CHRFAM7A

protein-coding

CHRNA7 (exons 5-10) and FAM7A (exons A-E) fusion

Gene summary

The nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. The family member CHRNA7, which is located on chromosome 15 in a region associated with several neuropsychiatric disorders, is partially duplicated and forms a hybrid with a novel gene from the family with sequence similarity 7 (FAM7A). Alternative splicing has been observed, and two variants exist, for this hybrid gene. The N-terminally truncated products predicted by the largest open reading frames for each variant would lack the majority of the neurotransmitter-gated ion-channel ligand binding domain but retain the transmembrane region that forms the ion channel. Although current evidence supports transcription of this hybrid gene, translation of the nicotinic acetylcholine receptor-like protein-encoding open reading frames has not been confirmed. [provided by RefSeq, Jul 2008]

MANE transcript

NM_139320.2

Inheritance

—

ClinVar variants

U:42B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr15:30,360,566-30,393,849

External References & Databases

Ensembl (ENSG00000166664)

Transcript & Mutation Effects

hg38 • Region Span ~33.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CHRFAM7A variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 42

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_139320.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense			41 clinvar	1 clinvar		42
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	42	3	0	45

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_139320.2	RefSeq	NP_647536.1	8	MANE Select
ENST00000299847.7	Ensembl	ENSP00000299847.3	8	MANE Select
NM_148911.1	RefSeq	NP_683709.1	5	Standard
ENST00000397827.7	Ensembl	ENSP00000380927.3	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

signal transduction
chemical synaptic transmission
synaptic transmission, cholinergic
ion transmembrane transport
regulation of membrane potential

Molecular Function

extracellular ligand-gated ion channel activity
acetylcholine receptor activity
acetylcholine binding

Cellular Component

integral component of plasma membrane
acetylcholine-gated channel complex
neuron projection
synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000299847
Coding exons: 8
Length: 32610
Individuals with no LoFs: 44386
Homozygous LoFs: 13735
Heterozygous LoFs: 67074
Defined: 125195
p: 0.405

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.585	108	127	0.854	0.00000733	2635
Missense (PolyPhen)		59	70.535	0.83646		1176
Synonymous	0.722	46	52.7	0.873	0.00000344	765
Loss of Function	1.06	7	10.7	0.651	4.57e-7	200

Population LoF Frequency

Population	CAF	p-value	Status
African	0.13	0.12	notable
Latino/Admixed American	0.52	0.54	notable
Ashkenazi Jewish	0.35	0.35	notable
East Asian	0.67	0.74	notable
Finnish	0.36	0.38	notable
European (Non-Finnish)	0.36	0.37	notable
South Asian	0.46	0.46	notable
Other	0.41	0.43	notable

dbNSFP Gene Annotations

Source: dbNSFP

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.137

Gene Damage Prediction

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