Nephrotic syndrome, type 22

disease

On this page

Also known as NPHS22

Summary

Nephrotic syndrome, type 22 (MONDO:0030895) is a disease caused by NOS1AP (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: NOS1AP (GenCC Strong)
Cohort genes: 1
ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nephrotic syndrome, type 22
Mondo ID	MONDO:0030895
OMIM	619155
DOID	DOID:0112268
UMLS	C5436909
MedGen	1745920
GARD	0016428
Is cancer (heuristic)	no

Also known as: nephrotic syndrome, type 22 · NPHS22

Data availability: 5 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › nephrotic syndrome › familial nephrotic syndrome › nephrotic syndrome, type 22

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 benign, 1 uncertain significance, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
995841	NM_014697.3(NOS1AP):c.428G>A (p.Cys143Tyr)	NOS1AP	Pathogenic	no assertion criteria provided
995842	NM_014697.3(NOS1AP):c.345-3T>G	NOS1AP	Pathogenic	no assertion criteria provided
1333195	NM_014697.3(NOS1AP):c.1259G>C (p.Gly420Ala)	NOS1AP	Uncertain significance	criteria provided, single submitter
1233083	NM_014697.3(NOS1AP):c.1002C>T (p.Arg334=)	NOS1AP	Benign	criteria provided, multiple submitters, no conflicts
36662	NM_014697.3(NOS1AP):c.864C>T (p.Ser288=)	NOS1AP	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
NOS1AP	Strong	Autosomal recessive	nephrotic syndrome, type 22	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NOS1AP	Orphanet:101016	Romano-Ward syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NOS1AP	HGNC:16859	ENSG00000198929	O75052	Carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NOS1AP	Carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase protein	Adapter protein involved in neuronal nitric-oxide (NO) synthesis regulation via its association with nNOS/NOS1.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NOS1AP	Other/Unknown	no		PTB/PI_dom, PH-like_dom_sf, Adapter_Engulfment-Domain

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
CA1 field of hippocampus	1
olfactory bulb	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NOS1AP	203	ubiquitous	marker	CA1 field of hippocampus, type B pancreatic cell, olfactory bulb

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NOS1AP	1,884

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
NOS1AP	O75052	65.59

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of heart rate by chemical signal	1	5617.3×	8e-04	NOS1AP
positive regulation of membrane repolarization during ventricular cardiac muscle cell action potential	1	5617.3×	8e-04	NOS1AP
regulation of cardiac muscle cell action potential	1	2808.7×	9e-04	NOS1AP
postsynaptic actin cytoskeleton organization	1	1872.4×	9e-04	NOS1AP
regulation of nitric oxide biosynthetic process	1	1685.2×	9e-04	NOS1AP
regulation of calcium ion transmembrane transport via high voltage-gated calcium channel	1	1685.2×	9e-04	NOS1AP
positive regulation of potassium ion transmembrane transport	1	991.3×	0.001	NOS1AP
regulation of ventricular cardiac muscle cell membrane repolarization	1	842.6×	0.001	NOS1AP
nitric oxide biosynthetic process	1	702.2×	0.001	NOS1AP

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NOS1AP	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	NOS1AP

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
NOS1AP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: NOS1AP