NOS1AP

protein-coding

nitric oxide synthase 1 adaptor protein, the group of MicroRNA protein coding host genes

Gene summary

This gene encodes a cytosolic protein that binds to the signaling molecule, neuronal nitric oxide synthase (nNOS). This protein has a C-terminal PDZ-binding domain that mediates interactions with nNOS and an N-terminal phosphotyrosine binding (PTB) domain that binds to the small monomeric G protein, Dexras1. Studies of the related mouse and rat proteins have shown that this protein functions as an adapter protein linking nNOS to specific targets, such as Dexras1 and the synapsins. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2009]

MANE transcript

NM_014697.3

Inheritance

ClinVar variants

P:2U:66B:33

Top phenotype

Nephrotic syndrome, type 22

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr1:162,069,691-162,370,475

External References & Databases

Ensembl (ENSG00000198929)

Transcript & Mutation Effects

hg38 • Region Span ~300.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

nephrotic syndrome, type 22STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030895

Submitter: PanelApp Australia

nephrotic syndrome, type 22LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0030895

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Nephrotic syndrome, type 22AR

Manifestation: Renal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Comments: Renal transplant has been described

Refs: 33523862

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NOS1AP variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 95

not providedTotal: 16

NOS1AP-related disorderTotal: 4

Nephrotic syndrome, type 22Total: 4

Long QT syndromeTotal: 2

Kidney failureTotal: 1

Cardiac arrhythmiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014697.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	23 clinvar	4 clinvar	28
missense	1 clinvar		63 clinvar	6 clinvar		70
nonsense						0
start loss						0
frameshift		1 clinvar	1 clinvar			2
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	1	66	29	4	101

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014697.3	RefSeq	NP_055512.1	10	MANE Select
ENST00000361897.10	Ensembl	ENSP00000355133.5	10	MANE Select
NM_001126060.2	RefSeq	NP_001119532.2	2	Standard
NM_001164757.2	RefSeq	NP_001158229.1	10	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
nos1apa	Danio rerio	Structure: action potential Quality: disrupted abnormal

Gene / Model

Organism

Observed Phenotype

nos1apa

Danio rerio

Structure: action potential

Quality: disrupted

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Circadian entrainment - Homo sapiens (human)
Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways

Biological Process

regulation of heart rate by chemical signal
positive regulation of gene expression
positive regulation of nitric oxide mediated signal transduction
regulation of nitric oxide biosynthetic process
positive regulation of nitric oxide biosynthetic process

Molecular Function

protein binding
nitric-oxide synthase binding

Cellular Component

nucleus
mitochondrion
cytosol
caveola
Z disc

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361897
Coding exons: 10
Length: 313758
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125748
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.04	203	303	0.671	0.0000196	3297
Missense (PolyPhen)		43	100.96	0.42593		1148
Synonymous	1.74	110	136	0.810	0.0000101	1002
Loss of Function	3.69	5	24.8	0.201	0.00000132	270

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Adapter protein involved in neuronal nitric-oxide (NO) synthesis regulation via its association with nNOS/NOS1. The complex formed with NOS1 and synapsins is necessary for specific NO and synapsin functions at a presynaptic level. Mediates an indirect interaction between NOS1 and RASD1 leading to enhance the ability of NOS1 to activate RASD1. Competes with DLG4 for interaction with NOS1, possibly affecting NOS1 activity by regulating the interaction between NOS1 and DLG4 (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.413

Intolerance Scores

LoFtool: 0.267
RVIS EVS: 0.02
RVIS percentile EVS: 55.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.763

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium