PC1 DEFICIENCY
MCID: PRP098
MIFTS: 36

Proprotein Convertase 1/3 Deficiency (PC1 DEFICIENCY)

Categories: Endocrine diseases, Genetic diseases, Metabolic diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Proprotein Convertase 1/3 Deficiency

MalaCards integrated aliases for Proprotein Convertase 1/3 Deficiency:

Name: Proprotein Convertase 1/3 Deficiency 57 12 29 6 15
Obesity with Impaired Prohormone Processing 57 12 13 39
Obesity and Endocrinopathy Due to Impaired Processing of Prohormones 57 12
Obesity Due to Prohormone Convertase I Deficiency 12 58
Proprotein Convertase 1 3 Deficiency 44 70
Pci Deficiency 12 58
Proprotein Convertase 1 Deficiency 72
Pc1 Deficiency 72

Characteristics:

Orphanet epidemiological data:

58
obesity due to prohormone convertase i deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 05-Apr-2021)
Miscellaneous:
phenotypic variability

Inheritance:
autosomal recessive


HPO:

31
proprotein convertase 1/3 deficiency:
Inheritance autosomal recessive inheritance sporadic


Classifications:

Orphanet: 58  
Rare infertility disorders
Rare gynaecological and obstetric diseases
Rare endocrine diseases


Summaries for Proprotein Convertase 1/3 Deficiency

Disease Ontology : 12 A syndrome characterized by severe childhood obesity, hypoadrenalism, hypogonadism, reactive hypoglycaemia, and elevated circulating levels of certain prohormones that has material basis in homozygous or compound heterozygous mutation in PCSK1 on chromosome 5q15.

MalaCards based summary : Proprotein Convertase 1/3 Deficiency, also known as obesity with impaired prohormone processing, is related to diarrhea and hypothyroidism, and has symptoms including diarrhea An important gene associated with Proprotein Convertase 1/3 Deficiency is PCSK1 (Proprotein Convertase Subtilisin/Kexin Type 1). Affiliated tissues include small intestine and pituitary, and related phenotypes are increased adipose tissue and polyphagia

UniProtKB/Swiss-Prot : 72 Proprotein convertase 1 deficiency: Characterized by obesity, hypogonadism, hypoadrenalism, reactive hypoglycemia as well as marked small-intestinal absorptive dysfunction It is due to impaired processing of prohormones.

More information from OMIM: 600955

Related Diseases for Proprotein Convertase 1/3 Deficiency

Graphical network of the top 20 diseases related to Proprotein Convertase 1/3 Deficiency:



Diseases related to Proprotein Convertase 1/3 Deficiency

Symptoms & Phenotypes for Proprotein Convertase 1/3 Deficiency

Human phenotypes related to Proprotein Convertase 1/3 Deficiency:

58 31 (show all 26)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 increased adipose tissue 58 31 obligate (100%) Obligate (100%) HP:0009126
2 polyphagia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002591
3 cholestasis 58 31 frequent (33%) Frequent (79-30%) HP:0001396
4 hypopigmentation of the skin 58 31 frequent (33%) Frequent (79-30%) HP:0001010
5 red hair 58 31 frequent (33%) Frequent (79-30%) HP:0002297
6 central adrenal insufficiency 58 31 frequent (33%) Frequent (79-30%) HP:0011734
7 childhood-onset truncal obesity 58 31 frequent (33%) Frequent (79-30%) HP:0008915
8 failure to thrive 58 31 occasional (7.5%) Occasional (29-5%) HP:0001508
9 delayed skeletal maturation 58 31 occasional (7.5%) Occasional (29-5%) HP:0002750
10 delayed puberty 58 31 occasional (7.5%) Occasional (29-5%) HP:0000823
11 hyperinsulinemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000842
12 acanthosis nigricans 58 31 occasional (7.5%) Occasional (29-5%) HP:0000956
13 pituitary hypothyroidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0008245
14 gonadotropin deficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0008213
15 hypoglycemic seizures 58 31 occasional (7.5%) Occasional (29-5%) HP:0002173
16 decreased response to growth hormone stimuation test 31 occasional (7.5%) HP:0000824
17 obesity 58 31 Obligate (100%) HP:0001513
18 malabsorption 31 HP:0002024
19 growth delay 58 Occasional (29-5%)
20 primary amenorrhea 31 HP:0000786
21 diarrhea 31 HP:0002014
22 growth hormone deficiency 58 Occasional (29-5%)
23 decreased circulating cortisol level 31 HP:0008163
24 villous atrophy 31 HP:0011473
25 reactive hypoglycemia 31 HP:0012051
26 hypogonadotropic hypogonadism 31 HP:0000044

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Endocrine Features:
primary amenorrhea
hypocortisolemia
hypogonadotropic hypogonadism
hypoglycemia, reactive
impaired processing of proopiomelanocortin (pomc, )

Growth Weight:
obesity, early-onset

Abdomen Gastrointestinal:
diarrhea
malabsorption (small intestine)
small intestine biopsy shows villous atrophy

Laboratory Abnormalities:
increased plasma proinsulin
decreased or normal plasma insulin
increased plasma progastrin
increased plasma proglucagon

Clinical features from OMIM®:

600955 (Updated 05-Apr-2021)

UMLS symptoms related to Proprotein Convertase 1/3 Deficiency:


diarrhea

Drugs & Therapeutics for Proprotein Convertase 1/3 Deficiency

Search Clinical Trials , NIH Clinical Center for Proprotein Convertase 1/3 Deficiency

Cochrane evidence based reviews: proprotein convertase 1 3 deficiency

Genetic Tests for Proprotein Convertase 1/3 Deficiency

Genetic tests related to Proprotein Convertase 1/3 Deficiency:

# Genetic test Affiliating Genes
1 Proprotein Convertase 1/3 Deficiency 29 PCSK1

Anatomical Context for Proprotein Convertase 1/3 Deficiency

MalaCards organs/tissues related to Proprotein Convertase 1/3 Deficiency:

40
Small Intestine, Pituitary

Publications for Proprotein Convertase 1/3 Deficiency

Articles related to Proprotein Convertase 1/3 Deficiency:

# Title Authors PMID Year
1
Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3. 6 57
17595246 2007
2
Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency. 57 6
14617756 2003
3
Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. 57 6
9207799 1997
4
Brief report: impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function. 57
7477119 1995
5
Hyperproinsulinaemia in obese fat/fat mice associated with a carboxypeptidase E mutation which reduces enzyme activity. 57
7663508 1995
6
A New Case of PCSK1 Pathogenic Variant With Congenital Proprotein Convertase 1/3 Deficiency and Literature Review. 61
30383237 2019
7
Proprotein Convertase 1/3 Deficiency. 61
28965329 2018
8
Long-Term Follow-up of a Case with Proprotein Convertase 1/3 Deficiency: Transient Diabetes Mellitus with Intervening Diabetic Ketoacidosis During Growth Hormone Therapy. 61
28588004 2017
9
Congenital proprotein convertase 1/3 deficiency causes malabsorptive diarrhea and other endocrinopathies in a pediatric cohort. 61
23562752 2013

Variations for Proprotein Convertase 1/3 Deficiency

ClinVar genetic disease variations for Proprotein Convertase 1/3 Deficiency:

6 (show top 50) (show all 96)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.1447G>A (p.Gly483Arg) SNV Pathogenic 14036 rs137852821 GRCh37: 5:95734724-95734724
GRCh38: 5:96399020-96399020
2 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.620+4A>C SNV Pathogenic 14037 rs1580764441 GRCh37: 5:95757580-95757580
GRCh38: 5:96421876-96421876
3 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.748G>T (p.Glu250Ter) SNV Pathogenic 14038 rs137852822 GRCh37: 5:95748156-95748156
GRCh38: 5:96412452-96412452
4 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.638_640del (p.Ala213del) Deletion Pathogenic 14039 rs137852823 GRCh37: 5:95751806-95751808
GRCh38: 5:96416102-96416104
5 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.920C>T (p.Ser307Leu) SNV Pathogenic 14041 rs137852824 GRCh37: 5:95746653-95746653
GRCh38: 5:96410949-96410949
6 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.238C>T (p.Arg80Ter) SNV Pathogenic 995956 GRCh37: 5:95764964-95764964
GRCh38: 5:96429260-96429260
7 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.1688C>G (p.Pro563Arg) SNV Likely pathogenic 807458 rs1580744791 GRCh37: 5:95733074-95733074
GRCh38: 5:96397370-96397370
8 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.1346T>C (p.Leu449Pro) SNV Likely pathogenic 807459 rs1580746829 GRCh37: 5:95735741-95735741
GRCh38: 5:96400037-96400037
9 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.1405G>A (p.Val469Ile) SNV Uncertain significance 432315 rs1026383684 GRCh37: 5:95735682-95735682
GRCh38: 5:96399978-96399978
10 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.1692A>G (p.Ile564Met) SNV Uncertain significance 1032360 GRCh37: 5:95733070-95733070
GRCh38: 5:96397366-96397366
11 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.1196+10A>G SNV Uncertain significance 354647 rs755372795 GRCh37: 5:95743917-95743917
GRCh38: 5:96408213-96408213
12 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*1164T>C SNV Uncertain significance 354624 rs886060882 GRCh37: 5:95727541-95727541
GRCh38: 5:96391837-96391837
13 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.1197-9C>T SNV Uncertain significance 354646 rs200973203 GRCh37: 5:95735899-95735899
GRCh38: 5:96400195-96400195
14 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*88G>C SNV Uncertain significance 354636 rs886060886 GRCh37: 5:95728617-95728617
GRCh38: 5:96392913-96392913
15 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.397-10T>C SNV Uncertain significance 354652 rs142423997 GRCh37: 5:95759173-95759173
GRCh38: 5:96423469-96423469
16 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*1401C>T SNV Uncertain significance 354620 rs886060880 GRCh37: 5:95727304-95727304
GRCh38: 5:96391600-96391600
17 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*2166C>T SNV Uncertain significance 354610 rs886060875 GRCh37: 5:95726539-95726539
GRCh38: 5:96390835-96390835
18 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*1231C>T SNV Uncertain significance 354623 rs886060881 GRCh37: 5:95727474-95727474
GRCh38: 5:96391770-96391770
19 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.-96C>T SNV Uncertain significance 354655 rs35753085 GRCh37: 5:95768842-95768842
GRCh38: 5:96433138-96433138
20 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*471C>G SNV Uncertain significance 354632 rs886060884 GRCh37: 5:95728234-95728234
GRCh38: 5:96392530-96392530
21 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.1414A>G (p.Asn472Asp) SNV Uncertain significance 354645 rs200969251 GRCh37: 5:95735673-95735673
GRCh38: 5:96399969-96399969
22 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*262del Deletion Uncertain significance 354635 rs886060885 GRCh37: 5:95728443-95728443
GRCh38: 5:96392739-96392739
23 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*1912G>A SNV Uncertain significance 354612 rs886060876 GRCh37: 5:95726793-95726793
GRCh38: 5:96391089-96391089
24 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.1764G>A (p.Lys588=) SNV Uncertain significance 354642 rs538803955 GRCh37: 5:95730688-95730688
GRCh38: 5:96394984-96394984
25 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*1414A>C SNV Uncertain significance 354619 rs886060879 GRCh37: 5:95727291-95727291
GRCh38: 5:96391587-96391587
26 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*1097C>A SNV Uncertain significance 354625 rs867846512 GRCh37: 5:95727608-95727608
GRCh38: 5:96391904-96391904
27 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.-21G>A SNV Uncertain significance 354654 rs188670849 GRCh37: 5:95768767-95768767
GRCh38: 5:96433063-96433063
28 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*1733G>A SNV Uncertain significance 354615 rs189919167 GRCh37: 5:95726972-95726972
GRCh38: 5:96391268-96391268
29 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*1842G>A SNV Uncertain significance 354614 rs10515236 GRCh37: 5:95726863-95726863
GRCh38: 5:96391159-96391159
30 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*1232G>A SNV Uncertain significance 354622 rs373852338 GRCh37: 5:95727473-95727473
GRCh38: 5:96391769-96391769
31 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.1503C>T (p.Ile501=) SNV Uncertain significance 354644 rs199524465 GRCh37: 5:95734668-95734668
GRCh38: 5:96398964-96398964
32 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*1443C>T SNV Uncertain significance 354618 rs182581645 GRCh37: 5:95727262-95727262
GRCh38: 5:96391558-96391558
33 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.709+11G>A SNV Uncertain significance 354650 rs199951150 GRCh37: 5:95751726-95751726
GRCh38: 5:96416022-96416022
34 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.2137C>T (p.Leu713Phe) SNV Uncertain significance 354638 rs886060888 GRCh37: 5:95728830-95728830
GRCh38: 5:96393126-96393126
35 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.2253G>A (p.Glu751=) SNV Uncertain significance 354637 rs886060887 GRCh37: 5:95728714-95728714
GRCh38: 5:96393010-96393010
36 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*905T>C SNV Uncertain significance 354627 rs886060883 GRCh37: 5:95727800-95727800
GRCh38: 5:96392096-96392096
37 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*837G>A SNV Uncertain significance 354628 rs772439505 GRCh37: 5:95727868-95727868
GRCh38: 5:96392164-96392164
38 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*287A>G SNV Uncertain significance 354633 rs373041583 GRCh37: 5:95728418-95728418
GRCh38: 5:96392714-96392714
39 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.1923G>A (p.Leu641=) SNV Uncertain significance 354641 rs6236 GRCh37: 5:95729044-95729044
GRCh38: 5:96393340-96393340
40 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*1333A>T SNV Uncertain significance 354621 rs6556922 GRCh37: 5:95727372-95727372
GRCh38: 5:96391668-96391668
41 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.284G>A (p.Arg95His) SNV Uncertain significance 354653 rs769203665 GRCh37: 5:95764918-95764918
GRCh38: 5:96429214-96429214
42 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*2019A>G SNV Uncertain significance 354611 rs558370034 GRCh37: 5:95726686-95726686
GRCh38: 5:96390982-96390982
43 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*1854T>A SNV Uncertain significance 354613 rs886060877 GRCh37: 5:95726851-95726851
GRCh38: 5:96391147-96391147
44 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*1571A>G SNV Uncertain significance 354616 rs886060878 GRCh37: 5:95727134-95727134
GRCh38: 5:96391430-96391430
45 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.1179T>C (p.Ala393=) SNV Uncertain significance 354648 rs142097318 GRCh37: 5:95743944-95743944
GRCh38: 5:96408240-96408240
46 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.-140C>T SNV Uncertain significance 354658 rs142567487 GRCh37: 5:95768886-95768886
GRCh38: 5:96433182-96433182
47 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.-147C>G SNV Uncertain significance 354659 rs886060890 GRCh37: 5:95768893-95768893
GRCh38: 5:96433189-96433189
48 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*2288A>G SNV Uncertain significance 354609 rs886060874 GRCh37: 5:95726417-95726417
GRCh38: 5:96390713-96390713
49 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.*597T>C SNV Uncertain significance 354631 rs115434587 GRCh37: 5:95728108-95728108
GRCh38: 5:96392404-96392404
50 PCSK1 , LOC101929710 NM_000439.5(PCSK1):c.1096-10C>T SNV Uncertain significance 354649 rs373951075 GRCh37: 5:95744037-95744037
GRCh38: 5:96408333-96408333

UniProtKB/Swiss-Prot genetic disease variations for Proprotein Convertase 1/3 Deficiency:

72
# Symbol AA change Variation ID SNP ID
1 PCSK1 p.Gly483Arg VAR_022778 rs137852821
2 PCSK1 p.Ser307Leu VAR_055002 rs137852824

Expression for Proprotein Convertase 1/3 Deficiency

Search GEO for disease gene expression data for Proprotein Convertase 1/3 Deficiency.

Pathways for Proprotein Convertase 1/3 Deficiency

GO Terms for Proprotein Convertase 1/3 Deficiency

Sources for Proprotein Convertase 1/3 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
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