DBPD
MCID: DBF001
MIFTS: 55

D-Bifunctional Protein Deficiency (DBPD)

Categories: Genetic diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for D-Bifunctional Protein Deficiency

MalaCards integrated aliases for D-Bifunctional Protein Deficiency:

Name: D-Bifunctional Protein Deficiency 57 12 20 43 72 36 13 54 15
Bifunctional Peroxisomal Enzyme Deficiency 43 29 6 70
17-Beta-Hydroxysteroid Dehydrogenase Iv Deficiency 57 20 43
Peroxisomal Bifunctional Enzyme Deficiency 57 20 43
Pbfe Deficiency 57 20 43
Dbp Deficiency 57 20 43
Bifunctional Enzyme Deficiency 20 58
Pseudo-Zellweger Syndrome 43 70
Protein Deficiency, D-Bifunctional 39
Zellweger-Like Syndrome 43
Dbpd 72

Characteristics:

OMIM®:

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

Miscellaneous:
onset in infancy
prevalence of 1 in 100,000
early death, usually before age 2 years


HPO:

31
d-bifunctional protein deficiency:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Inborn errors of metabolism


Summaries for D-Bifunctional Protein Deficiency

MedlinePlus Genetics : 43 D-bifunctional protein deficiency is a disorder that causes deterioration of nervous system functions (neurodegeneration) beginning in infancy. Newborns with D-bifunctional protein deficiency have weak muscle tone (hypotonia) and seizures. Most babies with this condition never acquire any developmental skills. Some may reach very early developmental milestones such as the ability to follow movement with their eyes or control their head movement, but they experience a gradual loss of these skills (developmental regression) within a few months. As the condition gets worse, affected children develop exaggerated reflexes (hyperreflexia), increased muscle tone (hypertonia), more severe and recurrent seizures (epilepsy), and loss of vision and hearing. Most children with D-bifunctional protein deficiency do not survive past the age of 2. A small number of individuals with this disorder are somewhat less severely affected. They may acquire additional basic skills, such as voluntary hand movements or unsupported sitting, before experiencing developmental regression, and they may survive longer into childhood than more severely affected individuals.Individuals with D-bifunctional protein deficiency may have unusual facial features, including a high forehead, widely spaced eyes (hypertelorism), a lengthened area between the nose and mouth (philtrum), and a high arch of the hard palate at the roof of the mouth. Affected infants may also have an unusually large space between the bones of the skull (fontanelle). An enlarged liver (hepatomegaly) occurs in about half of affected individuals. Because these features are similar to those of another disorder called Zellweger syndrome (part of a group of disorders called the Zellweger spectrum), D-bifunctional protein deficiency is sometimes called pseudo-Zellweger syndrome.

MalaCards based summary : D-Bifunctional Protein Deficiency, also known as bifunctional peroxisomal enzyme deficiency, is related to peroxisomal acyl-coa oxidase deficiency and perrault syndrome 1. An important gene associated with D-Bifunctional Protein Deficiency is HSD17B4 (Hydroxysteroid 17-Beta Dehydrogenase 4), and among its related pathways/superpathways are Primary bile acid biosynthesis and Biosynthesis of unsaturated fatty acids. The drugs Ursodeoxycholic acid and chenodeoxycholic acid have been mentioned in the context of this disorder. Affiliated tissues include liver, cortex and cerebellum, and related phenotypes are decreased nerve conduction velocity and cerebral hypoplasia

Disease Ontology : 12 A peroxisomal disease characterized by, in severe cases, infantile-onset of hypotonia, seizures, and abnormal facial features with most dieing before age 2 years that has material basis in homozygous or compound heterozygous mutation in the HSD17B4 gene on chromosome 5q2.

GARD : 20 D-bifunctional protein deficiency (DBP deficiency) is a genetic disorder that affects the ability of the body to effectively break down fat from our diet. It is typically characterized by hypotonia (low muscle tone) and seizures in the newborn period. Other symptoms include unusual facial features and an enlarged liver (hepatomegaly). Most babies with this condition never gain any developmental skills and do not survive past the age of 2. DBP deficiency is caused by mutations in the HSD17B4 gene and is inherited in an autosomal recessive manner. Some researchers have suggested classifying DBP deficiency into three subtypes, depending on how severely the mutation in the HSD17B4 gene affects the function of the gene and the protein that it codes for. Almost all individuals with types I, II, and III have similar signs and symptoms. A fourth subtype has additionally been proposed for individuals that have less severe symptoms. While there is no cure for DBP deficiency, treatment is focused on improving nutrition and growth, controlling symptoms, and limiting the progression of liver disease.

OMIM® : 57 D-bifunctional protein deficiency is a disorder of peroxisomal fatty acid beta-oxidation. See also peroxisomal acyl-CoA oxidase deficiency (264470), caused by mutation in the ACOX1 gene (609751) on chromosome 17q25. The clinical manifestations of these 2 deficiencies are similar to those of disorders of peroxisomal assembly, including X-linked adrenoleukodystrophy (ALD; 300100), Zellweger cerebrohepatorenal syndrome (see 214100) and neonatal adrenoleukodystrophy (NALD; see 601539) (Watkins et al., 1995). DBP deficiency has been classified into 3 subtypes depending upon the deficient enzyme activity. Type I is a deficiency of both 2-enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase; type II is a deficiency of hydratase activity alone; and type III is a deficiency of dehydrogenase activity alone. Virtually all patients with types I, II, and III have a severe phenotype characterized by infantile-onset of hypotonia, seizures, and abnormal facial features, and most die before age 2 years. McMillan et al. (2012) proposed a type IV deficiency on the basis of less severe features; these patients have a phenotype reminiscent of Perrault syndrome (PRLTS1; 233400). Pierce et al. (2010) noted that Perrault syndrome and DBP deficiency overlap clinically and suggested that DBP deficiency may be underdiagnosed. (261515) (Updated 20-May-2021)

KEGG : 36 D-bifunctional protein (DBP) deficiency is an autosomal recessive inborn error of peroxisomal fatty acid oxidation. DBP is a homodimeric enzyme with 79-kDa subunits, each of which consists of three functional units. And it catalyzes the second and third steps of peroxisomal beta-oxidation of fatty acids. The biochemical hallmark of this disorder is the accumulation of very long-chain fatty acids (VLCFA), 2-methyl branched-chain fatty acids, and the bile acid intermediates (DHCA/THCA). The clinical presentation is very severe, and most affected children die within the first 2 years of life. Virtually all patients present with neonatal hypotonia and seizures.

UniProtKB/Swiss-Prot : 72 D-bifunctional protein deficiency: Disorder of peroxisomal fatty acid beta-oxidation.

Wikipedia : 73 D-Bifunctional protein deficiency is an autosomal recessive peroxisomal fatty acid oxidation disorder.... more...

Related Diseases for D-Bifunctional Protein Deficiency

Diseases related to D-Bifunctional Protein Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 58)
# Related Disease Score Top Affiliating Genes
1 peroxisomal acyl-coa oxidase deficiency 32.2 SCP2 HSD17B4 ACOX1
2 perrault syndrome 1 31.1 LARS2 HSD17B4
3 leukodystrophy 30.1 SCP2 LARS2 HSD17B4 ACOX1 ABCD1
4 peroxisomal disease 30.1 SCP2 HSD17B4 HADHB ACOX1 ABCD3 ABCD1
5 46 xx gonadal dysgenesis 29.9 LARS2 HSD17B4 CLPP
6 perrault syndrome 29.8 TWNK RFLNA PPP4R4 LARS2 HSD17B4 DHRS11
7 peroxisomal biogenesis disorder 29.6 SCP2 HSD17B4 ACOX2 ACOX1 ABCD3 ABCD1
8 peroxisome biogenesis disorder 1b 29.6 SCP2 HSD17B4 ACOX1 ABCD3 ABCD1
9 adrenoleukodystrophy 29.2 SCP2 HSD17B4 HADHB ELOVL1 EHHADH ACOX1
10 zellweger syndrome 29.0 SCP2 HSD17B4 HADHB EHHADH ACOX3 ACOX2
11 alpha-methylacetoacetic aciduria 11.4
12 zellweger-like syndrome without peroxisomal anomalies 11.2
13 hypotonia 10.5
14 ataxia and polyneuropathy, adult-onset 10.3
15 neuropathy 10.3
16 branchiootic syndrome 1 10.2
17 polymicrogyria with or without vascular-type ehlers-danlos syndrome 10.2
18 autosomal recessive disease 10.2
19 hypogonadism 10.2
20 peripheral nervous system disease 10.2
21 pathologic nystagmus 10.2
22 polymicrogyria 10.2
23 adrenomyeloneuropathy 10.2
24 rare genetic deafness 10.2
25 neonatal adrenoleukodystrophy 10.1
26 rhizomelic chondrodysplasia punctata, type 1 10.1 SCP2 HSD17B4 HADHB ACOX1
27 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.0
28 ascites, chylous 10.0
29 retinitis pigmentosa 10.0
30 cyanosis, transient neonatal 10.0
31 acatalasemia 10.0
32 west syndrome 10.0
33 sensorineural hearing loss 10.0
34 neuroretinitis 10.0
35 retinitis 10.0
36 polyhydramnios 10.0
37 zellweger spectrum disorder 10.0
38 pachygyria 10.0
39 seizure disorder 10.0
40 spinocerebellar degeneration 10.0
41 primary adrenal insufficiency 10.0
42 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 3 10.0 TWNK LARS2
43 multiple synostoses syndrome 10.0 LARS2 HSD17B4 CLPP
44 colpocephaly 10.0
45 carbonic anhydrase va deficiency, hyperammonemia due to 9.9
46 liver disease 9.9
47 syndromic x-linked intellectual disability type 10 9.9 HADH DHRS11
48 mitochondrial trifunctional protein deficiency 9.9 HADHB HADH EHHADH
49 spondylocarpotarsal synostosis syndrome 9.9 RFLNA PPP4R4 GLTP ACOX2
50 carnitine deficiency, systemic primary 9.9 HADHB HADH

Graphical network of the top 20 diseases related to D-Bifunctional Protein Deficiency:



Diseases related to D-Bifunctional Protein Deficiency

Symptoms & Phenotypes for D-Bifunctional Protein Deficiency

Human phenotypes related to D-Bifunctional Protein Deficiency:

31 (show top 50) (show all 56)
# Description HPO Frequency HPO Source Accession
1 decreased nerve conduction velocity 31 very rare (1%) HP:0000762
2 cerebral hypoplasia 31 very rare (1%) HP:0006872
3 macrocephaly 31 HP:0000256
4 failure to thrive 31 HP:0001508
5 frontal bossing 31 HP:0002007
6 nystagmus 31 HP:0000639
7 high palate 31 HP:0000218
8 osteopenia 31 HP:0000938
9 global developmental delay 31 HP:0001263
10 hepatomegaly 31 HP:0002240
11 delayed skeletal maturation 31 HP:0002750
12 depressed nasal bridge 31 HP:0005280
13 hypertelorism 31 HP:0000316
14 abnormal facial shape 31 HP:0001999
15 visual impairment 31 HP:0000505
16 neonatal hypotonia 31 HP:0001319
17 feeding difficulties in infancy 31 HP:0008872
18 decreased muscle mass 31 HP:0003199
19 strabismus 31 HP:0000486
20 retrognathia 31 HP:0000278
21 micrognathia 31 HP:0000347
22 low-set ears 31 HP:0000369
23 hepatic steatosis 31 HP:0001397
24 elevated hepatic transaminase 31 HP:0002910
25 epicanthus 31 HP:0000286
26 pectus excavatum 31 HP:0000767
27 talipes equinovarus 31 HP:0001762
28 dolichocephaly 31 HP:0000268
29 upslanted palpebral fissure 31 HP:0000582
30 polyhydramnios 31 HP:0001561
31 aplasia/hypoplasia of the cerebellum 31 HP:0007360
32 long philtrum 31 HP:0000343
33 ventriculomegaly 31 HP:0002119
34 split hand 31 HP:0001171
35 high forehead 31 HP:0000348
36 large fontanelles 31 HP:0000239
37 polymicrogyria 31 HP:0002126
38 primary adrenal insufficiency 31 HP:0008207
39 delayed cranial suture closure 31 HP:0000270
40 cholestasis 31 HP:0001396
41 hypoplasia of the corpus callosum 31 HP:0002079
42 hammertoe 31 HP:0001765
43 renal cyst 31 HP:0000107
44 thoracic hypoplasia 31 HP:0005257
45 visual loss 31 HP:0000572
46 fetal ascites 31 HP:0001791
47 generalized cerebral atrophy/hypoplasia 31 HP:0007058
48 corpus callosum atrophy 31 HP:0007371
49 cortical dysplasia 31 HP:0002539
50 cerebral dysmyelination 31 HP:0007266

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Head:
macrocephaly
large fontanelles
scaphocephaly
delayed closure of the fontanelles

Head And Neck Eyes:
nystagmus
hypertelorism
strabismus
epicanthal folds
upslanting palpebral fissures
more
Muscle Soft Tissue:
decreased muscle mass

Skeletal Feet:
talipes equinovarus
hammertoes

Skeletal:
calcific stippling
delayed bone maturation
generalized osteopenia

Abdomen Gastrointestinal:
poor feeding

Chest External Features:
funnel chest
long, small thorax

Abdomen Liver:
abnormal liver function (26%)
hepatomegaly (43%)
histology shows normal numbers of peroxisomes (84%)
abnormal peroxisomes (53%)
absence of peroxisomes (16%)
more
Neurologic Central Nervous System:
hypotonia, neonatal (> 90%)
seizures (> 90%)
delayed psychomotor development, severe (> 90%)
polymicrogyria (64%)
ventricular dilatation (29%)
more
Endocrine Features:
adrenocortical insufficiency (uncommon)

Head And Neck Face:
frontal bossing
retrognathia
micrognathia
long philtrum
high forehead
more
Head And Neck Nose:
depressed nasal bridge

Head And Neck Ears:
low-set ears
loss of hearing (45%)

Prenatal Manifestations Amniotic Fluid:
polyhydramnios
fetal ascites

Head And Neck Mouth:
high-arched palate

Skeletal Hands:
claw hands

Growth Other:
failure to thrive (44% of patients)

Genitourinary Kidneys:
renal cysts (33%)
adrenal cortex atrophy (42%)

Neurologic Peripheral Nervous System:
delayed peripheral nerve motor conduction velocities (67%)

Laboratory Abnormalities:
increased plasma levels of very long-chain fatty acids (vlcfa)
increased plasma levels of bile acid intermediates
decreased peroxisomal fatty acid beta-oxidation
decreased or absent d-bifunctional protein activity and protein
normal serum plasmalogen

Clinical features from OMIM®:

261515 (Updated 20-May-2021)

Drugs & Therapeutics for D-Bifunctional Protein Deficiency

Drugs for D-Bifunctional Protein Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Ursodeoxycholic acid Approved, Investigational 128-13-2 31401
2
chenodeoxycholic acid Approved 474-25-9 10133
3 Cholic Acids
4 Cathartics
5 Gastrointestinal Agents
6 Bile Acids and Salts
7 Laxatives

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Study of Bile Acids in Patients With Peroxisomal Disorders Terminated NCT00004442 chenodeoxycholic acid;cholic acid;ursodiol

Search NIH Clinical Center for D-Bifunctional Protein Deficiency

Genetic Tests for D-Bifunctional Protein Deficiency

Genetic tests related to D-Bifunctional Protein Deficiency:

# Genetic test Affiliating Genes
1 Bifunctional Peroxisomal Enzyme Deficiency 29 HSD17B4

Anatomical Context for D-Bifunctional Protein Deficiency

MalaCards organs/tissues related to D-Bifunctional Protein Deficiency:

40
Liver, Cortex, Cerebellum, Adrenal Cortex, Bone

Publications for D-Bifunctional Protein Deficiency

Articles related to D-Bifunctional Protein Deficiency:

(show top 50) (show all 76)
# Title Authors PMID Year
1
Mutational spectrum of D-bifunctional protein deficiency and structure-based genotype-phenotype analysis. 54 57 61 6
16385454 2006
2
Specific combination of compound heterozygous mutations in 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4) defines a new subtype of D-bifunctional protein deficiency. 6 57 61
23181892 2012
3
D-bifunctional protein deficiency with fetal ascites, polyhydramnios, and contractures of hands and toes. 61 57 6
11743515 2001
4
Peroxisomal D-hydroxyacyl-CoA dehydrogenase deficiency: resolution of the enzyme defect and its molecular basis in bifunctional protein deficiency. 57 6 61
9482850 1998
5
D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency: a newly identified peroxisomal disorder. 61 6 57
9345094 1997
6
D-bifunctional protein deficiency: a cause of neonatal onset seizures and hypotonia. 6 61 20
25882080 2015
7
Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault Syndrome. 6 57
20673864 2010
8
Clinical and biochemical spectrum of D-bifunctional protein deficiency. 57 20 61
16278854 2006
9
A novel HPLC-based method to diagnose peroxisomal D-bifunctional protein enoyl-CoA hydratase deficiency. 6 57
12562856 2003
10
Reinvestigation of peroxisomal 3-ketoacyl-CoA thiolase deficiency: identification of the true defect at the level of d-bifunctional protein. 6 57
11992265 2002
11
Peroxisomal bifunctional protein deficiency revisited: resolution of its true enzymatic and molecular basis. 6 57
9915948 1999
12
Novel subtype of peroxisomal acyl-CoA oxidase deficiency and bifunctional enzyme deficiency with detectable enzyme protein: identification by means of complementation analysis. 57 6
8279468 1994
13
Peroxisomal bifunctional enzyme deficiency. 57 6
2921319 1989
14
Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency. 6 57
2882519 1987
15
Pseudo-Zellweger syndrome: deficiencies in several peroxisomal oxidative activities. 6 57
2868085 1986
16
Enoyl-CoA hydratase deficiency: identification of a new type of D-bifunctional protein deficiency. 6 54 61
10400999 1999
17
A homozygous missense variant in HSD17B4 identified in a consanguineous Chinese Han family with type II Perrault syndrome. 61 6
28830375 2017
18
Slowly progressive d-bifunctional protein deficiency with survival to adulthood diagnosed by whole-exome sequencing. 61 6
28017249 2017
19
Heterozygous mutations in HSD17B4 cause juvenile peroxisomal D-bifunctional protein deficiency. 6 61
27790638 2016
20
Peroxisomal D-bifunctional protein deficiency: First case reports from Slovakia. 61 6
25967389 2015
21
On the molecular basis of D-bifunctional protein deficiency type III. 6 61
23308274 2013
22
Typical cMRI pattern as diagnostic clue for D-bifunctional protein deficiency without apparent biochemical abnormalities in plasma. 61 57
20949532 2010
23
Molecular analysis of genomic DNA allows rapid, and accurate, prenatal diagnosis of peroxisomal D-bifunctional protein deficiency. 61 6
11810648 2002
24
Perrault syndrome with neurological features in a compound heterozygote for two TWNK mutations: overlap of TWNK-related recessive disorders. 6
31455392 2019
25
Expanding the genotypic spectrum of Perrault syndrome. 6
26970254 2017
26
Mini-Exome Coupled to Read-Depth Based Copy Number Variation Analysis in Patients with Inherited Ataxias. 6
27528516 2016
27
New perspective in diagnostics of mitochondrial disorders: two years' experience with whole-exome sequencing at a national paediatric centre. 6
27290639 2016
28
Targeted Next Generation Sequencing in Patients with Inborn Errors of Metabolism. 6
27243974 2016
29
Genetics of primary ovarian insufficiency: new developments and opportunities. 6
26243799 2015
30
Exome sequencing as a diagnostic tool for pediatric-onset ataxia. 6
24108619 2014
31
A clinical evaluation tool for SNP arrays, especially for autosomal recessive conditions in offspring of consanguineous parents. 6
23100014 2013
32
Hydratase activities of green fluorescent protein tagged human multifunctional enzyme type 2 hydratase domain and its variants. 6
22864515 2012
33
Inactivation of the peroxisomal multifunctional protein-2 in mice impedes the degradation of not only 2-methyl-branched fatty acids and bile acid intermediates but also of very long chain fatty acids. 6
10748062 2000
34
Molecular changes in the D-bifunctional protein cDNA sequence in Australasian patients belonging to the bifunctional protein complementation group. 6
11330053 2000
35
Yeast peroxisomal multifunctional enzyme: (3R)-hydroxyacyl-CoA dehydrogenase domains A and B are required for optimal growth on oleic acid. 6
10497229 1999
36
Characterization of the HSD17B4 gene: D-specific multifunctional protein 2/17beta-hydroxysteroid dehydrogenase IV. 6
10419023 1999
37
Prenatal diagnosis of peroxisomal D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency. 57
10319576 1999
38
Distinction between peroxisomal bifunctional enzyme and acyl-CoA oxidase deficiencies. 57
7668838 1995
39
A case of pseudo-Zellweger syndrome with a possible bifunctional enzyme deficiency but detectable enzyme protein. Comparison of two cases of Zellweger syndrome. 57
8147505 1993
40
Bifunctional enzyme deficiency: identification of a new type of peroxisomal disorder in a patient with an impairment in peroxisomal beta-oxidation of unknown aetiology by means of complementation analysis. 57
1357231 1992
41
Bile acid profiles in peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency. 57
2318981 1990
42
A bifunctional protein with deficient enzymic activity: identification of a new peroxisomal disorder using novel methods to measure the peroxisomal beta-oxidation enzyme activities. 57
2122104 1990
43
Neonatal seizures and retardation in a girl with biochemical features of X-linked adrenoleukodystrophy: a possible new peroxisomal disease entity. 57
3386829 1988
44
Sensitive analysis of serum 3alpha, 7alpha, 12alpha,24-tetrahydroxy- 5beta-cholestan-26-oic acid diastereomers using gas chromatography-mass spectrometry and its application in peroxisomal D-bifunctional protein deficiency. 61 54
9831634 1998
45
Rapid whole-genome sequencing identifies a homozygous novel variant, His540Arg, in HSD17B4 resulting in D-bifunctional protein deficiency disorder diagnosis. 61
33115767 2020
46
Eyes See what the Mind Knows: Clues to Pattern Recognition in Single Enzyme Deficiency-Related Peroxisomal Disorders. 61
33510602 2020
47
First Case of Peroxisomal D-bifunctional Protein Deficiency with Novel HSD17B4 Mutations and Progressive Neuropathy in Korea. 61
33045774 2020
48
Primary adrenal insufficiency in two siblings with D-bifunctional protein deficiency. 61
32528852 2020
49
Utility of metabolic screening in neurological presentations of infancy. 61
32495504 2020
50
Unusual Clinical Course and Imaging of D-Bifunctional Protein Deficiency, a Rare Leukodystrophy. 61
30396834 2019

