CNGB3

Chr 8AR

cyclic nucleotide gated channel subunit beta 3

Also known as: ACHM1

NCBI Gene: 54714 ENSG00000170289 UniProt: Q9NQW8 OMIM: 605080

This gene encodes the beta subunit of cyclic nucleotide-gated ion channels in cone photoreceptors that mediate phototransduction by converting changes in cGMP levels into electrical signals in response to light. Mutations cause achromatopsia 3, an autosomal recessive condition characterized by complete color blindness, reduced visual acuity, and photophobia affecting central vision from birth. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with the recessive inheritance pattern where both copies must be affected to cause disease.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the beta subunit of a cyclic nucleotide-gated ion channel. The encoded beta subunit appears to play a role in modulation of channel function in cone photoreceptors. This heterotetrameric channel is necessary for sensory transduction, and mutations in this gene have been associated with achromatopsia 3, progressive cone dystrophy, and juvenile macular degeneration, also known as Stargardt Disease. [provided by RefSeq, Feb 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Achromatopsia 3MIM #262300

UniProtStargardt disease 1

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · CNGB3-related retinopathy · AR · ClinGen 2022

Interpreting a novel variant

Curated mechanisms (Gene2Phenotype) include both loss of function and gain of function. Which applies is variant-dependent — do not assume a null variant is, or isn’t, the pathogenic class without checking the specific variant.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

1.02

LOEUF

Multiple

Mechanism· G2P

📖

GeneReview available — CNGB3

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.02LOEUF

pLI 0.000

Z-score 1.46

OE 0.76 (0.58–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.18Z-score

OE missense 1.16 (1.08–1.25)

485 obs / 417.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.76 (0.58–1.02)

0≤0.351.4

Missense OE?1.16 (1.08–1.25)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 34 / 44.5Missense obs/exp: 485 / 417.3Syn Z: -0.62

Background carrier burden — how many people carry a rare variant somewhere in CNGB3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 46

1,128 rare PASS variants

Rare truncating (LoF)

1 in 490

189 rare PASS variants

Rare synonymous (reference)

1 in 87

363 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CNGB3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 64	1 in 510
South Asian	~43k	1 in 51	1 in 420
Remaining (unassigned)	~30k	1 in 35	1 in 370
European (Finnish)	~27k	1 in 200	1 in 1,900
Admixed American	~22k	1 in 39	1 in 340
African / African American	~21k	1 in 46	1 in 290
East Asian	~20k	1 in 49	1 in 800
Ashkenazi Jewish	~13k	1 in 160	1 in 340
Middle Eastern	~2,884	1 in 39	1 in 560

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 15 of 18 coding exons well covered in gnomAD exomes; exons 7, 8, 9 marginal. Genomes: 17 of 18 (exon 10 below).? see exons ↓