Senior-Loken syndrome 5

Summary

Senior-Loken syndrome 5 (MONDO:0012225) is a disease caused by IQCB1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: IQCB1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 219

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Senior-Loken syndrome 5
Mondo ID	MONDO:0012225
MeSH	C563763
OMIM	609254
DOID	DOID:0061279
UMLS	C1836517
MedGen	332226
GARD	0015451
Is cancer (heuristic)	no

Also known as: IQCB1 Senior-Loken syndrome · Senior-Loken syndrome 5 · Senior-Loken syndrome caused by mutation in IQCB1 · Senior-Loken syndrome type 5 · SLSN5

Data availability: 219 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › ciliopathy › Senior-Loken syndrome › Senior-Loken syndrome 5

Related subtypes (8): Senior-Loken syndrome 1, senior-loken syndrome 3, Senior-Loken syndrome 4, Senior-Loken syndrome 6, Senior-Loken syndrome 7, nephronophthisis 15, Senior-Loken syndrome 8, Senior-Loken syndrome 9

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

219 retrieved; paginated sample, class counts are floors:

115 uncertain significance, 29 likely pathogenic, 28 pathogenic, 16 conflicting classifications of pathogenicity, 10 likely benign, 8 benign, 7 pathogenic/likely pathogenic, 6 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1361531	NM_001023570.4(IQCB1):c.757del (p.Cys253fs)	IQCB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458659	NM_001023570.4(IQCB1):c.1333C>T (p.Arg445Ter)	IQCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
156379	NM_001023570.4(IQCB1):c.1522_1523dup (p.Ala509fs)	IQCB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
167197	NM_001023570.4(IQCB1):c.1090C>T (p.Arg364Ter)	IQCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
167198	NM_001023570.4(IQCB1):c.264-2A>T	IQCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
1830	NM_001023570.4(IQCB1):c.1381C>T (p.Arg461Ter)	IQCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
1831	NM_001023570.4(IQCB1):c.424_425del (p.Phe142fs)	IQCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
1832	NM_001023570.4(IQCB1):c.445_448del (p.Leu149fs)	IQCB1	Pathogenic	no assertion criteria provided
1833	NM_001023570.4(IQCB1):c.825_828del (p.Arg275fs)	IQCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
1834	NM_001023570.4(IQCB1):c.1069C>T (p.Gln357Ter)	IQCB1	Pathogenic	no assertion criteria provided
1983358	NM_001023570.4(IQCB1):c.1532_1536dup (p.Gln513Ter)	IQCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
199049	NM_001023570.4(IQCB1):c.817G>T (p.Glu273Ter)	IQCB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2581020	NM_001023570.4(IQCB1):c.1332G>A (p.Trp444Ter)	IQCB1	Pathogenic	criteria provided, single submitter
285623	NM_001023570.4(IQCB1):c.214C>T (p.Arg72Ter)	IQCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
2910173	NM_001023570.4(IQCB1):c.493C>T (p.Gln165Ter)	IQCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
2955923	NM_001023570.4(IQCB1):c.100G>T (p.Glu34Ter)	IQCB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
30776	NM_001023570.4(IQCB1):c.333del (p.Ala112fs)	IQCB1	Pathogenic	no assertion criteria provided
30778	NM_001023570.4(IQCB1):c.1465C>T (p.Arg489Ter)	IQCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
30779	NM_001023570.4(IQCB1):c.1036G>T (p.Glu346Ter)	IQCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
3235246	NM_001023570.4(IQCB1):c.507dup (p.His171fs)	IQCB1	Pathogenic	criteria provided, single submitter
3241773	NM_001023570.4(IQCB1):c.814C>T (p.Gln272Ter)	IQCB1	Pathogenic	criteria provided, single submitter
3241775	NM_001023570.4(IQCB1):c.1342C>T (p.Gln448Ter)	IQCB1	Pathogenic	criteria provided, single submitter
3241776	NM_001023570.4(IQCB1):c.263+201del	IQCB1	Pathogenic	criteria provided, single submitter
3241779	NM_001023570.4(IQCB1):c.479_482del (p.Ile160fs)	IQCB1	Pathogenic	criteria provided, single submitter
403963	NM_001023570.4(IQCB1):c.897_900dup (p.Ile301fs)	IQCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
4530577	NM_001023570.4(IQCB1):c.394-2A>G	IQCB1	Pathogenic	criteria provided, single submitter
504877	NM_001023570.4(IQCB1):c.1363C>T (p.Arg455Ter)	IQCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
560468	NM_001023570.4(IQCB1):c.994C>T (p.Arg332Ter)	IQCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
569196	NM_001023570.4(IQCB1):c.1504C>T (p.Arg502Ter)	IQCB1	Pathogenic	criteria provided, multiple submitters, no conflicts
812120	NM_001023570.4(IQCB1):c.488-1G>A	IQCB1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
IQCB1	Definitive	Autosomal recessive	Senior-Loken syndrome 5	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IQCB1	Orphanet:3156	Senior-Loken syndrome
IQCB1	Orphanet:65	Leber congenital amaurosis

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
IQCB1	HGNC:28949	ENSG00000173226	Q15051	IQ calmodulin-binding motif-containing protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IQCB1	IQ calmodulin-binding motif-containing protein 1	Involved in ciliogenesis.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IQCB1	Other/Unknown	no		IQ_motif_EF-hand-BS, ARM-type_fold, P-loop_NTPase

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
epithelium of nasopharynx	1
nasopharynx	1
oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IQCB1	275	ubiquitous	marker	oocyte, epithelium of nasopharynx, nasopharynx

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IQCB1	3,562

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IQCB1	Q15051	83.05

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Anchoring of the basal body to the plasma membrane	1	113.1×	0.014	IQCB1
Cilium Assembly	1	108.8×	0.014	IQCB1
Organelle biogenesis and maintenance	1	66.0×	0.015	IQCB1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
maintenance of animal organ identity	1	3370.4×	6e-04	IQCB1
cytosolic ciliogenesis	1	3370.4×	6e-04	IQCB1
photoreceptor cell maintenance	1	358.6×	0.004	IQCB1
cilium assembly	1	73.6×	0.014	IQCB1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
IQCB1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	IQCB1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
IQCB1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.