 642847 3:42728129-42728129 3:42686637-42686637
46 KLHL40 NM_152393.4(KLHL40):c.1097G>A (p.Gly366Asp)SNV Uncertain significance 653866 3:42728207-42728207 3:42686715-42686715
47 KLHL40 NM_152393.4(KLHL40):c.1243T>C (p.Tyr415His)SNV Uncertain significance 662094 3:42729724-42729724 3:42688232-42688232
48 KLHL40 NM_152393.4(KLHL40):c.1396G>T (p.Val466Leu)SNV Uncertain significance 646499 3:42730184-42730184 3:42688692-42688692
49 KLHL40 NM_152393.4(KLHL40):c.1412_1415delinsC (p.Gly471_Ser472delinsAla)indel Uncertain significance 648873 3:42730200-42730203 3:42688708-42688711
50 KLHL40 NM_152393.4(KLHL40):c.1414A>G (p.Ser472Gly)SNV Uncertain significance 640159 3:42730202-42730202 3:42688710-42688710

UniProtKB/Swiss-Prot genetic disease variations for Nemaline Myopathy 8:

73 (show all 13)
# Symbol AA change Variation ID SNP ID
1 KLHL40 p.Asp34His VAR_069836 rs778565563
2 KLHL40 p.Leu86Pro VAR_069837
3 KLHL40 p.Val194Glu VAR_069838
4 KLHL40 p.Trp201Leu VAR_069839 rs397509420
5 KLHL40 p.Arg311Leu VAR_069840
6 KLHL40 p.Pro397Leu VAR_069841 rs773649133
7 KLHL40 p.His455Arg VAR_069842 rs770866675
8 KLHL40 p.Gly469Cys VAR_069843 rs367579275
9 KLHL40 p.Thr506Pro VAR_069844 rs778022582
10 KLHL40 p.Glu528Lys VAR_069845 rs397509419
11 KLHL40 p.Ala538Pro VAR_069846 rs397509421
12 KLHL40 p.Glu588Lys VAR_069847 rs201856772
13 KLHL40 p.Ala505Pro VAR_077952

Expression for Nemaline Myopathy 8

Search GEO for disease gene expression data for Nemaline Myopathy 8.

Pathways for Nemaline Myopathy 8

GO Terms for Nemaline Myopathy 8

Cellular components related to Nemaline Myopathy 8 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 M band GO:0031430 9.16 LMOD3 KLHL41
2 A band GO:0031672 8.96 LMOD3 KLHL40
3 Cul3-RING ubiquitin ligase complex GO:0031463 8.8 KLHL9 KLHL41 KLHL40

Biological processes related to Nemaline Myopathy 8 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein ubiquitination GO:0016567 9.5 KLHL9 KLHL41 KBTBD13
2 post-translational protein modification GO:0043687 9.43 KLHL9 KLHL41 KBTBD13
3 muscle contraction GO:0006936 9.37 MYBPC2 LMOD3
4 striated muscle contraction GO:0006941 9.16 LMOD3 KLHL41
5 myofibril assembly GO:0030239 8.96 LMOD3 KLHL41
6 skeletal muscle fiber development GO:0048741 8.8 LMOD3 KLHL41 KLHL40

Sources for Nemaline Myopathy 8

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
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68 SNOMED-CT via HPO
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