NPHS14
MCID: NPH102
MIFTS: 44

Nephrotic Syndrome, Type 14 (NPHS14)

Categories: Blood diseases, Endocrine diseases, Genetic diseases, Immune diseases, Metabolic diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Nephrotic Syndrome, Type 14

MalaCards integrated aliases for Nephrotic Syndrome, Type 14:

Name: Nephrotic Syndrome, Type 14 56 73
Nephrotic Syndrome Type 14 12 29 6 15
Nphs14 56 73
Primary Adrenal Insufficiency-Steroid-Resistant Nephrotic Syndrome Due to Sgpl1 Deficiency 58
Familial Steroid-Resistant Nephrotic Syndrome with Adrenal Insufficiency 58
Nephrotic Syndrome 14 73

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
highly variable phenotype
highly variable severity
later onset has been reported
onset usually in utero or infancy


HPO:

31
nephrotic syndrome, type 14:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity progressive


Classifications:

Orphanet: 58  
Rare renal diseases
Inborn errors of metabolism
Rare endocrine diseases


Summaries for Nephrotic Syndrome, Type 14

OMIM : 56 NPHS14 is an autosomal recessive syndromic form of steroid-resistant nephrotic syndrome with multisystemic manifestations. Most affected individuals present in infancy or early childhood with progressive renal dysfunction associated with focal segmental glomerulosclerosis (FSGS) and resulting in end-stage renal disease within a few years. Other infants present with primary adrenal insufficiency. Some patients present in utero with fetal hydrops and fetal demise. Additional features of the disorder can include ichthyosis, acanthosis, adrenal insufficiency, immunodeficiency, and neurologic defects (summary by Prasad et al., 2017 and Lovric et al., 2017). For a discussion of genetic heterogeneity of nephrotic syndrome and FSGS, see NPHS1 (256300). (617575)

MalaCards based summary : Nephrotic Syndrome, Type 14, also known as nephrotic syndrome type 14, is related to sphingosine phosphate lyase insufficiency syndrome and neuropathy, hereditary sensory and autonomic, type i, with cough and gastroesophageal reflux. An important gene associated with Nephrotic Syndrome, Type 14 is SGPL1 (Sphingosine-1-Phosphate Lyase 1), and among its related pathways/superpathways are Metabolism and Sphingolipid metabolism. Affiliated tissues include kidney and testis, and related phenotypes are global developmental delay and microcephaly

Disease Ontology : 12 A familial nephrotic syndrome that has material basis in autosomal recessive inheritance of homozygous or compound heterozygous mutation in the sphingosine-1-phosphate lyase 1 (SGPL1) gene on chromosome 10q21.

UniProtKB/Swiss-Prot : 73 Nephrotic syndrome 14: A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non- specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. NPHS14 is an autosomal recessive syndromic, steroid-resistant form that progresses to end-stage renal failure. Some NPHS14 patients manifest ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects.

Related Diseases for Nephrotic Syndrome, Type 14

Diseases in the Nephrotic Syndrome family:

Nephrotic Syndrome, Type 1 Nephrotic Syndrome, Type 4
Nephrotic Syndrome, Type 20 Nephrotic Syndrome, Type 2
Nephrotic Syndrome, Type 3 Nephrotic Syndrome, Type 6
Nephrotic Syndrome, Type 7 Nephrotic Syndrome, Type 8
Nephrotic Syndrome, Type 9 Nephrotic Syndrome, Type 10
Nephrotic Syndrome, Type 11 Nephrotic Syndrome, Type 12
Nephrotic Syndrome, Type 13 Nephrotic Syndrome, Type 14
Nephrotic Syndrome, Type 15 Nephrotic Syndrome, Type 16
Nephrotic Syndrome, Type 17 Nephrotic Syndrome, Type 18
Nephrotic Syndrome, Type 19 Nephrotic Syndrome, Type 21
Familial Nephrotic Syndrome

