MCID: PRP098
MIFTS: 29

Proprotein Convertase 1/3 Deficiency

Categories: Genetic diseases, Reproductive diseases, Endocrine diseases, Rare diseases, Metabolic 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 29 6 40
Obesity with Impaired Prohormone Processing 57 13
Obesity and Endocrinopathy Due to Impaired Processing of Prohormones 57
Obesity Due to Prohormone Convertase I Deficiency 59
Proprotein Convertase 1 3 Deficiency 73
Proprotein Convertase 1 Deficiency 75
Pci Deficiency 59
Pc1 Deficiency 75

Characteristics:

Orphanet epidemiological data:

59
obesity due to prohormone convertase i deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
phenotypic variability


HPO:

32
proprotein convertase 1/3 deficiency:
Onset and clinical course phenotypic variability
Inheritance sporadic


Classifications:



Summaries for Proprotein Convertase 1/3 Deficiency

UniProtKB/Swiss-Prot : 75 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.

MalaCards based summary : Proprotein Convertase 1/3 Deficiency, also known as obesity with impaired prohormone processing, is related to diabetes mellitus, ketosis-prone and diabetes mellitus, 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, pituitary and skin, and related phenotypes are obesity and increased adipose tissue

Description from OMIM: 600955

Related Diseases for Proprotein Convertase 1/3 Deficiency

Diseases related to Proprotein Convertase 1/3 Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 diabetes mellitus, ketosis-prone 10.2
2 diabetes mellitus 10.2
3 diarrhea 10.2
4 body mass index quantitative trait locus 12 9.0 LOC101929710 PCSK1

Symptoms & Phenotypes for Proprotein Convertase 1/3 Deficiency

Symptoms via clinical synopsis from OMIM:

57
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

Human phenotypes related to Proprotein Convertase 1/3 Deficiency:

59 32 (show all 25)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 obesity 59 32 Obligate (100%) HP:0001513
2 increased adipose tissue 59 32 obligate (100%) Obligate (100%) HP:0009126
3 polyphagia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002591
4 hypopigmentation of the skin 59 32 frequent (33%) Frequent (79-30%) HP:0001010
5 cholestasis 59 32 frequent (33%) Frequent (79-30%) HP:0001396
6 red hair 59 32 frequent (33%) Frequent (79-30%) HP:0002297
7 childhood-onset truncal obesity 59 32 frequent (33%) Frequent (79-30%) HP:0008915
8 central adrenal insufficiency 59 32 frequent (33%) Frequent (79-30%) HP:0011734
9 delayed puberty 59 32 occasional (7.5%) Occasional (29-5%) HP:0000823
10 growth hormone deficiency 59 32 occasional (7.5%) Occasional (29-5%) HP:0000824
11 hyperinsulinemia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000842
12 acanthosis nigricans 59 32 occasional (7.5%) Occasional (29-5%) HP:0000956
13 failure to thrive 59 32 occasional (7.5%) Occasional (29-5%) HP:0001508
14 hypoglycemic seizures 59 32 occasional (7.5%) Occasional (29-5%) HP:0002173
15 delayed skeletal maturation 59 32 occasional (7.5%) Occasional (29-5%) HP:0002750
16 gonadotropin deficiency 59 32 occasional (7.5%) Occasional (29-5%) HP:0008213
17 pituitary hypothyroidism 59 32 occasional (7.5%) Occasional (29-5%) HP:0008245
18 growth delay 59 Occasional (29-5%)
19 hypogonadotrophic hypogonadism 32 HP:0000044
20 primary amenorrhea 32 HP:0000786
21 diarrhea 32 HP:0002014
22 malabsorption 32 HP:0002024
23 decreased circulating cortisol level 32 HP:0008163
24 villous atrophy 32 HP:0011473
25 reactive hypoglycemia 32 HP:0012051

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

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:

41
Small Intestine, Pituitary, Skin

Publications for Proprotein Convertase 1/3 Deficiency

Articles related to Proprotein Convertase 1/3 Deficiency:

# Title Authors Year
1
Long-Term Follow-up of a Case with Proprotein Convertase 1/3 Deficiency: Transient Diabetes Mellitus with Intervening Diabetic Ketoacidosis During Growth Hormone Therapy. ( 28588004 )
2017
2
Proprotein Convertase 1/3 Deficiency. ( 28965329 )
2017
3
Congenital proprotein convertase 1/3 deficiency causes malabsorptive diarrhea and other endocrinopathies in a pediatric cohort. ( 23562752 )
2013

Variations for Proprotein Convertase 1/3 Deficiency

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

75
# Symbol AA change Variation ID SNP ID
1 PCSK1 p.Gly483Arg VAR_022778 rs137852821
2 PCSK1 p.Ser307Leu VAR_055002 rs137852824

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

6
(show top 50) (show all 111)
# Gene Variation Type Significance SNP ID Assembly Location
1 PCSK1 NM_000439.4(PCSK1): c.1447G> A (p.Gly483Arg) single nucleotide variant Pathogenic rs137852821 GRCh37 Chromosome 5, 95734724: 95734724
2 PCSK1 NM_000439.4(PCSK1): c.1447G> A (p.Gly483Arg) single nucleotide variant Pathogenic rs137852821 GRCh38 Chromosome 5, 96399020: 96399020
3 PCSK1 PCSK1, IVS5DS, A-C, +4 single nucleotide variant Pathogenic
4 PCSK1 NM_000439.4(PCSK1): c.748G> T (p.Glu250Ter) single nucleotide variant Pathogenic rs137852822 GRCh37 Chromosome 5, 95748156: 95748156
5 PCSK1 NM_000439.4(PCSK1): c.748G> T (p.Glu250Ter) single nucleotide variant Pathogenic rs137852822 GRCh38 Chromosome 5, 96412452: 96412452
6 PCSK1 NM_000439.4(PCSK1): c.637_639delGCA (p.Ala213del) deletion Pathogenic rs137852823 GRCh37 Chromosome 5, 95751807: 95751809
7 PCSK1 NM_000439.4(PCSK1): c.637_639delGCA (p.Ala213del) deletion Pathogenic rs137852823 GRCh38 Chromosome 5, 96416103: 96416105
8 PCSK1 NM_000439.4(PCSK1): c.920C> T (p.Ser307Leu) single nucleotide variant Pathogenic rs137852824 GRCh37 Chromosome 5, 95746653: 95746653
9 PCSK1 NM_000439.4(PCSK1): c.920C> T (p.Ser307Leu) single nucleotide variant Pathogenic rs137852824 GRCh38 Chromosome 5, 96410949: 96410949
10 PCSK1 NM_000439.4(PCSK1): c.*2288A> G single nucleotide variant Uncertain significance rs886060874 GRCh37 Chromosome 5, 95726417: 95726417
11 PCSK1 NM_000439.4(PCSK1): c.*2288A> G single nucleotide variant Uncertain significance rs886060874 GRCh38 Chromosome 5, 96390713: 96390713
12 PCSK1 NM_000439.4(PCSK1): c.*1912G> A single nucleotide variant Uncertain significance rs886060876 GRCh37 Chromosome 5, 95726793: 95726793
13 PCSK1 NM_000439.4(PCSK1): c.*1912G> A single nucleotide variant Uncertain significance rs886060876 GRCh38 Chromosome 5, 96391089: 96391089
14 PCSK1 NM_000439.4(PCSK1): c.*1530T> C single nucleotide variant Likely benign rs2882298 GRCh37 Chromosome 5, 95727175: 95727175
15 PCSK1 NM_000439.4(PCSK1): c.*1530T> C single nucleotide variant Likely benign rs2882298 GRCh38 Chromosome 5, 96391471: 96391471
16 PCSK1 NM_000439.4(PCSK1): c.*1333A> T single nucleotide variant Uncertain significance rs6556922 GRCh37 Chromosome 5, 95727372: 95727372
17 PCSK1 NM_000439.4(PCSK1): c.*1333A> T single nucleotide variant Uncertain significance rs6556922 GRCh38 Chromosome 5, 96391668: 96391668
18 PCSK1 NM_000439.4(PCSK1): c.*1232G> A single nucleotide variant Uncertain significance rs373852338 GRCh37 Chromosome 5, 95727473: 95727473
19 PCSK1 NM_000439.4(PCSK1): c.*1232G> A single nucleotide variant Uncertain significance rs373852338 GRCh38 Chromosome 5, 96391769: 96391769
20 PCSK1 NM_000439.4(PCSK1): c.*1164T> C single nucleotide variant Uncertain significance rs886060882 GRCh37 Chromosome 5, 95727541: 95727541
21 PCSK1 NM_000439.4(PCSK1): c.*1164T> C single nucleotide variant Uncertain significance rs886060882 GRCh38 Chromosome 5, 96391837: 96391837
22 PCSK1 NM_000439.4(PCSK1): c.*287A> G single nucleotide variant Uncertain significance rs373041583 GRCh38 Chromosome 5, 96392714: 96392714
23 PCSK1 NM_000439.4(PCSK1): c.*287A> G single nucleotide variant Uncertain significance rs373041583 GRCh37 Chromosome 5, 95728418: 95728418
24 PCSK1 NM_000439.4(PCSK1): c.*262delA deletion Uncertain significance rs886060885 GRCh38 Chromosome 5, 96392739: 96392739
25 PCSK1 NM_000439.4(PCSK1): c.*262delA deletion Uncertain significance rs886060885 GRCh37 Chromosome 5, 95728443: 95728443
26 PCSK1 NM_000439.4(PCSK1): c.1993C> G (p.Gln665Glu) single nucleotide variant Likely benign rs6234 GRCh38 Chromosome 5, 96393270: 96393270
27 PCSK1 NM_000439.4(PCSK1): c.1993C> G (p.Gln665Glu) single nucleotide variant Likely benign rs6234 GRCh37 Chromosome 5, 95728974: 95728974
28 PCSK1 NM_000439.4(PCSK1): c.1923G> A (p.Leu641=) single nucleotide variant Uncertain significance rs6236 GRCh38 Chromosome 5, 96393340: 96393340
29 PCSK1 NM_000439.4(PCSK1): c.1923G> A (p.Leu641=) single nucleotide variant Uncertain significance rs6236 GRCh37 Chromosome 5, 95729044: 95729044
30 PCSK1 NM_000439.4(PCSK1): c.1764G> A (p.Lys588=) single nucleotide variant Uncertain significance rs538803955 GRCh37 Chromosome 5, 95730688: 95730688
31 PCSK1 NM_000439.4(PCSK1): c.1764G> A (p.Lys588=) single nucleotide variant Uncertain significance rs538803955 GRCh38 Chromosome 5, 96394984: 96394984
32 PCSK1 NM_000439.4(PCSK1): c.709+11G> A single nucleotide variant Uncertain significance rs199951150 GRCh37 Chromosome 5, 95751726: 95751726
33 PCSK1 NM_000439.4(PCSK1): c.709+11G> A single nucleotide variant Uncertain significance rs199951150 GRCh38 Chromosome 5, 96416022: 96416022
34 PCSK1 NM_000439.4(PCSK1): c.*1854T> A single nucleotide variant Uncertain significance rs886060877 GRCh37 Chromosome 5, 95726851: 95726851
35 PCSK1 NM_000439.4(PCSK1): c.*1854T> A single nucleotide variant Uncertain significance rs886060877 GRCh38 Chromosome 5, 96391147: 96391147
36 PCSK1 NM_000439.4(PCSK1): c.*1733G> A single nucleotide variant Uncertain significance rs189919167 GRCh38 Chromosome 5, 96391268: 96391268
37 PCSK1 NM_000439.4(PCSK1): c.*1733G> A single nucleotide variant Uncertain significance rs189919167 GRCh37 Chromosome 5, 95726972: 95726972
38 PCSK1 NM_000439.4(PCSK1): c.*1443C> T single nucleotide variant Uncertain significance rs182581645 GRCh37 Chromosome 5, 95727262: 95727262
39 PCSK1 NM_000439.4(PCSK1): c.*1443C> T single nucleotide variant Uncertain significance rs182581645 GRCh38 Chromosome 5, 96391558: 96391558
40 PCSK1 NM_000439.4(PCSK1): c.*1414A> C single nucleotide variant Uncertain significance rs886060879 GRCh37 Chromosome 5, 95727291: 95727291
41 PCSK1 NM_000439.4(PCSK1): c.*1414A> C single nucleotide variant Uncertain significance rs886060879 GRCh38 Chromosome 5, 96391587: 96391587
42 PCSK1 NM_000439.4(PCSK1): c.*1401C> T single nucleotide variant Uncertain significance rs886060880 GRCh37 Chromosome 5, 95727304: 95727304
43 PCSK1 NM_000439.4(PCSK1): c.*1401C> T single nucleotide variant Uncertain significance rs886060880 GRCh38 Chromosome 5, 96391600: 96391600
44 PCSK1 NM_000439.4(PCSK1): c.*1097C> A single nucleotide variant Uncertain significance rs867846512 GRCh37 Chromosome 5, 95727608: 95727608
45 PCSK1 NM_000439.4(PCSK1): c.*1097C> A single nucleotide variant Uncertain significance rs867846512 GRCh38 Chromosome 5, 96391904: 96391904
46 PCSK1 NM_000439.4(PCSK1): c.*1041T> A single nucleotide variant Likely benign rs17085675 GRCh37 Chromosome 5, 95727664: 95727664
47 PCSK1 NM_000439.4(PCSK1): c.*1041T> A single nucleotide variant Likely benign rs17085675 GRCh38 Chromosome 5, 96391960: 96391960
48 PCSK1 NM_000439.4(PCSK1): c.*837G> A single nucleotide variant Uncertain significance rs772439505 GRCh38 Chromosome 5, 96392164: 96392164
49 PCSK1 NM_000439.4(PCSK1): c.*837G> A single nucleotide variant Uncertain significance rs772439505 GRCh37 Chromosome 5, 95727868: 95727868
50 PCSK1 NM_000439.4(PCSK1): c.*265T> C single nucleotide variant Likely benign rs3811942 GRCh38 Chromosome 5, 96392736: 96392736

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

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