IQCB1

Summary

IQCB1 (IQ motif containing B1, HGNC:28949) is a protein-coding gene on chromosome 3q13.33, encoding IQ calmodulin-binding motif-containing protein 1 (Q15051). Involved in ciliogenesis.

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.

Source: NCBI Gene 9657 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliopathy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 636 total — 54 pathogenic, 37 likely-pathogenic
• Phenotypes (HPO): 40
• MANE Select transcript: NM_001023570

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28949
Approved symbol	IQCB1
Name	IQ motif containing B1
Location	3q13.33
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0036, NPHP5, SLSN5
Ensembl gene	ENSG00000173226
Ensembl biotype	protein_coding
OMIM	609237
Entrez	9657

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 13 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000310864, ENST00000349820, ENST00000393650, ENST00000460108, ENST00000462442, ENST00000471726, ENST00000498104, ENST00000908847, ENST00000923629, ENST00000923630, ENST00000923631, ENST00000923632, ENST00000965826, ENST00000965827, ENST00000965828

RefSeq mRNA: 3 — MANE Select: NM_001023570 NM_001023570, NM_001023571, NM_001319107

CCDS: CCDS33836, CCDS33837

Canonical transcript exons

ENST00000310864 — 15 exons

Exon	Start	End
ENSE00001206158	121795457	121795566
ENSE00001206162	121797118	121797227
ENSE00001206166	121799196	121799374
ENSE00001352162	121834391	121834479
ENSE00001624309	121769761	121770574
ENSE00003503481	121828861	121828972
ENSE00003524785	121807344	121807443
ENSE00003571642	121788284	121788432
ENSE00003581536	121826051	121826180
ENSE00003630683	121772557	121772713
ENSE00003631220	121808916	121809009
ENSE00003654162	121781743	121781874
ENSE00003677398	121790073	121790215
ENSE00003789157	121828470	121828632
ENSE00003842212	121834966	121835060

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 91.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.5504 / max 165.9154, expressed in 1797 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44111	17.5504	1797

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	91.96	gold quality
epithelium of nasopharynx	UBERON:0001951	91.50	gold quality
nasopharynx	UBERON:0001728	91.48	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.66	gold quality
monocyte	CL:0000576	90.56	gold quality
mononuclear cell	CL:0000842	90.45	gold quality
ventricular zone	UBERON:0003053	90.11	gold quality
leukocyte	CL:0000738	89.91	gold quality
body of pancreas	UBERON:0001150	89.80	gold quality
calcaneal tendon	UBERON:0003701	89.68	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.35	gold quality
rectum	UBERON:0001052	89.04	gold quality
bronchial epithelial cell	CL:0002328	88.87	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.82	silver quality
secondary oocyte	CL:0000655	88.77	gold quality
right uterine tube	UBERON:0001302	88.58	gold quality
epithelium of bronchus	UBERON:0002031	88.50	gold quality
ganglionic eminence	UBERON:0004023	88.47	gold quality
lymph node	UBERON:0000029	88.32	gold quality
bronchus	UBERON:0002185	88.17	gold quality
granulocyte	CL:0000094	88.13	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.89	gold quality
left ovary	UBERON:0002119	87.86	gold quality
right testis	UBERON:0004534	87.70	gold quality
colonic epithelium	UBERON:0000397	87.67	gold quality
right ovary	UBERON:0002118	87.53	gold quality
pancreas	UBERON:0001264	87.33	gold quality
endocervix	UBERON:0000458	87.00	gold quality
testis	UBERON:0000473	86.98	gold quality
left testis	UBERON:0004533	86.96	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 20)

• nephrocystin-5, RPGR and calmodulin can be coimmunoprecipitated from retinal extracts, and that these proteins localize to connecting cilia of photoreceptors and to primary cilia of renal epithelial cells (PMID:15723066)
• Results show that the onset of renal failure in patients with IQCB1 mutations is highly variable, and that mutations are also found in Leber congenital amaurosis (LCA) patients without nephronophthisis, rendering IQCB1 a new gene for LCA. (PMID:20881296)
• Mutations in NPHP5 can cause Leber congenital amaurosis (LCA)without early-onset renal disease. (PMID:21220633)
• Cone photoreceptors are the main targets for gene therapy of NPHP5 (IQCB1) or NPHP6 (CEP290) blindness: generation of an all-cone Nphp6 hypomorph mouse that mimics the human retinal ciliopathy. (PMID:21245082)
• Data show that the minor allele (N) of I393N in IQCB1 and the common allele (R) of R744Q in RPGRIP1L were associated with severe disease in XlRP with RPGR mutations. (PMID:21857984)
• in a set of consanguineous patient families with Leber congenital amaurosis study identified five putative disease-causing mutations, including four novel alleles, in six families; These five mutations are located in four genes, ALMS1, IQCB1, CNGA3, and MYO7A (PMID:21901789)
• Genetic variation may affect severity of disease for X-linked retinitis pigmentosa. (PMID:22183348)
• NPHP5 mutations impair protein interaction with Cep290 and localize to centrosomes, thereby compromising cilia formation. (PMID:23446637)
• mutation is predicted to introduce a new open reading frame that results in the truncation of the C-terminal 235 amino acids of nephrocystin-5 and its consequent loss of function (PMID:24674142)
• NPHP5 and Cep290 regulate BBSome integrity, ciliary trafficking and cargo delivery. (PMID:25552655)
• High-throughput mutation analysis identified a homozygous truncating mutation (c.1504C>T, p.R502*) in the NPHP5 in 5 families in Iranian children with nephronophthisis. (PMID:25851290)
• that nephrocystin-5 is essential for photoreceptor outer segment formation (PMID:27328943)
• NPHP5-mutant dogs recapitulate the human phenotype of very early loss of rods, and relative retention of the central retinal cone photoreceptors that lack function. (PMID:27506978)
• Dynamic ubiquitination and deubiquitination of NPHP5 plays a crucial role in the regulation of ciliogenesis. NPHP5 directly binds to a deubiquitinating enzyme USP9X/FAM and two E3 ubiquitin ligases BBS11/TRIM32 and MARCH7/axotrophin. (PMID:28498859)
• Study demonstrates the interaction between CNNM4 and IQCB1, which provides the first link between CNNM4 and IQCB1 that causes Leber congenital amaurosis and retinal dystrophy when mutated, providing important insights into the molecular pathogenic mechanisms of retinal dystrophy in Jalili syndrome. (PMID:29322253)
• During ciliogenesis, the mother centriole transforms into a basal body competent to nucleate a cilium. The mother centriole and basal body possess sub-distal appendages (SDAs) and basal feet (BF), respectively. SDAs are distinguishable from BF and the protein NPHP5 is a novel SDA and BF component. NPHP5 regulates BF assembly. (PMID:31177295)
• Cone vision improvement potential in LCA due to CEP290 or NPHP5 mutations is predictable from retinal structure using a machine learning approach. This should allow individual prediction of the maximal efficacy in clinical trials and guide decisions about dosing. (PMID:31212307)
• SENIOR-LOKEN SYNDROME: A Case Series and Review of the Renoretinal Phenotype and Advances of Molecular Diagnosis. (PMID:33512896)
• Genetic variations in the CTLA-4 immune checkpoint pathway are associated with colon cancer risk, prognosis, and immune infiltration via regulation of IQCB1 expression. (PMID:33847778)
• IQCB1 (NPHP5)-Retinopathy: Clinical and Genetic Characterization and Natural History. (PMID:38522724)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	iqcb1	ENSDARG00000093431
danio_rerio	iqcb1	ENSDARG00000101032
mus_musculus	Iqcb1	ENSMUSG00000022837
rattus_norvegicus	Iqcb1	ENSRNOG00000038868

Protein

Protein identifiers

IQ calmodulin-binding motif-containing protein 1 — Q15051 (reviewed: Q15051)

Alternative names: Nephrocystin-5, p53 and DNA damage-regulated IQ motif protein

All UniProt accessions (4): Q15051, C9J6Z7, C9JVC4, C9JXD7

UniProt curated annotations — full annotation on UniProt →

Function. Involved in ciliogenesis. The function in an early step in cilia formation depends on its association with CEP290/NPHP6. 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.

Subunit / interactions. Interacts with CEP290/NPHP6; IQCB1/NPHP5 and CEP290 are proposed to form a functional NPHP5-6 module/NPHP6; localized to the centrosome. Interacts with calmodulin, ATXN10. Interacts with NPHP1, INVS, NPHP4 and RPGRIP1L; these interactions likely require additional interactors. Associates with the BBSome complex; interacts with BBS1, BBS2, BBS4, BBS5, BBS7, BBS8 and BBS9.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole.

Tissue specificity. Ubiquitously expressed in fetal and adult tissues. Localized to the outer segments and connecting cilia of photoreceptor cells. Up-regulated in a number of primary colorectal and gastric tumors.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The gene represented in this entry may be involved in disease pathogenesis.

Domain organisation. The IQ domains mediate the interaction with calmodulin.

Induction. Down-regulated by DNA damage in a p53-dependent manner.

Miscellaneous. Low abundance isoform.

Isoforms (3)

UniProt ID	Names	Canonical?
Q15051-1	1, PIQ-L	yes
Q15051-2	2, PIQ-S
Q15051-3	3

RefSeq proteins (3): NP_001018864, NP_001018865, NP_001306036 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000048	IQ_motif_EF-hand-BS	Binding_site
IPR016024	ARM-type_fold	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR028765	IQCB1	Family

Pfam: PF00612

UniProt features (19 total): domain 4, sequence variant 4, splice variant 3, region of interest 3, chain 1, mutagenesis site 1, sequence conflict 1, coiled-coil region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15051-F1	83.05	0.33

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 572

Mutagenesis-validated functional residues (1):

Position	Phenotype
549	disrupts interaction with cep290, no effect on interaction with bbs1, bbs2, bbs4, bbs8 and bbs9, abolishes ciliogenesis.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-5617833	Cilium Assembly

MSigDB gene sets: 208 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_PHOTORECEPTOR_CELL_MAINTENANCE, GOBP_CILIUM_ORGANIZATION, GOCC_CENTROSOME, GOBP_ORGANELLE_ASSEMBLY, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, TCCAGAG_MIR518C, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, FISCHER_DREAM_TARGETS, GOCC_NEURON_PROJECTION, GOBP_CELL_PROJECTION_ORGANIZATION

GO Biological Process (5): photoreceptor cell maintenance (GO:0045494), maintenance of animal organ identity (GO:0048496), cilium assembly (GO:0060271), cytosolic ciliogenesis (GO:0061824), cell projection organization (GO:0030030)

GO Molecular Function (5): calmodulin binding (GO:0005516), enzyme binding (GO:0019899), protein-macromolecule adaptor activity (GO:0030674), BBSome binding (GO:0062063), protein binding (GO:0005515)

GO Cellular Component (9): photoreceptor outer segment (GO:0001750), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), cilium (GO:0005929), photoreceptor connecting cilium (GO:0032391), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Assembly of the 9+0 primary cilium	1
Organelle biogenesis and maintenance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	3
cellular anatomical structure	3
photoreceptor cell cilium	2
microtubule organizing center	2
intracellular membraneless organelle	2
retina homeostasis	1
multicellular organismal process	1
negative regulation of cell differentiation	1
animal organ development	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
cilium assembly	1
cellular component organization	1
molecular adaptor activity	1
protein-containing complex binding	1
binding	1
centriole	1
cytoplasm	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
ciliary transition zone	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3045 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IQCB1	CEP290	O15078	996
IQCB1	RPGR	Q92834	985
IQCB1	SDCCAG8	Q86SQ7	963
IQCB1	NPHP4	O75161	951
IQCB1	NPHP3	Q7Z494	948
IQCB1	NPHP1	O15259	934
IQCB1	CALML6	Q8TD86	926
IQCB1	CALML3	P27482	926
IQCB1	CALML4	Q96GE6	926
IQCB1	CALML5	Q9NZT1	926
IQCB1	CALM1	P02593	905
IQCB1	RPGRIP1L	Q68CZ1	864
IQCB1	RPGRIP1	Q96KN7	853
IQCB1	ATXN10	Q9UBB4	798
IQCB1	AHI1	Q8N157	795

IntAct

167 interactions, top by confidence:

A	B	Type	Score
IQCB1	CEP290	psi-mi:“MI:2364”(proximity)	0.950
IQCB1	CEP290	psi-mi:“MI:0914”(association)	0.950
IQCB1	CEP290	psi-mi:“MI:0915”(physical association)	0.950
CEP290	IQCB1	psi-mi:“MI:0407”(direct interaction)	0.950
IQCB1	CEP290	psi-mi:“MI:0403”(colocalization)	0.950
RUBCN	BECN1	psi-mi:“MI:0914”(association)	0.920
CEP290	CCP110	psi-mi:“MI:2364”(proximity)	0.890
IQCB1	CALM1	psi-mi:“MI:0915”(physical association)	0.860
IQCB1	CALM1	psi-mi:“MI:0407”(direct interaction)	0.860
CALM1	IQCB1	psi-mi:“MI:0915”(physical association)	0.860
CEP290	CALM1	psi-mi:“MI:0914”(association)	0.810
EXOC1	EXOC5	psi-mi:“MI:0914”(association)	0.730
PEG10	RTL8C	psi-mi:“MI:0914”(association)	0.700
PEG10	RTL8C	psi-mi:“MI:0914”(association)	0.670
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640

BioGRID (350): IQCB1 (Affinity Capture-MS), IQCB1 (Affinity Capture-MS), IQCB1 (Affinity Capture-MS), IQCB1 (Affinity Capture-MS), IQCB1 (Affinity Capture-MS), IQCB1 (Affinity Capture-MS), IQCB1 (Affinity Capture-MS), IQCB1 (Affinity Capture-MS), IQCB1 (Affinity Capture-MS), IQCB1 (Proximity Label-MS), IQCB1 (Proximity Label-MS), IQCB1 (Proximity Label-MS), IQCB1 (Proximity Label-MS), IQCB1 (Proximity Label-MS), IQCB1 (Affinity Capture-MS)

ESM2 similar proteins: A0AUP1, A0JMY4, A3KQH2, D6REC4, E1C760, F1QRC1, F1RKB1, F7AEX0, Q15051, Q17QH9, Q2IA00, Q32KY1, Q3USS3, Q3V079, Q3ZC62, Q45GW3, Q4R6T7, Q4R7Y8, Q4R8R3, Q4R8Y5, Q4V8E4, Q5PQQ6, Q5XI65, Q5XIR6, Q6P0R8, Q6P5U8, Q7T0Y4, Q7Z4T9, Q80VN0, Q8BP00, Q8BRC6, Q8C6E0, Q8C9J3, Q8CDK3, Q8CDV6, Q8HZY8, Q8NA47, Q8NA54, Q8NCU4, Q8ND07

Diamond homologs: Q15051, Q8BP00

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MARCHF7	“down-regulates quantity by destabilization”	IQCB1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 142 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
BBSome-mediated cargo-targeting to cilium	9	47.5×	5e-11
Cargo trafficking to the periciliary membrane	8	21.1×	7e-07
Cilium Assembly	11	12.7×	3e-07
Translocation of SLC2A4 (GLUT4) to the plasma membrane	7	11.5×	3e-04
Organelle biogenesis and maintenance	12	8.4×	3e-06
Anchoring of the basal body to the plasma membrane	7	8.4×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of cytokinesis	7	24.8×	4e-06
non-motile cilium assembly	9	22.0×	1e-07
substantia nigra development	5	15.4×	2e-03
photoreceptor cell maintenance	5	15.1×	2e-03
fat cell differentiation	8	12.2×	8e-05
cilium assembly	16	9.9×	6e-09
cerebral cortex development	5	8.6×	9e-03
intracellular protein localization	8	7.0×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

636 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	54
Likely pathogenic	37
Uncertain significance	274
Likely benign	163
Benign	55

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1073920	NM_001023570.4(IQCB1):c.490del (p.Leu164fs)	Pathogenic
1213855	NM_001023570.4(IQCB1):c.1194G>A (p.Trp398Ter)	Pathogenic
1323120	NM_001023570.4(IQCB1):c.273dup (p.Val92fs)	Pathogenic
1365976	NM_001023570.4(IQCB1):c.729_754del (p.Glu243fs)	Pathogenic
1430806	NM_001023570.4(IQCB1):c.601A>T (p.Arg201Ter)	Pathogenic
1452622	NM_001023570.4(IQCB1):c.178C>T (p.Gln60Ter)	Pathogenic
1453820	NM_001023570.4(IQCB1):c.137T>A (p.Leu46Ter)	Pathogenic
1458659	NM_001023570.4(IQCB1):c.1333C>T (p.Arg445Ter)	Pathogenic
1460277	NC_000003.11:g.(?121526171)(121527876_?)del	Pathogenic
167197	NM_001023570.4(IQCB1):c.1090C>T (p.Arg364Ter)	Pathogenic
167198	NM_001023570.4(IQCB1):c.264-2A>T	Pathogenic
1810217	NM_001023570.4(IQCB1):c.1130-1G>C	Pathogenic
1830	NM_001023570.4(IQCB1):c.1381C>T (p.Arg461Ter)	Pathogenic
1831	NM_001023570.4(IQCB1):c.424_425del (p.Phe142fs)	Pathogenic
1832	NM_001023570.4(IQCB1):c.445_448del (p.Leu149fs)	Pathogenic
1833	NM_001023570.4(IQCB1):c.825_828del (p.Arg275fs)	Pathogenic
1834	NM_001023570.4(IQCB1):c.1069C>T (p.Gln357Ter)	Pathogenic
1953593	NM_001023570.4(IQCB1):c.759C>A (p.Cys253Ter)	Pathogenic
1974656	NM_001023570.4(IQCB1):c.1496del (p.Leu499fs)	Pathogenic
1983358	NM_001023570.4(IQCB1):c.1532_1536dup (p.Gln513Ter)	Pathogenic
2025068	NM_001023570.4(IQCB1):c.1510C>T (p.Gln504Ter)	Pathogenic
2050191	NM_001023570.4(IQCB1):c.1471C>T (p.Gln491Ter)	Pathogenic
2423483	NC_000003.11:g.(?121547297)(121547807_?)del	Pathogenic
2581020	NM_001023570.4(IQCB1):c.1332G>A (p.Trp444Ter)	Pathogenic
2767832	NM_001023570.4(IQCB1):c.823dup (p.Arg275fs)	Pathogenic
2852719	NM_001023570.4(IQCB1):c.1314_1315delinsCT (p.Lys438_Lys439delinsAsnTer)	Pathogenic
285623	NM_001023570.4(IQCB1):c.214C>T (p.Arg72Ter)	Pathogenic
2910173	NM_001023570.4(IQCB1):c.493C>T (p.Gln165Ter)	Pathogenic
30776	NM_001023570.4(IQCB1):c.333del (p.Ala112fs)	Pathogenic
30778	NM_001023570.4(IQCB1):c.1465C>T (p.Arg489Ter)	Pathogenic

SpliceAI

1790 predictions. Top by Δscore:

Variant	Effect	Δscore
3:121772555:A:AC	donor_gain	1.0000
3:121772556:C:CC	donor_gain	1.0000
3:121772556:CT:C	donor_gain	1.0000
3:121772559:ATTAG:A	donor_gain	1.0000
3:121772560:T:C	donor_gain	1.0000
3:121772563:G:C	donor_gain	1.0000
3:121772712:CC:C	acceptor_gain	1.0000
3:121772713:CC:C	acceptor_gain	1.0000
3:121781737:TCATA:T	donor_loss	1.0000
3:121781738:CATA:C	donor_loss	1.0000
3:121781739:ATACC:A	donor_loss	1.0000
3:121781740:TA:T	donor_loss	1.0000
3:121781741:A:AC	donor_gain	1.0000
3:121781741:A:AG	donor_loss	1.0000
3:121781742:C:CA	donor_loss	1.0000
3:121781742:C:CC	donor_gain	1.0000
3:121781870:AGCGC:A	acceptor_gain	1.0000
3:121781871:GCGC:G	acceptor_gain	1.0000
3:121781872:CGC:C	acceptor_gain	1.0000
3:121781872:CGCC:C	acceptor_gain	1.0000
3:121781873:GC:G	acceptor_gain	1.0000
3:121781873:GCC:G	acceptor_loss	1.0000
3:121781874:CC:C	acceptor_gain	1.0000
3:121781874:CCT:C	acceptor_loss	1.0000
3:121781875:C:CC	acceptor_gain	1.0000
3:121781876:T:A	acceptor_loss	1.0000
3:121790069:TCA:T	donor_loss	1.0000
3:121790070:CA:C	donor_loss	1.0000
3:121790071:A:AC	donor_gain	1.0000
3:121790072:C:CC	donor_gain	1.0000

AlphaMissense

3914 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:121795536:C:G	A303P	0.981
3:121770449:A:G	W565R	0.979
3:121770449:A:T	W565R	0.979
3:121770522:A:C	S540R	0.977
3:121770522:A:T	S540R	0.977
3:121770524:T:G	S540R	0.977
3:121795510:T:A	R311S	0.973
3:121795510:T:G	R311S	0.973
3:121828560:A:G	L58P	0.971
3:121770452:A:G	W564R	0.970
3:121770452:A:T	W564R	0.970
3:121826180:G:C	S88R	0.968
3:121826180:G:T	S88R	0.968
3:121828471:T:G	S88R	0.968
3:121770497:C:G	A549P	0.965
3:121828485:A:G	L83P	0.963
3:121770447:C:A	W565C	0.961
3:121770447:C:G	W565C	0.961
3:121795530:A:G	W305R	0.961
3:121795530:A:T	W305R	0.961
3:121826135:A:C	F103L	0.961
3:121826135:A:T	F103L	0.961
3:121826137:A:G	F103L	0.961
3:121795459:G:C	F328L	0.958
3:121795459:G:T	F328L	0.958
3:121795461:A:G	F328L	0.958
3:121828920:G:T	A14D	0.957
3:121795493:A:G	L317P	0.954
3:121808948:A:G	L152P	0.952
3:121772562:A:G	L521P	0.950

dbSNP variants (sampled 300 via entrez): RS1000125745 (3:121825953 A>G,T), RS1000156817 (3:121811004 T>C), RS1000183427 (3:121814993 T>C), RS1000204177 (3:121773886 A>C), RS1000224279 (3:121784316 G>A), RS1000318120 (3:121814633 T>A), RS1000350069 (3:121801326 A>G), RS1000357612 (3:121770786 G>A), RS1000371650 (3:121771386 T>C), RS1000443096 (3:121803025 A>G), RS1000453261 (3:121797640 G>C), RS1000458930 (3:121808021 GA>G), RS1000507268 (3:121794254 T>C), RS1000581483 (3:121789213 C>T), RS1000708659 (3:121836725 G>A,C,T)

Disease associations

OMIM: gene MIM:609237 | disease phenotypes: MIM:256100, MIM:609254, MIM:204000, MIM:266900, MIM:268000, MIM:209900

GenCC curated gene-disease

Disease	Classification	Inheritance
Senior-Loken syndrome 5	Definitive	Autosomal recessive
Senior-Loken syndrome	Supportive	Autosomal recessive
Leber congenital amaurosis	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
ciliopathy	Definitive	AR

Mondo (8): nephronophthisis (MONDO:0019005), Senior-Loken syndrome 5 (MONDO:0012225), Leber congenital amaurosis (MONDO:0018998), Senior-Loken syndrome (MONDO:0017842), inherited retinal dystrophy (MONDO:0019118), retinal disorder (MONDO:0005283), retinitis pigmentosa (MONDO:0019200), Bardet-Biedl syndrome (MONDO:0015229)

Orphanet (6): Nephronophthisis (Orphanet:655), Senior-Loken syndrome (Orphanet:3156), Leber congenital amaurosis (Orphanet:65), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791), Bardet-Biedl syndrome (Orphanet:110)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000090	Nephronophthisis
HP:0000365	Hearing impairment
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract
HP:0000529	Progressive visual loss
HP:0000540	Hypermetropia
HP:0000543	Optic disc pallor
HP:0000556	Retinal dystrophy
HP:0000563	Keratoconus
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000729	Autistic behavior
HP:0000822	Hypertension
HP:0001141	Severely reduced visual acuity
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001483	Eye poking
HP:0002084	Encephalocele
HP:0002269	Abnormality of neuronal migration
HP:0002612	Congenital hepatic fibrosis
HP:0003774	Stage 5 chronic kidney disease
HP:0004322	Short stature
HP:0004348	Abnormality of bone mineral density

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005531_111	Multiple sclerosis	7.000000e-22
GCST007122_3	Multiple sclerosis and triglyceride levels (pleiotropy)	7.000000e-08
GCST009597_16	Multiple sclerosis	5.000000e-20
GCST010083_30	Hemoglobin levels	8.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004509	hemoglobin measurement

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D020788	Bardet-Biedl Syndrome	C10.228.140.617.200; C11.270.684.624; C16.131.077.245.125; C16.320.184.125
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C537580	Senior Loken Syndrome (supp.)
C563763	Senior-Loken Syndrome 5 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	3
Cyclosporine	increases expression	3
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
K 7174	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases expression, increases abundance	1
Calcitriol	increases expression	1
Cisplatin	increases expression	1
Methyl Methanesulfonate	increases expression	1
Phenobarbital	affects expression	1
Piroxicam	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Selenium	decreases expression, affects cotreatment	1
Dihydrotestosterone	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Vanadates	decreases expression	1
Vitamin E	affects cotreatment, decreases expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	increases expression, increases abundance	1

Clinical trials (associated diseases)

286 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00999609	PHASE3	ACTIVE_NOT_RECRUITING	Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis
NCT06891443	PHASE3	RECRUITING	Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT01373476	PHASE2	COMPLETED	Multicentre, Randomized, Controlled Trial of Qideng Mingmu Capsule in The Treatment of Diabetic Retinopathy
NCT01793090	PHASE2	COMPLETED	EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene