PBD4A
MCID: PRX057
MIFTS: 32

Peroxisome Biogenesis Disorder 4a (PBD4A)

Categories: Ear 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 12 72 29 13 6 15 70
Pbd4a 57 72
Peroxisome Biogenesis Disorder Complementation Group 4 72
Peroxisome Biogenesis Disorder Complementation Group 6 72
Peroxisome Biogenesis Disorder Complementation Group C 72
Peroxisome Biogenesis Disorder, Type 4a 39
Pbd-Cg6 72
Pbd-Cgc 72
Pbd-Cg4 72
Cg4 72

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive


HPO:

31
peroxisome biogenesis disorder 4a:
Onset and clinical course death in infancy
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Peroxisome Biogenesis Disorder 4a

UniProtKB/Swiss-Prot : 72 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 and neuroblastoma. An important gene associated with Peroxisome Biogenesis Disorder 4a is PEX6 (Peroxisomal Biogenesis Factor 6). Affiliated tissues include eye, and related phenotypes are hepatomegaly and depressed nasal bridge

Disease Ontology : 12 A peroxisomal biogenesis disorder that has material basis in homozygous or compound heterozygous mutation in the PEX6 gene on chromosome 6p21.1.

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) (Updated 05-Apr-2021)

Related Diseases for Peroxisome Biogenesis Disorder 4a

Graphical network of the top 20 diseases related to Peroxisome Biogenesis Disorder 4a:



Diseases related to Peroxisome Biogenesis Disorder 4a

Symptoms & Phenotypes for Peroxisome Biogenesis Disorder 4a

Human phenotypes related to Peroxisome Biogenesis Disorder 4a:

31 (show all 12)
# Description HPO Frequency HPO Source Accession
1 hepatomegaly 31 HP:0002240
2 depressed nasal bridge 31 HP:0005280
3 hypertelorism 31 HP:0000316
4 feeding difficulties in infancy 31 HP:0008872
5 epiphyseal stippling 31 HP:0010655
6 upslanted palpebral fissure 31 HP:0000582
7 respiratory failure 31 HP:0002878
8 generalized neonatal hypotonia 31 HP:0008935
9 renal cyst 31 HP:0000107
10 generalized hypotonia 31 HP:0001290
11 epicanthus inversus 31 HP:0000537
12 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Abdomen Liver:
hepatomegaly

Head And Neck Nose:
low nasal bridge

Skeletal Limbs:
abnormal calcific stippling of patellae

Neurologic Central Nervous System:
clonic convulsions

Head And Neck Eyes:
hypertelorism
epicanthus inversus
upslanting palpebral fissures

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 (Updated 05-Apr-2021)

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:

40
Eye

Publications for Peroxisome Biogenesis Disorder 4a

Articles related to Peroxisome Biogenesis Disorder 4a:

(show all 21)
# Title Authors PMID Year
1
Human peroxisome assembly factor-2 (PAF-2): a gene responsible for group C peroxisome biogenesis disorder in humans. 6 57
8940266 1996
2
The peroxisome biogenesis disorder group 4 gene, PXAAA1, encodes a cytoplasmic ATPase required for stability of the PTS1 receptor. 6 57
8670792 1996
3
Spectrum of PEX1 and PEX6 variants in Heimler syndrome. 6
27302843 2016
4
The important role of biochemical and functional studies in the diagnostics of peroxisomal disorders. 6
26943801 2016
5
Absence of biochemical evidence at an early age delays diagnosis in a patient with a clinically severe peroxisomal biogenesis disorder. 6
26700162 2016
6
Zellweger spectrum disorders: clinical manifestations in patients surviving into adulthood. 6
26287655 2016
7
Heimler Syndrome Is Caused by Hypomorphic Mutations in the Peroxisome-Biogenesis Genes PEX1 and PEX6. 6
26387595 2015
8
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. 6
25525159 2015
9
Late-onset Zellweger spectrum disorder caused by PEX6 mutations mimicking X-linked adrenoleukodystrophy. 6
25079577 2014
10
Arginine improves peroxisome functioning in cells from patients with a mild peroxisome biogenesis disorder. 6
24016303 2013
11
Genetics and molecular basis of human peroxisome biogenesis disorders. 6
22871920 2012
12
A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population. 6
22894767 2012
13
Spectrum of PEX6 mutations in Zellweger syndrome spectrum patients. 6
19877282 2010
14
Rational diagnostic strategy for Zellweger syndrome spectrum patients. 6
19142205 2009
15
Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders. 6
19105186 2009
16
Peroxisome biogenesis disorders. 57
17055079 2006
17
Alternative splicing suggests extended function of PEX26 in peroxisome biogenesis. 6
15858711 2005
18
The PEX Gene Screen: molecular diagnosis of peroxisome biogenesis disorders in the Zellweger syndrome spectrum. 6
15542397 2004
19
The peroxin Pex6p gene is impaired in peroxisomal biogenesis disorders of complementation group 6. 6
11355018 2001
20
Temperature-sensitive mutation of PEX6 in peroxisome biogenesis disorders in complementation group C (CG-C): comparative study of PEX6 and PEX1. 6
11004248 2000
21
Genomic structure and identification of 11 novel mutations of the PEX6 (peroxisome assembly factor-2) gene in patients with peroxisome biogenesis disorders. 6
10408779 1999

Variations for Peroxisome Biogenesis Disorder 4a

ClinVar genetic disease variations for Peroxisome Biogenesis Disorder 4a:

6 (show top 50) (show all 133)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PEX6 PEX6, IVSAS, G-A, -1, 8-BP DEL Deletion Pathogenic 8119 GRCh37:
GRCh38:
2 PEX6 PEX6, 20-BP DEL/1-BP INS Indel Pathogenic 8120 GRCh37:
GRCh38:
3 PEX6 PEX6, 1-BP INS, NT511 Insertion Pathogenic 8121 GRCh37:
GRCh38:
4 PEX6 NM_000287.4(PEX6):c.1130+1G>A SNV Pathogenic 8122 rs267608213 GRCh37: 6:42941740-42941740
GRCh38: 6:42974002-42974002
5 PEX6 NM_000287.4(PEX6):c.1688+1G>A SNV Pathogenic 8123 rs112298166 GRCh37: 6:42936027-42936027
GRCh38: 6:42968289-42968289
6 PEX6 NM_000287.4(PEX6):c.1301del (p.Ser434fs) Deletion Pathogenic 8124 rs62641231 GRCh37: 6:42937472-42937472
GRCh38: 6:42969734-42969734
7 PEX6 NM_000287.4(PEX6):c.510_511del (p.Asp172fs) Deletion Pathogenic 802216 rs61753211 GRCh37: 6:42946378-42946379
GRCh38: 6:42978640-42978641
8 PEX6 NM_000287.4(PEX6):c.802_815del (p.Asp268fs) Deletion Pathogenic 555443 rs63749004 GRCh37: 6:42946074-42946087
GRCh38: 6:42978336-42978349
9 PEX6 NM_000287.4(PEX6):c.611C>G (p.Ser204Ter) SNV Pathogenic 973460 GRCh37: 6:42946278-42946278
GRCh38: 6:42978540-42978540
10 PEX6 NM_000287.4(PEX6):c.517del (p.Ser173fs) Deletion Pathogenic 557701 rs61753212 GRCh37: 6:42946372-42946372
GRCh38: 6:42978634-42978634
11 PEX6 NM_000287.4(PEX6):c.1962-1G>A SNV Pathogenic 550358 rs267608229 GRCh37: 6:42934396-42934396
GRCh38: 6:42966658-42966658
12 PEX6 NM_000287.4(PEX6):c.2440C>T (p.Arg814Ter) SNV Pathogenic 194165 rs267608241 GRCh37: 6:42933450-42933450
GRCh38: 6:42965712-42965712
13 PEX6 NM_000287.4(PEX6):c.882+1G>A SNV Pathogenic 973865 GRCh37: 6:42946006-42946006
GRCh38: 6:42978268-42978268
14 PEX6 NM_000287.4(PEX6):c.1314_1321del (p.Glu439fs) Deletion Pathogenic 224321 rs267608216 GRCh37: 6:42937452-42937459
GRCh38: 6:42969714-42969721
15 PEX6 NM_000287.4(PEX6):c.1802G>A (p.Arg601Gln) SNV Pathogenic 198709 rs34324426 GRCh37: 6:42935188-42935188
GRCh38: 6:42967450-42967450
16 PEX6 NM_000287.4(PEX6):c.406_407insT (p.Pro136fs) Insertion Likely pathogenic 619217 rs1561830903 GRCh37: 6:42946482-42946483
GRCh38: 6:42978744-42978745
17 PEX6 NM_000287.4(PEX6):c.1802G>A (p.Arg601Gln) SNV Likely pathogenic 198709 rs34324426 GRCh37: 6:42935188-42935188
GRCh38: 6:42967450-42967450
18 PEX6 NM_000287.4(PEX6):c.2362G>A (p.Val788Met) SNV Likely pathogenic 556244 rs267608240 GRCh37: 6:42933782-42933782
GRCh38: 6:42966044-42966044
19 PEX6 NM_000287.4(PEX6):c.1841del (p.Leu614fs) Deletion Likely pathogenic 217426 rs863225083 GRCh37: 6:42935149-42935149
GRCh38: 6:42967411-42967411
20 PEX6 NM_000287.4(PEX6):c.510dup (p.Gly171fs) Duplication Likely pathogenic 551023 rs1491384052 GRCh37: 6:42946378-42946379
GRCh38: 6:42978640-42978641
21 PEX6 NM_000287.4(PEX6):c.821C>T (p.Pro274Leu) SNV Likely pathogenic 217424 rs61753219 GRCh37: 6:42946068-42946068
GRCh38: 6:42978330-42978330
22 PEX6 NM_000287.4(PEX6):c.383_384GA[1] (p.Glu129fs) Microsatellite Likely pathogenic 555544 rs1554128501 GRCh37: 6:42946501-42946504
GRCh38: 6:42978763-42978766
23 PEX6 NM_000287.4(PEX6):c.2806+1G>A SNV Likely pathogenic 556094 rs751900826 GRCh37: 6:42932527-42932527
GRCh38: 6:42964789-42964789
24 PEX6 NM_000287.4(PEX6):c.42_43dup (p.Glu15fs) Duplication Likely pathogenic 556911 rs1554128586 GRCh37: 6:42946845-42946846
GRCh38: 6:42979107-42979108
25 PEX6 NM_000287.4(PEX6):c.406delinsAT (p.Pro136fs) Indel Likely pathogenic 557579 rs1554128488 GRCh37: 6:42946483-42946483
GRCh38: 6:42978745-42978745
26 PEX6 NM_000287.4(PEX6):c.1234-1G>T SNV Likely pathogenic 557825 rs1554127533 GRCh37: 6:42937540-42937540
GRCh38: 6:42969802-42969802
27 PEX6 NM_000287.4(PEX6):c.1479+2del Deletion Likely pathogenic 557926 rs1554127383 GRCh37: 6:42936610-42936610
GRCh38: 6:42968872-42968872
28 PEX6 NM_000287.4(PEX6):c.170T>C (p.Leu57Pro) SNV Likely pathogenic 631980 rs61752140 GRCh37: 6:42946719-42946719
GRCh38: 6:42978981-42978981
29 PEX6 NM_000287.4(PEX6):c.1801C>T (p.Arg601Trp) SNV Likely pathogenic 632484 rs61753225 GRCh37: 6:42935189-42935189
GRCh38: 6:42967451-42967451
30 PEX6 NM_000287.4(PEX6):c.160_243del (p.Val54_Leu81del) Deletion Likely pathogenic 931050 GRCh37: 6:42946646-42946729
GRCh38: 6:42978908-42978991
31 PEX6 NM_000287.4(PEX6):c.2663G>C (p.Arg888Pro) SNV Likely pathogenic 931051 GRCh37: 6:42932816-42932816
GRCh38: 6:42965078-42965078
32 PEX6 NM_000287.4(PEX6):c.2362+1G>A SNV Likely pathogenic 551145 rs1443107232 GRCh37: 6:42933781-42933781
GRCh38: 6:42966043-42966043
33 PEX6 NM_000287.4(PEX6):c.2692del (p.Leu898fs) Deletion Likely pathogenic 551147 rs1554126798 GRCh37: 6:42932642-42932642
GRCh38: 6:42964904-42964904
34 PEX6 NM_000287.4(PEX6):c.1130+2T>C SNV Likely pathogenic 551451 rs1416001981 GRCh37: 6:42941739-42941739
GRCh38: 6:42974001-42974001
35 PEX6 NM_000287.4(PEX6):c.462del (p.Leu155fs) Deletion Likely pathogenic 551682 rs1554128476 GRCh37: 6:42946427-42946427
GRCh38: 6:42978689-42978689
36 PEX6 NM_000287.4(PEX6):c.2472-2A>G SNV Likely pathogenic 551909 rs267608242 GRCh37: 6:42933108-42933108