Diseases related to Nephrotic Syndrome, Type 14 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 30)
# Related Disease Score Top Affiliating Genes
1 sphingosine phosphate lyase insufficiency syndrome 11.4
2 neuropathy, hereditary sensory and autonomic, type i, with cough and gastroesophageal reflux 10.2 SPTLC2 SPTLC1
3 neuropathy, hereditary sensory and autonomic, type ia 10.2 SPTSSA SPTLC2 SPTLC1
4 neuropathy, hereditary sensory and autonomic, type ic 10.2 SPTLC2 SPTLC1
5 hereditary sensory neuropathy 10.1 SPTSSA SPTLC2 SPTLC1
6 neuropathy, hereditary sensory, type ie 10.0 SPTLC2 SPTLC1
7 gangliosidosis 9.9 UGCG CTSA
8 autosomal recessive congenital ichthyosis 9.9 UGCG KDSR CERS3 ALDH3A2
9 salt and pepper syndrome 9.7 CTSA B4GALNT1
10 gaucher disease, type i 9.7 UGCG SMPD1 GALC
11 skin hemangioma 9.6 ETFA CTSA
12 niemann-pick disease 9.6 UGCG SMPD1 ASAH1
13 angiokeratoma 9.6 UGCG ETFA CTSA
14 c syndrome 9.5 UGCG SMPD1 CTSA
15 leukodystrophy 9.5 GALC DEGS1 ALDH3A2 ACER3
16 spinal muscular atrophy with progressive myoclonic epilepsy 9.5 SMPD1 KDSR ASAH1 ACER3
17 mucopolysaccharidosis iv 9.5 GALC CTSA
18 niemann-pick disease, type c1 9.5 UGCG SMPD1 CTSA
19 lipid storage disease 9.2 UGCG SMPD1 GALC ASAH1
20 gm1 gangliosidosis 9.2 UGCG GALC ETFA CTSA
21 mucopolysaccharidosis-plus syndrome 9.2 SMPD1 GALC CTSA
22 farber lipogranulomatosis 9.1 UGCG SMPD1 GALC ASAH1 ACER3
23 krabbe disease 8.9 SMPD1 GALC CTSA ASAH1
24 lysosomal storage disease 8.8 SMPD1 GALC CTSA
25 metachromatic leukodystrophy 8.8 SMPD1 GALC CTSA ASAH1
26 sandhoff disease 8.8 UGCG SMPD1 ETFA CTSA ASAH1
27 gm2 gangliosidosis 8.8 UGCG SMPD1 ETFA CTSA ASAH1
28 tay-sachs disease 8.8 UGCG SMPD1 ETFA CTSA ASAH1
29 sphingolipidosis 8.4 UGCG SMPD1 GALC ETFA CTSA ASAH1
30 hereditary sensory and autonomic neuropathy type 1 8.4 SPTSSA SPTLC2 SPTLC1 ORMDL3 KDSR DEGS1

Graphical network of the top 20 diseases related to Nephrotic Syndrome, Type 14:



Diseases related to Nephrotic Syndrome, Type 14

Symptoms & Phenotypes for Nephrotic Syndrome, Type 14

Human phenotypes related to Nephrotic Syndrome, Type 14:

31 (show all 27)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 31 HP:0001263
2 microcephaly 31 HP:0000252
3 sensorineural hearing impairment 31 HP:0000407
4 developmental regression 31 HP:0002376
5 ichthyosis 31 HP:0008064
6 proteinuria 31 HP:0000093
7 hypothyroidism 31 HP:0000821
8 hypoglycemia 31 HP:0001943
9 hypertriglyceridemia 31 HP:0002155
10 ataxia 31 HP:0001251
11 peripheral neuropathy 31 HP:0009830
12 edema 31 HP:0000969
13 strabismus 31 HP:0000486
14 cryptorchidism 31 HP:0000028
15 ptosis 31 HP:0000508
16 nephrotic syndrome 31 HP:0000100
17 lymphopenia 31 HP:0001888
18 micropenis 31 HP:0000054
19 mental deterioration 31 HP:0001268
20 hypoalbuminemia 31 HP:0003073
21 hypogonadism 31 HP:0000135
22 generalized hypotonia 31 HP:0001290
23 adrenal insufficiency 31 HP:0000846
24 stage 5 chronic kidney disease 31 HP:0003774
25 focal segmental glomerulosclerosis 31 HP:0000097
26 seizure 31 HP:0001250
27 diffuse mesangial sclerosis 31 HP:0001967

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
seizures
developmental regression
ataxia
developmental delay
cognitive decline
more
Skin Nails Hair Skin:
ichthyosis
hyperpigmentation

Endocrine Features:
hypothyroidism
hypoglycemia
hypogonadism
adrenal insufficiency
adrenal calcifications
more
Muscle Soft Tissue:
edema
hypotonia

Genitourinary External Genitalia Male:
cryptorchidism
micropenis
absence of testis

Immunology:
lymphopenia

Prenatal Manifestations:
fetal hydrops
fetal demise

Head And Neck Head:
microcephaly

Laboratory Abnormalities:
proteinuria
hypoalbuminemia
increased serum triglycerides
increased acth
increased plasma sphingolipid intermediates and ceramide species

Neurologic Peripheral Nervous System:
peripheral neuropathy

Head And Neck Eyes:
strabismus
ptosis

Genitourinary Kidneys:
nephrotic syndrome
focal segmental glomerulosclerosis
diffuse mesangial sclerosis
end-stage renal disease
renal podocyte effacement

Head And Neck Ears:
hearing loss, sensorineural

Clinical features from OMIM:

617575

GenomeRNAi Phenotypes related to Nephrotic Syndrome, Type 14 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00240-S-1 9.8 ASAH1
2 Decreased viability GR00249-S 9.8 ACER3 CTSA ETFA KDSR
3 Decreased viability GR00381-A-1 9.8 ASAH1 SMPD1 UGCG
4 Decreased viability GR00386-A-1 9.8 ASAH1 SPTLC1 SPTLC2
5 Decreased viability GR00402-S-2 9.8 B4GALNT1 DEGS1 SGPL1
6 Reduced mammosphere formation GR00396-S 9.1 B4GALNT1 CTSA ETFA GALC KDSR SPTLC1

MGI Mouse Phenotypes related to Nephrotic Syndrome, Type 14:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.23 ACER3 ALDH3A2 ASAH1 B4GALNT1 CERS3 CTSA
2 homeostasis/metabolism MP:0005376 10.2 ACER3 ALDH3A2 ASAH1 B4GALNT1 CERS3 CTSA
3 growth/size/body region MP:0005378 10.14 ASAH1 CERS3 CTSA DEGS1 GALC SGPL1
4 cellular MP:0005384 10.13 ALDH3A2 ASAH1 B4GALNT1 CTSA DEGS1 GALC
5 hematopoietic system MP:0005397 10.07 ALDH3A2 ASAH1 B4GALNT1 CTSA DEGS1 GALC
6 mortality/aging MP:0010768 9.97 ACER3 ASAH1 B4GALNT1 CERS3 CTSA DEGS1
7 liver/biliary system MP:0005370 9.8 ASAH1 CTSA DEGS1 GALC SLC13A1 SMPD1
8 renal/urinary system MP:0005367 9.5 ASAH1 B4GALNT1 CTSA GALC SGPL1 SLC13A1
9 reproductive system MP:0005389 9.23 ACER3 ASAH1 B4GALNT1 CTSA SGPL1 SLC13A1

Drugs & Therapeutics for Nephrotic Syndrome, Type 14

Search Clinical Trials , NIH Clinical Center for Nephrotic Syndrome, Type 14

Genetic Tests for Nephrotic Syndrome, Type 14

Genetic tests related to Nephrotic Syndrome, Type 14:

# Genetic test Affiliating Genes
1 Nephrotic Syndrome Type 14 29 SGPL1

Anatomical Context for Nephrotic Syndrome, Type 14

MalaCards organs/tissues related to Nephrotic Syndrome, Type 14:

40
Kidney, Testis

Publications for Nephrotic Syndrome, Type 14

Articles related to Nephrotic Syndrome, Type 14:

# Title Authors PMID Year
1
Deficiency of the sphingosine-1-phosphate lyase SGPL1 is associated with congenital nephrotic syndrome and congenital adrenal calcifications. 6 56
28181337 2017
2
Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency. 56 6
28165339 2017
3
Sphingosine-1-phosphate lyase mutations cause primary adrenal insufficiency and steroid-resistant nephrotic syndrome. 6 56
28165343 2017
4
Prenatal bilateral adrenal calcifications, hypogonadism, and nephrotic syndrome: beyond Wolman disease. 6 56
24777844 2014
5
A case report: Familial glucocorticoid deficiency associated with familial focal segmental glomerulosclerosis. 56 6
23232022 2012
6
Responsiveness of sphingosine phosphate lyase insufficiency syndrome to vitamin B6 cofactor supplementation. 61
32233035 2020
7
SGPL1 Deficiency: A Rare Cause of Primary Adrenal Insufficiency. 61
30517686 2019
8
Nephrotic syndrome and adrenal insufficiency caused by a variant in SGPL1. 61
30090628 2018

Variations for Nephrotic Syndrome, Type 14

ClinVar genetic disease variations for Nephrotic Syndrome, Type 14:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SGPL1 NM_003901.4(SGPL1):c.665G>A (p.Arg222Gln)SNV Pathogenic 430861 rs769259446 10:72628151-72628151 10:70868394-70868394
2 SGPL1 NM_003901.4(SGPL1):c.1632_1634CTT[1] (p.Phe545del)short repeat Pathogenic 430862 rs1131692252 10:72637016-72637018 10:70877259-70877261
3 SGPL1 NM_003901.4(SGPL1):c.261+1G>ASNV Pathogenic 430863 rs1131692253 10:72610968-72610968 10:70851211-70851211
4 SGPL1 NM_003901.4(SGPL1):c.7dup (p.Ser3fs)duplication Pathogenic 430864 rs1131692254 10:72576615-72576616 10:70816859-70816860
5 SGPL1 NM_003901.4(SGPL1):c.664C>T (p.Arg222Trp)SNV Pathogenic 430865 rs1131692255 10:72628150-72628150 10:70868393-70868393
6 SGPL1 NM_003901.4(SGPL1):c.1037G>T (p.Ser346Ile)SNV Pathogenic 430866 rs1131692256 10:72631721-72631721 10:70871964-70871964
7 SGPL1 NM_003901.4(SGPL1):c.1513C>T (p.Arg505Ter)SNV Pathogenic 430867 rs746887949 10:72636365-72636365 10:70876608-70876608
8 SGPL1 NM_003901.4(SGPL1):c.934del (p.Leu312fs)deletion Pathogenic 430868 rs1131692235 10:72631615-72631615 10:70871858-70871858
9 SGPL1 NM_003901.4(SGPL1):c.87del (p.Asn28_Tyr29insTer)deletion Likely pathogenic 599179 rs1564622701 10:72604289-72604289 10:70844532-70844532

UniProtKB/Swiss-Prot genetic disease variations for Nephrotic Syndrome, Type 14:

73
# Symbol AA change Variation ID SNP ID
1 SGPL1 p.Arg222Gln VAR_079213 rs769259446
2 SGPL1 p.Arg222Trp VAR_079214 rs113169225

Expression for Nephrotic Syndrome, Type 14

Search GEO for disease gene expression data for Nephrotic Syndrome, Type 14.

Pathways for Nephrotic Syndrome, Type 14

Pathways related to Nephrotic Syndrome, Type 14 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.74 UGCG SPTSSA SPTLC2 SPTLC1 SMPD1 SGPL1
2
Show member pathways
11.93 UGCG SPTSSA SPTLC2 SPTLC1 SMPD1 SGPL1
3 11.67 SMPD1 GALC CTSA ASAH1
4 11.58 SPTLC2 SPTLC1 SMPD1 SGPL1 DEGS1 CERS3

GO Terms for Nephrotic Syndrome, Type 14

Cellular components related to Nephrotic Syndrome, Type 14 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.27 UGCG SPTSSA SPTLC2 SPTLC1 SMPD1 SLC13A1
2 integral component of membrane GO:0016021 10.13 UGCG SPTSSA SPTLC2 SPTLC1 SMPD1 SLC13A1
3 lysosome GO:0005764 9.73 SMPD1 GALC CTSA ASAH1
4 endoplasmic reticulum membrane GO:0005789 9.65 SPTSSA SPTLC2 SPTLC1 SGPL1 ORMDL3 KDSR
5 lysosomal lumen GO:0043202 9.62 SMPD1 GALC CTSA ASAH1
6 SPOTS complex GO:0035339 9.4 SPTLC1 ORMDL3
7 endoplasmic reticulum GO:0005783 9.4 SPTSSA SPTLC2 SPTLC1 SGPL1 ORMDL3 KDSR
8 serine C-palmitoyltransferase complex GO:0017059 9.33 SPTSSA SPTLC2 SPTLC1

Biological processes related to Nephrotic Syndrome, Type 14 according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 sphingolipid biosynthetic process GO:0030148 9.81 SPTSSA SPTLC2 SPTLC1 SGPL1 KDSR DEGS1
2 glycosphingolipid metabolic process GO:0006687 9.8 UGCG SMPD1 GALC CTSA B4GALNT1 ASAH1
3 ceramide biosynthetic process GO:0046513 9.8 SPTSSA SPTLC2 SPTLC1 SMPD1 DEGS1 CERS3
4 fatty acid metabolic process GO:0006631 9.71 SGPL1 DEGS1 ALDH3A2
5 ceramide metabolic process GO:0006672 9.71 SMPD1 SGPL1 ORMDL3 ACER3
6 epidermis development GO:0008544 9.7 UGCG CERS3 ALDH3A2
7 sphingolipid metabolic process GO:0006665 9.7 UGCG SPTSSA SPTLC2 SPTLC1 SGPL1 KDSR
8 sphingosine biosynthetic process GO:0046512 9.67 SPTLC2 SPTLC1 ASAH1 ACER3
9 keratinocyte differentiation GO:0030216 9.65 UGCG CERS3 ASAH1
10 ceramide catabolic process GO:0046514 9.51 ASAH1 ACER3
11 sphingomyelin biosynthetic process GO:0006686 9.49 SPTLC2 SPTLC1
12 positive regulation of lipophagy GO:1904504 9.46 SPTLC2 SPTLC1
13 lipid metabolic process GO:0006629 9.44 UGCG SPTSSA SPTLC2 SPTLC1 SGPL1 KDSR
14 sphinganine biosynthetic process GO:0046511 9.43 SPTLC2 SPTLC1

Molecular functions related to Nephrotic Syndrome, Type 14 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 pyridoxal phosphate binding GO:0030170 9.43 SPTLC2 SPTLC1 SGPL1
2 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides GO:0016811 9.32 ASAH1 ACER3
3 N-acylsphingosine amidohydrolase activity GO:0017040 9.16 ASAH1 ACER3
4 ceramidase activity GO:0102121 8.96 ASAH1 ACER3
5 serine C-palmitoyltransferase activity GO:0004758 8.8 SPTSSA SPTLC2 SPTLC1

Sources for Nephrotic Syndrome, Type 14

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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