PBD4A
MCID: PRX057
MIFTS: 25

Peroxisome Biogenesis Disorder 4a (PBD4A)

Categories: Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Liver diseases, Mental diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Peroxisome Biogenesis Disorder 4a

MalaCards integrated aliases for Peroxisome Biogenesis Disorder 4a:

Name: Peroxisome Biogenesis Disorder 4a 57 75 29 13 6 73
Pbd4a 57 75
Peroxisome Biogenesis Disorder Complementation Group 4 75
Peroxisome Biogenesis Disorder Complementation Group 6 75
Peroxisome Biogenesis Disorder Complementation Group C 75
Peroxisome Biogenesis Disorder, Type 4a 40
Pbd-Cg6 75
Pbd-Cgc 75
Pbd-Cg4 75
Cg4 75

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive


HPO:

32
peroxisome biogenesis disorder 4a:
Mortality/Aging death in infancy
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Peroxisome Biogenesis Disorder 4a

UniProtKB/Swiss-Prot : 75 Peroxisome biogenesis disorder 4A: A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and clinically characterized by severe neurologic dysfunction with profound psychomotor retardation, severe hypotonia and neonatal seizures, craniofacial abnormalities, liver dysfunction, and biochemically by the absence of peroxisomes. Additional features include cardiovascular and skeletal defects, renal cysts, ocular abnormalities, and hearing impairment. Most severely affected individuals with the classic form of the disease (classic Zellweger syndrome) die within the first year of life. Peroxisome biogenesis disorder complementation group 4: A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS).

MalaCards based summary : Peroxisome Biogenesis Disorder 4a, also known as pbd4a, is related to peroxisome biogenesis disorder 4b. An important gene associated with Peroxisome Biogenesis Disorder 4a is PEX6 (Peroxisomal Biogenesis Factor 6). Affiliated tissues include liver and eye, and related phenotypes are hypertelorism and seizures

OMIM : 57 The peroxisomal biogenesis disorder (PBD) Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group 4 (CG4, equivalent to CG6 and CGC) have mutations in the PEX6 gene. For information on the history of PBD complementation groups, see 214100. (614862)

Symptoms & Phenotypes for Peroxisome Biogenesis Disorder 4a

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
epicanthus inversus
upslanting palpebral fissures

Head And Neck Nose:
low nasal bridge

Skeletal Limbs:
abnormal calcific stippling of patellae

Neurologic Central Nervous System:
clonic convulsions

Abdomen Liver:
hepatomegaly

Respiratory:
severe asphyxia
respiratory failure (leading to death at 7 months)

Muscle Soft Tissue:
hypotonia, profound

Laboratory Abnormalities:
elevated serum very long chain fatty acids (vlcfa)
absence of peroxisomes
zellweger complementation group c
zellweger complementation group 4


Clinical features from OMIM:

614862

Human phenotypes related to Peroxisome Biogenesis Disorder 4a:

32 (show all 12)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 32 HP:0000316
2 seizures 32 HP:0001250
3 hepatomegaly 32 HP:0002240
4 depressed nasal bridge 32 HP:0005280
5 feeding difficulties in infancy 32 HP:0008872
6 epiphyseal stippling 32 HP:0010655
7 respiratory failure 32 HP:0002878
8 upslanted palpebral fissure 32 HP:0000582
9 generalized hypotonia 32 HP:0001290
10 renal cyst 32 HP:0000107
11 generalized neonatal hypotonia 32 HP:0008935
12 epicanthus inversus 32 HP:0000537

Drugs & Therapeutics for Peroxisome Biogenesis Disorder 4a

Search Clinical Trials , NIH Clinical Center for Peroxisome Biogenesis Disorder 4a

Genetic Tests for Peroxisome Biogenesis Disorder 4a

Genetic tests related to Peroxisome Biogenesis Disorder 4a:

# Genetic test Affiliating Genes
1 Peroxisome Biogenesis Disorder 4a (zellweger) 29 PEX6

Anatomical Context for Peroxisome Biogenesis Disorder 4a

MalaCards organs/tissues related to Peroxisome Biogenesis Disorder 4a:

41
Liver, Eye

Publications for Peroxisome Biogenesis Disorder 4a

Variations for Peroxisome Biogenesis Disorder 4a

UniProtKB/Swiss-Prot genetic disease variations for Peroxisome Biogenesis Disorder 4a:

75
# Symbol AA change Variation ID SNP ID
1 PEX6 p.Arg812Gln VAR_007918 rs61753229
2 PEX6 p.Arg812Trp VAR_007919 rs61753228
3 PEX6 p.Asn849Thr VAR_058384 rs267608244
4 PEX6 p.Arg860Gln VAR_058385 rs61753231
5 PEX6 p.Arg860Trp VAR_058386 rs61753230
6 PEX6 p.Leu534Pro VAR_075872 rs387906809
7 PEX6 p.Gly413Val VAR_077508

ClinVar genetic disease variations for Peroxisome Biogenesis Disorder 4a:

6 (show top 50) (show all 116)
# Gene Variation Type Significance SNP ID Assembly Location
1 PEX6 PEX6, IVSAS, G-A, -1, 8-BP DEL deletion Pathogenic
2 PEX6 PEX6, 20-BP DEL/1-BP INS indel Pathogenic
3 PEX6 PEX6, 1-BP INS, NT511 insertion Pathogenic
4 PEX6 PEX6, IVS3DS, G-A, +1 single nucleotide variant Pathogenic
5 PEX6 PEX6, IVS7, G-A, +1 single nucleotide variant Pathogenic
6 PEX6 PEX6, 1-BP DEL, 1301C deletion Pathogenic
7 PEX6 NM_000287.3(PEX6): c.1338_1339delTG (p.Ala447Cysfs) deletion Pathogenic rs398123303 GRCh37 Chromosome 6, 42937434: 42937435
8 PEX6 NM_000287.3(PEX6): c.1338_1339delTG (p.Ala447Cysfs) deletion Pathogenic rs398123303 GRCh38 Chromosome 6, 42969696: 42969697
9 PEX6 NM_000287.3(PEX6): c.689_690dupAG (p.Ser232Hisfs) duplication Pathogenic rs398123305 GRCh37 Chromosome 6, 42946199: 42946200
10 PEX6 NM_000287.3(PEX6): c.689_690dupAG (p.Ser232Hisfs) duplication Pathogenic rs398123305 GRCh38 Chromosome 6, 42978461: 42978462
11 PEX6 NM_000287.3(PEX6): c.2440C> T (p.Arg814Ter) single nucleotide variant Pathogenic/Likely pathogenic rs267608241 GRCh37 Chromosome 6, 42933450: 42933450
12 PEX6 NM_000287.3(PEX6): c.2440C> T (p.Arg814Ter) single nucleotide variant Pathogenic/Likely pathogenic rs267608241 GRCh38 Chromosome 6, 42965712: 42965712
13 PEX6 NM_000287.3(PEX6): c.1802G> A (p.Arg601Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs34324426 GRCh37 Chromosome 6, 42935188: 42935188
14 PEX6 NM_000287.3(PEX6): c.1802G> A (p.Arg601Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs34324426 GRCh38 Chromosome 6, 42967450: 42967450
15 PEX6 NM_000287.3(PEX6): c.821C> T (p.Pro274Leu) single nucleotide variant Pathogenic/Likely pathogenic rs61753219 GRCh37 Chromosome 6, 42946068: 42946068
16 PEX6 NM_000287.3(PEX6): c.821C> T (p.Pro274Leu) single nucleotide variant Pathogenic/Likely pathogenic rs61753219 GRCh38 Chromosome 6, 42978330: 42978330
17 PEX6 NM_000287.3(PEX6): c.1841delT (p.Leu614Argfs) deletion Likely pathogenic rs863225083 GRCh37 Chromosome 6, 42935149: 42935149
18 PEX6 NM_000287.3(PEX6): c.1841delT (p.Leu614Argfs) deletion Likely pathogenic rs863225083 GRCh38 Chromosome 6, 42967411: 42967411
19 PEX6 NM_000287.3(PEX6): c.1314_1321delGGAGGCCT (p.Glu439Glyfs) deletion Pathogenic rs267608216 GRCh38 Chromosome 6, 42969714: 42969721
20 PEX6 NM_000287.3(PEX6): c.1314_1321delGGAGGCCT (p.Glu439Glyfs) deletion Pathogenic rs267608216 GRCh37 Chromosome 6, 42937452: 42937459
21 PEX6 NM_000287.3(PEX6): c.654C> G (p.Phe218Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs886037779 GRCh38 Chromosome 6, 42978497: 42978497
22 PEX6 NM_000287.3(PEX6): c.654C> G (p.Phe218Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs886037779 GRCh37 Chromosome 6, 42946235: 42946235
23 PEX6 NM_000287.3(PEX6): c.2730G> A (p.Thr910=) single nucleotide variant Likely benign rs774721609 GRCh38 Chromosome 6, 42964866: 42964866
24 PEX6 NM_000287.3(PEX6): c.2730G> A (p.Thr910=) single nucleotide variant Likely benign rs774721609 GRCh37 Chromosome 6, 42932604: 42932604
25 PEX6 NM_000287.3(PEX6): c.684dupC (p.Arg229Glnfs) duplication Pathogenic rs886043908 GRCh37 Chromosome 6, 42946205: 42946205
26 PEX6 NM_000287.3(PEX6): c.684dupC (p.Arg229Glnfs) duplication Pathogenic rs886043908 GRCh38 Chromosome 6, 42978467: 42978467
27 PEX6 NM_000287.3(PEX6): c.1202T> A (p.Leu401Ter) single nucleotide variant Pathogenic rs886044436 GRCh37 Chromosome 6, 42937654: 42937654
28 PEX6 NM_000287.3(PEX6): c.1202T> A (p.Leu401Ter) single nucleotide variant Pathogenic rs886044436 GRCh38 Chromosome 6, 42969916: 42969916
