HFM
MCID: FLT009
MIFTS: 50

Folate Malabsorption, Hereditary (HFM)

Categories: Blood diseases, Gastrointestinal diseases, Genetic diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Folate Malabsorption, Hereditary

MalaCards integrated aliases for Folate Malabsorption, Hereditary:

Name: Folate Malabsorption, Hereditary 57 20 13 44 39 70
Hereditary Folate Malabsorption 12 25 20 43 58 72 36 15
Congenital Defect of Folate Absorption 12 20 43 29 6
Congenital Folate Malabsorption 12 25 20 43 58
Folic Acid Transport Defect 20 43
Hfm 72

Characteristics:

Orphanet epidemiological data:

58
hereditary folate malabsorption
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

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

Miscellaneous:
onset in infancy
early diagnosis and proper treatment with folate replacement therapy can avoid neurologic sequelae


HPO:

31
folate malabsorption, hereditary:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare gastroenterological diseases
Inborn errors of metabolism
Rare haematological diseases
Rare immunological diseases


Summaries for Folate Malabsorption, Hereditary

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 90045 Definition Hereditary folate malabsorption (HFM) is an inherited disorder of folate transport characterized by a systemic and central nervous system (CNS) folate deficiency manifesting as megaloblastic anemia, failure to thrive, diarrhea and/or oral mucositis, immunologic dysfunction and neurological disorders. Epidemiology The prevalence is unknown. Approximately 30 cases have been reported to date. Clinical description Disease onset usually occurs a few months after birth. Manifestations include failure to thrive, diarrhea and/or mouth ulcers, various neurological manifestations (motor impairment, seizures, developmental delay, cognitive and behavioral disorders), megaloblastic anemia and hypoimmunoglobulinemia. Megaloblastic anemia is the primary manifestation of HFM and can be very severe if untreated. Hypoimmunoglobulinemia results in unusual infections with Pneumocystis jiroveccii, C. difficile and cytomegalovirus (CMV) which can be recurrent and life-threatening in undiagnosed infants. Neurological manifestations may be the presenting symptoms in some but are absent in others. Seizures, if present, begin in infancy or later in childhood. Intracranial calcifications have been observed in some. Etiology HFM is caused by mutations in the SLC46A1 gene found on chromosome 17q11.2 which encodes the proton-coupled folate transporter (PCFT). PCFT is essential for intestinal folate absorption and transport of folates across the blood-cerebrospinal fluid (CSF) barrier. A defect in this protein leads to a systemic folate and CNS folate deficiency. Infants cannot absorb adequate folate from breast milk/formula and become deficient once their stores accumulated during gestation are exhausted. Diagnostic methods Diagnosis is based on clinical and laboratory findings. It is confirmed by findings of an impaired absorption of an oral folate load (even after correction of serum folate concentration) and a low CSF folate concentration (0-1.5nM). Bone marrow biopsy confirms the presence of megaloblastic anemia. Sequence analysis of the SLC46A1 coding region can identify any mutations present in the gene, also confirming diagnosis of HFM. Differential diagnosis The immunodeficiency seen in HFM may resemble severe combined immune deficiency (SCID; see this term). Other differential diagnoses include methionine synthase deficiency with megaloblastic anemia and developmental delay, formiminoglutamic aciduria, tyrosinemia type 1, methylenetetrahydrofolate reductase deficiency and erythroleukemia (see these terms). Antenatal diagnosis Antenatal diagnosis is possible via prenatal testing. Screening of newborns with a family history of HFM allows for early diagnosis and treatment with folate immediately after birth, before symptoms occur. Genetic counseling HFM is inherited autosomal recessively. Genetic counseling is possible. Management and treatment High dose oral or parenteral 5-formyltetrahydrofolate (5-formylTHF) and oral L-5-methyltetrahydrofolate (L-5-methylTHF) are the two types of reduced folates used to treat HFM. Dosage is monitored and adjusted (individualized for each patient) so that the CSF folate levels remain within the normal range (around 100nM in infants-2 year olds). Folic acid should not be used as it binds to folate receptors and blocks folate transport. If anemia is severe, a transfusion may be necessary. Early treatment with reduced folates before the appearance of symptoms can prevent the metabolic consequences of HFM. Patients should have regular blood tests to monitor complete blood count, serum and CSF folate and homocysteine concentrations and serum immunoglobulin concentrations. Prognosis With proper treatment the prognosis is good and reversal of most of the systemic consequences of the disease is usually achieved. Only when untreated is the prognosis poor.

MalaCards based summary : Folate Malabsorption, Hereditary, also known as hereditary folate malabsorption, is related to megaloblastic anemia and deficiency anemia, and has symptoms including seizures, ataxia and diarrhea. An important gene associated with Folate Malabsorption, Hereditary is SLC46A1 (Solute Carrier Family 46 Member 1), and among its related pathways/superpathways are Vitamin digestion and absorption and Mineral absorption. Affiliated tissues include bone marrow, skeletal muscle and pancreas, and related phenotypes are failure to thrive and nausea and vomiting

Disease Ontology : 12 A vitamin metabolic disorder characterized by impaired intestinal folate absorption and impaired transport of folate into the central nervous system resulting in megaloblastic anemia, diarrhea, immune deficiency, infections, and neurologic deficits that has material basis in homozygous or compound heterozygous mutation in SLC46A1 on chromosome 17q11.2.

MedlinePlus Genetics : 43 Hereditary folate malabsorption is a disorder that interferes with the body's ability to absorb certain B vitamins (called folates) from food. Folates are important for many cell functions, including the production of DNA and its chemical cousin, RNA.Infants with hereditary folate malabsorption are born with normal amounts of folates in their body because they obtain these vitamins from their mother's blood before birth. They generally begin to show signs and symptoms of the disorder within the first few months of life because their ability to absorb folates from food is impaired.Infants with hereditary folate malabsorption experience feeding difficulties, diarrhea, and failure to gain weight and grow at the expected rate (failure to thrive). Affected individuals usually develop a blood disorder called megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic). The symptoms of this blood disorder may include decreased appetite, lack of energy, headaches, pale skin, and tingling or numbness in the hands and feet. People with hereditary folate malabsorption may also have a deficiency of white blood cells (leukopenia), leading to increased susceptibility to infections. In addition, they may have a reduction in the amount of platelets (thrombocytopenia), which can result in easy bruising and abnormal bleeding.Some infants with hereditary folate malabsorption exhibit neurological problems such as developmental delay and seizures. Over time, untreated individuals may develop intellectual disability and difficulty coordinating movements (ataxia).

OMIM® : 57 Hereditary folate malabsorption is an autosomal recessive disorder characterized by signs and symptoms of folate deficiency that appear within a few months after birth. Infants exhibit low blood and cerebrospinal fluid folate levels with megaloblastic anemia, diarrhea, immune deficiency, infections, and neurologic deficits. Treatment with folate supplementation results in resolution of the signs and symptoms. The disorder is caused by impaired intestinal folate absorption and impaired transport of folate into the central nervous system (summary by Qiu et al., 2006). (229050) (Updated 20-May-2021)

KEGG : 36 Hereditary folate malabsorption (HFM) is a rare autosomal recessive disorder caused by impaired intestinal folate absorption. HFM is characterized by anemia, hypoimmunoglobulinemia, and recurrent infections. When diagnosed early, the signs and symptoms can be obviated by high oral doses of folates. Recently, several mutations were identified in the proton-coupled folate transporter (PCFT/SLC46A1) gene from patients with HFM.

UniProtKB/Swiss-Prot : 72 Hereditary folate malabsorption: Rare autosomal recessive disorder characterized by impaired intestinal folate absorption with folate deficiency resulting in anemia, hypoimmunoglobulinemia with recurrent infections, and recurrent or chronic diarrhea. In many patients, neurological abnormalities such as seizures or mental retardation become apparent during early childhood, attributed to impaired transport of folates into the central nervous system. When diagnosed early, the disorder can be treated by administration of folate. If untreated, it can be fatal and, if treatment is delayed, the neurological defects can become permanent.

Wikipedia : 73 Hereditary folate malabsorption (HFM) is a rare autosomal recessive disorder caused by loss-of-function... more...

