FMRD
MCID: FMR004
MIFTS: 52

Fumarase Deficiency (FMRD)

Categories: Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Fumarase Deficiency

MalaCards integrated aliases for Fumarase Deficiency:

Name: Fumarase Deficiency 57 12 73 20 43 58 72 36 29 13 54 6 15 70
Fumaric Aciduria 57 12 73 20 43 58 72 44 70
Fmrd 57 12 72
Fumarate Hydratase Deficiency 20 43
Deficiency, Fumarase 39

Characteristics:

Orphanet epidemiological data:

58
fumaric aciduria
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM®:

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

Miscellaneous:
allelic to hereditary multiple leiomyoma of skin (see ) and hereditary leiomyomatosis and renal cell cancer


HPO:

31
fumarase deficiency:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Fumarase Deficiency

MedlinePlus Genetics : 43 Fumarase deficiency is a condition that primarily affects the nervous system, especially the brain. Affected infants may have an abnormally small head size (microcephaly), abnormal brain structure, severe developmental delay, weak muscle tone (hypotonia), and failure to gain weight and grow at the expected rate (failure to thrive). They may also experience seizures. Some people with this disorder have unusual facial features, including a prominent forehead (frontal bossing), low-set ears, a small jaw (micrognathia), widely spaced eyes (ocular hypertelorism), and a depressed nasal bridge. An enlarged liver and spleen (hepatosplenomegaly) may also be associated with this disorder, as well as an excess of red blood cells (polycythemia) or deficiency of white blood cells (leukopenia) in infancy. Affected individuals usually survive only a few months, but a few have lived into early adulthood.

MalaCards based summary : Fumarase Deficiency, also known as fumaric aciduria, is related to organic acidemia and fumarate hydratase deficiency, and has symptoms including seizures An important gene associated with Fumarase Deficiency is FH (Fumarate Hydratase), and among its related pathways/superpathways are Citrate cycle (TCA cycle) and Metabolism. The drug Axitinib has been mentioned in the context of this disorder. Affiliated tissues include skin, spleen and liver, and related phenotypes are agenesis of corpus callosum and failure to thrive

Disease Ontology : 12 An amino acid metabolic disorder characterized by metabolic acidosis, elevated levels of fumaric acid in the urine, early-onset hypotonia, profound psychomotor retardation, and brain abnormalities that has material basis in homozygous or compound heterozygous mutation in FH on 1q43.

GARD : 20 Fumarase deficiency is an inherited condition that affects the brain and other parts of the nervous system. Signs and symptoms may include a small head ( microcephaly ), severe developmental delay, poor feeding, weak muscle tone ( hypotonia ), failure to thrive, seizures, and distinctive facial features. Most people with this deficiency are not able to speak or walk. A variety of brain abnormalities may be detected on MRI. Fumarase deficiency is caused by mutations in the FH gene and inheritance is autosomal recessive. Unfortunately, there is no effective treatment at this time. Management aims to improve symptoms and increase quality of life. Many children with fumarase deficiency do not survive past early childhood, but some are less severely affected, have mild cognitive impairment, and survive beyond this time.

OMIM® : 57 Fumarase deficiency is a severe autosomal recessive metabolic disorder characterized by early-onset hypotonia, profound psychomotor retardation, and brain abnormalities, such as agenesis of the corpus callosum, gyral defects, and ventriculomegaly. Many patients show neonatal distress, metabolic acidosis, and/or encephalopathy (summary by Kerrigan et al., 2000 and Mroch et al., 2012). (606812) (Updated 05-Apr-2021)

KEGG : 36 Fumarase deficiency (fumaric aciduria) is a rare autosomal recessive metabolic disorder caused by deficient activity of fumarate hydratase (FH, fumarase), one of the constituent enzymes of the Krebs tricarboxylic acid cycle. Patients usually present early in infancy with a severe encephalopathy, including hypotonia, developmental retardation, and seizures. Many of them have died during the first several years of life.

UniProtKB/Swiss-Prot : 72 Fumarase deficiency: A severe autosomal recessive metabolic disorder characterized by early-onset hypotonia, profound psychomotor retardation, and brain abnormalities, such as agenesis of the corpus callosum, gyral defects, and ventriculomegaly. Many patients show neonatal distress, metabolic acidosis, and/or encephalopathy.

Wikipedia : 73 Fumarase deficiency (or fumaric aciduria) is an exceedingly rare autosomal recessive metabolic disorder... more...

Related Diseases for Fumarase Deficiency

Diseases related to Fumarase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 78)
# Related Disease Score Top Affiliating Genes
1 organic acidemia 30.1 TMEM70 SUCLA2 HMGCL
2 fumarate hydratase deficiency 11.3
3 tricarboxylic acid cycle, defect of 11.1
4 tumor predisposition syndrome 10.4
5 cutaneous telangiectasia and cancer syndrome, familial 10.4
6 inherited cancer-predisposing syndrome 10.4
7 leiomyomatosis 10.3
8 intravenous leiomyomatosis 10.3
9 encephalopathy 10.3
10 hypotonia 10.3
11 pyrimidine metabolic disorder 10.3 ASL ADSL
12 hereditary leiomyomatosis and renal cell cancer 10.3
13 dermis tumor 10.3 SDHA FH
14 3-methylglutaconic aciduria, type iv 10.3 TMEM70 SUCLA2
15 cardiomyopathy, dilated, 1gg 10.3 SDHA FH
16 optic atrophy 9 10.2 SUCLA2 ACO2
17 hereditary renal cell carcinoma 10.2 SDHA FH
18 microcephaly 10.2
19 persistent generalized lymphadenopathy 10.2 SDHA FH
20 3-methylglutaconic aciduria, type v 10.2 TMEM70 SUCLA2
21 hypoxia 10.2
22 argininosuccinic aciduria 10.2 ASL ADSL
23 3-methylglutaconic aciduria with deafness, encephalopathy, and leigh-like syndrome 10.2 TMEM70 SUCLA2
24 urea cycle disorder 10.2 ASL ADSL
25 orotic aciduria 10.2 ASL ADSL
26 3-methylcrotonyl-coa carboxylase deficiency 10.2 ETHE1 ADSL
27 encephalopathy, ethylmalonic 10.2 TMEM70 ETHE1
28 autosomal recessive disease 10.2
29 paraganglioma and gastric stromal sarcoma 10.1 SDHA FH
30 mitochondrial dna depletion syndrome 5 10.1 TMEM70 SUCLA2 ETHE1
31 mitochondrial metabolism disease 10.1 SUCLA2 SDHA ETHE1
32 leiomyoma 10.1
33 dystonia 10.1
34 cerebral atrophy 10.1
35 maple syrup urine disease 10.1 HMGCL ASL ADSL
36 alcohol-related neurodevelopmental disorder 10.1
37 scoliosis 10.1
38 status epilepticus 10.1
39 cerebral palsy 10.1
40 acute pancreatitis 10.1
41 cystic kidney disease 10.1
42 bilateral polymicrogyria 10.1
43 2-hydroxyglutaric aciduria 10.0 L2HGDH D2HGDH
44 hypertelorism 10.0
45 leiomyoma, uterine 10.0
46 plethora of newborn 10.0
47 inherited metabolic disorder 10.0
48 colpocephaly 10.0
49 spastic paraparesis 10.0
50 d-2-hydroxyglutaric aciduria 2 10.0 L2HGDH D2HGDH

Graphical network of the top 20 diseases related to Fumarase Deficiency:



Diseases related to Fumarase Deficiency

Symptoms & Phenotypes for Fumarase Deficiency

Human phenotypes related to Fumarase Deficiency:

31 (show all 32)
# Description HPO Frequency HPO Source Accession
1 agenesis of corpus callosum 31 HP:0001274
2 failure to thrive 31 HP:0001508
3 frontal bossing 31 HP:0002007
4 neurological speech impairment 31 HP:0002167
5 high palate 31 HP:0000218
6 global developmental delay 31 HP:0001263
7 depressed nasal bridge 31 HP:0005280
8 hypertelorism 31 HP:0000316
9 microcephaly 31 HP:0000252
10 anteverted nares 31 HP:0000463
11 visual impairment 31 HP:0000505
12 optic atrophy 31 HP:0000648
13 aminoaciduria 31 HP:0003355
14 pallor 31 HP:0000980
15 hepatic failure 31 HP:0001399
16 polymicrogyria 31 HP:0002126
17 polycythemia 31 HP:0001901
18 cholestasis 31 HP:0001396
19 hyperbilirubinemia 31 HP:0002904
20 lactic acidosis 31 HP:0003128
21 status epilepticus 31 HP:0002133
22 metabolic acidosis 31 HP:0001942
23 intellectual disability, profound 31 HP:0002187
24 cerebral atrophy 31 HP:0002059
25 relative macrocephaly 31 HP:0004482
26 generalized hypotonia 31 HP:0001290
27 choroid plexus cyst 31 HP:0002190
28 cutaneous leiomyoma 31 HP:0007620
29 reduced subcutaneous adipose tissue 31 HP:0003758
30 hypoplasia of the brainstem 31 HP:0002365
31 open operculum 31 HP:0100954
32 hypotonia 31 HP:0001252

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
polymicrogyria
status epilepticus
cerebral atrophy
open operculum
more
Head And Neck Face:
frontal bossing

Head And Neck Eyes:
hypertelorism
visual impairment
optic atrophy
optic pallor

Metabolic Features:
metabolic acidosis

Head And Neck Mouth:
high-arched palate

Laboratory Abnormalities:
lactic acidemia
pyruvic acidemia
fumaric aciduria
fumarase activity (mitochondrial and cytosolic) is decreased
increased urinary citric acid cycle intermediates
more
Hematology:
polycythemia, neonatal
coagulopathy in those with liver failure

Growth Other:
failure to thrive

Head And Neck Nose:
depressed nasal bridge
anteverted nares

Abdomen Liver:
cholestasis
fibrosis
liver failure
iron deposition
abnormal swollen mitochondria with flat, haphazardly arranged cristae

Muscle Soft Tissue:
decreased subcutaneous fat
hypotonia
decreased muscle bulk

Head And Neck Head:
macrocephaly, relative

Skin Nails Hair Skin:
cutaneous leiomyomata (heterozygote carriers)

Clinical features from OMIM®:

606812 (Updated 05-Apr-2021)

UMLS symptoms related to Fumarase Deficiency:


seizures

Drugs & Therapeutics for Fumarase Deficiency

Drugs for Fumarase Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Axitinib Approved, Investigational Phase 2 319460-85-0 6450551

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Single-arm Phase II Clinical Trial to Evaluate the Initial Efficacy and Safety of Sintilimab Injection Combined With Inlyta in Fumarate Hydratase- Deficient Renal Cell Carcinoma Not yet recruiting NCT04387500 Phase 2 Sintilimab injection

Search NIH Clinical Center for Fumarase Deficiency

Cochrane evidence based reviews: fumaric aciduria

Genetic Tests for Fumarase Deficiency

Genetic tests related to Fumarase Deficiency:

# Genetic test Affiliating Genes
1 Fumarase Deficiency 29 FH

Anatomical Context for Fumarase Deficiency

MalaCards organs/tissues related to Fumarase Deficiency:

40
Skin, Spleen, Liver, Kidney, Testis

Publications for Fumarase Deficiency

Articles related to Fumarase Deficiency:

(show top 50) (show all 116)
# Title Authors PMID Year
1
Mutation of the fumarase gene in two siblings with progressive encephalopathy and fumarase deficiency. 61 57 6 54
8200987 1994
2
Fumarase deficiency is an autosomal recessive encephalopathy affecting both the mitochondrial and the cytosolic enzymes. 61 54 57 6
2314594 1990
3
Fumarase deficiency: a rare disorder on the crossroads of clinical and metabolic genetics, neurology and cancer. 57 6 61
27541980 2017
4
Detection of a novel FH whole gene deletion in the propositus leading to subsequent prenatal diagnosis in a sibship with fumarase deficiency. 6 57 61
22069215 2012
5
Molecular and biochemical investigations in fumarase deficiency. 61 54 6
16510303 2006
6
Fumarase deficiency caused by homozygous P131R mutation and paternal partial isodisomy of chromosome 1. 61 54 6
16575891 2006
7
Fumarase deficiency presenting with periventricular cysts. 6 54 61
16151915 2005
8
Abnormalities in succinylpurines in fumarase deficiency: possible role in pathogenesis of CNS impairment. 6 61 54
10896297 2000
9
Fumaric aciduria: clinical and imaging features. 61 54 57
10805328 2000
10
Molecular analysis and prenatal diagnosis of human fumarase deficiency. 6 61 54
9635293 1998
11
Fumarase deficiency in dichorionic diamniotic twins. 61 6
24182348 2013
12
Mild clinical presentation and prolonged survival of a patient with fumarase deficiency due to the combination of a known and a novel mutation in FH gene. 6 61
23612258 2013
13
Mild fumarase deficiency and a trial of low protein diet. 61 6
22595425 2012
14
Clinical and biochemical heterogeneity associated with fumarase deficiency. 6 61
21560188 2011
15
Fumaric aciduria: an overview and the first Brazilian case report. 6 61
20549362 2010
16
A novel mutation of the fumarase gene in a family with autosomal recessive fumarase deficiency. 61 6
15221078 2004
17
Fumarase deficiency. 57 61
3807970 1987
18
Fumarase deficiency: a new cause of mitochondrial encephalomyopathy. 57 61
3736629 1986
19
Fumaric aciduria: a new organic aciduria, associated with mental retardation and speech impairment. 61 57
6616883 1983
20
Hereditary Leiomyomatosis and Renal Cell Cancer: Clinical, Molecular, and Screening Features in a Cohort of 185 Affected Individuals. 6
31831373 2020
21
Fumarate hydratase c.914T > C (p.Phe305Ser) is a pathogenic variant associated with hereditary leiomyomatosis and renal cell cancer syndrome. 6
32463173 2020
22
Clinical report and biochemical analysis of a patient with fumarate hydratase deficiency. 6
31746132 2020
23
Fumarate hydratase FH c.1431_1433dupAAA (p.Lys477dup) variant is not associated with cancer including renal cell carcinoma. 6
31444830 2020
24
Metabolome-guided genomics to identify pathogenic variants in isocitrate dehydrogenase, fumarate hydratase, and succinate dehydrogenase genes in pheochromocytoma and paraganglioma. 6
30050099 2019
25
Biochemical Characterization of Two Clinically-Relevant Human Fumarase Variants Defective for Oligomerization. 6
29456767 2018
26
Reassessing the clinical spectrum associated with hereditary leiomyomatosis and renal cell carcinoma syndrome in French FH mutation carriers. 6
28300276 2017
27