29 PEX6 NM_000287.3(PEX6): c.718G> A (p.Ala240Thr) single nucleotide variant Uncertain significance rs886061412 GRCh37 Chromosome 6, 42946171: 42946171
30 PEX6 NM_000287.3(PEX6): c.718G> A (p.Ala240Thr) single nucleotide variant Uncertain significance rs886061412 GRCh38 Chromosome 6, 42978433: 42978433
31 PEX6 NM_000287.3(PEX6): c.295C> T (p.Arg99Trp) single nucleotide variant Uncertain significance rs772383329 GRCh37 Chromosome 6, 42946594: 42946594
32 PEX6 NM_000287.3(PEX6): c.295C> T (p.Arg99Trp) single nucleotide variant Uncertain significance rs772383329 GRCh38 Chromosome 6, 42978856: 42978856
33 PEX6 NM_000287.3(PEX6): c.1947delG (p.Ile650Serfs) deletion Pathogenic rs267608227 GRCh38 Chromosome 6, 42966796: 42966796
34 PEX6 NM_000287.3(PEX6): c.1947delG (p.Ile650Serfs) deletion Pathogenic rs267608227 GRCh37 Chromosome 6, 42934534: 42934534
35 PEX6 NM_000287.3(PEX6): c.273G> A (p.Trp91Ter) single nucleotide variant Pathogenic/Likely pathogenic rs1010184002 GRCh38 Chromosome 6, 42978878: 42978878
36 PEX6 NM_000287.3(PEX6): c.273G> A (p.Trp91Ter) single nucleotide variant Pathogenic/Likely pathogenic rs1010184002 GRCh37 Chromosome 6, 42946616: 42946616
37 PEX6 NM_000287.3(PEX6): c.311delG (p.Gly104Valfs) deletion Pathogenic/Likely pathogenic rs61753209 GRCh38 Chromosome 6, 42978840: 42978840
38 PEX6 NM_000287.3(PEX6): c.311delG (p.Gly104Valfs) deletion Pathogenic/Likely pathogenic rs61753209 GRCh37 Chromosome 6, 42946578: 42946578
39 PEX6 NM_000287.3(PEX6): c.659G> T (p.Gly220Val) single nucleotide variant Uncertain significance rs267608203 GRCh38 Chromosome 6, 42978492: 42978492
40 PEX6 NM_000287.3(PEX6): c.659G> T (p.Gly220Val) single nucleotide variant Uncertain significance rs267608203 GRCh37 Chromosome 6, 42946230: 42946230
41 PEX6 NM_000287.3(PEX6): c.2806+1G> A single nucleotide variant Likely pathogenic rs751900826 GRCh37 Chromosome 6, 42932527: 42932527
42 PEX6 NM_000287.3(PEX6): c.2806+1G> A single nucleotide variant Likely pathogenic rs751900826 GRCh38 Chromosome 6, 42964789: 42964789
43 PEX6 NM_000287.3(PEX6): c.2692delC (p.Leu898Trpfs) deletion Likely pathogenic GRCh37 Chromosome 6, 42932641: 42932642
44 PEX6 NM_000287.3(PEX6): c.2692delC (p.Leu898Trpfs) deletion Likely pathogenic GRCh38 Chromosome 6, 42964904: 42964904
45 PEX6 NM_000287.3(PEX6): c.2626C> T (p.Arg876Trp) single nucleotide variant Uncertain significance rs267608246 GRCh37 Chromosome 6, 42932853: 42932853
46 PEX6 NM_000287.3(PEX6): c.2626C> T (p.Arg876Trp) single nucleotide variant Uncertain significance rs267608246 GRCh38 Chromosome 6, 42965115: 42965115
47 PEX6 NM_000287.3(PEX6): c.2362G> A (p.Val788Met) single nucleotide variant Likely pathogenic rs267608240 GRCh37 Chromosome 6, 42933782: 42933782
48 PEX6 NM_000287.3(PEX6): c.2362G> A (p.Val788Met) single nucleotide variant Likely pathogenic rs267608240 GRCh38 Chromosome 6, 42966044: 42966044
49 PEX6 NM_000287.3(PEX6): c.2356C> T (p.Arg786Trp) single nucleotide variant Uncertain significance rs267608239 GRCh37 Chromosome 6, 42933788: 42933788
50 PEX6 NM_000287.3(PEX6): c.2356C> T (p.Arg786Trp) single nucleotide variant Uncertain significance rs267608239 GRCh38 Chromosome 6, 42966050: 42966050

Expression for Peroxisome Biogenesis Disorder 4a

Search GEO for disease gene expression data for Peroxisome Biogenesis Disorder 4a.

Pathways for Peroxisome Biogenesis Disorder 4a

GO Terms for Peroxisome Biogenesis Disorder 4a

Sources for Peroxisome Biogenesis Disorder 4a

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....