NLGN4X
neuroligin 4 X-linked, the group of Neuroligins
Basic information
Region (hg38): X:5840637-6228867
Previous symbols: [ "NLGN4" ]
Links
Phenotypes
GenCC
Source:
- autism, susceptibility to, X-linked 2 (Strong), mode of inheritance: XL
- autism, susceptibility to, X-linked 2 (Strong), mode of inheritance: XL
- autism, susceptibility to, X-linked 2 (Strong), mode of inheritance: XL
- X-linked complex neurodevelopmental disorder (Definitive), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Autism susceptibility, X-linked 2 | XL | General | 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 | Neurologic | 12669065; 14963808; 18231125; 19645625; 19726642 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (179 variants)
- Inborn_genetic_diseases (93 variants)
- not_specified (28 variants)
- NLGN4X-related_disorder (28 variants)
- Autism,_susceptibility_to,_X-linked_2 (27 variants)
- Asperger_syndrome,_X-linked,_susceptibility_to,_2 (4 variants)
- Intellectual_disability (2 variants)
- X-linked_intellectual_disability (1 variants)
- History_of_neurodevelopmental_disorder (1 variants)
- Autism_spectrum_disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NLGN4X gene is commonly pathogenic or not. These statistics are base on transcript: NM_000181332.3. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 56 | 67 | ||||
| missense | 178 | 19 | 199 | |||
| nonsense | 5 | |||||
| start loss | 0 | |||||
| frameshift | 4 | |||||
| splice donor/acceptor (+/-2bp) | 2 | |||||
| Total | 5 | 2 | 189 | 75 | 6 |
Highest pathogenic variant AF is 0.0000018211819
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| NLGN4X | protein_coding | protein_coding | ENST00000381095 | 5 | 388227 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.993 | 0.00733 | 125744 | 1 | 2 | 125747 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.70 | 222 | 368 | 0.604 | 0.0000331 | 5371 |
| Missense in Polyphen | 105 | 213.71 | 0.49131 | 3005 | ||
| Synonymous | -1.51 | 193 | 168 | 1.15 | 0.0000173 | 1627 |
| Loss of Function | 3.84 | 1 | 19.1 | 0.0524 | 0.00000137 | 320 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000378 | 0.0000264 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Putative neuronal cell surface protein involved in cell- cell-interactions.;
- Disease
- DISEASE: Asperger syndrome, X-linked, 2 (ASPGX2) [MIM:300497]: A syndrome with features similar to autism. Affected individuals exhibit qualitative impairment in social interaction, as manifest by impairment in the use of non-verbal behaviors such as eye-to- eye gaze, facial expression, body postures, and gestures, failure to develop appropriate peer relationships, and lack of social sharing or reciprocity. Patients also exhibit restricted, repetitive and stereotyped patterns of behavior, interests, and activities, including abnormal preoccupation with certain activities and inflexible adherence to routines or rituals. Asperger syndrome is primarily distinguished from autism by the higher cognitive abilities and a more normal and timely development of language and communicative phrases. {ECO:0000269|PubMed:14963808}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
- Pathway
- Cell adhesion molecules (CAMs) - Homo sapiens (human);Neuronal System;Neurexins and neuroligins;Protein-protein interactions at synapses
(Consensus)
Recessive Scores
- pRec
- 0.227
Intolerance Scores
- loftool
- 0.149
- rvis_EVS
- -0.84
- rvis_percentile_EVS
- 11.18
Haploinsufficiency Scores
- pHI
- 0.816
- hipred
- Y
- hipred_score
- 0.507
- ghis
- 0.607
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.791
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Gene ontology
- Biological process
- brainstem development;neuron cell-cell adhesion;learning;cerebellum development;neuron differentiation;adult behavior;social behavior;organ growth;cell-cell junction organization;synaptic vesicle endocytosis;modulation of chemical synaptic transmission;synapse organization;vocalization behavior;negative regulation of excitatory postsynaptic potential;postsynaptic membrane assembly;presynaptic membrane assembly;presynapse assembly
- Cellular component
- plasma membrane;integral component of plasma membrane;cell surface;postsynaptic density;integral component of membrane;cell junction;dendrite;synapse;postsynaptic membrane;excitatory synapse;spanning component of membrane;presynapse;symmetric, GABA-ergic, inhibitory synapse;asymmetric, glutamatergic, excitatory synapse
- Molecular function
- protein binding;chloride ion binding;signaling receptor activity;neurexin family protein binding;protein homodimerization activity;cell adhesion molecule binding;scaffold protein binding