Multiple cutaneous leiomyomas leading to discovery of novel splice mutation in the fumarate hydratase gene associated with HLRCC. 6
28266706 2017
28
Cascade Fumarate Hydratase mutation screening allows early detection of kidney tumour: a case report. 6
28747166 2017
29
Comprehensive genomic and phenotypic characterization of germline FH deletion in hereditary leiomyomatosis and renal cell carcinoma. 6
28196407 2017
30
Isolated cutaneous leiomyosarcoma revealing a novel germline mutation of the fumarate hydratase gene. 6
25913776 2016
31
Human Fumarate Hydratase Is Dual Localized by an Alternative Transcription Initiation Mechanism. 6
27037871 2016
32
Fumarate Hydratase-deficient Renal Cell Carcinoma Is Strongly Correlated With Fumarate Hydratase Mutation and Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome. 6
26900816 2016
33
Fumarate Hydratase-deficient Uterine Leiomyomas Occur in Both the Syndromic and Sporadic Settings. 6
26574848 2016
34
Hereditary leiomyomatosis and renal cell cancer syndrome. 6
26323704 2016
35
Novel splice site mutation in the fumarate hydratase (FH) gene is associated with multiple cutaneous leiomyomas in a Japanese patient. 6
26173633 2016
36
Morphology and Immunohistochemistry for 2SC and FH Aid in Detection of Fumarate Hydratase Gene Aberrations in Uterine Leiomyomas From Young Patients. 6
26457356 2015
37
Genetic testing of leiomyoma tissue in women younger than 30 years old might provide an effective screening approach for the hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC). 6
25985877 2015
38
Fumarate Hydratase Mutation in a Young Woman With Uterine Leiomyomas and a Family History of Renal Cell Cancer. 6
25923021 2015
39
An unusual case of sporadic hereditary leiomyomatosis and renal cell carcinoma syndrome. 6
25750977 2015
40
Hereditary leiomyomatosis associated with renal cell carcinoma. 6
25477250 2015
41
Use of Whole Genome Sequencing for Diagnosis and Discovery in the Cancer Genetics Clinic. 6
26023681 2015
42
Fumarate hydratase immunohistochemical staining may help to identify patients with multiple cutaneous and uterine leiomyomatosis (MCUL) and hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. 6
25292446 2014
43
Germline FH mutations presenting with pheochromocytoma. 6
25004247 2014
44
Germline mutations in FH confer predisposition to malignant pheochromocytomas and paragangliomas. 6
24334767 2014
45
Hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cancer: recognition of the syndrome by pathologic features and the utility of detecting aberrant succination by immunohistochemistry. 6
24441663 2014
46
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC): a rapid autopsy report of metastatic renal cell carcinoma. 6
24625422 2014
47
Novel missense mutation in the FH gene in familial renal cell cancer patients lacking cutaneous leiomyomas. 6
24684806 2014
48
Fumarate hydratase gene mutation in two young patients with sporadic uterine fibroids. 6
22764886 2013
49
Morphologic and molecular characteristics of uterine leiomyomas in hereditary leiomyomatosis and renal cancer (HLRCC) syndrome. 6
23211287 2013
50
No evidence for the role of somatic mutations and promoter hypermethylation of FH gene in the tumorigenesis of nonsyndromic uterine leiomyomas. 6
22528940 2012

