COACH syndrome 3

Summary

COACH syndrome 3 (MONDO:0030862) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 359

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	COACH syndrome 3
Mondo ID	MONDO:0030862
OMIM	619113
UMLS	C5436841
MedGen	1755565
GARD	0016423
Is cancer (heuristic)	no

Also known as: COACH3

Data availability: 359 ClinVar variants.

Disease family

Classification path: human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive cerebellar ataxia › autosomal recessive congenital cerebellar ataxia › Joubert syndrome and related disorders › COACH syndrome › COACH syndrome 3

Related subtypes (2): COACH syndrome 2, COACH syndrome 1

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

359 retrieved; paginated sample, class counts are floors:

207 uncertain significance, 50 pathogenic/likely pathogenic, 35 likely pathogenic, 28 conflicting classifications of pathogenicity, 25 likely benign, 7 pathogenic, 6 benign/likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069	NM_015272.5(RPGRIP1L):c.1843A>C (p.Thr615Pro)	RPGRIP1L	Pathogenic	criteria provided, multiple submitters, no conflicts
1069014	NM_015272.5(RPGRIP1L):c.2432del (p.Pro811fs)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069456	NM_015272.5(RPGRIP1L):c.3607del (p.Tyr1203fs)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070	NM_015272.5(RPGRIP1L):c.757C>T (p.Gln253Ter)	RPGRIP1L	Pathogenic	criteria provided, multiple submitters, no conflicts
1071109	NM_015272.5(RPGRIP1L):c.170T>A (p.Leu57Ter)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071183	NM_015272.5(RPGRIP1L):c.2149_2152del (p.Ile717fs)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071605	NM_015272.5(RPGRIP1L):c.1645G>T (p.Glu549Ter)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071757	NM_015272.5(RPGRIP1L):c.1372G>T (p.Glu458Ter)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072021	NM_015272.5(RPGRIP1L):c.772C>T (p.Gln258Ter)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072712	NM_015272.5(RPGRIP1L):c.2093T>G (p.Leu698Ter)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074	NM_015272.5(RPGRIP1L):c.2614C>T (p.Gln872Ter)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076	NM_015272.5(RPGRIP1L):c.2050C>T (p.Gln684Ter)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1079	NM_015272.5(RPGRIP1L):c.2413C>T (p.Arg805Ter)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1080	NM_015272.5(RPGRIP1L):c.1975T>C (p.Ser659Pro)	RPGRIP1L	Pathogenic	criteria provided, single submitter
1185043	NM_015272.5(RPGRIP1L):c.1351-11A>G	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1358982	NM_015272.5(RPGRIP1L):c.1171C>T (p.Gln391Ter)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1442552	NM_015272.5(RPGRIP1L):c.1978C>T (p.Gln660Ter)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1446214	NM_015272.5(RPGRIP1L):c.2493del (p.Ser832fs)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451391	NM_015272.5(RPGRIP1L):c.599T>G (p.Leu200Ter)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451910	NM_015272.5(RPGRIP1L):c.1608_1614del (p.Met537fs)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1453353	NM_015272.5(RPGRIP1L):c.71dup (p.Met24fs)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454714	NM_015272.5(RPGRIP1L):c.2591_2592del (p.Tyr864fs)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1456256	NM_015272.5(RPGRIP1L):c.1959del (p.Glu654fs)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457129	NM_015272.5(RPGRIP1L):c.2451C>A (p.Tyr817Ter)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1459489	NM_015272.5(RPGRIP1L):c.2239C>T (p.Arg747Ter)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188192	NM_015272.5(RPGRIP1L):c.1709dup (p.Asp571fs)	RPGRIP1L	Pathogenic	criteria provided, multiple submitters, no conflicts
1896983	NM_015272.5(RPGRIP1L):c.3682C>T (p.Gln1228Ter)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208609	NM_015272.5(RPGRIP1L):c.3299_3300dup (p.Ala1101fs)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217694	NM_015272.5(RPGRIP1L):c.3529C>T (p.Arg1177Ter)	RPGRIP1L	Pathogenic	criteria provided, multiple submitters, no conflicts
2187926	NM_015272.5(RPGRIP1L):c.541C>T (p.Gln181Ter)	RPGRIP1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPGRIP1L	Orphanet:1454	Joubert syndrome with hepatic defect
RPGRIP1L	Orphanet:220497	Joubert syndrome with renal defect
RPGRIP1L	Orphanet:564	Meckel syndrome

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
RPGRIP1L	HGNC:29168	ENSG00000103494	Q68CZ1	Protein fantom	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPGRIP1L	Protein fantom	Negatively regulates signaling through the G-protein coupled thromboxane A2 receptor (TBXA2R).

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)
RPGRIP1L	Other/Unknown	no		C2_dom, C2-C2_1, RPGRIP1_fam

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
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPGRIP1L	207	ubiquitous	marker	bronchial epithelial cell, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RPGRIP1L	2,027

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPGRIP1L	Q68CZ1	1

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
Hedgehog ‘off’ state	1	178.4×	0.009	RPGRIP1L
Anchoring of the basal body to the plasma membrane	1	113.1×	0.009	RPGRIP1L

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
neural tube patterning	1	2808.7×	0.003	RPGRIP1L
nose development	1	2407.4×	0.003	RPGRIP1L
pericardium development	1	1872.4×	0.003	RPGRIP1L
retinal rod cell development	1	1685.2×	0.003	RPGRIP1L
lateral ventricle development	1	1296.3×	0.003	RPGRIP1L
negative regulation of G protein-coupled receptor signaling pathway	1	1203.7×	0.003	RPGRIP1L
establishment of planar polarity	1	1053.2×	0.003	RPGRIP1L
corpus callosum development	1	842.6×	0.003	RPGRIP1L
olfactory bulb development	1	766.0×	0.003	RPGRIP1L
regulation of smoothened signaling pathway	1	624.1×	0.003	RPGRIP1L
embryonic hindlimb morphogenesis	1	581.1×	0.003	RPGRIP1L
embryonic forelimb morphogenesis	1	495.6×	0.003	RPGRIP1L
cochlea development	1	468.1×	0.003	RPGRIP1L
establishment or maintenance of cell polarity	1	401.2×	0.004	RPGRIP1L
cerebellum development	1	358.6×	0.004	RPGRIP1L
non-motile cilium assembly	1	290.6×	0.004	RPGRIP1L
determination of left/right symmetry	1	255.3×	0.005	RPGRIP1L
liver development	1	221.7×	0.005	RPGRIP1L
kidney development	1	140.4×	0.007	RPGRIP1L
in utero embryonic development	1	72.0×	0.014	RPGRIP1L

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
RPGRIP1L	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	RPGRIP1L

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)
RPGRIP1L	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.