GeneReviews: NBK1673

Related Diseases for Folate Malabsorption, Hereditary

Diseases related to Folate Malabsorption, Hereditary via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 53)
# Related Disease Score Top Affiliating Genes
1 megaloblastic anemia 29.0 SLC46A1 SLC19A3 SLC19A2 SLC19A1 MTR DHFR
2 deficiency anemia 28.3 SLC48A1 SLC46A1 SLC25A38 SLC25A37 SLC19A2 MTR
3 hemifacial microsomia 11.4
4 epilepsy with bilateral occipital calcifications 11.2
5 craniofacial microsomia 11.0
6 folic acid deficiency anemia 10.3 SLC46A1 FOLR3
7 posterior column ataxia 10.3 FLVCR2 FLVCR1
8 dry beriberi 10.2 SLC19A3 SLC19A2
9 beriberi 10.2 SLC19A3 SLC19A2
10 wet beriberi 10.2 SLC19A3 SLC19A2
11 pearson marrow-pancreas syndrome 10.2 SLC25A38 SLC19A2
12 thiamine deficiency disease 10.2 SLC19A3 SLC19A2
13 immune deficiency disease 10.2
14 wernicke encephalopathy 10.2 SLC19A3 SLC19A2
15 thiamine-responsive megaloblastic anemia syndrome 10.1 SLC19A3 SLC19A2 SLC19A1
16 cutaneous porphyria 10.1 SLC25A37 FLVCR1
17 porphyria, acute intermittent 10.0 FLVCR2 FLVCR1
18 wernicke-korsakoff syndrome 10.0 SLC19A3 SLC19A2
19 thrombocytopenia 10.0
20 thiamine metabolism dysfunction syndrome 2 10.0 SLC46A1 SLC19A3 SLC19A2 SLC19A1
21 pulmonary hypertension 10.0
22 immunoglobulin alpha deficiency 10.0
23 mucositis 10.0
24 pneumocystosis 10.0
25 cerebral palsy 10.0
26 agammaglobulinemia 10.0
27 lymphopenia 10.0
28 stomatitis 10.0
29 aphthous stomatitis 10.0
30 diarrhea 10.0
31 anemia, sideroblastic, and spinocerebellar ataxia 10.0 SLC25A38 SLC25A37
32 aceruloplasminemia 10.0 SLC46A1 SLC25A37 FLVCR1
33 vitamin metabolic disorder 10.0 SLC46A1 MTR
34 anemia, sideroblastic, 1 9.9 SLC25A38 SLC25A37 FLVCR1
35 cutis laxa, autosomal dominant 3 9.9 MTR DHFR
36 pediatric osteosarcoma 9.9 SLC19A1 MTR DHFR
37 cutis laxa, autosomal dominant 2 9.9 MTR DHFR
38 agenesis of corpus callosum, cardiac, ocular, and genital syndrome 9.9
39 autosomal recessive disease 9.9
40 combined immunodeficiency 9.9
41 microcephaly 9.9
42 neutropenia 9.9
43 pancytopenia 9.9
44 epilepsy 9.9
45 macrocytic anemia 9.9
46 microtia 9.9
47 childhood leukemia 9.9 SLC19A1 MTR DHFR
48 methotrexate toxicity 9.8 SLC46A1 SLC19A1 MTR DHFR
49 protoporphyria, erythropoietic, 1 9.8 SLC25A38 SLC25A37
50 anencephaly 9.7 SLC25A32 MTR FOLR1 DHFR

Graphical network of the top 20 diseases related to Folate Malabsorption, Hereditary:



Diseases related to Folate Malabsorption, Hereditary

Symptoms & Phenotypes for Folate Malabsorption, Hereditary

Human phenotypes related to Folate Malabsorption, Hereditary:

58 31 (show all 42)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 58 31 hallmark (90%) Very frequent (99-80%) HP:0001508
2 nausea and vomiting 58 31 hallmark (90%) Very frequent (99-80%) HP:0002017
3 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
4 pallor 58 31 hallmark (90%) Very frequent (99-80%) HP:0000980
5 anorexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002039
6 cheilitis 58 31 hallmark (90%) Very frequent (99-80%) HP:0100825
7 glossitis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000206
8 diarrhea 58 31 hallmark (90%) Very frequent (99-80%) HP:0002014
9 megaloblastic anemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001889
10 decreased circulating antibody level 31 hallmark (90%) HP:0004313
11 behavioral abnormality 58 31 frequent (33%) Frequent (79-30%) HP:0000708
12 gastroesophageal reflux 58 31 frequent (33%) Frequent (79-30%) HP:0002020
13 peripheral neuropathy 58 31 frequent (33%) Frequent (79-30%) HP:0009830
14 seizure 31 frequent (33%) HP:0001250
15 hyperreflexia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001347
16 cerebral calcification 58 31 occasional (7.5%) Occasional (29-5%) HP:0002514
17 recurrent respiratory infections 58 31 occasional (7.5%) Occasional (29-5%) HP:0002205
18 immunodeficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0002721
19 skeletal muscle atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0003202
20 thrombocytopenia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001873
21 recurrent urinary tract infections 58 31 occasional (7.5%) Occasional (29-5%) HP:0000010
22 eosinophilia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001880
23 pancytopenia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001876
24 intellectual disability 31 HP:0001249
25 seizures 58 Frequent (79-30%)
26 ataxia 31 HP:0001251
27 malabsorption 31 HP:0002024
28 dyskinesia 31 HP:0100660
29 feeding difficulties in infancy 31 HP:0008872
30 abnormality of movement 58 Very frequent (99-80%)
31 irritability 31 HP:0000737
32 decreased antibody level in blood 58 Very frequent (99-80%)
33 abnormality of the immune system 58 Very frequent (99-80%)
34 neutropenia 31 HP:0001875
35 recurrent infections 31 HP:0002719
36 athetosis 31 HP:0002305
37 generalized hypotonia 31 HP:0001290
38 leukopenia 31 HP:0001882
39 oral ulcer 31 HP:0000155
40 basal ganglia calcification 31 HP:0002135
41 hypotonia 31 HP:0001252
42 folate-responsive megaloblastic anemia 31 HP:0004851