Variations for Fumarase Deficiency

ClinVar genetic disease variations for Fumarase Deficiency:

6 (show top 50) (show all 669)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FH NM_000143.3(FH):c.793G>A (p.Ala265Thr) SNV Pathogenic 16230 rs387906545 GRCh37: 1:241669414-241669414
GRCh38: 1:241506114-241506114
2 FH NM_000143.3(FH):c.1084G>C (p.Glu362Gln) SNV Pathogenic 16231 rs121913119 GRCh37: 1:241667366-241667366
GRCh38: 1:241504066-241504066
3 FH FH, DEL Deletion Pathogenic 29706 GRCh37:
GRCh38:
4 FH NM_000143.3(FH):c.478A>G (p.Arg160Gly) SNV Pathogenic 237116 rs878853694 GRCh37: 1:241675344-241675344
GRCh38: 1:241512044-241512044
5 FH NM_000143.3(FH):c.267+1G>C SNV Pathogenic 237112 rs878853691 GRCh37: 1:241680481-241680481
GRCh38: 1:241517181-241517181
6 FH NC_000001.11:g.(?_241497557)_(241519785_?)del Deletion Pathogenic 417361 GRCh37: 1:241660857-241683085
GRCh38: 1:241497557-241519785
7 FH NM_000143.3(FH):c.1052C>A (p.Ser351Ter) SNV Pathogenic 405912 rs1060500896 GRCh37: 1:241667398-241667398
GRCh38: 1:241504098-241504098
8 FH NC_000001.11:g.(?_241497557)_(241504245_?)del Deletion Pathogenic 417362 GRCh37: 1:241660857-241667545
GRCh38: 1:241497557-241504245
9 FH NM_000143.3(FH):c.1347del (p.Met449fs) Deletion Pathogenic 405924 rs1060500903 GRCh37: 1:241663780-241663780
GRCh38: 1:241500480-241500480
10 FH NM_000143.3(FH):c.1391-1G>A SNV Pathogenic 405909 rs863223978 GRCh37: 1:241661271-241661271
GRCh38: 1:241497971-241497971
11 FH NM_000143.3(FH):c.40dup (p.Leu14fs) Duplication Pathogenic 405920 rs1060500900 GRCh37: 1:241682982-241682983
GRCh38: 1:241519682-241519683
12 FH NM_000143.3(FH):c.267+1G>A SNV Pathogenic 405927 rs878853691 GRCh37: 1:241680481-241680481
GRCh38: 1:241517181-241517181
13 FH NM_000143.3(FH):c.204T>A (p.Tyr68Ter) SNV Pathogenic 405883 rs1060500883 GRCh37: 1:241680545-241680545
GRCh38: 1:241517245-241517245
14 FH NM_000143.3(FH):c.679C>T (p.Gln227Ter) SNV Pathogenic 405913 rs11545658 GRCh37: 1:241671962-241671962
GRCh38: 1:241508662-241508662
15 FH NM_000143.3(FH):c.786_806del (p.Lys263_Ile269del) Deletion Pathogenic 185496 rs786202220 GRCh37: 1:241669401-241669421
GRCh38: 1:241506101-241506121
16 FH NM_000143.3(FH):c.1479_1483AGCAG[1] (p.Glu495fs) Microsatellite Pathogenic 405937 rs1060500907 GRCh37: 1:241661173-241661177
GRCh38: 1:241497873-241497877
17 FH NM_000143.3(FH):c.560C>A (p.Ser187Ter) SNV Pathogenic 405935 rs398123166 GRCh37: 1:241672081-241672081
GRCh38: 1:241508781-241508781
18 FH NM_000143.3(FH):c.1112del (p.Lys371fs) Deletion Pathogenic 405928 rs1060500904 GRCh37: 1:241665867-241665867
GRCh38: 1:241502567-241502567
19 FH NM_000143.3(FH):c.583A>G (p.Met195Val) SNV Pathogenic 460368 rs1553341364 GRCh37: 1:241672058-241672058
GRCh38: 1:241508758-241508758
20 FH NM_000143.3(FH):c.634C>T (p.Gln212Ter) SNV Pathogenic 460367 rs1553341353 GRCh37: 1:241672007-241672007
GRCh38: 1:241508707-241508707
21 FH NM_000143.3(FH):c.1251dup (p.His418fs) Duplication Pathogenic 460337 rs1553340708 GRCh37: 1:241663875-241663876
GRCh38: 1:241500575-241500576
22 FH NM_000143.3(FH):c.760C>T (p.Gln254Ter) SNV Pathogenic 92457 rs398123167 GRCh37: 1:241669447-241669447
GRCh38: 1:241506147-241506147
23 FH NC_000001.11:g.(?_241505997)_(241506174_?)del Deletion Pathogenic 460334 GRCh37:
GRCh38: 1:241505997-241506174
24 FH NM_000143.3(FH):c.379-1G>A SNV Pathogenic 460352 rs1553341623 GRCh37: 1:241675444-241675444
GRCh38: 1:241512144-241512144
25 FH NM_000143.3(FH):c.6C>G (p.Tyr2Ter) SNV Pathogenic 460375 rs199971078 GRCh37: 1:241683017-241683017
GRCh38: 1:241519717-241519717
26 FH NM_000143.3(FH):c.439A>G (p.Thr147Ala) SNV Pathogenic 214395 rs863223983 GRCh37: 1:241675383-241675383
GRCh38: 1:241512083-241512083
27 FH NM_000143.3(FH):c.999C>A (p.Cys333Ter) SNV Pathogenic 529804 rs1553341031 GRCh37: 1:241667451-241667451
GRCh38: 1:241504151-241504151
28 FH NM_000143.3(FH):c.560C>G (p.Ser187Ter) SNV Pathogenic 92456 rs398123166 GRCh37: 1:241672081-241672081
GRCh38: 1:241508781-241508781
29 FH NM_000143.3(FH):c.991dup (p.Thr331fs) Duplication Pathogenic 529808 rs1553341034 GRCh37: 1:241667458-241667459
GRCh38: 1:241504158-241504159
30 FH NM_000143.3(FH):c.1028del (p.Arg343fs) Deletion Pathogenic 529809 rs1553341026 GRCh37: 1:241667422-241667422
GRCh38: 1:241504122-241504122
31 FH NM_000143.3(FH):c.1082del (p.Asn361fs) Deletion Pathogenic 529815 rs1553341012 GRCh37: 1:241667368-241667368
GRCh38: 1:241504068-241504068
32 FH NM_000143.3(FH):c.919del (p.Thr307fs) Deletion Pathogenic 529816 rs1553341049 GRCh37: 1:241667531-241667531
GRCh38: 1:241504231-241504231
33 FH NM_000143.3(FH):c.1236+1G>A SNV Pathogenic 529817 rs1131691249 GRCh37: 1:241665742-241665742
GRCh38: 1:241502442-241502442
34 FH NM_000143.3(FH):c.568_569del (p.Thr190fs) Deletion Pathogenic 529823 rs1553341367 GRCh37: 1:241672072-241672073
GRCh38: 1:241508772-241508773
35 FH NM_000143.3(FH):c.1138dup (p.Met380fs) Duplication Pathogenic 393579 rs781466938 GRCh37: 1:241665840-241665841
GRCh38: 1:241502540-241502541
36 FH NM_000143.3(FH):c.301_319del (p.Arg101fs) Deletion Pathogenic 569195 rs1558401094 GRCh37: 1:241676962-241676980
GRCh38: 1:241513662-241513680
37 FH NM_000143.3(FH):c.1041del (p.Gly348fs) Deletion Pathogenic 393576 rs1060499641 GRCh37: 1:241667409-241667409
GRCh38: 1:241504109-241504109
38 FH NM_000143.3(FH):c.1138del (p.Ala379_Met380insTer) Deletion Pathogenic 572058 rs781466938 GRCh37: 1:241665841-241665841
GRCh38: 1:241502541-241502541
39 FH NM_000143.3(FH):c.1052C>G (p.Ser351Ter) SNV Pathogenic 429168 rs1060500896 GRCh37: 1:241667398-241667398
GRCh38: 1:241504098-241504098
40 FH NM_000143.3(FH):c.65T>A (p.Leu22Ter) SNV Pathogenic 573460 rs1031919395 GRCh37: 1:241682958-241682958
GRCh38: 1:241519658-241519658
41 FH NM_000143.3(FH):c.739G>T (p.Glu247Ter) SNV Pathogenic 429182 rs1131691243 GRCh37: 1:241669468-241669468
GRCh38: 1:241506168-241506168
42 FH NM_000143.3(FH):c.322C>T (p.Gln108Ter) SNV Pathogenic 393560 rs1060499630 GRCh37: 1:241676959-241676959
GRCh38: 1:241513659-241513659
43 FH NM_000143.3(FH):c.1351G>T (p.Glu451Ter) SNV Pathogenic 575998 rs1558396320 GRCh37: 1:241663776-241663776
GRCh38: 1:241500476-241500476
44 FH NM_000143.3(FH):c.353del (p.Asn118fs) Deletion Pathogenic 576345 rs1558401064 GRCh37: 1:241676928-241676928
GRCh38: 1:241513628-241513628
45 FH NM_000143.3(FH):c.201T>G (p.Tyr67Ter) SNV Pathogenic 576558 rs1558402241 GRCh37: 1:241680548-241680548
GRCh38: 1:241517248-241517248
46 FH NM_000143.3(FH):c.442C>T (p.Gln148Ter) SNV Pathogenic 578830 rs1558400571 GRCh37: 1:241675380-241675380
GRCh38: 1:241512080-241512080
47 FH NM_000143.3(FH):c.1205del (p.His402fs) Deletion Pathogenic 578880 rs1558397011 GRCh37: 1:241665774-241665774
GRCh38: 1:241502474-241502474
48 FH NM_000143.3(FH):c.174_177dup (p.Leu60Ter) Duplication Pathogenic 429185 rs1131691246 GRCh37: 1:241680571-241680572
GRCh38: 1:241517271-241517272
49 FH NM_000143.3(FH):c.185_188dup (p.Asn64fs) Duplication Pathogenic 583198 rs1558402255 GRCh37: 1:241680560-241680561
GRCh38: 1:241517260-241517261
50 FH NC_000001.11:g.(?_241505993)_(241506178_?)del Deletion Pathogenic 583507 GRCh37: 1:241669293-241669478
GRCh38: 1:241505993-241506178

