CHRNA7

cholinergic receptor nicotinic alpha 7 subunit, the group of Cholinergic receptors nicotinic subunits

Basic information

Region (hg38): 15:31923437-32173018

Links

ENSG00000175344 ∙ NCBI:1139 ∙ OMIM:118511 ∙ HGNC:1960 ∙ Uniprot:P36544 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Limited), mode of inheritance: AD
• epilepsy (Refuted Evidence), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurocognitive dysfunction with distinctive craniofacial features	AD	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	Craniofacial; Neurologic	22775350

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHRNA7 gene.

• not provided (49 variants)
• Inborn genetic diseases (19 variants)
• not specified (2 variants)
• Chromosome 15q13.3 microdeletion syndrome (1 variants)
• Epilepsy, idiopathic generalized, susceptibility to, 7 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHRNA7 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				12	2	14
missense			21	2	1	24
nonsense			1			1
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2	3	5
non coding				4	19	23
Total	0	0	23	18	22

Variants in CHRNA7

This is a list of pathogenic ClinVar variants found in the CHRNA7 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-32030401-G-C			Likely benign (Dec 04, 2020)
15-32030404-G-A			Likely benign (Dec 05, 2020)
15-32030509-C-T			Benign (Jul 09, 2018)
15-32030549-G-T			Benign (Jul 14, 2018)
15-32030597-G-A			Uncertain significance (Sep 03, 2022)
15-32030620-G-T		not specified	Uncertain significance (Apr 12, 2022)
15-32030639-G-A		CHRNA7-related disorder	Benign/Likely benign (Dec 31, 2019)
15-32030684-G-T		CHRNA7-related disorder	Likely benign (Oct 06, 2021)
15-32030726-G-A			Benign (Jul 09, 2018)
15-32030892-C-G		CHRNA7-related disorder	Likely benign (May 25, 2021)
15-32030901-C-T			Uncertain significance (Mar 01, 2022)
15-32030902-C-T			Likely benign (Jul 26, 2018)
15-32030931-A-G		not specified	Uncertain significance (Jul 20, 2015)
15-32030932-C-G			Uncertain significance (Jul 25, 2018)
15-32030998-C-G			Likely benign (Dec 31, 2019)
15-32031021-T-C		not specified	Uncertain significance (May 03, 2023)
15-32031251-A-G			Benign (Jul 09, 2018)
15-32101283-CT-C			Benign (Jun 18, 2021)
15-32101283-C-CT			Benign (Oct 21, 2019)
15-32101283-C-CTT			Benign (Oct 21, 2019)
15-32101299-G-T			Likely benign (Dec 31, 2019)
15-32101457-A-AAG			Benign (Oct 05, 2019)
15-32101460-C-A			Benign (Oct 02, 2019)
15-32111732-A-G			Likely benign (Jul 21, 2018)
15-32111781-G-A			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHRNA7	protein_coding	protein_coding	ENST00000454250	10	142032

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000415	0.992	125714	0	34	125748	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.25	190	245	0.776	0.0000139	3347
Missense in Polyphen		51	88.223	0.57808		1264
Synonymous	0.706	98	107	0.913	0.00000701	1010
Loss of Function	2.34	9	20.4	0.440	9.48e-7	266

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000560	0.000547
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000172	0.000167
Middle Eastern	0.00	0.00
South Asian	0.0000338	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is blocked by alpha-bungarotoxin.
• Pathway: Nicotine addiction - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Chemical carcinogenesis - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Sympathetic Nerve Pathway (Pre- and Post- Ganglionic Junction);Phosphodiesterases in neuronal function;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Neuronal System;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Highly calcium permeable postsynaptic nicotinic acetylcholine receptors;Postsynaptic nicotinic acetylcholine receptors;Activation of Nicotinic Acetylcholine Receptors;Acetylcholine binding and downstream events (Consensus)

Recessive Scores

• pRec: 0.345

Haploinsufficiency Scores

• pHI: 0.452
• ghis: 0.444

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.792

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chrna7
• Phenotype: endocrine/exocrine gland phenotype; taste/olfaction phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; limbs/digits/tail phenotype; 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); digestive/alimentary phenotype; pigmentation phenotype; normal 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); reproductive system phenotype; hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype; embryo phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype

Gene ontology

• Biological process: activation of MAPK activity;response to hypoxia;positive regulation of protein phosphorylation;ion transport;calcium ion transport;cellular calcium ion homeostasis;signal transduction;chemical synaptic transmission;synaptic transmission, cholinergic;learning or memory;memory;short-term memory;positive regulation of cell population proliferation;negative regulation of tumor necrosis factor production;ion transmembrane transport;response to nicotine;regulation of membrane potential;positive regulation of angiogenesis;synapse organization;nervous system process;cognition;sensory processing;positive regulation of protein metabolic process;excitatory postsynaptic potential;positive regulation of ERK1 and ERK2 cascade;calcium ion transmembrane transport;acetylcholine receptor signaling pathway;dendritic spine organization;modulation of excitatory postsynaptic potential;dendrite arborization;positive regulation of long-term synaptic potentiation;regulation of neuron death;positive regulation of amyloid-beta formation;negative regulation of amyloid-beta formation;regulation of amyloid precursor protein catabolic process;response to amyloid-beta;response to acetylcholine;regulation of amyloid fibril formation;positive regulation of CoA-transferase activity;positive regulation of excitatory postsynaptic potential
• Cellular component: plasma membrane;integral component of plasma membrane;acetylcholine-gated channel complex;integral component of membrane;cell junction;neuron projection;plasma membrane raft;synapse;postsynaptic membrane;postsynapse
• Molecular function: amyloid-beta binding;transmembrane signaling receptor activity;ion channel activity;extracellular ligand-gated ion channel activity;calcium channel activity;protein binding;acetylcholine receptor activity;toxic substance binding;chloride channel regulator activity;acetylcholine-gated cation-selective channel activity;acetylcholine binding;protein homodimerization activity