Galloway-Mowat syndrome 4

Summary

Galloway-Mowat syndrome 4 (MONDO:0033008) is a disease caused by TP53RK (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: TP53RK (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 59

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Galloway-Mowat syndrome 4
Mondo ID	MONDO:0033008
OMIM	617730
DOID	DOID:0080246
UMLS	C4540270
MedGen	1613511
GARD	0016248
Is cancer (heuristic)	no

Also known as: Galloway-Mowat syndrome 4 · GAMOS4

Data availability: 59 ClinVar variants · 4 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 4

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 5

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

59 retrieved; paginated sample, class counts are floors:

40 uncertain significance, 6 conflicting classifications of pathogenicity, 5 likely pathogenic, 4 pathogenic, 3 likely benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
813579	NM_033550.4(TP53RK):c.15_16dup (p.Ala6fs)	LOC130065998	Pathogenic	criteria provided, single submitter
444880	NM_033550.4(TP53RK):c.179del (p.Lys60fs)	TP53RK	Pathogenic	no assertion criteria provided
444881	NM_033550.4(TP53RK):c.242C>G (p.Thr81Arg)	TP53RK	Pathogenic	no assertion criteria provided
444882	NM_033550.4(TP53RK):c.125G>A (p.Gly42Asp)	TP53RK	Pathogenic	no assertion criteria provided
3587313	NM_033550.4(TP53RK):c.37G>T (p.Glu13Ter)	LOC130065998	Likely pathogenic	criteria provided, single submitter
1210333	NM_033550.4(TP53RK):c.193A>C (p.Lys65Gln)	TP53RK	Likely pathogenic	criteria provided, single submitter
3587281	NM_033550.4(TP53RK):c.675C>G (p.Tyr225Ter)	TP53RK	Likely pathogenic	criteria provided, single submitter
3587283	NM_033550.4(TP53RK):c.602_603del (p.Tyr201fs)	TP53RK	Likely pathogenic	criteria provided, single submitter
3587287	NM_033550.4(TP53RK):c.520dup (p.Leu174fs)	TP53RK	Likely pathogenic	criteria provided, single submitter
1032341	NM_033550.4(TP53RK):c.337A>G (p.Met113Val)	TP53RK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1676441	NM_033550.4(TP53RK):c.309dup (p.Val104fs)	TP53RK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2193242	NM_033550.4(TP53RK):c.317A>C (p.Tyr106Ser)	TP53RK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2628379	NM_033550.4(TP53RK):c.335_338del (p.Tyr112fs)	TP53RK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
444883	NM_033550.4(TP53RK):c.728G>T (p.Arg243Leu)	TP53RK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
812787	NM_033550.4(TP53RK):c.727C>T (p.Arg243Cys)	TP53RK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1922102	NM_033550.4(TP53RK):c.11C>T (p.Ala4Val)	LOC130065998	Uncertain significance	criteria provided, multiple submitters, no conflicts
3587310	NM_033550.4(TP53RK):c.91C>A (p.Arg31Ser)	LOC130065998	Uncertain significance	criteria provided, single submitter
3587311	NM_033550.4(TP53RK):c.83G>T (p.Arg28Leu)	LOC130065998	Uncertain significance	criteria provided, single submitter
3587314	NM_033550.4(TP53RK):c.17C>T (p.Ala6Val)	LOC130065998	Uncertain significance	criteria provided, single submitter
1029039	NM_033550.4(TP53RK):c.598C>G (p.Leu200Val)	TP53RK	Uncertain significance	criteria provided, multiple submitters, no conflicts
1032343	NM_033550.4(TP53RK):c.544A>G (p.Ile182Val)	TP53RK	Uncertain significance	criteria provided, single submitter
1804894	NM_033550.4(TP53RK):c.185G>A (p.Arg62His)	TP53RK	Uncertain significance	criteria provided, single submitter
1806243	NM_033550.4(TP53RK):c.616G>C (p.Ala206Pro)	TP53RK	Uncertain significance	criteria provided, single submitter
1946253	NM_033550.4(TP53RK):c.689A>C (p.Lys230Thr)	TP53RK	Uncertain significance	criteria provided, multiple submitters, no conflicts
2081583	NM_033550.4(TP53RK):c.358G>A (p.Val120Met)	TP53RK	Uncertain significance	criteria provided, multiple submitters, no conflicts
3356996	NM_033550.4(TP53RK):c.238C>G (p.Arg80Gly)	TP53RK	Uncertain significance	criteria provided, single submitter
3587279	NM_033550.4(TP53RK):c.754G>T (p.Val252Phe)	TP53RK	Uncertain significance	criteria provided, single submitter
3587280	NM_033550.4(TP53RK):c.754G>A (p.Val252Ile)	TP53RK	Uncertain significance	criteria provided, single submitter
3587282	NM_033550.4(TP53RK):c.661T>A (p.Phe221Ile)	TP53RK	Uncertain significance	criteria provided, single submitter
3587284	NM_033550.4(TP53RK):c.592G>A (p.Val198Ile)	TP53RK	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 1 · 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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TP53RK	Orphanet:2065	Galloway-Mowat syndrome

Cohort genes → proteins

2 cohort genes, 1 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
TP53RK-DT	HGNC:55243	ENSG00000271784		TP53RK divergent transcript	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.

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
TP53RK-DT	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
ganglionic eminence	1
ventricular zone	1
liver	1
primordial germ cell in gonad	1
right lobe of liver	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
TP53RK-DT	125		yes	primordial germ cell in gonad, right lobe of liver, liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53RK	1,354
TP53RK-DT	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TP53RK	Q96S44	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
tRNA modification in the nucleus and cytosol	1	292.8×	0.007	TP53RK
Regulation of TP53 Activity through Phosphorylation	1	117.7×	0.008	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 1 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 metabolic process	1	2808.7×	0.001	TP53RK
tRNA processing	1	842.6×	0.002	TP53RK
regulation of signal transduction by p53 class mediator	1	383.0×	0.003	TP53RK
protein phosphorylation	1	68.0×	0.015	TP53RK

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
TP53RK-DT	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

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: 1; 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	TP53RK-DT

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)
TP53RK-DT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.