MCID: INT088
MIFTS: 35

Intrinsic Factor Deficiency

Categories: Genetic diseases, Rare diseases, Metabolic diseases

Aliases & Classifications for Intrinsic Factor Deficiency

MalaCards integrated aliases for Intrinsic Factor Deficiency:

Name: Intrinsic Factor Deficiency 57 53 29 13 6 40 73
Ifd 57 53 75
Pernicious Anemia, Congenital, Due to Defect of Intrinsic Factor 57 53
Congenital Pernicious Anemia Due to Defect of Intrinsic Factor 53
Intrinsic Factor Deficiency, Congenital, Susceptibility to 6
Megaloblastic Anemia Due to Inborn Errors of Metabolism 73
Intrinsic Factor, Congenital Deficiency of 53
Congenital Deficiency of Intrinsic Factor 73
Congenital Intrinsic Factor Deficiency 53
Hereditary Intrinsic Factor Deficiency 75
Congenital Pernicious Anemia 75

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in childhood


HPO:

32
intrinsic factor deficiency:
Onset and clinical course juvenile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Intrinsic Factor Deficiency

NIH Rare Diseases : 53 Intrinsic factor deficiency is a rare condition that is characterized by pernicious anemia and neurological abnormalities. Most affected people develop signs and symptoms of the condition before age 5 years which may include failure to thrive and symptoms related to anemia (i.e. fatigue, pale skin, etc). Without early diagnosis and treatment, nervous system damage may occur which can be associated with confusion; depression; and numbness or tingling in the hands and/or feet. Intrinsic factor deficiency is caused by changes (mutations) in the GIF gene and is inherited in an autosomal recessive manner. Treatment generally consists of vitamin B12 injections.

MalaCards based summary : Intrinsic Factor Deficiency, also known as ifd, is related to pernicious anemia and congenital intrinsic factor deficiency. An important gene associated with Intrinsic Factor Deficiency is GIF (Gastric Intrinsic Factor). The drugs Hydroxocobalamin and Cyanocobalamin have been mentioned in the context of this disorder. Affiliated tissues include skin, small intestine and lung, and related phenotypes are malabsorption and abnormality of metabolism/homeostasis

OMIM : 57 Congenital pernicious anemia (PA), or intrinsic factor deficiency, is a rare disorder characterized by the lack of gastric intrinsic factor in the presence of normal acid secretion and mucosal cytology and the absence of GIF antibodies that are found in the acquired form of pernicious anemia (170900). See also pernicious anemia due to defect in the receptor for vitamin B12/intrinsic factor (261100). (261000)

UniProtKB/Swiss-Prot : 75 Hereditary intrinsic factor deficiency: Autosomal recessive disorder characterized by megaloblastic anemia.

Wikipedia : 76 Intrinsic factor (IF), also known as gastric intrinsic factor (GIF), is a glycoprotein produced by the... more...

Related Diseases for Intrinsic Factor Deficiency

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

# Related Disease Score Top Affiliating Genes
1 pernicious anemia 29.0 FUT2 GIF
2 congenital intrinsic factor deficiency 12.6
3 deficiency anemia 9.6
4 diabetes mellitus 9.6

Symptoms & Phenotypes for Intrinsic Factor Deficiency

Symptoms via clinical synopsis from OMIM:

57
Neurologic Peripheral Nervous System:
peripheral neuropathy
sensory impairment
paresthesias

Abdomen Gastrointestinal:
vitamin b12 deficiency caused by intestinal malabsorption
absence of intrinsic factor by immunoassay of gastric juices
normal gastric mucosa
normal gastric acid secretion
normal pepsin secretion

Laboratory Abnormalities:
decreased serum b12 levels

Hematology:
increased mean corpuscular volume
megaloblastic anemia
bone marrow biopsy shows megaloblastic erythroid hyperplasia

Immunology:
absence of auto-antibodies to intrinsic factor or parietal cells


Clinical features from OMIM:

261000

Human phenotypes related to Intrinsic Factor Deficiency:

32 (show all 10)
# Description HPO Frequency HPO Source Accession
1 malabsorption 32 HP:0002024
2 abnormality of metabolism/homeostasis 32 HP:0001939
3 paresthesia 32 HP:0003401
4 abnormality of the immune system 32 HP:0002715
5 increased mean corpuscular volume 32 HP:0005518
6 sensory impairment 32 HP:0003474
7 megaloblastic anemia 32 HP:0001889
8 malabsorption of vitamin b12 32 HP:0200118
9 absence of intrinsic factor 32 HP:0005219
10 megaloblastic erythroid hyperplasia 32 HP:0200143

Drugs & Therapeutics for Intrinsic Factor Deficiency

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

(show all 34)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Hydroxocobalamin Approved Phase 4,Phase 2 13422-51-0 11953898 44475014
2
Cyanocobalamin Approved, Nutraceutical Phase 4,Phase 2 68-19-9 44176380
3
Folic Acid Approved, Nutraceutical, Vet_approved Phase 4,Phase 2 59-30-3 6037
4
Methylcobalamin Approved, Experimental, Investigational, Nutraceutical Phase 4,Phase 2 13422-55-4
5
Pyridoxal Approved, Nutraceutical Phase 4 66-72-8 1050
6
Pyridoxine Approved, Investigational, Nutraceutical, Vet_approved Phase 4 65-23-6 1054
7
Thiamine Approved, Investigational, Nutraceutical, Vet_approved Phase 4 59-43-8, 70-16-6 1130
8 Hematinics Phase 4,Phase 2
9 Micronutrients Phase 4,Phase 2
10 Trace Elements Phase 4,Phase 2
11 Vitamin B 12 Phase 4,Phase 2
12 Vitamin B Complex Phase 4,Phase 2
13 Vitamins Phase 4,Phase 2
14 Vitamin B 6 Phase 4
15
Cobalamin Nutraceutical Phase 4,Phase 2 13408-78-1 6438156
16 Folate Nutraceutical Phase 4,Phase 2
17 Vitamin B12 Nutraceutical Phase 4,Phase 2
18 Vitamin B9 Nutraceutical Phase 4,Phase 2
19 Thiamin Nutraceutical Phase 4
20 Vaccines Phase 3
21
Apremilast Approved, Investigational Phase 2 608141-41-9 11561674
22 Analgesics Phase 2
23 Analgesics, Non-Narcotic Phase 2
24 Angiogenesis Inhibitors Phase 2
25 Angiogenesis Modulating Agents Phase 2
26 Anti-Bacterial Agents Phase 2
27 Anti-Infective Agents Phase 2
28 Anti-Inflammatory Agents Phase 2
29 Anti-Inflammatory Agents, Non-Steroidal Phase 2
30 Antirheumatic Agents Phase 2
31 Immunosuppressive Agents Phase 2
32 Peripheral Nervous System Agents Phase 2
33 Antibodies
34 Immunoglobulins

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Megadose of Hydroxocobalamin for the Treatment of Pernicious Anemia Recruiting NCT03372447 Phase 4 Hydroxocobalamin 10,000mcg, Thiamin 100mg, Pyridoxine 50mg
2 Study to Evaluate Immunogenicity of the Hepatitis B Antigen of the GSK Biologicals' Candidate Malaria Vaccine (257049) Completed NCT01345240 Phase 3
3 Oral Vitamin B12 Administration for Vitamin B12 Deficiency After Total Gastrectomy Completed NCT00699478 Phase 2 mecobalamin
4 Combined Therapy With Narrow-Band Ultraviolet B Phototherapy and Apremilast for the Treatment of Vitiligo Recruiting NCT03123016 Phase 2 Apremilast
5 Clinical Course of Interstitial Lung Diseases: European IPF Registry and Biobank Recruiting NCT02951416

Search NIH Clinical Center for Intrinsic Factor Deficiency

Genetic Tests for Intrinsic Factor Deficiency

Genetic tests related to Intrinsic Factor Deficiency:

# Genetic test Affiliating Genes
1 Intrinsic Factor Deficiency 29 GIF

Anatomical Context for Intrinsic Factor Deficiency

MalaCards organs/tissues related to Intrinsic Factor Deficiency:

41
Skin, Small Intestine, Lung, Bone, Bone Marrow

Publications for Intrinsic Factor Deficiency

Articles related to Intrinsic Factor Deficiency:

(show all 12)
# Title Authors Year
1
Gastric intrinsic factor deficiency with combined GIF heterozygous mutations and FUT2 secretor variant. ( 23402911 )
2013
2
Hereditary intrinsic factor deficiency in chaldeans. ( 23430489 )
2013
3
A genetic polymorphism in the coding region of the gastric intrinsic factor gene (GIF) is associated with congenital intrinsic factor deficiency. ( 14695536 )
2004
4
Identification of a 4-base deletion in the gene in inherited intrinsic factor deficiency. ( 14576042 )
2004
5
Congenital intrinsic factor deficiency in a Spanish patient. ( 1581408 )
1992
6
[Congenital intrinsic factor deficiency. Apropos of 3 cases in a sibship]. ( 3395196 )
1988
7
Intrinsic factor deficiency in adults with normal hydrochloric acid production. ( 7450447 )
1981
8
Vitamin B 12 malabsorption due to intrinsic factor deficiency in Indian subjects. ( 5078931 )
1972
9
Simultaneous administration of gastric juice--bound and free radioactive cyanocobalamin: rapid procedure for differentiating between intrinsic factor deficiency and other causes of vitamin B 12 malabsorption. ( 14031310 )
1963
10
INTRINSIC FACTOR DEFICIENCY IN MALIGNANT NEOPLASIA OF THE STOMACH. ( 14082869 )
1963
11
Intrinsic factor deficiency, achlorhydria, and malignancy in polyps of the stomach and duodenum. ( 13889742 )
1962
12
Some observations on nontropical sprue; a case with hypocalcemia, intrinsic factor deficiency anemia and diabetes mellitus. ( 13595357 )
1958

Variations for Intrinsic Factor Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Intrinsic Factor Deficiency:

75
# Symbol AA change Variation ID SNP ID
1 GIF p.Ser46Leu VAR_022743 rs121434322

ClinVar genetic disease variations for Intrinsic Factor Deficiency:

6
(show all 47)
# Gene Variation Type Significance SNP ID Assembly Location
1 GIF GIF, 4-BP DEL, 183GAAT deletion Pathogenic
2 GIF GIF, IVS1DS, G-A, +1 single nucleotide variant Pathogenic
3 GIF GIF, IVS1AS, G-A, -1 single nucleotide variant Pathogenic
4 GIF NM_005142.2(GIF): c.137C> T (p.Ser46Leu) single nucleotide variant Pathogenic rs121434322 GRCh37 Chromosome 11, 59611471: 59611471
5 GIF NM_005142.2(GIF): c.137C> T (p.Ser46Leu) single nucleotide variant Pathogenic rs121434322 GRCh38 Chromosome 11, 59843998: 59843998
6 GIF GIF, 1-BP DEL 161A deletion Pathogenic
7 GIF GIF, 1-BP INS, 1175T insertion Pathogenic
8 GIF NM_005142.2(GIF): c.435_437delGAA (p.Lys145del) deletion not provided rs770530971 GRCh38 Chromosome 11, 59842517: 59842519
9 GIF NM_005142.2(GIF): c.435_437delGAA (p.Lys145del) deletion not provided rs770530971 GRCh37 Chromosome 11, 59609990: 59609992
10 GIF NM_005142.2(GIF): c.346C> T (p.Gln116Ter) single nucleotide variant not provided rs796064508 GRCh38 Chromosome 11, 59843052: 59843052
11 GIF NM_005142.2(GIF): c.346C> T (p.Gln116Ter) single nucleotide variant not provided rs796064508 GRCh37 Chromosome 11, 59610525: 59610525
12 GIF NM_005142.2(GIF): c.-376A> T single nucleotide variant not provided rs796064509 GRCh38 Chromosome 11, 59845829: 59845829
13 GIF NM_005142.2(GIF): c.-376A> T single nucleotide variant not provided rs796064509 GRCh37 Chromosome 11, 59613302: 59613302
14 GIF NM_005142.2(GIF): c.1107C> T (p.Val369=) single nucleotide variant Uncertain significance rs537424617 GRCh37 Chromosome 11, 59599236: 59599236
15 GIF NM_005142.2(GIF): c.1107C> T (p.Val369=) single nucleotide variant Uncertain significance rs537424617 GRCh38 Chromosome 11, 59831763: 59831763
16 GIF NM_005142.2(GIF): c.990C> T (p.Asn330=) single nucleotide variant Benign/Likely benign rs2867802 GRCh37 Chromosome 11, 59603364: 59603364
17 GIF NM_005142.2(GIF): c.990C> T (p.Asn330=) single nucleotide variant Benign/Likely benign rs2867802 GRCh38 Chromosome 11, 59835891: 59835891
18 GIF NM_005142.2(GIF): c.764A> G (p.Asn255Ser) single nucleotide variant Benign/Likely benign rs35867471 GRCh37 Chromosome 11, 59604754: 59604754
19 GIF NM_005142.2(GIF): c.764A> G (p.Asn255Ser) single nucleotide variant Benign/Likely benign rs35867471 GRCh38 Chromosome 11, 59837281: 59837281
20 GIF NM_005142.2(GIF): c.455C> T (p.Pro152Leu) single nucleotide variant Uncertain significance rs148081315 GRCh37 Chromosome 11, 59609972: 59609972
21 GIF NM_005142.2(GIF): c.455C> T (p.Pro152Leu) single nucleotide variant Uncertain significance rs148081315 GRCh38 Chromosome 11, 59842499: 59842499
22 GIF NM_005142.2(GIF): c.246C> T (p.Ser82=) single nucleotide variant Likely benign rs35792306 GRCh37 Chromosome 11, 59611362: 59611362
23 GIF NM_005142.2(GIF): c.246C> T (p.Ser82=) single nucleotide variant Likely benign rs35792306 GRCh38 Chromosome 11, 59843889: 59843889
24 GIF NM_005142.2(GIF): c.834G> C (p.Lys278Asn) single nucleotide variant Uncertain significance rs886048403 GRCh37 Chromosome 11, 59604684: 59604684
25 GIF NM_005142.2(GIF): c.834G> C (p.Lys278Asn) single nucleotide variant Uncertain significance rs886048403 GRCh38 Chromosome 11, 59837211: 59837211
26 GIF NM_005142.2(GIF): c.371-15C> T single nucleotide variant Uncertain significance rs759810252 GRCh37 Chromosome 11, 59610071: 59610071
27 GIF NM_005142.2(GIF): c.371-15C> T single nucleotide variant Uncertain significance rs759810252 GRCh38 Chromosome 11, 59842598: 59842598
28 GIF NM_005142.2(GIF): c.218A> G (p.Lys73Arg) single nucleotide variant Uncertain significance rs139444835 GRCh37 Chromosome 11, 59611390: 59611390
29 GIF NM_005142.2(GIF): c.218A> G (p.Lys73Arg) single nucleotide variant Uncertain significance rs139444835 GRCh38 Chromosome 11, 59843917: 59843917
30 GIF NM_005142.2(GIF): c.*56T> G single nucleotide variant Uncertain significance rs886048401 GRCh38 Chromosome 11, 59829428: 59829428
31 GIF NM_005142.2(GIF): c.*56T> G single nucleotide variant Uncertain significance rs886048401 GRCh37 Chromosome 11, 59596901: 59596901
32 GIF NM_005142.2(GIF): c.379G> A (p.Ala127Thr) single nucleotide variant Uncertain significance rs760404861 GRCh37 Chromosome 11, 59610048: 59610048
33 GIF NM_005142.2(GIF): c.379G> A (p.Ala127Thr) single nucleotide variant Uncertain significance rs760404861 GRCh38 Chromosome 11, 59842575: 59842575
34 GIF NM_005142.2(GIF): c.79+3G> A single nucleotide variant Uncertain significance rs146396839 GRCh37 Chromosome 11, 59612845: 59612845
35 GIF NM_005142.2(GIF): c.79+3G> A single nucleotide variant Uncertain significance rs146396839 GRCh38 Chromosome 11, 59845372: 59845372
36 GIF NM_005142.2(GIF): c.910C> T (p.Pro304Ser) single nucleotide variant Uncertain significance rs150926439 GRCh37 Chromosome 11, 59603444: 59603444
37 GIF NM_005142.2(GIF): c.910C> T (p.Pro304Ser) single nucleotide variant Uncertain significance rs150926439 GRCh38 Chromosome 11, 59835971: 59835971
38 GIF NM_005142.2(GIF): c.854A> G (p.Gln285Arg) single nucleotide variant Uncertain significance rs886048402 GRCh37 Chromosome 11, 59604664: 59604664
39 GIF NM_005142.2(GIF): c.854A> G (p.Gln285Arg) single nucleotide variant Uncertain significance rs886048402 GRCh38 Chromosome 11, 59837191: 59837191
40 GIF NM_005142.2(GIF): c.524T> C (p.Met175Thr) single nucleotide variant Uncertain significance rs886048404 GRCh37 Chromosome 11, 59608785: 59608785
41 GIF NM_005142.2(GIF): c.524T> C (p.Met175Thr) single nucleotide variant Uncertain significance rs886048404 GRCh38 Chromosome 11, 59841312: 59841312
42 GIF NM_005142.2(GIF): c.290T> C (p.Met97Thr) single nucleotide variant Likely benign rs150884181 GRCh37 Chromosome 11, 59610581: 59610581
43 GIF NM_005142.2(GIF): c.290T> C (p.Met97Thr) single nucleotide variant Likely benign rs150884181 GRCh38 Chromosome 11, 59843108: 59843108
44 GIF NM_005142.2(GIF): c.247G> A (p.Asp83Asn) single nucleotide variant Uncertain significance rs115964827 GRCh37 Chromosome 11, 59611361: 59611361
45 GIF NM_005142.2(GIF): c.247G> A (p.Asp83Asn) single nucleotide variant Uncertain significance rs115964827 GRCh38 Chromosome 11, 59843888: 59843888
46 GIF NM_005142.2(GIF): c.154T> A (p.Tyr52Asn) single nucleotide variant Uncertain significance rs144916324 GRCh37 Chromosome 11, 59611454: 59611454
47 GIF NM_005142.2(GIF): c.154T> A (p.Tyr52Asn) single nucleotide variant Uncertain significance rs144916324 GRCh38 Chromosome 11, 59843981: 59843981

Expression for Intrinsic Factor Deficiency

Search GEO for disease gene expression data for Intrinsic Factor Deficiency.

Pathways for Intrinsic Factor Deficiency

GO Terms for Intrinsic Factor Deficiency

Sources for Intrinsic Factor Deficiency

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