Variations for D-Bifunctional Protein Deficiency

ClinVar genetic disease variations for D-Bifunctional Protein Deficiency:

6 (show top 50) (show all 239)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 HSD17B4 NM_000414.4(HSD17B4):c.1212_1261+2del Deletion Pathogenic 7653 rs1554065670 GRCh37: 5:118837734-118837785
GRCh38: 5:119502039-119502090
2 HSD17B4 NM_000414.4(HSD17B4):c.974_1209+1del Deletion Pathogenic 7654 rs1554065254 GRCh37: 5:118835010-118835246
GRCh38: 5:119499315-119499551
3 HSD17B4 NM_000414.4(HSD17B4):c.317G>C (p.Arg106Pro) SNV Pathogenic 7657 rs25640 GRCh37: 5:118811533-118811533
GRCh38: 5:119475838-119475838
4 HSD17B4 HSD17B4, 138-BP DEL Deletion Pathogenic 7658 GRCh37:
GRCh38:
5 HSD17B4 NM_000414.4(HSD17B4):c.423_424del (p.Lys142fs) Deletion Pathogenic 7659 rs775832137 GRCh37: 5:118813184-118813185
GRCh38: 5:119477489-119477490
6 HSD17B4 NM_000414.4(HSD17B4):c.302+3_302+6del Deletion Pathogenic 218138 rs863225438 GRCh37: 5:118811423-118811426
GRCh38: 5:119475728-119475731
7 HSD17B4 NM_000414.4(HSD17B4):c.1369A>T (p.Asn457Tyr) SNV Pathogenic 7656 rs137853097 GRCh37: 5:118844871-118844871
GRCh38: 5:119509176-119509176
8 HSD17B4 NM_000414.4(HSD17B4):c.46G>A (p.Gly16Ser) SNV Pathogenic 7655 rs137853096 GRCh37: 5:118788316-118788316
GRCh38: 5:119452621-119452621
9 HSD17B4 NM_000414.4(HSD17B4):c.1578del (p.Phe526fs) Deletion Pathogenic 582190 rs1561485663 GRCh37: 5:118861613-118861613
GRCh38: 5:119525918-119525918
10 HSD17B4 NM_000414.4(HSD17B4):c.1628_1629GT[5] (p.Leu545fs) Microsatellite Pathogenic 371505 rs1057517323 GRCh37: 5:118861665-118861666
GRCh38: 5:119525970-119525971
11 HSD17B4 NM_000414.4(HSD17B4):c.2029C>T (p.Gln677Ter) SNV Pathogenic 551750 rs751646311 GRCh37: 5:118872153-118872153
GRCh38: 5:119536458-119536458
12 HSD17B4 NM_000414.4(HSD17B4):c.1704T>A (p.Tyr568Ter) SNV Pathogenic 655256 rs1038744864 GRCh37: 5:118862851-118862851
GRCh38: 5:119527156-119527156
13 HSD17B4 NM_000414.4(HSD17B4):c.742C>T (p.Arg248Cys) SNV Pathogenic 371366 rs969485098 GRCh37: 5:118829515-118829515
GRCh38: 5:119493820-119493820
14 HSD17B4 NM_000414.4(HSD17B4):c.936_937del (p.His312_Thr313insTer) Deletion Pathogenic 504023 rs758055753 GRCh37: 5:118832304-118832305
GRCh38: 5:119496609-119496610
15 HSD17B4 NM_000414.4(HSD17B4):c.1993+1G>A SNV Pathogenic 802151 rs1580711803 GRCh37: 5:118867100-118867100
GRCh38: 5:119531405-119531405
16 HSD17B4 GRCh37/hg19 5q23.1(chr5:118811401-118814716) copy number loss Pathogenic 813314 GRCh37: 5:118811401-118814716
GRCh38:
17 HSD17B4 NM_000414.4(HSD17B4):c.1715_1716CT[1] (p.Leu573fs) Microsatellite Pathogenic 371008 rs1057516936 GRCh37: 5:118862862-118862863
GRCh38: 5:119527167-119527168
18 HSD17B4 NM_000414.4(HSD17B4):c.1352del (p.Lys451fs) Deletion Pathogenic 854726 GRCh37: 5:118844853-118844853
GRCh38: 5:119509158-119509158
19 HSD17B4 NM_000414.4(HSD17B4):c.1147C>T (p.Gln383Ter) SNV Pathogenic 861128 GRCh37: 5:118835186-118835186
GRCh38: 5:119499491-119499491
20 HSD17B4 NM_000414.4(HSD17B4):c.1424C>G (p.Ser475Ter) SNV Pathogenic 939009 GRCh37: 5:118844926-118844926
GRCh38: 5:119509231-119509231
21 HSD17B4 NM_000414.4(HSD17B4):c.58+1G>C SNV Pathogenic 945823 GRCh37: 5:118788329-118788329
GRCh38: 5:119452634-119452634
22 HSD17B4 NM_000414.4(HSD17B4):c.1659_1660dup (p.Ser554fs) Microsatellite Pathogenic 949620 GRCh37: 5:118861693-118861694
GRCh38: 5:119525998-119525999
23 HSD17B4 NM_000414.4(HSD17B4):c.936_937del (p.His312_Thr313insTer) Deletion Pathogenic 504023 rs758055753 GRCh37: 5:118832304-118832305
GRCh38: 5:119496609-119496610
24 HSD17B4 NM_000414.4(HSD17B4):c.1704T>A (p.Tyr568Ter) SNV Pathogenic 655256 rs1038744864 GRCh37: 5:118862851-118862851
GRCh38: 5:119527156-119527156
25 HSD17B4 NM_000414.4(HSD17B4):c.1516C>T (p.Arg506Cys) SNV Pathogenic 495866 rs766199971 GRCh37: 5:118860923-118860923
GRCh38: 5:119525228-119525228
26 HSD17B4 NM_000414.4(HSD17B4):c.1516C>T (p.Arg506Cys) SNV Pathogenic 495866 rs766199971 GRCh37: 5:118860923-118860923
GRCh38: 5:119525228-119525228
27 HSD17B4 NM_000414.4(HSD17B4):c.868+1del Deletion Pathogenic/Likely pathogenic 632857 rs749532705 GRCh37: 5:118829641-118829641
GRCh38: 5:119493946-119493946
28 HSD17B4 NM_000414.4(HSD17B4):c.46G>A (p.Gly16Ser) SNV Pathogenic/Likely pathogenic 7655 rs137853096 GRCh37: 5:118788316-118788316
GRCh38: 5:119452621-119452621
29 HSD17B4 NM_000414.4(HSD17B4):c.1369A>T (p.Asn457Tyr) SNV Pathogenic/Likely pathogenic 7656 rs137853097 GRCh37: 5:118844871-118844871
GRCh38: 5:119509176-119509176
30 HSD17B4 NM_000414.4(HSD17B4):c.742C>T (p.Arg248Cys) SNV Pathogenic/Likely pathogenic 371366 rs969485098 GRCh37: 5:118829515-118829515
GRCh38: 5:119493820-119493820
31 HSD17B4 NM_000414.4(HSD17B4):c.1210-1G>A SNV Pathogenic/Likely pathogenic 551541 rs1554065671 GRCh37: 5:118837735-118837735
GRCh38: 5:119502040-119502040
32 HSD17B4 NM_000414.4(HSD17B4):c.2029C>T (p.Gln677Ter) SNV Pathogenic/Likely pathogenic 551750 rs751646311 GRCh37: 5:118872153-118872153
GRCh38: 5:119536458-119536458
33 HSD17B4 NM_000414.4(HSD17B4):c.623-1G>A SNV Likely pathogenic 552445 rs1554064083 GRCh37: 5:118824886-118824886
GRCh38: 5:119489191-119489191
34 HSD17B4 NM_000414.4(HSD17B4):c.435-2A>T SNV Likely pathogenic 550447 rs1171426785 GRCh37: 5:118814527-118814527
GRCh38: 5:119478832-119478832
35 HSD17B4 NM_000414.4(HSD17B4):c.1334-2A>T SNV Likely pathogenic 551172 rs1554066421 GRCh37: 5:118844834-118844834
GRCh38: 5:119509139-119509139
36 HSD17B4 NM_000414.4(HSD17B4):c.281-2A>G SNV Likely pathogenic 552986 rs1554062343 GRCh37: 5:118811399-118811399
GRCh38: 5:119475704-119475704
37 HSD17B4 NM_000414.4(HSD17B4):c.2121+1G>C SNV Likely pathogenic 553177 rs1554069610 GRCh37: 5:118872246-118872246
GRCh38: 5:119536551-119536551
38 HSD17B4 NM_000414.4(HSD17B4):c.1994-2A>G SNV Likely pathogenic 553841 rs1554069592 GRCh37: 5:118872116-118872116
GRCh38: 5:119536421-119536421
39 HSD17B4 NM_000414.4(HSD17B4):c.56_58+3del Deletion Likely pathogenic 554249 rs1554059509 GRCh37: 5:118788325-118788330
GRCh38: 5:119452630-119452635
40 HSD17B4 NM_000414.4(HSD17B4):c.1748_1749del (p.Arg583fs) Deletion Likely pathogenic 554583 rs1554068426 GRCh37: 5:118862894-118862895
GRCh38: 5:119527199-119527200
41 HSD17B4 NM_000414.4(HSD17B4):c.1504-2A>C SNV Likely pathogenic 550182 rs1554068134 GRCh37: 5:118860909-118860909
GRCh38: 5:119525214-119525214
42 HSD17B4 NM_000414.4(HSD17B4):c.113-1G>T SNV Likely pathogenic 550255 rs1224475289 GRCh37: 5:118809602-118809602
GRCh38: 5:119473907-119473907
43 HSD17B4 NM_000414.4(HSD17B4):c.270del (p.Phe90fs) Deletion Likely pathogenic 550351 rs1276397342 GRCh37: 5:118810142-118810142
GRCh38: 5:119474447-119474447
44 HSD17B4 NM_000414.4(HSD17B4):c.1440_1441del (p.Ala481fs) Deletion Likely pathogenic 370908 rs1057516859 GRCh37: 5:118850678-118850679
GRCh38: 5:119514983-119514984
45 HSD17B4 NM_000414.4(HSD17B4):c.1300_1303del (p.Asp434fs) Deletion Likely pathogenic 371150 rs1057517045 GRCh37: 5:118842549-118842552
GRCh38: 5:119506854-119506857
46 HSD17B4 NM_000414.4(HSD17B4):c.1907del (p.Lys636fs) Deletion Likely pathogenic 370204 rs1057516312 GRCh37: 5:118867011-118867011
GRCh38: 5:119531316-119531316
47 HSD17B4 NM_000414.4(HSD17B4):c.1628_1629GT[5] (p.Leu545fs) Microsatellite Likely pathogenic 371505 rs1057517323 GRCh37: 5:118861665-118861666
GRCh38: 5:119525970-119525971
48 HSD17B4 NM_000414.4(HSD17B4):c.1715_1716CT[1] (p.Leu573fs) Microsatellite Likely pathogenic 371008 rs1057516936 GRCh37: 5:118862862-118862863
GRCh38: 5:119527167-119527168
49 HSD17B4 NM_000414.4(HSD17B4):c.296dup (p.Asn99fs) Duplication Likely pathogenic 370669 rs1057516672 GRCh37: 5:118811414-118811415
GRCh38: 5:119475719-119475720
50 HSD17B4 NM_000414.4(HSD17B4):c.1369A>G (p.Asn457Asp) SNV Likely pathogenic 371413 rs137853097 GRCh37: 5:118844871-118844871
GRCh38: 5:119509176-119509176

