IQCB1

IQ motif containing B1, the group of Armadillo like helical domain containing

Basic information

Region (hg38): 3:121769760-121835079

Links

ENSG00000173226 ∙ NCBI:9657 ∙ OMIM:609237 ∙ HGNC:28949 ∙ Uniprot:Q15051 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Senior-Loken syndrome (Supportive), mode of inheritance: AR
• Leber congenital amaurosis (Supportive), mode of inheritance: AD
• Senior-Loken syndrome 5 (Strong), mode of inheritance: AR
• Leber congenital amaurosis 9 (Definitive), mode of inheritance: AR
• Senior-Loken syndrome 5 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Senior-Loken syndrome 5	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic; Renal	15723066; 21220633; 23661368

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IQCB1 gene.

• Nephronophthisis (351 variants)
• Senior-Loken syndrome 5 (136 variants)
• not provided (95 variants)
• Inborn genetic diseases (24 variants)
• not specified (13 variants)
• Retinal dystrophy (7 variants)
• Renal dysplasia and retinal aplasia (6 variants)
• Leber congenital amaurosis (5 variants)
• Retinitis pigmentosa (2 variants)
• IQCB1-related condition (2 variants)
• Bardet-Biedl syndrome (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IQCB1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	55	1	57
missense			176	4	4	184
nonsense	19	7	3			29
start loss						0
frameshift	13	10	1			24
inframe indel			1			1
splice donor/acceptor (+/-2bp)	3	9				12
splice region			13	9	2	24
non coding			15	68	48	131
Total	35	26	197	127	53

Highest pathogenic variant AF is 0.000126

Variants in IQCB1

This is a list of pathogenic ClinVar variants found in the IQCB1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-121769946-T-C		Senior-Loken syndrome 5	Uncertain significance (Jan 12, 2018)
3-121770018-A-G		Senior-Loken syndrome 5	Uncertain significance (Jan 12, 2018)
3-121770119-A-G		Senior-Loken syndrome 5	Uncertain significance (Jan 12, 2018)
3-121770127-C-T		Senior-Loken syndrome 5	Uncertain significance (Jan 12, 2018)
3-121770148-C-G		Senior-Loken syndrome 5	Benign (Nov 12, 2018)
3-121770185-G-A		Senior-Loken syndrome 5	Uncertain significance (Jan 12, 2018)
3-121770194-A-G		Senior-Loken syndrome 5	Uncertain significance (Jan 13, 2018)
3-121770197-A-G		Senior-Loken syndrome 5	Uncertain significance (Jan 13, 2018)
3-121770373-A-C		Nephronophthisis	Uncertain significance (Jan 13, 2021)
3-121770379-T-G		Inborn genetic diseases	Uncertain significance (Sep 27, 2021)
3-121770390-A-G		Nephronophthisis	Likely benign (Nov 28, 2022)
3-121770391-C-T		Nephronophthisis	Uncertain significance (May 08, 2023)
3-121770396-C-T		Nephronophthisis	Likely benign (Dec 30, 2023)
3-121770401-C-G		Nephronophthisis • Senior-Loken syndrome 5	Uncertain significance (Feb 03, 2022)
3-121770403-T-G		Senior-Loken syndrome 5	Uncertain significance (Jan 12, 2018)
3-121770404-T-G		Nephronophthisis	Uncertain significance (Feb 10, 2022)
3-121770415-A-G		Nephronophthisis • Senior-Loken syndrome 5	Uncertain significance (Jul 26, 2022)
3-121770422-C-T		Nephronophthisis	Uncertain significance (Mar 04, 2022)
3-121770431-C-A		Nephronophthisis	Uncertain significance (Feb 08, 2022)
3-121770435-T-A		Nephronophthisis	Likely benign (Mar 13, 2022)
3-121770436-C-G		Nephronophthisis	Uncertain significance (Jun 07, 2022)
3-121770439-A-G		Nephronophthisis • IQCB1-related disorder	Likely benign (Jan 29, 2024)
3-121770453-G-A		Nephronophthisis	Likely benign (Sep 11, 2020)
3-121770454-G-C		Nephronophthisis	Uncertain significance (Jul 18, 2021)
3-121770455-G-C		Nephronophthisis	Uncertain significance (Jan 22, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IQCB1	protein_coding	protein_coding	ENST00000310864	13	65317

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.36e-12	0.923	125583	0	165	125748	0.000656

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.309	280	295	0.949	0.0000143	3898
Missense in Polyphen		72	85.466	0.84244		1208
Synonymous	0.996	91	104	0.876	0.00000480	1118
Loss of Function	2.07	25	38.9	0.642	0.00000241	432

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000696	0.000695
Ashkenazi Jewish	0.00149	0.00149
East Asian	0.000925	0.000925
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000908	0.000906
Middle Eastern	0.000925	0.000925
South Asian	0.000298	0.000294
Other	0.000816	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in ciliogenesis. The function in an early step in cilia formation depends on its association with CEP290/NPHP6 (PubMed:21565611, PubMed:23446637). Involved in regulation of the BBSome complex integrity, specifically for presence of BBS2 and BBS5 in the complex, and in ciliary targeting of selected BBSome cargos. May play a role in controlling entry of the BBSome complex to cilia possibly implicating CEP290/NPHP6 (PubMed:25552655). {ECO:0000269|PubMed:23446637, ECO:0000269|PubMed:25552655}.
• Disease: DISEASE: Senior-Loken syndrome 5 (SLSN5) [MIM:609254]: A renal- retinal disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life. {ECO:0000269|PubMed:15723066}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Leber congenital amaurosis 10 (LCA10) [MIM:611755]: A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. {ECO:0000269|PubMed:23446637}. Note=The gene represented in this entry may be involved in disease pathogenesis.
• Pathway: Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.176

Intolerance Scores

• loftool: 0.985
• rvis_EVS: 0.6
• rvis_percentile_EVS: 82.78

Haploinsufficiency Scores

• pHI: 0.170
• hipred: Y
• hipred_score: 0.607
• ghis: 0.534

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0000268

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Iqcb1

Zebrafish Information Network

• Gene name: iqcb1
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: curved ventral

Gene ontology

• Biological process: photoreceptor cell maintenance;maintenance of animal organ identity;cilium assembly;ciliary basal body-plasma membrane docking
• Cellular component: photoreceptor outer segment;nucleoplasm;centrosome;centriole;cytosol;microtubule cytoskeleton;photoreceptor connecting cilium;intercellular bridge;extracellular exosome;mitotic spindle
• Molecular function: protein binding;calmodulin binding;enzyme binding