GRCh38: 6:42965370-42965370
37 PEX6 NM_000287.4(PEX6):c.2082del (p.Gly695fs) Deletion Likely pathogenic 553235 rs766483138 GRCh37: 6:42934275-42934275
GRCh38: 6:42966537-42966537
38 PEX6 NM_000287.4(PEX6):c.2439dup (p.Arg814fs) Duplication Likely pathogenic 553359 rs1554126955 GRCh37: 6:42933450-42933451
GRCh38: 6:42965712-42965713
39 PEX6 NM_000287.4(PEX6):c.1368-2del Deletion Likely pathogenic 553545 rs1554127415 GRCh37: 6:42936725-42936725
GRCh38: 6:42968987-42968987
40 PEX6 NM_000287.4(PEX6):c.311del (p.Gly104fs) Deletion Likely pathogenic 499109 rs61753209 GRCh37: 6:42946578-42946578
GRCh38: 6:42978840-42978840
41 PEX6 NM_000287.4(PEX6):c.1046+1G>A SNV Likely pathogenic 553942 rs1554127968 GRCh37: 6:42942612-42942612
GRCh38: 6:42974874-42974874
42 PEX6 NM_000287.4(PEX6):c.133G>T (p.Glu45Ter) SNV Likely pathogenic 553970 rs1356280167 GRCh37: 6:42946756-42946756
GRCh38: 6:42979018-42979018
43 PEX6 NM_000287.4(PEX6):c.504_505AG[1] (p.Glu169fs) Microsatellite Likely pathogenic 554303 rs1554128461 GRCh37: 6:42946382-42946383
GRCh38: 6:42978644-42978645
44 PEX6 NM_000287.4(PEX6):c.2T>G (p.Met1Arg) SNV Likely pathogenic 555083 rs1554128597 GRCh37: 6:42946887-42946887
GRCh38: 6:42979149-42979149
45 PEX6 NM_000287.4(PEX6):c.2435G>A (p.Arg812Gln) SNV Likely pathogenic 555170 rs61753229 GRCh37: 6:42933455-42933455
GRCh38: 6:42965717-42965717
46 PEX6 NM_000287.4(PEX6):c.541_543GTG[1] (p.Val182del) Microsatellite Uncertain significance 552092 rs1554128449 GRCh37: 6:42946343-42946345
GRCh38: 6:42978605-42978607
47 PEX6 NM_000287.4(PEX6):c.295C>T (p.Arg99Trp) SNV Uncertain significance 356806 rs772383329 GRCh37: 6:42946594-42946594
GRCh38: 6:42978856-42978856
48 PEX6 NM_000287.4(PEX6):c.2225T>C (p.Leu742Pro) SNV Uncertain significance 552309 rs267608235 GRCh37: 6:42934055-42934055
GRCh38: 6:42966317-42966317
49 PEX6 NM_000287.4(PEX6):c.548_550CCT[1] (p.Ser184del) Microsatellite Uncertain significance 552800 rs1554128446 GRCh37: 6:42946336-42946338
GRCh38: 6:42978598-42978600
50 PEX6 NM_000287.4(PEX6):c.202_219del (p.Gly68_Gln73del) Deletion Uncertain significance 553026 rs1162020526 GRCh37: 6:42946670-42946687
GRCh38: 6:42978932-42978949

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

72
# 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 rs155412753

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 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-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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