Rothmund-Thomson syndrome type 3

Summary

Rothmund-Thomson syndrome type 3 (MONDO:0014347) is a disease caused by CRIPT (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CRIPT (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Rothmund-Thomson syndrome type 3
Mondo ID	MONDO:0014347
OMIM	615789
UMLS	C4014339
MedGen	862776
GARD	0027860
Is cancer (heuristic)	no

Also known as: Rothmund-Thomson syndrome, type 3 · short stature with microcephaly and distinctive facies

Data availability: 12 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › Rothmund-Thomson syndrome › Rothmund-Thomson syndrome type 3

Related subtypes (3): Rothmund-Thomson syndrome type 1, Rothmund-Thomson syndrome type 2, Rothmund-Thomson syndrome type 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

12 retrieved; paginated sample, class counts are floors:

8 pathogenic, 2 uncertain significance, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
127249	NM_014171.6(CRIPT):c.133_134insGG (p.Ala45fs)	CRIPT	Pathogenic	no assertion criteria provided
127250	NM_014171.6(CRIPT):c.141del (p.Phe47fs)	CRIPT	Pathogenic	no assertion criteria provided
1343340	NM_014171.6(CRIPT):c.7_8del (p.Cys3fs)	CRIPT	Pathogenic	criteria provided, single submitter
221619	NM_014171.5(CRIPT):c.-422_17-582del	CRIPT	Pathogenic	criteria provided, single submitter
3233412	NM_014171.6(CRIPT):c.227G>A (p.Cys76Tyr)	CRIPT	Pathogenic	no assertion criteria provided
3896326	NC_000002.11:g.(?46844353)(46846821_46850902)del	CRIPT	Pathogenic	criteria provided, single submitter
625543	GRCh37/hg19 2p21(chr2:46844284-46844565)	CRIPT	Pathogenic	criteria provided, single submitter
976761	NM_014171.6(CRIPT):c.132del (p.Ala45fs)	CRIPT	Pathogenic	criteria provided, multiple submitters, no conflicts
1704565	NC_000002.11:g.(?46844310)(46844438_46845911)del	CRIPT	Likely pathogenic	criteria provided, single submitter
221618	NM_014171.6(CRIPT):c.8G>A (p.Cys3Tyr)	CRIPT	Likely pathogenic	criteria provided, single submitter
1029251	NM_014171.6(CRIPT):c.242-19A>T	CRIPT	Uncertain significance	criteria provided, single submitter
3586711	NM_014171.6(CRIPT):c.191C>T (p.Ser64Phe)	CRIPT	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
CRIPT	Strong	Autosomal recessive	Rothmund-Thomson syndrome type 3	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CRIPT	Orphanet:715640	Rothmund-Thomson syndrome type 3

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
CRIPT	HGNC:14312	ENSG00000119878	Q9P021	Cysteine-rich PDZ-binding protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CRIPT	Cysteine-rich PDZ-binding protein	As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CRIPT	Scaffold/PPI	no		PDZ-binding_CRIPT

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
caput epididymis	1
corpus epididymis	1
endothelial cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CRIPT	284	ubiquitous	marker	endothelial cell, corpus epididymis, caput epididymis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CRIPT	901

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CRIPT	Q9P021	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
regulation of postsynaptic density protein 95 clustering	1	4213.0×	0.001	CRIPT
protein localization to microtubule	1	1296.3×	0.002	CRIPT
regulation of postsynaptic density assembly	1	887.0×	0.002	CRIPT
cytoplasmic microtubule organization	1	343.9×	0.004	CRIPT
RNA splicing	1	88.2×	0.013	CRIPT
mRNA processing	1	78.8×	0.013	CRIPT

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
CRIPT	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	CRIPT

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)
CRIPT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.