Senior-Loken syndrome 9

Summary

Senior-Loken syndrome 9 (MONDO:0014712) is a disease caused by IFT54 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: IFT54 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 21

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Senior-Loken syndrome 9
Mondo ID	MONDO:0014712
OMIM	616629
DOID	DOID:0061283
UMLS	C4225263
MedGen	899086
GARD	0016145
Is cancer (heuristic)	no

Also known as: Senior-Loken syndrome 9 · Senior-Loken syndrome 9; SLSN9 · Senior-Loken syndrome caused by mutation in TRAF3IP1 · Senior-Loken syndrome type 9 · SLSN9 · TRAF3IP1 Senior-Loken syndrome

Data availability: 21 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 9

Related subtypes (8): Senior-Loken syndrome 1, senior-loken syndrome 3, Senior-Loken syndrome 4, Senior-Loken syndrome 5, Senior-Loken syndrome 6, Senior-Loken syndrome 7, nephronophthisis 15, Senior-Loken syndrome 8

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

21 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 4 pathogenic, 3 conflicting classifications of pathogenicity, 2 pathogenic/likely pathogenic, 1 benign, 1 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
837046	NC_000002.12:g.238332824_238332827del	IFT54	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
254146	NM_015650.4(TRAF3IP1):c.463C>T (p.Arg155Ter)	TRAF3IP1	Pathogenic	criteria provided, single submitter
254148	NM_015650.4(TRAF3IP1):c.1575+6T>G	TRAF3IP1	Pathogenic	no assertion criteria provided
254149	NM_015650.4(TRAF3IP1):c.373G>A (p.Val125Met)	TRAF3IP1	Pathogenic	no assertion criteria provided
254150	NM_015650.4(TRAF3IP1):c.51T>G (p.Ile17Met)	TRAF3IP1	Pathogenic	no assertion criteria provided
3235031	NM_015650.4(TRAF3IP1):c.551_554del (p.Gln184fs)	TRAF3IP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4077701	NM_015650.4(TRAF3IP1):c.761dup (p.Lys257fs)	TRAF3IP1	Likely pathogenic	criteria provided, single submitter
254147	NM_015650.4(IFT54):c.1559T>G (p.Met520Arg)	IFT54	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
446657	NM_015650.4(IFT54):c.1368-1del	IFT54	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1054876	NM_015650.4(TRAF3IP1):c.436T>C (p.Ser146Pro)	TRAF3IP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1013755	NM_015650.4(TRAF3IP1):c.1408C>T (p.Arg470Trp)	TRAF3IP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1027992	NM_015650.4(TRAF3IP1):c.152G>A (p.Gly51Asp)	TRAF3IP1	Uncertain significance	criteria provided, single submitter
1041743	NM_015650.4(TRAF3IP1):c.811C>T (p.Arg271Trp)	TRAF3IP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1492301	NM_015650.4(TRAF3IP1):c.1763C>T (p.Thr588Met)	TRAF3IP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1523605	NM_015650.4(TRAF3IP1):c.1064G>A (p.Gly355Glu)	TRAF3IP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2437221	NM_015650.4(TRAF3IP1):c.812G>A (p.Arg271Gln)	TRAF3IP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
254145	NM_015650.4(TRAF3IP1):c.374T>C (p.Val125Ala)	TRAF3IP1	Uncertain significance	criteria provided, single submitter
951276	NM_015650.4(TRAF3IP1):c.88C>T (p.Pro30Ser)	TRAF3IP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
959623	NM_015650.4(TRAF3IP1):c.685G>A (p.Glu229Lys)	TRAF3IP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1168003	NM_015650.4(TRAF3IP1):c.69C>A (p.Thr23=)	TRAF3IP1	Benign	criteria provided, multiple submitters, no conflicts
773666	NM_015650.4(TRAF3IP1):c.1282+8A>T	TRAF3IP1	Benign/Likely benign	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
IFT54	Definitive	Autosomal recessive	Senior-Loken syndrome 9	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IFT54	Orphanet:3156	Senior-Loken syndrome
IFT54	Orphanet:93269	Short rib-polydactyly syndrome, Majewski type

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
IFT54	HGNC:17861	ENSG00000204104	Q8TDR0	TRAF3-interacting protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IFT54	TRAF3-interacting protein 1	Plays an inhibitory role on IL13 signaling by binding to IL13RA1.

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)
IFT54	Other/Unknown	no		TRAF3IP1, TRAF3IP1_N, TRAF3IP1_C

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
bronchial epithelial cell	1
oocyte	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IFT54	265	ubiquitous	marker	oocyte, bronchial epithelial cell, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IFT54	1,363

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IFT54	Q8TDR0	2

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
Intraflagellar transport	1	200.3×	0.014	IFT54
Cilium Assembly	1	108.8×	0.014	IFT54
Organelle biogenesis and maintenance	1	66.0×	0.015	IFT54

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
morphogenesis of a polarized epithelium	1	4213.0×	0.003	IFT54
negative regulation of defense response to virus	1	1296.3×	0.003	IFT54
embryonic camera-type eye development	1	1203.7×	0.003	IFT54
negative regulation of interferon-beta production	1	1053.2×	0.003	IFT54
intraciliary anterograde transport	1	887.0×	0.003	IFT54
dorsal/ventral neural tube patterning	1	802.5×	0.003	IFT54
embryonic heart tube development	1	766.0×	0.003	IFT54
post-anal tail morphogenesis	1	732.7×	0.003	IFT54
negative regulation of protein phosphorylation	1	581.1×	0.003	IFT54
intraciliary transport	1	561.7×	0.003	IFT54
regulation of microtubule cytoskeleton organization	1	543.6×	0.003	IFT54
negative regulation of type I interferon production	1	495.6×	0.003	IFT54
negative regulation of protein-containing complex assembly	1	455.5×	0.003	IFT54
negative regulation of smoothened signaling pathway	1	455.5×	0.003	IFT54
embryonic digit morphogenesis	1	300.9×	0.004	IFT54
kidney development	1	140.4×	0.008	IFT54
cilium assembly	1	73.6×	0.014	IFT54
defense response to virus	1	69.3×	0.014	IFT54

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
IFT54	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	IFT54

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)
IFT54	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.