CNGB1

Chr 16AR

cyclic nucleotide gated channel subunit beta 1

Also known as: CNCG2, CNCG3L, CNCG4, CNG4, CNGB1B, GAR1, GARP, GARP2

NCBI Gene: 1258 ENSG00000070729 UniProt: Q14028 OMIM: 600724

The protein forms the beta subunit of rod photoreceptor cyclic nucleotide-gated channels, mediating phototransduction by converting light-induced cGMP changes into electrical signals, and also functions in olfactory sensory neurons for odor detection. Mutations cause retinitis pigmentosa 45, a progressive retinal degeneration affecting vision, with autosomal recessive inheritance. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with the recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

In humans, the rod photoreceptor cGMP-gated cation channel helps regulate ion flow into the rod photoreceptor outer segment in response to light-induced alteration of the levels of intracellular cGMP. This channel consists of two subunits, alpha and beta, with the protein encoded by this gene representing the beta subunit. Defects in this gene are a cause of cause of retinitis pigmentosa type 45. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Retinitis pigmentosa 45MIM #613767

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · CNGB1-related retinopathy · AR · ClinGen 2022

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.15

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — CNGB1

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?

1.15LOEUF

pLI 0.000

Z-score 0.53

OE 0.93 (0.75–1.15)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.83Z-score

OE missense 1.09 (1.02–1.15)

779 obs / 716.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.93 (0.75–1.15)

0≤0.351.4

Missense OE?1.09 (1.02–1.15)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 59 / 63.6Missense obs/exp: 779 / 716.6Syn Z: 0.29

Background carrier burden — how many people carry a rare variant somewhere in CNGB1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 26

1,857 rare PASS variants

Rare truncating (LoF)

1 in 220

280 rare PASS variants

Rare synonymous (reference)

1 in 67

656 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CNGB1. 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 36	1 in 410
South Asian	~43k	1 in 23	1 in 300
Remaining (unassigned)	~30k	1 in 26	1 in 280
European (Finnish)	~27k	1 in 110	1 in 1,700
Admixed American	~22k	1 in 22	1 in 340
African / African American	~21k	1 in 18	1 in 180
East Asian	~20k	1 in 24	1 in 340
Ashkenazi Jewish	~13k	1 in 150	1 in 1,800
Middle Eastern	~2,884	1 in 22	1 in 290

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): All 32 coding exons well covered in gnomAD exomes and genomes.? see exons ↓