CHRFAM7A

Chr 15

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

Also known as: CHRNA7, CHRNA7-DR1, D-10

NCBI Gene: 89832ENSG00000166664UniProt: Q494W8

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]

171
ClinVar variants
95
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CHRFAM7A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
95 Pathogenic / Likely Pathogenic· 65 VUS of 171 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.22LOEUF
pLI 0.000
Z-score 1.06
OE 0.65 (0.37–1.22)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.59Z-score
OE missense 0.85 (0.73–1.00)
108 obs / 126.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.65 (0.37–1.22)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.73–1.00)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.87
0≤1.21.6
LoF obs/exp: 7 / 10.7Missense obs/exp: 108 / 126.5Syn Z: 0.72

ClinVar Variant Classifications

171 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic92
Likely Pathogenic3
VUS65
Likely Benign5
Benign1
Conflicting2
92
Pathogenic
3
Likely Pathogenic
65
VUS
5
Likely Benign
1
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
92
0
92
Likely Pathogenic
0
0
3
0
3
VUS
0
41
24
0
65
Likely Benign
0
2
1
2
5
Benign
0
0
1
0
1
Conflicting
—2
Total0431212168

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CHRFAM7A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The human CHRNA7 and CHRFAM7A genes: A review of the genetics, regulation, and function.
Sinkus ML et al.·Neuropharmacology
2015Review
CHRFAM7A diversifies human immune adaption through Ca(2+) signalling and actin cytoskeleton reorganization.
Szigeti K et al.·EBioMedicine
2024
CHRFAM7A gene expression in schizophrenia: clinical correlates and the effect of antipsychotic treatment.
Kalmady SV et al.·J Neural Transm (Vienna)
2018
Genetic variation in CHRNA7 and CHRFAM7A is associated with nicotine dependence and response to varenicline treatment.
Cameli C et al.·Eur J Hum Genet
2018
CHRFAM7A alters binding to the neuronal alpha-7 nicotinic acetylcholine receptor.
Chan T et al.·Neurosci Lett
2019
Translational implications of CHRFAM7A, an elusive human-restricted fusion gene.
Ihnatovych I et al.·Mol Psychiatry
2024Review
Effect of CHRFAM7A Δ2bp gene variant on secondary inflammation after spinal cord injury.
Lin M et al.·PLoS One
2021
iPSC model of CHRFAM7A effect on α7 nicotinic acetylcholine receptor function in the human context.
Ihnatovych I et al.·Transl Psychiatry
2019Functional
CHRFAM7A Overexpression Attenuates Cerebral Ischemia-Reperfusion Injury via Inhibiting Microglia Pyroptosis Mediated by the NLRP3/Caspase-1 pathway.
Cao X et al.·Inflammation
2021
The emergence of the uniquely human α7 nicotinic acetylcholine receptor gene and its roles in inflammation.
Peng W et al.·Gene
2022Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools