Senior-Loken syndrome 4
disease diseaseOn this page
Also known as NPHP4 Senior-Loken syndromeSenior-Loken syndrome caused by mutation in NPHP4Senior-Loken syndrome type 4SLSN4
Summary
Senior-Loken syndrome 4 (MONDO:0011756) is a disease caused by NPHP4 (GenCC Definitive), with 1 cohort gene.
At a glance
- Causal gene: NPHP4 (GenCC Definitive)
- Cohort genes: 1
- ClinVar variants: 563
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | Senior-Loken syndrome 4 |
| Mondo ID | MONDO:0011756 |
| MeSH | C537581 |
| OMIM | 606996 |
| DOID | DOID:0061278 |
| UMLS | C1846979 |
| MedGen | 337697 |
| GARD | 0015406 |
| Is cancer (heuristic) | no |
Also known as: NPHP4 Senior-Loken syndrome · Senior-Loken syndrome 4 · Senior-Loken syndrome caused by mutation in NPHP4 · Senior-Loken syndrome type 4 · SLSN4
Data availability: 563 ClinVar variants · 2 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 4
Related subtypes (8): Senior-Loken syndrome 1, senior-loken syndrome 3, Senior-Loken syndrome 5, 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
563 retrieved; paginated sample, class counts are floors:
359 uncertain significance, 84 conflicting classifications of pathogenicity, 29 likely benign, 26 benign/likely benign, 21 likely pathogenic, 20 pathogenic/likely pathogenic, 16 benign, 8 pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1068634 | NM_015102.5(NPHP4):c.3083del (p.Gly1028fs) | NPHP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1072607 | NM_015102.5(NPHP4):c.2908dup (p.Leu970fs) | NPHP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1073618 | NM_015102.5(NPHP4):c.1271del (p.Lys424fs) | NPHP4 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1179132 | NM_015102.5(NPHP4):c.3644+1G>T | NPHP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1387867 | NM_015102.5(NPHP4):c.3773_3776del (p.Val1258fs) | NPHP4 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1388969 | NM_015102.5(NPHP4):c.3368_3369del (p.Val1123fs) | NPHP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1433031 | NM_015102.5(NPHP4):c.2007del (p.Phe670fs) | NPHP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1694483 | NM_015102.5(NPHP4):c.3506del (p.Pro1169fs) | NPHP4 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 2156394 | NM_015102.5(NPHP4):c.3418G>T (p.Glu1140Ter) | NPHP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2719506 | NM_015102.5(NPHP4):c.3148del (p.Gln1050fs) | NPHP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2872668 | NM_015102.5(NPHP4):c.1692_1704del (p.Ala565fs) | NPHP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3403 | NM_015102.5(NPHP4):c.3272del (p.Val1091fs) | NPHP4 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 3404 | NM_015102.5(NPHP4):c.2335C>T (p.Gln779Ter) | NPHP4 | Pathogenic | no assertion criteria provided |
| 3405 | NM_015102.5(NPHP4):c.1972C>T (p.Arg658Ter) | NPHP4 | Pathogenic | criteria provided, single submitter |
| 3586786 | NM_015102.5(NPHP4):c.1843C>T (p.Gln615Ter) | NPHP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3587242 | NM_015102.5(NPHP4):c.111G>A (p.Trp37Ter) | NPHP4 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 498434 | NM_015102.5(NPHP4):c.2011C>T (p.Gln671Ter) | NPHP4 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 503803 | NM_015102.5(NPHP4):c.1421_1423delinsCGTGG (p.Lys474fs) | NPHP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 562355 | NM_015102.5(NPHP4):c.133C>T (p.Gln45Ter) | NPHP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 562366 | NM_015102.5(NPHP4):c.1889_1892del (p.Pro630fs) | NPHP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 595124 | NM_015102.5(NPHP4):c.2611+1G>A | NPHP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 596144 | NM_015102.5(NPHP4):c.1357G>T (p.Glu453Ter) | NPHP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 598365 | NM_015102.5(NPHP4):c.3409_3412del (p.Tyr1137fs) | NPHP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 639470 | NM_015102.5(NPHP4):c.3325C>T (p.Arg1109Ter) | NPHP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 867163 | NM_015102.5(NPHP4):c.3644+1G>A | NPHP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 931168 | NM_015102.5(NPHP4):c.12G>A (p.Trp4Ter) | NPHP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 943026 | NM_015102.5(NPHP4):c.834_841del (p.Ala279fs) | NPHP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 956880 | NM_015102.5(NPHP4):c.1585_1586del (p.Gly529fs) | NPHP4 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1030411 | NM_015102.5(NPHP4):c.3490_3491delinsA (p.Leu1164fs) | NPHP4 | Likely pathogenic | criteria provided, single submitter |
| 1179061 | NM_015102.5(NPHP4):c.1504-1G>A | NPHP4 | Likely pathogenic | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 9 · 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 |
|---|---|---|---|---|
| NPHP4 | Definitive | Autosomal recessive | Senior-Loken syndrome 4 | 9 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| NPHP4 | Orphanet:3156 | Senior-Loken syndrome |
| NPHP4 | Orphanet:93592 | Juvenile nephronophthisis |
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 |
|---|---|---|---|---|---|
| NPHP4 | HGNC:19104 | ENSG00000131697 | O75161 | Nephrocystin-4 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| NPHP4 | Nephrocystin-4 | Involved in the organization of apical junctions; the function is proposed to implicate a NPHP1-4-8 module. |
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) |
|---|---|---|---|---|
| NPHP4 | Other/Unknown | no | NPHP4, Ig_NPHP4_4th, Ig_NPHP4_3rd |
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 |
|---|---|
| adenohypophysis | 1 |
| right lobe of thyroid gland | 1 |
| right uterine tube | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| NPHP4 | 165 | ubiquitous | marker | right uterine tube, adenohypophysis, right lobe of thyroid gland |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| NPHP4 | 1,579 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| NPHP4 | O75161 | 72.44 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 2. 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 |
|---|---|---|---|---|
| Signaling by Hippo | 1 | 543.8× | 0.004 | NPHP4 |
| Anchoring of the basal body to the plasma membrane | 1 | 113.1× | 0.009 | NPHP4 |
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 |
|---|---|---|---|---|
| visual behavior | 1 | 2808.7× | 0.002 | NPHP4 |
| protein localization to ciliary transition zone | 1 | 2407.4× | 0.002 | NPHP4 |
| positive regulation of bicellular tight junction assembly | 1 | 1685.2× | 0.002 | NPHP4 |
| photoreceptor cell outer segment organization | 1 | 1053.2× | 0.003 | NPHP4 |
| photoreceptor cell maintenance | 1 | 358.6× | 0.006 | NPHP4 |
| retina development in camera-type eye | 1 | 255.3× | 0.007 | NPHP4 |
| negative regulation of canonical Wnt signaling pathway | 1 | 117.8× | 0.012 | NPHP4 |
| flagellated sperm motility | 1 | 117.0× | 0.012 | NPHP4 |
| cell-cell adhesion | 1 | 101.5× | 0.012 | NPHP4 |
| actin cytoskeleton organization | 1 | 79.1× | 0.014 | NPHP4 |
| signal transduction | 1 | 16.1× | 0.062 | NPHP4 |
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 |
|---|---|---|
| NPHP4 | 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 | NPHP4 |
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) |
|---|---|---|
| NPHP4 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: NPHP4