CNBD1

Chr 8

cyclic nucleotide binding domain containing 1

NCBI Gene: 168975 ENSG00000176571 UniProt: Q8NA66

This gene encodes a cyclic nucleotide-binding domain-containing protein that regulates cellular signaling pathways involving cyclic AMP and cyclic GMP. Mutations cause autosomal recessive cone-rod dystrophy, a progressive retinal degeneration that typically begins in childhood with decreased central vision and color discrimination deficits, followed by progressive loss of peripheral vision. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected families.

Research

ResearchGenerating clinical summary…

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

1.70

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.70LOEUF

pLI 0.000

Z-score -0.92

OE 1.22 (0.88–1.70)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.33Z-score

OE missense 1.26 (1.14–1.40)

255 obs / 201.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.22 (0.88–1.70)

0≤0.351.4

Missense OE?1.26 (1.14–1.40)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 24 / 19.6Missense obs/exp: 255 / 201.8Syn Z: 0.80

Background carrier burden — how many people carry a rare variant somewhere in CNBD1?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 45

854 rare PASS variants

Rare truncating (LoF)

1 in 280

212 rare PASS variants

Rare synonymous (reference)

1 in 150

238 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CNBD1. 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 83	1 in 490
South Asian	~43k	1 in 43	1 in 320
Remaining (unassigned)	~30k	1 in 32	1 in 420
European (Finnish)	~27k	1 in 250	1 in 510
Admixed American	~22k	1 in 55	1 in 260
African / African American	~21k	1 in 59	1 in 290
East Asian	~20k	1 in 60	1 in 190
Ashkenazi Jewish	~13k	1 in 180	1 in 1,200
Middle Eastern	~2,884	1 in 72	1 in 460

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.