UniProtKB/Swiss-Prot genetic disease variations for Fumarase Deficiency:

72
# Symbol AA change Variation ID SNP ID
1 FH p.Lys230Arg VAR_002445 rs752232718
2 FH p.Ala308Thr VAR_002446 rs121913118
3 FH p.Phe312Cys VAR_002447 rs155334104
4 FH p.Asp425Val VAR_002448

Copy number variations for Fumarase Deficiency from CNVD:

7
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 28402 1 222100000 228800000 Copy number FH Fumarase deficiency

Expression for Fumarase Deficiency

Search GEO for disease gene expression data for Fumarase Deficiency.

Pathways for Fumarase Deficiency

Pathways related to Fumarase Deficiency according to KEGG:

36
# Name Kegg Source Accession
1 Citrate cycle (TCA cycle) hsa00020

Pathways related to Fumarase Deficiency according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.75 SUCLA2 SDHA L2HGDH HMGCL FH ETHE1
2
Show member pathways
13.04 SUCLA2 SDHA L2HGDH FH ETFB D2HGDH
3
Show member pathways
11.68 SUCLA2 SDHA FH ASL ACO2
4
Show member pathways
11.57 SUCLA2 SDHA FH ACO2
5 11.42 SDHA HMGCL FH ACO2
6
Show member pathways
11.22 SUCLA2 SDHA L2HGDH FH D2HGDH ACO2
7
Show member pathways
11.01 L2HGDH HMGCL
8 10.97 ASL ADSL

GO Terms for Fumarase Deficiency

Cellular components related to Fumarase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.7 TMEM70 SUCLA2 SDHAF1 SDHA L2HGDH HMGCL
2 mitochondrial matrix GO:0005759 9.23 SUCLA2 SDHAF1 HMGCL FH ETHE1 ETFB

Biological processes related to Fumarase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.43 SDHA L2HGDH ETHE1 ETFB D2HGDH ACOX2
2 response to starvation GO:0042594 9.37 HMGCL ADSL
3 respiratory electron transport chain GO:0022904 9.32 SDHA ETFB
4 2-oxoglutarate metabolic process GO:0006103 9.26 L2HGDH D2HGDH
5 succinate metabolic process GO:0006105 9.16 SUCLA2 SDHA
6 tricarboxylic acid cycle GO:0006099 8.92 SUCLA2 SDHA FH ACO2

Molecular functions related to Fumarase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity GO:0016491 9.65 SDHA L2HGDH ETHE1 D2HGDH ACOX2
2 catalytic activity GO:0003824 9.43 SUCLA2 HMGCL FH D2HGDH ASL ADSL
3 FAD binding GO:0071949 9.37 D2HGDH ACOX2
4 flavin adenine dinucleotide binding GO:0050660 9.33 SDHA D2HGDH ACOX2
5 oxidoreductase activity, acting on the CH-CH group of donors GO:0016627 9.32 SDHA ACOX2
6 lyase activity GO:0016829 9.02 HMGCL FH ASL ADSL ACO2

Sources for Fumarase 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 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....