IQCB1

Chr 3

IQ motif containing B1

Also known as: NPHP5, PIQ, SLSN5

NCBI Gene: 9657 ENSG00000173226 UniProt: Q15051

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 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 ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.90

Clinical Summary— IQCB1

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Gene-Disease Validity (ClinGen)

ciliopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

99 unique Pathogenic / Likely Pathogenic· 273 VUS of 636 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — IQCB1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveIQCB1-related Leber congenital amaurosisLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.5771th %ile

GOF

0.72top 25%

LOF

0.2581th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

636 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic55

Likely Pathogenic44

VUS273

Likely Benign169

Benign55

Conflicting20

Pathogenic

Likely Pathogenic

273

VUS

169

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	50	0	5	0	55
Likely Pathogenic	43	0	1	0	44
VUS	7	237	29	0	273
Likely Benign	0	3	89	77	169
Benign	0	4	50	1	55
Conflicting	—				20
Total	100	244	174	78	616

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

View in ClinVar →

18 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap IQCB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →