NPAS4
Basic information
Region (hg38): 11:66421035-66426707
Links
Phenotypes
GenCC
Source:
- complex neurodevelopmental disorder (Limited), mode of inheritance: AD
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NPAS4 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
---|---|---|---|---|---|---|
synonymous | 3 | |||||
missense | 46 | 49 | ||||
nonsense | 1 | |||||
start loss | 0 | |||||
frameshift | 1 | |||||
inframe indel | 0 | |||||
splice donor/acceptor (+/-2bp) | 0 | |||||
splice region | 0 | |||||
non coding | 0 | |||||
Total | 0 | 0 | 48 | 3 | 3 |
Variants in NPAS4
This is a list of pathogenic ClinVar variants found in the NPAS4 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
11-66421345-T-C | not specified | Uncertain significance (Apr 26, 2024) | ||
11-66422141-C-A | not specified | Uncertain significance (Dec 11, 2024) | ||
11-66422146-C-T | not specified | Uncertain significance (Oct 12, 2021) | ||
11-66422155-G-T | not specified | Uncertain significance (Aug 09, 2021) | ||
11-66422263-C-A | not specified | Uncertain significance (Jul 06, 2021) | ||
11-66422266-T-C | not specified | Uncertain significance (Apr 20, 2024) | ||
11-66422484-G-A | not specified | Uncertain significance (Aug 28, 2023) | ||
11-66422529-A-G | not specified | Uncertain significance (Mar 29, 2022) | ||
11-66422686-G-A | not specified | Uncertain significance (Nov 20, 2024) | ||
11-66422720-CCAGAGTG-C | Microcephaly | Uncertain significance (Mar 23, 2023) | ||
11-66422745-C-T | not specified | Uncertain significance (Apr 04, 2024) | ||
11-66422776-C-A | not specified | Uncertain significance (Feb 22, 2025) | ||
11-66422776-C-T | not specified | Uncertain significance (Dec 25, 2024) | ||
11-66422841-C-T | not specified | Uncertain significance (May 21, 2024) | ||
11-66422848-G-T | not specified | Uncertain significance (Oct 26, 2021) | ||
11-66422853-G-A | not specified | Uncertain significance (Mar 18, 2024) | ||
11-66423132-C-G | Uncertain significance (Dec 05, 2024) | |||
11-66423199-C-G | not specified | Uncertain significance (Feb 10, 2025) | ||
11-66423208-G-A | not specified | Uncertain significance (Apr 07, 2023) | ||
11-66423644-C-T | Likely benign (Oct 01, 2023) | |||
11-66423718-G-T | Uncertain significance (Dec 05, 2024) | |||
11-66423839-A-G | not specified | Uncertain significance (Jun 28, 2022) | ||
11-66423840-T-A | not specified | Uncertain significance (Apr 25, 2022) | ||
11-66423851-A-G | not specified | Uncertain significance (Jun 27, 2023) | ||
11-66423857-C-T | not specified | Uncertain significance (Feb 01, 2025) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
NPAS4 | protein_coding | protein_coding | ENST00000311034 | 8 | 5704 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.973 | 0.0267 | 125744 | 0 | 4 | 125748 | 0.0000159 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 1.52 | 348 | 438 | 0.795 | 0.0000234 | 5163 |
Missense in Polyphen | 75 | 134.28 | 0.55851 | 1549 | ||
Synonymous | -0.974 | 206 | 189 | 1.09 | 0.0000105 | 1703 |
Loss of Function | 4.28 | 4 | 28.8 | 0.139 | 0.00000145 | 322 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.00 | 0.00 |
Ashkenazi Jewish | 0.000102 | 0.0000992 |
East Asian | 0.0000544 | 0.0000544 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.00000880 | 0.00000879 |
Middle Eastern | 0.0000544 | 0.0000544 |
South Asian | 0.0000327 | 0.0000327 |
Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Transcription factor expressed in neurons of the brain that regulates the excitatory-inhibitory balance within neural circuits and is required for contextual memory in the hyppocampus (By similarity). Plays a key role in the structural and functional plasticity of neurons (By similarity). Acts as an early-response transcription factor in both excitatory and inhibitory neurons, where it induces distinct but overlapping sets of late-response genes in these two types of neurons, allowing the synapses that form on inhibitory and excitatory neurons to be modified by neuronal activity in a manner specific to their function within a circuit, thereby facilitating appropriate circuit responses to sensory experience (By similarity). In excitatory neurons, activates transcription of BDNF, which in turn controls the number of GABA-releasing synapses that form on excitatory neurons, thereby promoting an increased number of inhibitory synapses on excitatory neurons (By similarity). In inhibitory neurons, regulates a distinct set of target genes that serve to increase excitatory input onto somatostatin neurons, probably resulting in enhanced feedback inhibition within cortical circuits (By similarity). The excitatory and inhibitory balance in neurons affects a number of processes, such as short-term and long-term memory, acquisition of experience, fear memory, response to stress and social behavior (By similarity). Acts as a regulator of dendritic spine development in olfactory bulb granule cells in a sensory-experience-dependent manner by regulating expression of MDM2 (By similarity). Efficient DNA binding requires dimerization with another bHLH protein, such as ARNT, ARNT2 or BMAL1 (PubMed:14701734). Can activate the CME (CNS midline enhancer) element (PubMed:14701734). {ECO:0000250|UniProtKB:Q8BGD7, ECO:0000269|PubMed:14701734}.;
Recessive Scores
- pRec
- 0.115
Intolerance Scores
- loftool
- 0.246
- rvis_EVS
- -0.66
- rvis_percentile_EVS
- 15.95
Haploinsufficiency Scores
- pHI
- 0.540
- hipred
- Y
- hipred_score
- 0.726
- ghis
- 0.504
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.900
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Npas4
- Phenotype
- mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype;
Zebrafish Information Network
- Gene name
- npas4a
- Affected structure
- brain
- Phenotype tag
- abnormal
- Phenotype quality
- increased process quality
Gene ontology
- Biological process
- regulation of transcription by RNA polymerase II;learning;short-term memory;long-term memory;cell differentiation;regulation of synaptic transmission, GABAergic;social behavior;positive regulation of transcription by RNA polymerase II;regulation of synaptic plasticity;excitatory postsynaptic potential;inhibitory postsynaptic potential;cellular response to corticosterone stimulus;inhibitory synapse assembly
- Cellular component
- nucleus;transcription factor complex;postsynapse
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;protein binding;protein heterodimerization activity