HFTC3
MCID: TMR020
MIFTS: 26

Tumoral Calcinosis, Hyperphosphatemic, Familial, 3 (HFTC3)

Categories: Blood diseases, Bone diseases, Endocrine diseases, Fetal diseases, Genetic diseases, Metabolic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Tumoral Calcinosis, Hyperphosphatemic, Familial, 3

MalaCards integrated aliases for Tumoral Calcinosis, Hyperphosphatemic, Familial, 3:

Name: Tumoral Calcinosis, Hyperphosphatemic, Familial, 3 57 72 17
Hyperphosphatemic Familial Tumoral Calcinosis 3 29 6
Hftc3 57 72

Characteristics:

OMIM®:

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

Miscellaneous:
based on description of 1 patient (last curated may 2020)


HPO:

31
tumoral calcinosis, hyperphosphatemic, familial, 3:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Tumoral Calcinosis, Hyperphosphatemic, Familial, 3

OMIM® : 57 Hyperphosphatemic familial tumoral calcinosis is a rare autosomal recessive metabolic disorder characterized by the progressive deposition of basic calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone (Chefetz et al., 2005). The biochemical hallmark of tumoral calcinosis is hyperphosphatemia caused by increased renal absorption of phosphate due to loss-of-function mutations in the FGF23 (605380) or GALNT3 (601756) gene. The term 'hyperostosis-hyperphosphatemia syndrome' is sometimes used when the disorder is characterized by involvement of the long bones associated with the radiographic findings of periosteal reaction and cortical hyperostosis. Although some have distinguished HHS from FTC by the presence of bone involvement and the absence of skin involvement (Frishberg et al., 2005), Ichikawa et al. (2010) concluded that the 2 entities represent a continuous spectrum of the same disease, best described as familial hyperphosphatemic tumoral calcinosis. HFTC is considered to be the clinical converse of autosomal dominant hypophosphatemic rickets (ADHR; 193100), an allelic disorder caused by gain-of-function mutations in the FGF23 gene and associated with hypophosphatemia and decreased renal phosphate absorption (Chefetz et al., 2005; Ichikawa et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of HFTC, see 211900. (617994) (Updated 20-May-2021)

MalaCards based summary : Tumoral Calcinosis, Hyperphosphatemic, Familial, 3, is also known as hyperphosphatemic familial tumoral calcinosis 3. An important gene associated with Tumoral Calcinosis, Hyperphosphatemic, Familial, 3 is KL (Klotho). Related phenotypes are cerebral calcification and osteopenia

UniProtKB/Swiss-Prot : 72 Tumoral calcinosis, hyperphosphatemic, familial, 3: A form of hyperphosphatemic tumoral calcinosis, a rare autosomal recessive metabolic disorder that manifests with hyperphosphatemia and massive calcium deposits in the skin and subcutaneous tissues. Some patients have recurrent, transient, painful swellings of the long bones associated with the radiographic findings of periosteal reaction and cortical hyperostosis and absence of skin involvement.

Related Diseases for Tumoral Calcinosis, Hyperphosphatemic, Familial, 3

Diseases in the Tumoral Calcinosis, Hyperphosphatemic, Familial, 1 family:

Tumoral Calcinosis, Hyperphosphatemic, Familial, 2 Tumoral Calcinosis, Hyperphosphatemic, Familial, 3

Symptoms & Phenotypes for Tumoral Calcinosis, Hyperphosphatemic, Familial, 3

Human phenotypes related to Tumoral Calcinosis, Hyperphosphatemic, Familial, 3:

31 (show all 12)
# Description HPO Frequency HPO Source Accession
1 cerebral calcification 31 very rare (1%) HP:0002514
2 osteopenia 31 very rare (1%) HP:0000938
3 fatigue 31 very rare (1%) HP:0012378
4 hypercalcemia 31 very rare (1%) HP:0003072
5 headache 31 very rare (1%) HP:0002315
6 hyperphosphatemia 31 very rare (1%) HP:0002905
7 elevated circulating parathyroid hormone level 31 very rare (1%) HP:0003165
8 parathyroid hyperplasia 31 very rare (1%) HP:0008208
9 calvarial osteosclerosis 31 very rare (1%) HP:0005450
10 high serum calcitriol 31 very rare (1%) HP:0031415
11 metacarpal periosteal thickening 31 very rare (1%) HP:0006051
12 achilles tendon calcification 31 very rare (1%) HP:0025441

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Laboratory Abnormalities:
hypercalcemia
hyperphosphatemia
elevated serum parathyroid hormone
elevated 1,25-dihydroxyvitamin d
elevated renal tubular reabsorption of phosphate
more
Skeletal Limbs:
sclerosis

Skeletal Feet:
sclerosis
achilles tendon calcifications

Cardiovascular Vascular:
carotid artery calcifications

Neurologic Central Nervous System:
dural calcifications

Skeletal:
tumoral calcinosis
diffuse oseopenia

Skeletal Hands:
sclerosis
metacarpal periosteal reaction

Head And Neck Teeth:
short, bulbous tooth roots

Skeletal Skull:
calvarial sclerosis

Endocrine Features:
hyperplastic parathyroid gland

Clinical features from OMIM®:

617994 (Updated 20-May-2021)

Drugs & Therapeutics for Tumoral Calcinosis, Hyperphosphatemic, Familial, 3

Search Clinical Trials , NIH Clinical Center for Tumoral Calcinosis, Hyperphosphatemic, Familial, 3

Genetic Tests for Tumoral Calcinosis, Hyperphosphatemic, Familial, 3

Genetic tests related to Tumoral Calcinosis, Hyperphosphatemic, Familial, 3:

# Genetic test Affiliating Genes
1 Hyperphosphatemic Familial Tumoral Calcinosis 3 29 KL

Anatomical Context for Tumoral Calcinosis, Hyperphosphatemic, Familial, 3

Publications for Tumoral Calcinosis, Hyperphosphatemic, Familial, 3

Articles related to Tumoral Calcinosis, Hyperphosphatemic, Familial, 3:

# Title Authors PMID Year
1
A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis. 6 57
17710231 2007
2
Clinical variability of familial tumoral calcinosis caused by novel GALNT3 mutations. 57
20358599 2010
3
A novel homozygous missense mutation in FGF23 causes Familial Tumoral Calcinosis associated with disseminated visceral calcification. 57
16151858 2005
4
A novel GALNT3 mutation in a pseudoautosomal dominant form of tumoral calcinosis: evidence that the disorder is autosomal recessive. 57
15687324 2005
5
Identification of a recurrent mutation in GALNT3 demonstrates that hyperostosis-hyperphosphatemia syndrome and familial tumoral calcinosis are allelic disorders. 57
15599692 2005

Variations for Tumoral Calcinosis, Hyperphosphatemic, Familial, 3

ClinVar genetic disease variations for Tumoral Calcinosis, Hyperphosphatemic, Familial, 3:

6 (show top 50) (show all 118)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 KL NM_004795.4(KL):c.578A>G (p.His193Arg) SNV Likely pathogenic 5346 rs121908423 GRCh37: 13:33591156-33591156
GRCh38: 13:33017018-33017018
2 KL NM_004795.4(KL):c.1811C>A (p.Pro604His) SNV Uncertain significance 311700 rs751229348 GRCh37: 13:33635027-33635027
GRCh38: 13:33060890-33060890
3 KL NM_004795.4(KL):c.2626G>A (p.Asp876Asn) SNV Uncertain significance 311706 rs146235320 GRCh37: 13:33635842-33635842
GRCh38: 13:33061705-33061705
4 KL NM_004795.4(KL):c.*1870G>A SNV Uncertain significance 883950 GRCh37: 13:33640193-33640193
GRCh38: 13:33066056-33066056
5 KL NM_004795.4(KL):c.426C>G (p.Leu142=) SNV Uncertain significance 882960 GRCh37: 13:33591004-33591004
GRCh38: 13:33016866-33016866
6 KL NM_004795.4(KL):c.442C>T (p.Arg148Cys) SNV Uncertain significance 882961 GRCh37: 13:33591020-33591020
GRCh38: 13:33016882-33016882
7 KL NM_004795.4(KL):c.450C>A (p.Ser150=) SNV Uncertain significance 882962 GRCh37: 13:33591028-33591028
GRCh38: 13:33016890-33016890
8 KL NM_004795.4(KL):c.1419G>A (p.Arg473=) SNV Uncertain significance 883027 GRCh37: 13:33629272-33629272
GRCh38: 13:33055135-33055135
9 KL NM_004795.4(KL):c.1557T>A (p.Phe519Leu) SNV Uncertain significance 883028 GRCh37: 13:33629410-33629410
GRCh38: 13:33055273-33055273
10 KL NM_004795.4(KL):c.1626C>T (p.Thr542=) SNV Uncertain significance 883029 GRCh37: 13:33634842-33634842
GRCh38: 13:33060705-33060705
11 KL NM_004795.4(KL):c.1718T>C (p.Val573Ala) SNV Uncertain significance 883030 GRCh37: 13:33634934-33634934
GRCh38: 13:33060797-33060797
12 KL NM_004795.4(KL):c.2874T>G (p.Thr958=) SNV Uncertain significance 883105 GRCh37: 13:33638158-33638158
GRCh38: 13:33064021-33064021
13 KL NM_004795.4(KL):c.2904C>T (p.Thr968=) SNV Uncertain significance 883106 GRCh37: 13:33638188-33638188
GRCh38: 13:33064051-33064051
14 KL NM_004795.4(KL):c.2995C>A (p.Leu999Ile) SNV Uncertain significance 883107 GRCh37: 13:33638279-33638279
GRCh38: 13:33064142-33064142
15 KL NM_004795.4(KL):c.*17A>G SNV Uncertain significance 883108 GRCh37: 13:33638340-33638340
GRCh38: 13:33064203-33064203
16 KL NM_004795.4(KL):c.*1486T>C SNV Uncertain significance 883170 GRCh37: 13:33639809-33639809
GRCh38: 13:33065672-33065672
17 KL NM_004795.4(KL):c.535C>T (p.Arg179Trp) SNV Uncertain significance 883757 GRCh37: 13:33591113-33591113
GRCh38: 13:33016975-33016975
18 KL NM_004795.4(KL):c.611A>G (p.Tyr204Cys) SNV Uncertain significance 883758 GRCh37: 13:33591189-33591189
GRCh38: 13:33017051-33017051
19 KL NM_004795.4(KL):c.656A>T (p.Tyr219Phe) SNV Uncertain significance 883760 GRCh37: 13:33591234-33591234
GRCh38: 13:33017096-33017096
20 KL NM_004795.4(KL):c.747C>T (p.Ala249=) SNV Uncertain significance 883761 GRCh37: 13:33591325-33591325
GRCh38: 13:33017187-33017187
21 KL NM_004795.4(KL):c.1848G>A (p.Leu616=) SNV Uncertain significance 883809 GRCh37: 13:33635064-33635064
GRCh38: 13:33060927-33060927
22 KL NM_004795.4(KL):c.1858C>T (p.Arg620Cys) SNV Uncertain significance 883810 GRCh37: 13:33635074-33635074
GRCh38: 13:33060937-33060937
23 KL NM_004795.4(KL):c.1860C>A (p.Arg620=) SNV Uncertain significance 883811 GRCh37: 13:33635076-33635076
GRCh38: 13:33060939-33060939
24 KL NM_004795.4(KL):c.1873G>A (p.Glu625Lys) SNV Uncertain significance 883812 GRCh37: 13:33635089-33635089
GRCh38: 13:33060952-33060952
25 KL NM_004795.4(KL):c.1945C>T (p.Arg649Cys) SNV Uncertain significance 883813 GRCh37: 13:33635161-33635161
GRCh38: 13:33061024-33061024
26 KL NM_004795.4(KL):c.2226C>T (p.Ser742=) SNV Uncertain significance 883814 GRCh37: 13:33635442-33635442
GRCh38: 13:33061305-33061305
27 KL NM_004795.4(KL):c.*93A>C SNV Uncertain significance 883880 GRCh37: 13:33638416-33638416
GRCh38: 13:33064279-33064279
28 KL NM_004795.4(KL):c.*203G>T SNV Uncertain significance 883881 GRCh37: 13:33638526-33638526
GRCh38: 13:33064389-33064389
29 KL NM_004795.4(KL):c.*218G>A SNV Uncertain significance 883882 GRCh37: 13:33638541-33638541
GRCh38: 13:33064404-33064404
30 KL NM_004795.4(KL):c.*263A>G SNV Uncertain significance 883883 GRCh37: 13:33638586-33638586
GRCh38: 13:33064449-33064449
31 KL NM_004795.4(KL):c.*380A>G SNV Uncertain significance 883884 GRCh37: 13:33638703-33638703
GRCh38: 13:33064566-33064566
32 KL NM_004795.4(KL):c.2702-1G>C SNV Uncertain significance 631699 rs1566510826 GRCh37: 13:33637985-33637985
GRCh38: 13:33063848-33063848
33 KL NM_004795.4(KL):c.967G>A (p.Val323Ile) SNV Uncertain significance 311689 rs143344388 GRCh37: 13:33628051-33628051
GRCh38: 13:33053914-33053914
34 KL NM_004795.4(KL):c.*1950C>A SNV Uncertain significance 311735 rs886050130 GRCh37: 13:33640273-33640273
GRCh38: 13:33066136-33066136
35 KL NM_004795.4(KL):c.*1603C>A SNV Uncertain significance 311729 rs886050128 GRCh37: 13:33639926-33639926
GRCh38: 13:33065789-33065789
36 KL NM_004795.4(KL):c.*1728A>G SNV Uncertain significance 311732 rs556620337 GRCh37: 13:33640051-33640051
GRCh38: 13:33065914-33065914
37 KL NM_004795.4(KL):c.*934T>A SNV Uncertain significance 311721 rs151258919 GRCh37: 13:33639257-33639257
GRCh38: 13:33065120-33065120
38 KL NM_004795.4(KL):c.2572T>A (p.Trp858Arg) SNV Uncertain significance 311704 rs757603569 GRCh37: 13:33635788-33635788
GRCh38: 13:33061651-33061651
39 KL NM_004795.4(KL):c.911A>G (p.Asn304Ser) SNV Uncertain significance 311687 rs745640577 GRCh37: 13:33627995-33627995
GRCh38: 13:33053858-33053858
40 KL NM_004795.4(KL):c.2779C>T (p.Leu927Phe) SNV Uncertain significance 311707 rs777126851 GRCh37: 13:33638063-33638063
GRCh38: 13:33063926-33063926
41 KL NM_004795.4(KL):c.*8C>T SNV Uncertain significance 311710 rs773877611 GRCh37: 13:33638331-33638331
GRCh38: 13:33064194-33064194
42 KL NM_004795.4(KL):c.*1509T>G SNV Uncertain significance 311727 rs886050126 GRCh37: 13:33639832-33639832
GRCh38: 13:33065695-33065695
43 KL NM_004795.4(KL):c.511C>A (p.Arg171Ser) SNV Uncertain significance 311684 rs200517420 GRCh37: 13:33591089-33591089
GRCh38: 13:33016951-33016951
44 KL NM_004795.4(KL):c.*1750T>C SNV Uncertain significance 311733 rs886050129 GRCh37: 13:33640073-33640073
GRCh38: 13:33065936-33065936
45 KL NM_004795.4(KL):c.1331-3C>A SNV Uncertain significance 311693 rs748430461 GRCh37: 13:33629181-33629181
GRCh38: 13:33055044-33055044
46 KL NM_004795.4(KL):c.*174A>G SNV Uncertain significance 311713 rs886050121 GRCh37: 13:33638497-33638497
GRCh38: 13:33064360-33064360
47 KL NM_004795.4(KL):c.*735G>A SNV Uncertain significance 311719 rs527723516 GRCh37: 13:33639058-33639058
GRCh38: 13:33064921-33064921
48 KL NM_004795.4(KL):c.2259G>A (p.Leu753=) SNV Uncertain significance 311702 rs200040161 GRCh37: 13:33635475-33635475
GRCh38: 13:33061338-33061338
49 KL NM_004795.4(KL):c.*1007T>C SNV Uncertain significance 311722 rs886050124 GRCh37: 13:33639330-33639330
GRCh38: 13:33065193-33065193
50 KL NM_004795.4(KL):c.*1372T>A SNV Uncertain significance 311725 rs189084711 GRCh37: 13:33639695-33639695
GRCh38: 13:33065558-33065558

UniProtKB/Swiss-Prot genetic disease variations for Tumoral Calcinosis, Hyperphosphatemic, Familial, 3:

72
# Symbol AA change Variation ID SNP ID
1 KL p.His193Arg VAR_064554 rs121908423

Expression for Tumoral Calcinosis, Hyperphosphatemic, Familial, 3

Search GEO for disease gene expression data for Tumoral Calcinosis, Hyperphosphatemic, Familial, 3.

Pathways for Tumoral Calcinosis, Hyperphosphatemic, Familial, 3

GO Terms for Tumoral Calcinosis, Hyperphosphatemic, Familial, 3

Sources for Tumoral Calcinosis, Hyperphosphatemic, Familial, 3

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
Content
Loading form....