HMLR2
MCID: HML046
MIFTS: 30

Heimler Syndrome 2 (HMLR2)

Categories: Ear diseases, Fetal diseases, Genetic diseases, Metabolic diseases, Oral diseases, Rare diseases, Skin diseases

Aliases & Classifications for Heimler Syndrome 2

MalaCards integrated aliases for Heimler Syndrome 2:

Name: Heimler Syndrome 2 56 12 73 29 6 15
Peroxisome Biogenesis Disorder 4c 56 73
Hmlr2 56 73
Pbd4c 56 73
Peroxisome Biogenesis Disorder 4c; Pbd4c 56
Peroxisomal Biogenesis Disorder 4c 12
Heimler Syndrome, Type 2 39

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
based on a report of 2 monozygotic twin girls (last curated october 2015)


HPO:

31
heimler syndrome 2:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0080624
OMIM 56 616617
OMIM Phenotypic Series 56 PS214100

Summaries for Heimler Syndrome 2

OMIM : 56 Heimler syndrome, which represents the mildest end of the peroxisomal biogenesis disorder spectrum (see PBD1A, 214100), is a rare autosomal recessive disorder characterized by sensorineural hearing loss, enamel hypoplasia of the secondary dentition, and nail abnormalities (Ratbi et al., 2015). For a discussion of genetic heterogeneity of Heimler syndrome, see HMLR1 (234580). (616617)

MalaCards based summary : Heimler Syndrome 2, is also known as peroxisome biogenesis disorder 4c. An important gene associated with Heimler Syndrome 2 is PEX6 (Peroxisomal Biogenesis Factor 6). Related phenotypes are pes planus and dental crowding

Disease Ontology : 12 A peroxisomal biogenesis disorder that is characterised by sensorineural hearing loss, generalised enamel hypoplasia of the permanent dentition with normal primary dentition, and nail defects and has material basis in compound heterozygous mutation in the PEX6 gene on chromosome 6p21.

UniProtKB/Swiss-Prot : 73 Heimler syndrome 2: A form of Heimler syndrome, a very mild peroxisome biogenesis disorder characterized by sensorineural hearing loss, amelogenesis imperfecta resulting in enamel hyoplasia of the secondary dentition, nail defects, and occasional or late-onset retinal pigmentation abnormalities.

Related Diseases for Heimler Syndrome 2

Diseases in the Heimler Syndrome 1 family:

Heimler Syndrome 2

Symptoms & Phenotypes for Heimler Syndrome 2

Human phenotypes related to Heimler Syndrome 2:

31
# Description HPO Frequency HPO Source Accession
1 pes planus 31 HP:0001763
2 dental crowding 31 HP:0000678
3 leukonychia 31 HP:0001820

Symptoms via clinical synopsis from OMIM:

56
Skeletal Feet:
pes planus
congenital club feet

Neurologic Central Nervous System:
normal intellectual development

Head And Neck Ears:
sensorineural hearing loss in early childhood

Skeletal Hands:
slightly broad thumbs
leukonychia of fingernails

Skin Nails Hair Nails:
leukonychia
beau lines on toenails

Head And Neck Teeth:
dental overcrowding
hypoplastic enamel of secondary dentition
hypoplasia or hypocalcification of lower canines, premolars, and molars
hypoplasia or hypocalcification of upper second and third molars
enlarged pulp chambers (taurodontism) of maxillary molars

Head And Neck Eyes:
retinal pigmentation abnormalities

Clinical features from OMIM:

616617

GenomeRNAi Phenotypes related to Heimler Syndrome 2 according to GeneCards Suite gene sharing:

26 (show all 26)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-119 9.8 RIMS3
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-136 9.8 PRODH
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-139 9.8 PRODH
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-152 9.8 RIMS3
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-185 9.8 RIMS3
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-192 9.8 PRODH
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-198 9.8 PRODH
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-200 9.8 PRODH
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-4 9.8 PRODH
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-5 9.8 PRODH RIMS3
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-55 9.8 PRODH
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-86 9.8 PRODH
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-99 9.8 RIMS3
14 Increased shRNA abundance (Z-score > 2) GR00366-A-112 9.47 RIMS3
15 Increased shRNA abundance (Z-score > 2) GR00366-A-13 9.47 PRODH
16 Increased shRNA abundance (Z-score > 2) GR00366-A-148 9.47 PRODH
17 Increased shRNA abundance (Z-score > 2) GR00366-A-156 9.47 RIMS3
18 Increased shRNA abundance (Z-score > 2) GR00366-A-2 9.47 PRODH
19 Increased shRNA abundance (Z-score > 2) GR00366-A-203 9.47 RIMS3
20 Increased shRNA abundance (Z-score > 2) GR00366-A-23 9.47 PRODH
21 Increased shRNA abundance (Z-score > 2) GR00366-A-33 9.47 PRODH
22 Increased shRNA abundance (Z-score > 2) GR00366-A-58 9.47 PRODH RIMS3
23 Increased shRNA abundance (Z-score > 2) GR00366-A-66 9.47 PRODH
24 Increased shRNA abundance (Z-score > 2) GR00366-A-70 9.47 PRODH
25 Increased shRNA abundance (Z-score > 2) GR00366-A-9 9.47 PRODH
26 Increased shRNA abundance (Z-score > 2) GR00366-A-99 9.47 PRODH

Drugs & Therapeutics for Heimler Syndrome 2

Search Clinical Trials , NIH Clinical Center for Heimler Syndrome 2

Genetic Tests for Heimler Syndrome 2

Genetic tests related to Heimler Syndrome 2:

# Genetic test Affiliating Genes
1 Heimler Syndrome 2 29 PEX6

Anatomical Context for Heimler Syndrome 2

Publications for Heimler Syndrome 2

Articles related to Heimler Syndrome 2:

# Title Authors PMID Year
1
Heimler Syndrome Is Caused by Hypomorphic Mutations in the Peroxisome-Biogenesis Genes PEX1 and PEX6. 56 6
26387595 2015
2
Sensorineural deafness, enamel abnormalities and nail abnormalities: a case report of Heimler syndrome in identical twin girls. 56 6
16530715 2006
3
Spectrum of PEX6 mutations in Zellweger syndrome spectrum patients. 6
19877282 2010
4
Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders. 6
19105186 2009
5
The PEX Gene Screen: molecular diagnosis of peroxisome biogenesis disorders in the Zellweger syndrome spectrum. 6
15542397 2004

Variations for Heimler Syndrome 2

ClinVar genetic disease variations for Heimler Syndrome 2:

6 (show all 14) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PEX6 NM_000287.4(PEX6):c.2714G>T (p.Cys905Phe)SNV Pathogenic 224322 rs886037782 6:42932620-42932620 6:42964882-42964882
2 PEX6 NM_000287.4(PEX6):c.1715C>T (p.Thr572Ile)SNV Pathogenic 224323 rs61753224 6:42935275-42935275 6:42967537-42967537
3 PEX6 NM_000287.4(PEX6):c.1314_1321del (p.Glu439fs)deletion Pathogenic 224321 rs267608216 6:42937452-42937459 6:42969714-42969721
4 PEX6 NM_000287.4(PEX6):c.1930C>T (p.Arg644Trp)SNV Pathogenic 217425 rs769896492 6:42934551-42934551 6:42966813-42966813
5 PEX6 NM_000287.4(PEX6):c.296G>T (p.Arg99Leu)SNV Pathogenic 224320 rs886037781 6:42946593-42946593 6:42978855-42978855
6 PEX6 NM_000287.4(PEX6):c.275T>G (p.Val92Gly)SNV Pathogenic 224319 rs886037780 6:42946614-42946614 6:42978876-42978876
7 PEX6 NM_000287.4(PEX6):c.1841del (p.Leu614fs)deletion Pathogenic/Likely pathogenic 217426 rs863225083 6:42935149-42935149 6:42967411-42967411
8 PEX6 NM_000287.4(PEX6):c.821C>T (p.Pro274Leu)SNV Pathogenic/Likely pathogenic 217424 rs61753219 6:42946068-42946068 6:42978330-42978330
9 PEX6 NM_000287.4(PEX6):c.2440C>T (p.Arg814Ter)SNV Pathogenic/Likely pathogenic 194165 rs267608241 6:42933450-42933450 6:42965712-42965712
10 PEX6 NM_000287.4(PEX6):c.386A>T (p.Glu129Val)SNV Likely pathogenic 625158 rs1561831003 6:42946503-42946503 6:42978765-42978765
11 PEX6 NM_000287.4(PEX6):c.2300+2T>CSNV Likely pathogenic 804456 6:42933978-42933978 6:42966240-42966240
12 PEX6 NM_000287.4(PEX6):c.1802G>A (p.Arg601Gln)SNV Conflicting interpretations of pathogenicity 198709 rs34324426 6:42935188-42935188 6:42967450-42967450
13 PEX6 NM_000287.4(PEX6):c.654C>G (p.Phe218Leu)SNV Conflicting interpretations of pathogenicity 224318 rs886037779 6:42946235-42946235 6:42978497-42978497
14 PEX6 NM_000287.4(PEX6):c.719C>G (p.Ala240Gly)SNV Uncertain significance 288056 rs372269200 6:42946170-42946170 6:42978432-42978432

UniProtKB/Swiss-Prot genetic disease variations for Heimler Syndrome 2:

73
# Symbol AA change Variation ID SNP ID
1 PEX6 p.Pro274Leu VAR_058382 rs61753219
2 PEX6 p.Arg644Trp VAR_074110 rs769896492
3 PEX6 p.Thr572Ile VAR_077509 rs61753224
4 PEX6 p.Cys905Phe VAR_077510 rs886037782

Expression for Heimler Syndrome 2

Search GEO for disease gene expression data for Heimler Syndrome 2.

Pathways for Heimler Syndrome 2

GO Terms for Heimler Syndrome 2

Cellular components related to Heimler Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 presynaptic membrane GO:0042734 9.26 RIMS4 RIMS3
2 presynaptic active zone GO:0048786 9.16 RIMS4 RIMS3
3 presynaptic active zone cytoplasmic component GO:0098831 8.96 RIMS4 RIMS3
4 cytoskeleton of presynaptic active zone GO:0048788 8.62 RIMS4 RIMS3

Biological processes related to Heimler Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 exocytosis GO:0006887 9.4 RIMS4 RIMS3
2 regulation of membrane potential GO:0042391 9.37 RIMS4 RIMS3
3 regulation of synaptic vesicle exocytosis GO:2000300 9.32 RIMS4 RIMS3
4 regulation of synaptic plasticity GO:0048167 9.26 RIMS4 RIMS3
5 neurotransmitter transport GO:0006836 9.16 RIMS4 RIMS3
6 positive regulation of synaptic transmission GO:0050806 8.96 RIMS4 RIMS3
7 calcium ion-regulated exocytosis of neurotransmitter GO:0048791 8.62 RIMS4 RIMS3

Molecular functions related to Heimler Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Rab GTPase binding GO:0017137 8.96 RIMS4 RIMS3
2 ion channel binding GO:0044325 8.62 RIMS4 RIMS3

Sources for Heimler Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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