Senior-Boichis syndrome

Summary

Senior-Boichis syndrome (MONDO:0019394) is a disease with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 2
• Phenotypes (HPO): 34

Clinical features

Signs & symptoms

Clinical features (HPO)

34 HPO clinical features (Orphanet curated; top 34 by frequency):

HPO ID	Term	Frequency
HP:0000089	Renal hypoplasia	Frequent (30-79%)
HP:0000108	Renal corticomedullary cysts	Frequent (30-79%)
HP:0000822	Hypertension	Frequent (30-79%)
HP:0001395	Hepatic fibrosis	Frequent (30-79%)
HP:0001396	Cholestasis	Frequent (30-79%)
HP:0001409	Portal hypertension	Frequent (30-79%)
HP:0001433	Hepatosplenomegaly	Frequent (30-79%)
HP:0001959	Polydipsia	Frequent (30-79%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Frequent (30-79%)
HP:0003155	Elevated circulating alkaline phosphatase concentration	Frequent (30-79%)
HP:0003573	Increased total bilirubin	Frequent (30-79%)
HP:0004719	Hyperechogenic kidneys	Frequent (30-79%)
HP:0005565	Reduced renal corticomedullary differentiation	Frequent (30-79%)
HP:0006563	Malformation of the hepatic ductal plate	Frequent (30-79%)
HP:0006571	Reduced number of intrahepatic bile ducts	Frequent (30-79%)
HP:0012591	Abnormal urinary electrolyte concentration	Frequent (30-79%)
HP:0012622	Chronic kidney disease	Frequent (30-79%)
HP:0020132	Thickening of the tubular basement membrane	Frequent (30-79%)
HP:0032581	Abnormal renal insterstitial morphology	Frequent (30-79%)
HP:0032622	Tubular luminal dilatation	Frequent (30-79%)
HP:0000713	Agitation	Occasional (5-29%)
HP:0000718	Aggressive behavior	Occasional (5-29%)
HP:0001394	Cirrhosis	Occasional (5-29%)
HP:0001541	Ascites	Occasional (5-29%)
HP:0001903	Anemia	Occasional (5-29%)
HP:0002040	Esophageal varix	Occasional (5-29%)
HP:0002500	Abnormal cerebral white matter morphology	Occasional (5-29%)
HP:0002506	Diffuse cerebral atrophy	Occasional (5-29%)
HP:0002612	Congenital hepatic fibrosis	Occasional (5-29%)
HP:0003774	Stage 5 chronic kidney disease	Occasional (5-29%)
HP:0007018	Attention deficit hyperactivity disorder	Occasional (5-29%)
HP:0012163	Carotid artery dilatation	Occasional (5-29%)
HP:0012585	Renal atrophy	Occasional (5-29%)
HP:0031589	Suicidal ideation	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Senior-Boichis syndrome
Mondo ID	MONDO:0019394
Orphanet	84081
SNOMED CT	717187000
UMLS	C4274018
MedGen	902988
GARD	0016730
Is cancer (heuristic)	no

Also known as: Boichis disease · nephronophthisis-hepatic fibrosis syndrome

Data availability: 2 GenCC gene-disease records.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › renal tubule disorder › inherited renal tubular disease › Senior-Boichis syndrome

Related subtypes (27): cranioectodermal dysplasia, cystinuria, hereditary renal hypouricemia, nephrogenic diabetes insipidus-intracranial calcification syndrome, Gitelman syndrome, nephrogenic syndrome of inappropriate antidiuresis, oculocerebrorenal syndrome, RHYNS syndrome, renal tubular acidosis, distal, 3, with or without sensorineural hearing loss, autosomal recessive proximal renal tubular acidosis, EAST syndrome, familial juvenile hyperuricemic nephropathy type 2, hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome, Bartter syndrome, Dent disease, nephrogenic diabetes insipidus, autosomal dominant proximal renal tubular acidosis, Senior-Loken syndrome, familial primary hypomagnesemia, mitochondrial DNA depletion syndrome, hepatocerebrorenal form, Jeune syndrome, nephronophthisis, pseudohypoaldosteronism type 1, pseudohypoparathyroidism, psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome, HELIX syndrome, inherited Fanconi renotubular syndrome

Subtypes (1): nephronophthisis 11

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 27 · Orphanet: 8 · 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
DCDC2	Supportive	Autosomal recessive	Senior-Boichis syndrome	14
TMEM67	Supportive	Autosomal recessive	Senior-Boichis syndrome	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DCDC2	Orphanet:480556	Isolated neonatal sclerosing cholangitis
DCDC2	Orphanet:84081	Senior-Boichis syndrome
DCDC2	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
TMEM67	Orphanet:140976	RHYNS syndrome
TMEM67	Orphanet:1454	Joubert syndrome with hepatic defect
TMEM67	Orphanet:475	Isolated Joubert syndrome
TMEM67	Orphanet:564	Meckel syndrome
TMEM67	Orphanet:84081	Senior-Boichis syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DCDC2	HGNC:18141	ENSG00000146038	Q9UHG0	Doublecortin domain-containing protein 2	gencc
TMEM67	HGNC:28396	ENSG00000164953	Q5HYA8	Meckelin	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DCDC2	Doublecortin domain-containing protein 2	Protein that plays a role in the inhibition of canonical Wnt signaling pathway.
TMEM67	Meckelin	Required for ciliary structure and function.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DCDC2	Other/Unknown	no		Doublecortin_dom, DCDC2_DCX_dom2, Doublecortin_dom_sf
TMEM67	Other/Unknown	no		Growth_fac_rcpt_cys_sf, Meckelin

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	1
oviduct epithelium	1
secondary oocyte	1
buccal mucosa cell	1
calcaneal tendon	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DCDC2	156	broad	marker	secondary oocyte, oocyte, oviduct epithelium
TMEM67	203	ubiquitous	marker	buccal mucosa cell, right uterine tube, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TMEM67	1,194
DCDC2	1,025

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DCDC2	Q9UHG0	1
TMEM67	Q5HYA8	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 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	TMEM67
Cilium Assembly	1	108.8×	0.014	TMEM67
Organelle biogenesis and maintenance	1	66.0×	0.015	TMEM67

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cilium assembly	2	73.6×	0.002	DCDC2, TMEM67
negative regulation of centrosome duplication	1	1685.2×	0.004	TMEM67
regulation of Wnt signaling pathway	1	443.5×	0.008	DCDC2
regulation of cilium assembly	1	300.9×	0.008	DCDC2
non-canonical Wnt signaling pathway	1	290.6×	0.008	TMEM67
dendrite morphogenesis	1	216.1×	0.008	DCDC2
positive regulation of smoothened signaling pathway	1	210.7×	0.008	DCDC2
cellular defense response	1	159.0×	0.009	DCDC2
ERAD pathway	1	90.6×	0.015	TMEM67
neuron migration	1	66.9×	0.018	DCDC2
sensory perception of sound	1	50.5×	0.022	DCDC2
intracellular signal transduction	1	19.1×	0.052	DCDC2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
DCDC2	0	0
TMEM67	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	DCDC2, TMEM67

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DCDC2	0	—
TMEM67	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.