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
seizures
ataxia
athetosis
hypotonia
head lag
more
Neurologic Behavioral Psychiatric Manifestations:
irritability

Neurologic Peripheral Nervous System:
peripheral neuropathy

Abdomen Gastrointestinal:
diarrhea
poor feeding
folate malabsorption

Laboratory Abnormalities:
decreased serum folate
decreased csf folate
low plasma methionine
increased urinary formiminoglutamic acid (figlu)

Growth Other:
failure to thrive

Hematology:
thrombocytopenia
neutropenia
leukopenia
megaloblastic anemia, folate-responsive

Immunology:
recurrent infections
increased susceptibility to pneumocystis and cytomegalovirus infections
hypoimmunoglobulinemia

Head And Neck Mouth:
oral ulcers

Clinical features from OMIM®:

229050 (Updated 20-May-2021)

UMLS symptoms related to Folate Malabsorption, Hereditary:


seizures; ataxia; diarrhea; athetosis

GenomeRNAi Phenotypes related to Folate Malabsorption, Hereditary according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 FOXO1 nuclear localization GR00247-A-1 9.1 SARM1 SLC19A1 SLC46A2 SLCO2B1
2 FOXO1 nuclear localization GR00247-A-2 9.1 SARM1 SLC46A2

Drugs & Therapeutics for Folate Malabsorption, Hereditary

Search Clinical Trials , NIH Clinical Center for Folate Malabsorption, Hereditary

Cochrane evidence based reviews: folate malabsorption, hereditary

Genetic Tests for Folate Malabsorption, Hereditary

Genetic tests related to Folate Malabsorption, Hereditary:

# Genetic test Affiliating Genes
1 Congenital Defect of Folate Absorption 29 SLC46A1

Anatomical Context for Folate Malabsorption, Hereditary

MalaCards organs/tissues related to Folate Malabsorption, Hereditary:

40
Bone Marrow, Skeletal Muscle, Pancreas

Publications for Folate Malabsorption, Hereditary

Articles related to Folate Malabsorption, Hereditary:

(show top 50) (show all 64)
# Title Authors PMID Year
1
Identification of novel mutations in the proton-coupled folate transporter (PCFT-SLC46A1) associated with hereditary folate malabsorption. 61 6 57
21333572 2011
2
A novel loss-of-function mutation in the proton-coupled folate transporter from a patient with hereditary folate malabsorption reveals that Arg 113 is crucial for function. 61 57 6
18559978 2008
3
The spectrum of mutations in the PCFT gene, coding for an intestinal folate transporter, that are the basis for hereditary folate malabsorption. 61 6 57
17446347 2007
4
Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. 61 6 57
17129779 2006
5
Hereditary folate malabsorption: family report and review of the literature. 6 61 57
11807405 2002
6
A family study of congenital malabsorption of folate. 57 6
11804211 2001
7
Congenital folate malabsorption. 57 6
3987728 1985
8
Mutation of the proton-coupled folate transporter gene (PCFT-SLC46A1) in Turkish siblings with hereditary folate malabsorption. 61 6
20795774 2010
9
Neurological manifestations of folate transport defect: case report and review of the literature. 57
17641272 2007
10
Congenital folate malabsorption: reversible clinical and neurophysiologic abnormalities. 57
2381546 1990
11
Progressive intracranial calcification in dihydropteridine reductase deficiency prior to folinic acid therapy. 57
2785251 1989
12
Congenital isolated folic acid malabsorption. 57
3813642 1987
13
Letter: Congenital folate deficiency. 57
176588 1976
14
Congenital isolated defect of folic acid absorption. 57
4540608 1973
15
Congenital malabsorption of folate. 57
5450108 1970
16
Isolated defect of folic acid absorption associated with mental retardation and cerebral calcification. 57
4980683 1969
17
A proton-coupled folate transporter mutation causing hereditary folate malabsorption locks the protein in an inward-open conformation. 61
32893190 2020
18
Treatable Cause of Pancytopenia, Recurrent Infections and Refractory Epilepsy: Secondary to Hereditary Folate Malabsorption (HFM) Due to Novel Pathogenic Variant. 61
33146883 2020
19
Pulmonary hypertension related to hereditary folate malabsorption in an infant. 61
32893915 2020
20
Immunodeficiency and inborn disorders of vitamin B12 and folate metabolism. 61
32412981 2020
21
Successful Treatment of Hereditary Folate Malabsorption With Intramuscular Folinic Acid. 61
31371121 2020
22
A deep intronic mutation of c.1166-285 T > G in SLC46A1 is shared by four unrelated Japanese patients with hereditary folate malabsorption (HFM). 61
31494288 2019
23
Hereditary folate malabsorption due to a mutation in the external gate of the proton-coupled folate transporter SLC46A1. 61
29344585 2018
24
Role of Intramuscular Levofolinate Administration in the Treatment of Hereditary Folate Malabsorption: Report of Three Cases. 61
28685492 2018
25
Hereditary folate malabsorption with a novel mutation on SLC46A1: A case report. 61
29390264 2017
26
The proton-coupled folate transporter (PCFT-SLC46A1) and the syndrome of systemic and cerebral folate deficiency of infancy: Hereditary folate malabsorption. 61
27664775 2017
27
[Two cases with generalized intracranial calcification due to hereditary folate malabsorption and literature review]. 61
27938595 2016
28
Reversible pancytopenia and immunodeficiency in a patient with hereditary folate malabsorption. 61
25504888 2015
29
CSF 5-Methyltetrahydrofolate Serial Monitoring to Guide Treatment of Congenital Folate Malabsorption Due to Proton-Coupled Folate Transporter (PCFT) Deficiency. 61
26006721 2015
30
Hereditary folate malabsorption with extensive intracranial calcification. 61
25638192 2015
31
The first Chinese case report of hereditary folate malabsorption with a novel mutation on SLC46A1. 61
24534056 2015
32
Impact of folate therapy on combined immunodeficiency secondary to hereditary folate malabsorption. 61
24691418 2014
33
The major facilitative folate transporters solute carrier 19A1 and solute carrier 46A1: biology and role in antifolate chemotherapy of cancer. 61
24396145 2014
34
The intestinal absorption of folates. 61
24512081 2014
35
Biology of the major facilitative folate transporters SLC19A1 and SLC46A1. 61
24745983 2014
36
The proton-coupled folate transporter: physiological and pharmacological roles. 61
24383099 2013
37
A novel deletion mutation in the proton-coupled folate transporter (PCFT; SLC46A1) in a Nicaraguan child with hereditary folate malabsorption. 61
23816405 2013
38
Inhibition of the proton-coupled folate transporter (PCFT-SLC46A1) by bicarbonate and other anions. 61
23609145 2013
39
Role of the fourth transmembrane domain in proton-coupled folate transporter function as assessed by the substituted cysteine accessibility method. 61
23552283 2013
40
Folate and thiamine transporters mediated by facilitative carriers (SLC19A1-3 and SLC46A1) and folate receptors. 61
23506878 2013
41
The human proton-coupled folate transporter: Biology and therapeutic applications to cancer. 61
22954694 2012
42
Functional roles of the A335 and G338 residues of the proton-coupled folate transporter (PCFT-SLC46A1) mutated in hereditary folate malabsorption. 61
22843796 2012
43
Identification of a functionally critical GXXG motif and its relationship to the folate binding site of the proton-coupled folate transporter (PCFT-SLC46A1). 61
22785121 2012
44
Update and new concepts in vitamin responsive disorders of folate transport and metabolism. 61
22108709 2012
45
A P425R mutation of the proton-coupled folate transporter causing hereditary folate malabsorption produces a highly selective alteration in folate binding. 61
22345511 2012
46
Identification and functional impact of homo-oligomers of the human proton-coupled folate transporter. 61
22179615 2012
47
Prevalence of a loss-of-function mutation in the proton-coupled folate transporter gene (PCFT-SLC46A1) causing hereditary folate malabsorption in Puerto Rico. 61
21489556 2011
48
Mechanisms of membrane transport of folates into cells and across epithelia. 61
21568705 2011
49
Random mutagenesis of the proton-coupled folate transporter (SLC46A1), clustering of mutations, and the bases for associated losses of function. 61
21602279 2011
50
A mouse model of hereditary folate malabsorption: deletion of the PCFT gene leads to systemic folate deficiency. 61
21346251 2011

Variations for Folate Malabsorption, Hereditary

ClinVar genetic disease variations for Folate Malabsorption, Hereditary:

6 (show top 50) (show all 147)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SLC46A1 SLC46A1, 1-BP INS, 17C Insertion Pathogenic 30922 GRCh37:
GRCh38:
2 SLC46A1 NM_080669.6(SLC46A1):c.204_205del (p.Asn68fs) Deletion Pathogenic 30924 rs397515391 GRCh37: 17:26732928-26732929
GRCh38: 17:28405910-28405911
3 SLC46A1 NM_080669.6(SLC46A1):c.1012G>C (p.Gly338Arg) SNV Pathogenic 30925 rs281875209 GRCh37: 17:26731703-26731703
GRCh38: 17:28404685-28404685
4 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.1127G>A (p.Arg376Gln) SNV Pathogenic 65749 rs281875211 GRCh37: 17:26729294-26729294
GRCh38: 17:28402276-28402276
5 SLC46A1 NM_080669.6(SLC46A1):c.466G>T (p.Asp156Tyr) SNV Pathogenic 65753 rs281875210 GRCh37: 17:26732249-26732249
GRCh38: 17:28405231-28405231
6 SLC46A1 NM_080669.6(SLC46A1):c.197_198delinsAA (p.Cys66Ter) Indel Pathogenic 21744 rs154623632 GRCh37: 17:26732935-26732936
GRCh38: 17:28405917-28405918
7 SLC46A1 NM_080669.6(SLC46A1):c.194dup (p.Cys66fs) Duplication Pathogenic 65750 rs80338769 GRCh37: 17:26732938-26732939
GRCh38: 17:28405920-28405921
8 SLC46A1 NM_080669.6(SLC46A1):c.23dup (p.Glu9fs) Duplication Pathogenic 65752 rs397515574 GRCh37: 17:26733109-26733110
GRCh38: 17:28406091-28406092
9 SLC46A1 NM_080669.6(SLC46A1):c.194del (p.Gly65fs) Deletion Pathogenic 851 rs80338769 GRCh37: 17:26732939-26732939
GRCh38: 17:28405921-28405921
10 SLC46A1 NM_080669.6(SLC46A1):c.337C>A (p.Arg113Ser) SNV Pathogenic 852 rs80338770 GRCh37: 17:26732378-26732378
GRCh38: 17:28405360-28405360
11 SLC46A1 NM_080669.6(SLC46A1):c.954C>G (p.Ser318Arg) SNV Pathogenic 853 rs80338772 GRCh37: 17:26731761-26731761
GRCh38: 17:28404743-28404743
12 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.1126C>T (p.Arg376Trp) SNV Pathogenic 854 rs80338773 GRCh37: 17:26729295-26729295
GRCh38: 17:28402277-28402277
13 SLC46A1 NM_080669.6(SLC46A1):c.337C>T (p.Arg113Cys) SNV Pathogenic 855 rs80338770 GRCh37: 17:26732378-26732378
GRCh38: 17:28405360-28405360
14 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.1274C>G (p.Pro425Arg) SNV Pathogenic 21743 rs80338774 GRCh37: 17:26727674-26727674
GRCh38: 17:28400658-28400658
15 SLC46A1 NM_080669.6(SLC46A1):c.439G>C (p.Gly147Arg) SNV Pathogenic 21745 rs80338771 GRCh37: 17:26732276-26732276
GRCh38: 17:28405258-28405258
16 SLC46A1 NM_080669.6(SLC46A1):c.1004C>A (p.Ala335Asp) SNV Pathogenic 30923 rs281875208 GRCh37: 17:26731711-26731711
GRCh38: 17:28404693-28404693
17 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.1082-1G>A SNV Pathogenic 850 rs80338775 GRCh37: 17:26729340-26729340
GRCh38: 17:28402322-28402322
18 SLC46A1 NM_080669.6(SLC46A1):c.1061T>G (p.Ile354Ser) SNV Uncertain significance 1031063 GRCh37: 17:26731654-26731654
GRCh38: 17:28404636-28404636
19 SLC46A1 NM_080669.6(SLC46A1):c.623A>T (p.Tyr208Phe) SNV Uncertain significance 252777 rs201837257 GRCh37: 17:26732092-26732092
GRCh38: 17:28405074-28405074
20 SLC46A1 NM_080669.6(SLC46A1):c.512T>A (p.Val171Asp) SNV Uncertain significance 322409 rs189103810 GRCh37: 17:26732203-26732203
GRCh38: 17:28405185-28405185
21 SLC46A1 NM_080669.6(SLC46A1):c.972C>T (p.Leu324=) SNV Uncertain significance 713611 rs188529539 GRCh37: 17:26731743-26731743
GRCh38: 17:28404725-28404725
22 SLC46A1 NM_080669.6(SLC46A1):c.22C>T (p.Pro8Ser) SNV Uncertain significance 193480 rs41297065 GRCh37: 17:26733111-26733111
GRCh38: 17:28406093-28406093
23 SLC46A1 NM_080669.6(SLC46A1):c.158C>T (p.Ala53Val) SNV Uncertain significance 193481 rs41297069 GRCh37: 17:26732975-26732975
GRCh38: 17:28405957-28405957
24 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*2945G>A SNV Uncertain significance 888618 GRCh37: 17:26723730-26723730
GRCh38: 17:28396711-28396711
25 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*1839G>A SNV Uncertain significance 888671 GRCh37: 17:26724836-26724836
GRCh38: 17:28397817-28397817
