Galloway-Mowat syndrome 5

Summary

Galloway-Mowat syndrome 5 (MONDO:0033009) is a disease caused by TPRKB (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: TPRKB (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Galloway-Mowat syndrome 5
Mondo ID	MONDO:0033009
OMIM	617731
DOID	DOID:0080247
UMLS	C4540274
MedGen	1617227
GARD	0016249
Is cancer (heuristic)	no

Also known as: Galloway-Mowat syndrome 5 · GAMOS5

Data availability: 8 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Galloway-Mowat syndrome › Galloway-Mowat syndrome 5

Related subtypes (9): Galloway-Mowat syndrome 9, Galloway-Mowat syndrome 10, Galloway-Mowat syndrome 6, Galloway-Mowat syndrome 7, Galloway-Mowat syndrome 8, Galloway-Mowat syndrome 1, Galloway-Mowat syndrome 2, X-linked, Galloway-Mowat syndrome 3, Galloway-Mowat syndrome 4

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

8 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
444885	NM_016058.5(TPRKB):c.446A>G (p.Tyr149Cys)	TPRKB	Pathogenic	no assertion criteria provided
3065453	NM_016058.5(TPRKB):c.445T>A (p.Tyr149Asn)	TPRKB	Likely pathogenic	criteria provided, single submitter
444884	NM_016058.5(TPRKB):c.407T>C (p.Leu136Pro)	TPRKB	Conflicting classifications of pathogenicity	no assertion criteria provided
1334895	NM_016058.5(TPRKB):c.89GAA[1] (p.Arg31del)	TPRKB	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892702	NM_016058.5(TPRKB):c.445T>C (p.Tyr149His)	TPRKB	Uncertain significance	criteria provided, multiple submitters, no conflicts
3897979	NM_016058.5(TPRKB):c.295T>G (p.Ser99Ala)	TPRKB	Uncertain significance	criteria provided, single submitter
1253010	NM_016058.5(TPRKB):c.474T>C (p.Ile158=)	TPRKB	Benign	criteria provided, multiple submitters, no conflicts
764552	NM_016058.5(TPRKB):c.390G>A (p.Gln130=)	TPRKB	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · 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
TP53RK	Strong	Autosomal recessive	Galloway-Mowat syndrome 4	11
TPRKB	Strong	Autosomal recessive	Galloway-Mowat syndrome 5	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TP53RK	Orphanet:2065	Galloway-Mowat syndrome
TPRKB	Orphanet:2065	Galloway-Mowat 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
TP53RK	HGNC:16197	ENSG00000172315	Q96S44	EKC/KEOPS complex subunit TP53RK	gencc,clinvar
TPRKB	HGNC:24259	ENSG00000144034	Q9Y3C4	EKC/KEOPS complex subunit TPRKB	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TP53RK	EKC/KEOPS complex subunit TP53RK	Component of the EKC/KEOPS complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine.
TPRKB	EKC/KEOPS complex subunit TPRKB	Component of the EKC/KEOPS complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Kinase	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TP53RK	Kinase	yes	2.7.11.1	Prot_kinase_dom, Tyr_kinase_AS, Kinase-like_dom_sf
TPRKB	Other/Unknown	no		CGI121/TPRKB, CGI121/TPRKB_sf

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
ganglionic eminence	2
cortical plate	1
ventricular zone	1
right testis	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TP53RK	222	ubiquitous	marker	ventricular zone, ganglionic eminence, cortical plate
TPRKB	284	ubiquitous	marker	right uterine tube, ganglionic eminence, right testis

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TPRKB	1,426
TP53RK	1,354

Intra-cohort edges

A	B	Sources
TP53RK	TPRKB	biogrid_interaction, intact, string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TPRKB	Q9Y3C4	7
TP53RK	Q96S44	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
tRNA modification in the nucleus and cytosol	2	292.8×	2e-05	TP53RK, TPRKB
Regulation of TP53 Activity through Phosphorylation	1	58.9×	0.017	TP53RK

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
tRNA threonylcarbamoyladenosine modification	1	1685.2×	0.002	TPRKB
tRNA threonylcarbamoyladenosine metabolic process	1	1404.3×	0.002	TP53RK
tRNA processing	1	421.3×	0.004	TP53RK
regulation of signal transduction by p53 class mediator	1	191.5×	0.007	TP53RK
protein phosphorylation	1	34.0×	0.029	TP53RK

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
TP53RK	GILTERITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53RK	6	4
TPRKB	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GILTERITINIB	4	TP53RK
SILMITASERTIB	2	TP53RK
DECERNOTINIB	2	TP53RK
BGT-226 FREE BASE	2	TP53RK
GSK-1059615	1	TP53RK
RGB-286638	1	TP53RK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TP53RK	40	Binding:40
TPRKB	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TP53RK	2.7.11.1	non-specific serine/threonine protein kinase

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

6 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.

Compound	Max phase	Cohort target (bioactivity)
GILTERITINIB	4	TP53RK
SILMITASERTIB	2	TP53RK
DECERNOTINIB	2	TP53RK
BGT-226 FREE BASE	2	TP53RK
GSK-1059615	1	TP53RK
RGB-286638	1	TP53RK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TP53RK
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	TPRKB

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)
TPRKB	1	TP53RK

Clinical trials & evidence

Clinical trials

Clinical trials: 0.