UniProtKB/Swiss-Prot genetic disease variations for D-Bifunctional Protein Deficiency:

72
# Symbol AA change Variation ID SNP ID
1 HSD17B4 p.Gly16Ser VAR_037576 rs137853096
2 HSD17B4 p.Arg106Pro VAR_065906 rs25640
3 HSD17B4 p.Asn457Tyr VAR_065908 rs137853097

Expression for D-Bifunctional Protein Deficiency

Search GEO for disease gene expression data for D-Bifunctional Protein Deficiency.

Pathways for D-Bifunctional Protein Deficiency

Pathways related to D-Bifunctional Protein Deficiency according to KEGG:

36
# Name Kegg Source Accession
1 Primary bile acid biosynthesis hsa00120
2 Biosynthesis of unsaturated fatty acids hsa01040
3 Peroxisome hsa04146

Pathways related to D-Bifunctional Protein Deficiency according to GeneCards Suite gene sharing:

(show all 15)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.91 SCP2 MOCS1 HSD17B4 HADHB HADH GLTP
2
Show member pathways
12.38 SCP2 HSD17B4 HADHB HADH ELOVL1 EHHADH
3
Show member pathways
11.77 HADHB HADH EHHADH
4 11.65 LARS2 HADH EHHADH
5 11.65 SCP2 EHHADH ACOX3 ACOX2 ACOX1
6
Show member pathways
11.55 SCP2 HSD17B4 HADHB HADH ELOVL1 ACOX3
7
Show member pathways
11.53 SCP2 HSD17B4 EHHADH ACOX3 ACOX2 ACOX1
8
Show member pathways
11.43 SCP2 HADHB HADH EHHADH
9
Show member pathways
11.42 SCP2 HSD17B4 HADHB HADH EHHADH ACOX2
10 11.16 EHHADH ACOX3 ACOX1
11 11.14 SCP2 HSD17B4 EHHADH ACOX3 ACOX2 ACOX1
12
Show member pathways
11.13 EHHADH ACOX3 ACOX1
13 10.96 SCP2 EHHADH
14
Show member pathways
10.84 HADHB EHHADH
15
Show member pathways
10.49 HADHB HADH

GO Terms for D-Bifunctional Protein Deficiency

Cellular components related to D-Bifunctional Protein Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.86 TWNK SCP2 LARS2 HADHB HADH CLPP
2 mitochondrial matrix GO:0005759 9.62 TWNK LARS2 HADH CLPP
3 peroxisome GO:0005777 9.56 SCP2 HSD17B4 EHHADH ACOX3 ACOX2 ACOX1
4 peroxisomal membrane GO:0005778 9.46 HSD17B4 ACOX1 ABCD3 ABCD1
5 peroxisomal matrix GO:0005782 9.17 SCP2 HSD17B4 EHHADH ACOX3 ACOX2 ACOX1

Biological processes related to D-Bifunctional Protein Deficiency according to GeneCards Suite gene sharing:

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 10.02 HSD17B4 HADHB HADH ELOVL1 EHHADH DHRS11
2 oxidation-reduction process GO:0055114 9.98 HSD17B4 HADH EHHADH DHRS11 ACOX3 ACOX2
3 fatty acid metabolic process GO:0006631 9.86 HSD17B4 HADHB HADH ELOVL1 EHHADH ACOX3
4 protein targeting to peroxisome GO:0006625 9.8 SCP2 HSD17B4 EHHADH ACOX3 ACOX2 ACOX1
5 steroid biosynthetic process GO:0006694 9.72 SCP2D1 SCP2 DHRS11
6 very long-chain fatty acid metabolic process GO:0000038 9.71 HSD17B4 ACOX2 ACOX1 ABCD1
7 lipid homeostasis GO:0055088 9.7 ACOX3 ACOX2 ACOX1
8 bile acid biosynthetic process GO:0006699 9.67 SCP2 HSD17B4 ACOX2
9 peroxisome organization GO:0007031 9.63 SCP2 ABCD3 ABCD1
10 linoleic acid metabolic process GO:0043651 9.56 ELOVL1 ABCD1
11 alpha-linolenic acid metabolic process GO:0036109 9.55 SCP2 HSD17B4 ELOVL1 ACOX1 ABCD1
12 very long-chain fatty acid catabolic process GO:0042760 9.54 ABCD3 ABCD1
13 peroxisomal long-chain fatty acid import GO:0015910 9.51 ABCD3 ABCD1
14 fatty acid beta-oxidation using acyl-CoA oxidase GO:0033540 9.5 SCP2 HSD17B4 EHHADH ACOX3 ACOX2 ACOX1
15 positive regulation of intracellular cholesterol transport GO:0032385 9.48 SCP2D1 SCP2
16 fatty acid beta-oxidation GO:0006635 9.32 SCP2 HSD17B4 HADHB HADH EHHADH ACOX3

Molecular functions related to D-Bifunctional Protein Deficiency according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 protein homodimerization activity GO:0042803 9.95 HSD17B4 ACOX2 ACOX1 ABCD3 ABCD1
2 oxidoreductase activity GO:0016491 9.8 HSD17B4 HADH EHHADH DHRS11 ACOX3 ACOX2
3 lyase activity GO:0016829 9.74 MOCS1 HSD17B4 EHHADH
4 flavin adenine dinucleotide binding GO:0050660 9.69 ACOX3 ACOX2 ACOX1
5 FAD binding GO:0071949 9.63 ACOX3 ACOX2 ACOX1
6 transferase activity, transferring acyl groups other than amino-acyl groups GO:0016747 9.56 SCP2 HADHB
7 long-chain fatty acid transporter activity GO:0005324 9.54 ABCD3 ABCD1
8 oxidoreductase activity, acting on the CH-CH group of donors GO:0016627 9.54 ACOX3 ACOX2 ACOX1
9 sterol binding GO:0032934 9.52 SCP2D1 SCP2
10 fatty acid binding GO:0005504 9.5 ACOX3 ACOX2 ACOX1
11 acetyl-CoA C-acyltransferase activity GO:0003988 9.49 SCP2 HADHB
12 palmitoyl-CoA oxidase activity GO:0016401 9.48 ACOX2 ACOX1
13 acetyl-CoA C-myristoyltransferase activity GO:0050633 9.43 SCP2 HADHB
14 long-chain-enoyl-CoA hydratase activity GO:0016508 9.4 HSD17B4 EHHADH
15 enoyl-CoA hydratase activity GO:0004300 9.33 HSD17B4 HADHB EHHADH
16 acyl-CoA oxidase activity GO:0003997 9.13 ACOX3 ACOX2 ACOX1
17 3-hydroxyacyl-CoA dehydrogenase activity GO:0003857 8.92 HSD17B4 HADHB HADH EHHADH

Sources for D-Bifunctional Protein Deficiency

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
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