26 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*1521G>A SNV Uncertain significance 888672 GRCh37: 17:26725151-26725151
GRCh38: 17:28398135-28398135
27 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*4158G>A SNV Uncertain significance 890268 GRCh37: 17:26722517-26722517
GRCh38: 17:28395498-28395498
28 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*4091C>A SNV Uncertain significance 890269 GRCh37: 17:26722584-26722584
GRCh38: 17:28395565-28395565
29 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*4071G>A SNV Uncertain significance 890270 GRCh37: 17:26722604-26722604
GRCh38: 17:28395585-28395585
30 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*3985A>T SNV Uncertain significance 890272 GRCh37: 17:26722690-26722690
GRCh38: 17:28395671-28395671
31 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*2901C>T SNV Uncertain significance 890317 GRCh37: 17:26723774-26723774
GRCh38: 17:28396755-28396755
32 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*2868G>A SNV Uncertain significance 890318 GRCh37: 17:26723807-26723807
GRCh38: 17:28396788-28396788
33 SLC46A1 NM_080669.6(SLC46A1):c.898G>A (p.Asp300Asn) SNV Uncertain significance 890431 GRCh37: 17:26731817-26731817
GRCh38: 17:28404799-28404799
34 SLC46A1 NM_080669.6(SLC46A1):c.849G>A (p.Gly283=) SNV Uncertain significance 890432 GRCh37: 17:26731866-26731866
GRCh38: 17:28404848-28404848
35 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*2724G>C SNV Uncertain significance 890877 GRCh37: 17:26723951-26723951
GRCh38: 17:28396932-28396932
36 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*2486T>C SNV Uncertain significance 890878 GRCh37: 17:26724189-26724189
GRCh38: 17:28397170-28397170
37 SLC46A1 NM_080669.6(SLC46A1):c.501C>G (p.Ser167=) SNV Uncertain significance 891002 GRCh37: 17:26732214-26732214
GRCh38: 17:28405196-28405196
38 SLC46A1 NM_080669.6(SLC46A1):c.389T>C (p.Val130Ala) SNV Uncertain significance 891003 GRCh37: 17:26732326-26732326
GRCh38: 17:28405308-28405308
39 SLC46A1 NM_080669.6(SLC46A1):c.295T>C (p.Phe99Leu) SNV Uncertain significance 891004 GRCh37: 17:26732420-26732420
GRCh38: 17:28405402-28405402
40 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*4804T>A SNV Uncertain significance 892030 GRCh37: 17:26721871-26721871
GRCh38: 17:28394852-28394852
41 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*3456G>C SNV Uncertain significance 892076 GRCh37: 17:26723219-26723219
GRCh38: 17:28396200-28396200
42 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*3279C>T SNV Uncertain significance 892077 GRCh37: 17:26723396-26723396
GRCh38: 17:28396377-28396377
43 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*2262G>A SNV Uncertain significance 892118 GRCh37: 17:26724413-26724413
GRCh38: 17:28397394-28397394
44 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*1383A>G SNV Uncertain significance 890375 GRCh37: 17:26725289-26725289
GRCh38: 17:28398273-28398273
45 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*1336G>A SNV Uncertain significance 890376 GRCh37: 17:26725336-26725336
GRCh38: 17:28398320-28398320
46 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*1335C>T SNV Uncertain significance 890377 GRCh37: 17:26725337-26725337
GRCh38: 17:28398321-28398321
47 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*1298G>A SNV Uncertain significance 890378 GRCh37: 17:26725374-26725374
GRCh38: 17:28398358-28398358
48 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*1249G>A SNV Uncertain significance 890379 GRCh37: 17:26725423-26725423
GRCh38: 17:28398407-28398407
49 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*4418C>T SNV Uncertain significance 888568 GRCh37: 17:26722257-26722257
GRCh38: 17:28395238-28395238
50 SLC46A1 , SARM1 NM_080669.6(SLC46A1):c.*4184T>G SNV Uncertain significance 888569 GRCh37: 17:26722491-26722491
GRCh38: 17:28395472-28395472

UniProtKB/Swiss-Prot genetic disease variations for Folate Malabsorption, Hereditary:

72
# Symbol AA change Variation ID SNP ID
1 SLC46A1 p.Arg113Ser VAR_032825 rs80338770
2 SLC46A1 p.Gly147Arg VAR_032826 rs80338771
3 SLC46A1 p.Ser318Arg VAR_032827 rs80338772
4 SLC46A1 p.Arg376Trp VAR_032828 rs80338773
5 SLC46A1 p.Pro425Arg VAR_032829 rs80338774
6 SLC46A1 p.Arg113Cys VAR_058210 rs80338770
7 SLC46A1 p.Asp156Tyr VAR_067960 rs281875210
8 SLC46A1 p.Ala335Asp VAR_067961 rs281875208
9 SLC46A1 p.Gly338Arg VAR_067962 rs281875209
10 SLC46A1 p.Arg376Gln VAR_067963 rs281875211

Expression for Folate Malabsorption, Hereditary

Search GEO for disease gene expression data for Folate Malabsorption, Hereditary.

Pathways for Folate Malabsorption, Hereditary

Pathways related to Folate Malabsorption, Hereditary according to KEGG:

36
# Name Kegg Source Accession
1 Vitamin digestion and absorption hsa04977
2 Mineral absorption hsa04978

GO Terms for Folate Malabsorption, Hereditary

Cellular components related to Folate Malabsorption, Hereditary according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.16 SLCO2B1 SLC48A1 SLC46A3 SLC46A2 SLC46A1 SLC25A38
2 integral component of membrane GO:0016021 9.8 SLCO2B1 SLC48A1 SLC46A3 SLC46A2 SLC46A1 SLC25A38
3 apical plasma membrane GO:0016324 9.62 SLCO2B1 SLC46A1 SLC19A1 FOLR1
4 brush border membrane GO:0031526 9.33 SLC46A1 SLC19A1 FOLR1
5 anchored component of external side of plasma membrane GO:0031362 8.8 FOLR3 FOLR2 FOLR1

Biological processes related to Folate Malabsorption, Hereditary according to GeneCards Suite gene sharing:

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 transmembrane transport GO:0055085 9.91 SLCO2B1 SLC46A3 SLC46A2 SLC46A1 SLC19A3 SLC19A2
2 response to axon injury GO:0048678 9.7 SARM1 MTR FOLR1
3 fusion of sperm to egg plasma membrane involved in single fertilization GO:0007342 9.65 FOLR3 FOLR2 FOLR1
4 sperm-egg recognition GO:0035036 9.63 FOLR3 FOLR2 FOLR1
5 axon regeneration GO:0031103 9.61 MTR FOLR1 DHFR
6 organic anion transport GO:0015711 9.58 SLCO2B1 SLC19A1
7 mitochondrial transport GO:0006839 9.58 SLC25A32 FLVCR1
8 heme transport GO:0015886 9.58 SLC48A1 SLC46A1 FLVCR1
9 thiamine-containing compound metabolic process GO:0042723 9.57 SLC19A3 SLC19A2
10 heme export GO:0097037 9.56 FLVCR2 FLVCR1
11 thiamine transmembrane transport GO:0071934 9.55 SLC19A3 SLC19A2
12 thiamine transport GO:0015888 9.54 SLC19A3 SLC19A2
13 vitamin transport GO:0051180 9.54 SLC19A3 SLC19A2 SLC19A1
14 cellular response to folic acid GO:0071231 9.51 FOLR2 FOLR1
15 vitamin transmembrane transport GO:0035461 9.5 SLC19A3 SLC19A2 SLC19A1
16 methotrexate transport GO:0051958 9.49 SLC46A1 SLC19A1
17 folate import across plasma membrane GO:1904447 9.46 SLC46A1 SLC19A1 FOLR2 FOLR1
18 folic acid metabolic process GO:0046655 9.43 SLC46A1 SLC25A32 SLC19A1 FOLR2 FOLR1 DHFR
19 folic acid transport GO:0015884 9.17 SLC46A1 SLC25A32 SLC19A2 SLC19A1 FOLR3 FOLR2

Molecular functions related to Folate Malabsorption, Hereditary according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 heme binding GO:0020037 9.78 SLC48A1 HEBP1 FLVCR2 FLVCR1
2 transmembrane transporter activity GO:0022857 9.77 SLC46A3 SLC46A2 SLC46A1 FLVCR2 FLVCR1
3 vitamin transmembrane transporter activity GO:0090482 9.5 SLC19A3 SLC19A2 SLC19A1
4 organic anion transmembrane transporter activity GO:0008514 9.49 SLCO2B1 SLC19A1
5 thiamine transmembrane transporter activity GO:0015234 9.46 SLC19A3 SLC19A2
6 heme transporter activity GO:0015232 9.46 SLC48A1 SLC46A1 FLVCR2 FLVCR1
7 folic acid receptor activity GO:0061714 9.43 FOLR2 FOLR1
8 methotrexate binding GO:0051870 9.43 FOLR2 FOLR1 DHFR
9 methotrexate transmembrane transporter activity GO:0015350 9.4 SLC46A1 SLC19A1
10 folic acid transmembrane transporter activity GO:0008517 9.26 SLC46A1 SLC25A32 SLC19A2 SLC19A1
11 folic acid binding GO:0005542 9.1 SLC46A1 SLC19A1 FOLR3 FOLR2 FOLR1 DHFR

Sources for Folate Malabsorption, Hereditary

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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