IQCB1

Chr 3AR

IQ motif containing B1

Also known as: NPHP5, PIQ, SLSN5

NCBI Gene: 9657 ENSG00000173226 UniProt: Q15051 OMIM: 609237

This nephrocystin protein localizes to primary cilia and connecting cilia of photoreceptor cells, where it regulates ciliogenesis and BBSome complex integrity for proper ciliary function. Mutations cause Senior-Loken syndrome type 5, a ciliopathy characterized by nephronophthisis (progressive kidney disease) and retinal degeneration, inherited in an autosomal recessive pattern. The gene shows minimal constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a nephrocystin protein that interacts with calmodulin and the retinitis pigmentosa GTPase regulator protein. The encoded protein has a central coiled-coil region and two calmodulin-binding IQ domains. It is localized to the primary cilia of renal epithelial cells and connecting cilia of photoreceptor cells. The protein is thought to play a role in ciliary function. Defects in this gene result in Senior-Loken syndrome type 5. Alternative splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Jan 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Senior-Loken syndrome 5MIM #609254

UniProtLeber congenital amaurosis 10

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · ciliopathy · AR · ClinGen 2024

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

0.90

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — IQCB1

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?

0.90LOEUF

pLI 0.000

Z-score 2.07

OE 0.64 (0.47–0.90)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.31Z-score

OE missense 0.95 (0.86–1.05)

280 obs / 294.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.64 (0.47–0.90)

0≤0.351.4

Missense OE?0.95 (0.86–1.05)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 25 / 38.9Missense obs/exp: 280 / 294.9Syn Z: 1.00

Background carrier burden — how many people carry a rare variant somewhere in IQCB1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

679 rare PASS variants

Rare truncating (LoF)

1 in 500

123 rare PASS variants

Rare synonymous (reference)

1 in 300

231 rare PASS variants

Rare missense and truncating variants are carried at similar rates in IQCB1; this gene does not show strong loss-of-function constraint by this measure. 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 180	1 in 450
South Asian	~43k	1 in 86	1 in 920
Remaining (unassigned)	~30k	1 in 110	1 in 630
European (Finnish)	~27k	1 in 610	1 in 5,300
Admixed American	~22k	1 in 84	1 in 1,100
African / African American	~21k	1 in 86	1 in 800
East Asian	~20k	1 in 86	1 in 690
Ashkenazi Jewish	~13k	1 in 320	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 110	≈ 1 in 870

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 13 coding exons well covered in gnomAD exomes; exons 3, 6, 7, 8, 9, 10 marginal. Genomes: all 13.? see exons ↓