CHRNG

cholinergic receptor nicotinic gamma subunit, the group of Cholinergic receptors nicotinic subunits

Basic information

Region (hg38): 2:232539691-232548115

Previous symbols: [ "ACHRG" ]

Links

ENSG00000196811 ∙ NCBI:1146 ∙ OMIM:100730 ∙ HGNC:1967 ∙ Uniprot:P07510 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive multiple pterygium syndrome (Definitive), mode of inheritance: AR
• transient neonatal myasthenia gravis (Strong), mode of inheritance: AR
• lethal multiple pterygium syndrome (Strong), mode of inheritance: AR
• autosomal recessive multiple pterygium syndrome (Strong), mode of inheritance: AR
• autosomal recessive multiple pterygium syndrome (Supportive), mode of inheritance: AR
• lethal multiple pterygium syndrome (Supportive), mode of inheritance: AR
• lethal multiple pterygium syndrome (Strong), mode of inheritance: AR
• CHRNG-associated hypo-akinesia disorder of prenatal onset (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Multiple pterygium syndrome, lethal type; Escobar syndrome	AR	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; Musculoskeletal	16826520; 16826531; 22167768; 25608830

ClinVar

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

• not provided (191 variants)
• Autosomal recessive multiple pterygium syndrome (104 variants)
• Lethal multiple pterygium syndrome (81 variants)
• Inborn genetic diseases (38 variants)
• not specified (19 variants)
• Autosomal recessive multiple pterygium syndrome;Lethal multiple pterygium syndrome (6 variants)
• CHRNG-Related Disorders (5 variants)
• Lethal multiple pterygium syndrome;Autosomal recessive multiple pterygium syndrome (3 variants)
• Arthrogryposis-like hand anomaly;Ankle flexion contracture;Scoliosis (2 variants)
• Arthrogryposis multiplex congenita;Fetal akinesia deformation sequence 1 (1 variants)
• CHRNG-related condition (1 variants)
• Peripheral neuropathy (1 variants)
• Congenital Myasthenic Syndrome, Dominant/Recessive (1 variants)
• Rheumatoid arthritis (1 variants)
• Progressive congenital scoliosis (1 variants)
• Abnormality of prenatal development or birth (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHRNG 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			7	47	1	55
missense	2	4	59	2		67
nonsense	8	4	3			15
start loss						0
frameshift	12					12
inframe indel		1	2			3
splice donor/acceptor (+/-2bp)	3	6			1	10
splice region	1		5	9	1	16
non coding			22	47	23	92
Total	25	15	93	96	25

Highest pathogenic variant AF is 0.000453

Variants in CHRNG

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

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

Position	Type	Phenotype	Significance	ClinVar
2-232539752-A-T		Autosomal recessive multiple pterygium syndrome • Lethal multiple pterygium syndrome	Uncertain significance (Jan 13, 2018)
2-232539753-T-C			Likely benign (Mar 29, 2023)
2-232539756-G-C			Likely benign (Mar 27, 2023)
2-232539759-C-A			Likely benign (Nov 20, 2023)
2-232539760-C-T		Autosomal recessive multiple pterygium syndrome • Arthrogryposis-like hand anomaly;Ankle flexion contracture;Scoliosis	Likely pathogenic (Oct 16, 2019)
2-232539767-C-T		Inborn genetic diseases	Likely benign (Feb 26, 2024)
2-232539768-G-A			Likely benign (Jan 20, 2024)
2-232539771-G-A			Likely benign (Jul 24, 2023)
2-232539777-C-T			Likely benign (Jan 14, 2024)
2-232539780-G-A			Likely benign (Nov 27, 2023)
2-232539803-G-A			Likely pathogenic (-)
2-232539807-G-A		Autosomal recessive multiple pterygium syndrome	Pathogenic (Jun 15, 2023)
2-232539809-C-G			Likely benign (Dec 13, 2023)
2-232539814-A-G			Likely benign (Jul 31, 2023)
2-232539815-G-A			Likely benign (Apr 17, 2023)
2-232539880-G-C			Benign (Oct 02, 2019)
2-232539972-C-G			Likely benign (Jul 31, 2023)
2-232539976-C-T			Benign (Feb 01, 2024)
2-232539977-G-A			Likely benign (Dec 20, 2023)
2-232539979-C-T			Likely benign (Sep 24, 2023)
2-232539983-C-G			Likely benign (Jun 07, 2023)
2-232539990-A-G		Autosomal recessive multiple pterygium syndrome	Pathogenic (Jun 15, 2023)
2-232539991-G-A			Pathogenic (Dec 09, 2023)
2-232539993-G-C		Autosomal recessive multiple pterygium syndrome • Lethal multiple pterygium syndrome	Conflicting classifications of pathogenicity (Jan 24, 2024)
2-232539998-A-G		Inborn genetic diseases	Uncertain significance (Sep 17, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHRNG	protein_coding	protein_coding	ENST00000389494	12	6677

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.33e-19	0.00462	125488	0	260	125748	0.00103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.118	310	304	1.02	0.0000209	3325
Missense in Polyphen		110	121.31	0.9068		1437
Synonymous	0.0280	135	135	0.997	0.00000963	1101
Loss of Function	0.177	29	30.0	0.965	0.00000187	275

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00204	0.00204
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000870	0.000870
Finnish	0.000786	0.000786
European (Non-Finnish)	0.00120	0.00119
Middle Eastern	0.000870	0.000870
South Asian	0.00121	0.00105
Other	0.00147	0.00147

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.
• Disease: DISEASE: Multiple pterygium syndrome, lethal type (LMPS) [MIM:253290]: Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. In lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia, and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies are frequent. {ECO:0000269|PubMed:16826520, ECO:0000269|PubMed:16826531}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Multiple pterygium syndrome, Escobar variant (EVMPS) [MIM:265000]: Non-lethal form of arthrogryposis multiplex congenita. It is an autosomal recessive condition characterized by excessive webbing (pterygia), congenital contractures (arthrogryposis), and scoliosis. Variable other features include intrauterine death, congenital respiratory distress, short stature, faciocranial dysmorphism, ptosis, low-set ears, arachnodactyly and cryptorchism in males. Congenital contractures are common and may be caused by reduced fetal movements at sensitive times of development. Possible causes of decreased fetal mobility include space constraints such as oligohydramnion, drugs, metabolic conditions or neuromuscular disorders including myasthenia gravis. {ECO:0000269|PubMed:16826520, ECO:0000269|PubMed:16826531}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Neuroactive ligand-receptor interaction - Homo sapiens (human);Highly sodium permeable acetylcholine nicotinic receptors;Neuronal System;role of nicotinic acetylcholine receptors in the regulation of apoptosis;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Presynaptic nicotinic acetylcholine receptors;Postsynaptic nicotinic acetylcholine receptors;Activation of Nicotinic Acetylcholine Receptors;Acetylcholine binding and downstream events (Consensus)

Recessive Scores

• pRec: 0.0850

Intolerance Scores

• loftool: 0.308
• rvis_EVS: -0.42
• rvis_percentile_EVS: 25.79

Haploinsufficiency Scores

• pHI: 0.0665
• hipred: N
• hipred_score: 0.251
• ghis: 0.505

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.616

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chrng
• Phenotype: muscle phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); 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); growth/size/body region 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; embryo phenotype; pigmentation phenotype

Gene ontology

• Biological process: muscle contraction;signal transduction;chemical synaptic transmission;synaptic transmission, cholinergic;neuromuscular synaptic transmission;ion transmembrane transport;response to nicotine;regulation of membrane potential;nervous system process;excitatory postsynaptic potential
• Cellular component: plasma membrane;integral component of plasma membrane;acetylcholine-gated channel complex;cell junction;neuron projection;synapse;postsynaptic membrane
• Molecular function: extracellular ligand-gated ion channel activity;protein binding;channel activity;acetylcholine receptor activity;acetylcholine-gated cation-selective channel activity;acetylcholine binding