CHRND

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

Basic information

Region (hg38): 2:232525993-232536667

Previous symbols: [ "ACHRD" ]

Links

ENSG00000135902 ∙ NCBI:1144 ∙ OMIM:100720 ∙ HGNC:1965 ∙ Uniprot:Q07001 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital myasthenic syndrome 3A (Strong), mode of inheritance: AD
• congenital myasthenic syndrome 3C (Strong), mode of inheritance: AR
• congenital myasthenic syndrome 3B (Strong), mode of inheritance: AR
• congenital myasthenic syndrome 3A (Strong), mode of inheritance: AD
• congenital myasthenic syndrome 3B (Strong), mode of inheritance: AR
• lethal multiple pterygium syndrome (Supportive), mode of inheritance: AR
• postsynaptic congenital myasthenic syndrome (Supportive), mode of inheritance: AR
• congenital myasthenic syndrome 3A (Strong), mode of inheritance: AD
• congenital myasthenic syndrome 3C (Strong), mode of inheritance: AR
• lethal multiple pterygium syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myasthenic syndrome, congenital, 3A, slow-channel; Myasthenic syndrome, congenital, 3B, fast-channel; Myasthenic syndrome, congenital, 3C, associated with acetylcholine receptor deficiency	AD/AR	Musculoskeletal; Neurologic; Pharmacogenomic	Most individuals with Myasthenic syndrome, congenital benefit from AChE inhibitors and/or potassium channel blocker 3,4-diaminopyridine (3,4-DAP), though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes; For Slow-channel congenital myasthenic syndrome, effective treatment has been reported with therapies such as quinidine, fluoxetine, and ephedrine, while cholinesterase inhibitors and amifampridine should be avoided; Additional neurologic monitoring in pregnancy may be beneficial	Musculoskeletal; Neurologic	11435464; 11782989; 18252226; 12499478; 16916845; 18398509; 23108489; 25792100

ClinVar

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

• Lethal multiple pterygium syndrome (13 variants)
• Congenital myasthenic syndrome 3B (2 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHRND 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	77	2	86
missense	1	5	210	3	2	221
nonsense	4	2				6
start loss	1					1
frameshift	7	5	2			14
inframe indel			4			4
splice donor/acceptor (+/-2bp)	1	6	1			8
splice region			9	9	1	19
non coding			27	68	16	111
Total	14	18	251	148	20

Highest pathogenic variant AF is 0.0000131

Variants in CHRND

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

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

Position	Type	Phenotype	Significance	ClinVar
2-232525995-C-T			Benign (Jul 08, 2018)
2-232526217-T-C		Lethal multiple pterygium syndrome	Pathogenic (Oct 31, 2022)
2-232526223-G-C			Uncertain significance (-)
2-232526227-A-G		not specified • Congenital myasthenic syndrome • Lethal multiple pterygium syndrome	Benign (Feb 01, 2024)
2-232526228-G-T		Lethal multiple pterygium syndrome	Uncertain significance (Jun 20, 2023)
2-232526234-A-C			Uncertain significance (Mar 01, 2021)
2-232526242-G-C		Lethal multiple pterygium syndrome	Conflicting classifications of pathogenicity (Jun 25, 2023)
2-232526242-G-T		Lethal multiple pterygium syndrome	Likely benign (Apr 03, 2023)
2-232526244-T-C		Lethal multiple pterygium syndrome	Uncertain significance (Mar 11, 2022)
2-232526246-C-T		Lethal multiple pterygium syndrome	Likely benign (Oct 04, 2022)
2-232526249-G-A		Lethal multiple pterygium syndrome	Uncertain significance (Oct 13, 2022)
2-232526250-CT-C		Lethal multiple pterygium syndrome	Pathogenic (Mar 08, 2023)
2-232526256-T-G		Lethal multiple pterygium syndrome	Uncertain significance (Sep 08, 2023)
2-232526257-G-C		Lethal multiple pterygium syndrome	Likely benign (Mar 18, 2022)
2-232526259-C-T		not specified • Lethal multiple pterygium syndrome	Conflicting classifications of pathogenicity (Jan 29, 2024)
2-232526260-G-A		Lethal multiple pterygium syndrome • Congenital myasthenic syndrome	Conflicting classifications of pathogenicity (Nov 21, 2023)
2-232526268-G-A		Congenital myasthenic syndrome 3B	Likely pathogenic (May 22, 2022)
2-232526273-G-A		Lethal multiple pterygium syndrome	Uncertain significance (Sep 20, 2021)
2-232526274-G-A		Congenital myasthenic syndrome • Lethal multiple pterygium syndrome • CHRND-related disorder	Uncertain significance (Jan 12, 2018)
2-232526282-C-A		Lethal multiple pterygium syndrome	Likely benign (Nov 28, 2022)
2-232526285-C-A		Lethal multiple pterygium syndrome	Likely benign (Jul 18, 2022)
2-232526285-C-G		Lethal multiple pterygium syndrome	Likely benign (Jan 10, 2023)
2-232526513-C-T		Lethal multiple pterygium syndrome	Likely benign (Sep 27, 2022)
2-232526514-G-A		Lethal multiple pterygium syndrome	Likely benign (Oct 13, 2023)
2-232526535-G-A		Lethal multiple pterygium syndrome	Pathogenic (Apr 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHRND	protein_coding	protein_coding	ENST00000258385	12	10675

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.45e-9	0.850	125630	0	118	125748	0.000469

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0540	296	299	0.991	0.0000201	3377
Missense in Polyphen		128	124.89	1.0249		1434
Synonymous	-0.0584	124	123	1.01	0.00000796	1058
Loss of Function	1.65	17	26.1	0.652	0.00000149	272

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000514	0.000514
Ashkenazi Jewish	0.00	0.00
East Asian	0.000326	0.000326
Finnish	0.000832	0.000832
European (Non-Finnish)	0.000673	0.000668
Middle Eastern	0.000326	0.000326
South Asian	0.0000980	0.0000980
Other	0.000652	0.000652

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. {ECO:0000269|PubMed:27375219}.
• 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:18252226}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myasthenic syndrome, congenital, 3A, slow-channel (CMS3A) [MIM:616321]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS3A is a slow-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in prolonged AChR channel opening episodes, prolonged endplate currents, and depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane. {ECO:0000269|PubMed:11782989, ECO:0000269|PubMed:8872460}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myasthenic syndrome, congenital, 3B, fast-channel (CMS3B) [MIM:616322]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS3B is a fast-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in brief opening and activity of the channel, with a rapid decay in endplate current, failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential. {ECO:0000269|PubMed:11435464, ECO:0000269|PubMed:12499478, ECO:0000269|PubMed:18398509}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myasthenic syndrome, congenital, 3C, associated with acetylcholine receptor deficiency (CMS3C) [MIM:616323]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS3C is an autosomal recessive disorder of postsynaptic neuromuscular transmission, due to deficiency of AChR at the endplate that results in low amplitude of the miniature endplate potential and current. {ECO:0000269|PubMed:16916845, ECO:0000269|PubMed:18398509}. 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;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: 0.172

Intolerance Scores

• loftool: 0.230
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.93

Haploinsufficiency Scores

• pHI: 0.168
• hipred: N
• hipred_score: 0.369
• ghis: 0.542

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.524

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chrnd

Zebrafish Information Network

• Gene name: chrnd
• Affected structure: fast muscle cell
• Phenotype tag: abnormal
• Phenotype quality: decreased object quality

Gene ontology

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