NPHS14
MCID: NPH102
MIFTS: 39

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 acute adrenal insufficiency. An important gene associated with Nephrotic Syndrome, Type 14 is SGPL1 (Sphingosine-1-Phosphate Lyase 1), and among its related pathways/superpathways are Peptide hormone metabolism and G alpha (s) signalling events. Affiliated tissues include kidney and testis, and related phenotypes are ptosis and hypothyroidism

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 Congenital and Infantile Nephrotic Syndrome

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

(show top 50) (show all 60)
# Related Disease Score Top Affiliating Genes
1 sphingosine phosphate lyase insufficiency syndrome 11.4
2 acute adrenal insufficiency 10.0 REN POMC
3 hypoaldosteronism 10.0 REN POMC
4 premenstrual tension 10.0 REN POMC
5 familial glucocorticoid deficiency 10.0 REN POMC
6 inappropriate adh syndrome 10.0 REN POMC
7 benign essential hypertension 10.0 REN POMC
8 steroid inherited metabolic disorder 9.9 REN POMC
9 apparent mineralocorticoid excess 9.9 REN POMC
10 adrenal cortical hypofunction 9.9 REN POMC
11 hyperaldosteronism, familial, type i 9.9 REN POMC
12 achalasia-addisonianism-alacrima syndrome 9.9 SGPL1 POMC
13 adult syndrome 9.9 REN POMC
14 adrenal cortical carcinoma 9.9 REN POMC
15 endocrine pancreas disease 9.9 REN POMC
16 adrenal cortical adenoma 9.9 REN POMC
17 hypoadrenocorticism, familial 9.9 REN POMC
18 liddle syndrome 1 9.9 REN POMC
19 adrenal adenoma 9.9 REN POMC
20 sleep disorder 9.9 REN POMC
21 diabetes insipidus 9.9 REN POMC
22 lipoid congenital adrenal hyperplasia 9.9 REN POMC
23 hypokalemia 9.9 REN POMC
24 adrenal carcinoma 9.9 REN POMC
25 overnutrition 9.8 REN POMC
26 glucose metabolism disease 9.8 REN POMC
27 renal tubular transport disease 9.8 REN PTH
28 parathyroid gland disease 9.8 REN PTH
29 pseudohypoparathyroidism 9.8 REN PTH
30 scleredema adultorum 9.7 PTH POMC
31 anal spasm 9.7 PTH POMC
32 graves disease 1 9.7 PTH POMC
33 conn's syndrome 9.7 REN POMC
34 hyperuricemia 9.7 REN PTH
35 uremia 9.7 REN PTH
36 thyroid gland disease 9.7 PTH POMC
37 hyperprolactinemia 9.7 PTH POMC
38 nephrocalcinosis 9.6 REN PTH
39 leptin deficiency or dysfunction 9.6 PTH POMC
40 primary hyperparathyroidism 9.6 PTH POMC
41 multiple endocrine neoplasia, type i 9.6 PTH POMC
42 cystic kidney disease 9.6 REN PTH
43 nephrolithiasis, calcium oxalate 9.6 REN PTH
44 restless legs syndrome 9.5 PTH POMC
45 end stage renal failure 9.4 SGPL1 REN PTH
46 urinary system disease 9.4 REN PTH
47 adrenal cortex disease 9.4 REN PTH POMC
48 adrenal gland disease 9.4 REN PTH POMC
49 mineral metabolism disease 9.4 REN PTH POMC
50 endocrine organ benign neoplasm 9.3 REN PTH POMC

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

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
ptosis
strabismus

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

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

Neurologic Peripheral Nervous System:
peripheral neuropathy

Immunology:
lymphopenia

Prenatal Manifestations:
fetal hydrops
fetal demise

Endocrine Features:
hypothyroidism
hypoglycemia
hypogonadism
adrenal insufficiency
adrenal calcifications
more
Genitourinary External Genitalia Male:
cryptorchidism
micropenis
absence of testis

Head And Neck Head:
microcephaly

Muscle Soft Tissue:
edema
hypotonia

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 (show all 13)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-101 9.73 POMC
2 Increased shRNA abundance (Z-score > 2) GR00366-A-102 9.73 POMC
3 Increased shRNA abundance (Z-score > 2) GR00366-A-126 9.73 SGPL1
4 Increased shRNA abundance (Z-score > 2) GR00366-A-127 9.73 POMC
5 Increased shRNA abundance (Z-score > 2) GR00366-A-147 9.73 SGPL1
6 Increased shRNA abundance (Z-score > 2) GR00366-A-178 9.73 SGPL1
7 Increased shRNA abundance (Z-score > 2) GR00366-A-29 9.73 POMC
8 Increased shRNA abundance (Z-score > 2) GR00366-A-32 9.73 POMC
9 Increased shRNA abundance (Z-score > 2) GR00366-A-47 9.73 SGPL1
10 Increased shRNA abundance (Z-score > 2) GR00366-A-88 9.73 POMC
11 Increased shRNA abundance (Z-score > 2) GR00366-A-9 9.73 POMC SGPL1
12 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-1 9.02 PTH REN
13 Synthetic lethal with MLN4924 (a NAE inhibitor) GR00250-A-2 9.02 PTH REN SGPL1

MGI Mouse Phenotypes related to Nephrotic Syndrome, Type 14:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.26 POMC PTH REN SGPL1
2 hematopoietic system MP:0005397 8.92 POMC PTH REN SGPL1

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. 56 6
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. 56 6
28165343 2017
4
Prenatal bilateral adrenal calcifications, hypogonadism, and nephrotic syndrome: beyond Wolman disease. 56 6
24777844 2014
5
A case report: Familial glucocorticoid deficiency associated with familial focal segmental glomerulosclerosis. 6 56
23232022 2012
6
SGPL1 Deficiency: A Rare Cause of Primary Adrenal Insufficiency. 61
30517686 2019
7
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 10:72637018-72637020 10:70877261-70877263
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 10:72576616-72576616 10:70816860-70816860
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 10:72631618-72631618 10:70871861-70871861
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
11.22 REN POMC
2 10.79 PTH POMC

GO Terms for Nephrotic Syndrome, Type 14

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

# Name GO ID Score Top Affiliating Genes
1 kidney development GO:0001822 8.96 SGPL1 REN
2 regulation of blood pressure GO:0008217 8.62 REN POMC

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

# Name GO ID Score Top Affiliating Genes
1 hormone activity GO:0005179 8.62 PTH POMC

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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