Short-rib thoracic dysplasia 13 with or without polydactyly

Summary

Short-rib thoracic dysplasia 13 with or without polydactyly (MONDO:0014577) is a disease caused by CEP120 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: CEP120 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 421

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	short-rib thoracic dysplasia 13 with or without polydactyly
Mondo ID	MONDO:0014577
OMIM	616300
DOID	DOID:0110093
UMLS	C4225378
MedGen	898712
GARD	0016079
Is cancer (heuristic)	no

Also known as: short-rib thoracic dysplasia 13 with or without polydactyly · SRTD13

Data availability: 421 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › ciliopathy › Jeune syndrome › short-rib thoracic dysplasia 13 with or without polydactyly

Related subtypes (23): asphyxiating thoracic dystrophy 1, Ellis-van Creveld syndrome, short-rib thoracic dysplasia 6 with or without polydactyly, short-rib thoracic dysplasia 9 with or without polydactyly, Beemer-Langer syndrome, asphyxiating thoracic dystrophy 2, asphyxiating thoracic dystrophy 3, asphyxiating thoracic dystrophy 4, short-rib thoracic dysplasia 7 with or without polydactyly, asphyxiating thoracic dystrophy 5, short-rib thoracic dysplasia 8 with or without polydactyly, short-rib thoracic dysplasia 10 with or without polydactyly, short-rib thoracic dysplasia 11 with or without polydactyly, short-rib thoracic dysplasia 14 with polydactyly, short-rib thoracic dysplasia 15 with polydactyly, short-rib thoracic dysplasia 16 with or without polydactyly, short-rib thoracic dysplasia 21 without polydactyly, short-rib thoracic dysplasia 19 with or without polydactyly, short-rib thoracic dysplasia 18 with polydactyly, short-rib thoracic dysplasia 20 with polydactyly, short-rib thoracic dysplasia 17 with or without polydactyly, Jeune syndrome - GRK2-related, short-rib thoracic dysplasia 22 without polydactyly

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

421 retrieved; paginated sample, class counts are floors:

199 likely benign, 128 uncertain significance, 30 benign, 19 conflicting classifications of pathogenicity, 16 pathogenic, 15 benign/likely benign, 10 likely pathogenic, 4 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1027811	NM_001375405.1(CEP120):c.762del (p.Ser254fs)	CEP120	Pathogenic	criteria provided, single submitter
1069907	NM_001375405.1(CEP120):c.1684dup (p.Thr562fs)	CEP120	Pathogenic	criteria provided, single submitter
1076569	NM_001375405.1(CEP120):c.2206dup (p.Glu736fs)	CEP120	Pathogenic	criteria provided, single submitter
1076850	NM_001375405.1(CEP120):c.1028dup (p.Asp344fs)	CEP120	Pathogenic	criteria provided, single submitter
1324047	NM_001375405.1(CEP120):c.1615A>T (p.Lys539Ter)	CEP120	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1376162	NM_001375405.1(CEP120):c.1397del (p.Leu466fs)	CEP120	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1460221	NC_000005.9:g.(?122682213)(122758692_?)del	CEP120	Pathogenic	criteria provided, single submitter
1685613	NM_001375405.1(CEP120):c.1558C>T (p.Gln520Ter)	CEP120	Pathogenic	criteria provided, single submitter
189370	NM_001375405.1(CEP120):c.595G>C (p.Ala199Pro)	CEP120	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1980289	NM_001375405.1(CEP120):c.2164C>T (p.Arg722Ter)	CEP120	Pathogenic	criteria provided, single submitter
2060553	NM_001375405.1(CEP120):c.2449C>T (p.Gln817Ter)	CEP120	Pathogenic	criteria provided, single submitter
2858930	NM_001375405.1(CEP120):c.2377A>T (p.Lys793Ter)	CEP120	Pathogenic	criteria provided, single submitter
3013485	NM_001375405.1(CEP120):c.2743C>T (p.Gln915Ter)	CEP120	Pathogenic	criteria provided, single submitter
3670898	NM_001375405.1(CEP120):c.2548C>T (p.Arg850Ter)	CEP120	Pathogenic	criteria provided, single submitter
3723419	NM_001375405.1(CEP120):c.1175C>G (p.Ser392Ter)	CEP120	Pathogenic	criteria provided, single submitter
446143	NM_001375405.1(CEP120):c.2924T>G (p.Ile975Ser)	CEP120	Pathogenic	no assertion criteria provided
4531963	NM_001375405.1(CEP120):c.1789_1792del (p.Ser597fs)	CEP120	Pathogenic	criteria provided, single submitter
4721985	NM_001375405.1(CEP120):c.2026G>T (p.Glu676Ter)	CEP120	Pathogenic	criteria provided, single submitter
4735625	NM_001375405.1(CEP120):c.674_675insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNGACCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCTCTTTTACTACTCTTT (p.Leu225delinsPhePhePhePhePhePhePheXaaXaaXaaXaaThrSerTer)	CEP120	Pathogenic	criteria provided, single submitter
623651	NM_001375405.1(CEP120):c.2323C>T (p.Gln775Ter)	CEP120	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1466157	NM_001375405.1(CEP120):c.1039-2A>T	CEP120	Likely pathogenic	criteria provided, single submitter
1696573	NM_001375405.1(CEP120):c.50-2113_206+103del	CEP120	Likely pathogenic	criteria provided, single submitter
2053431	NM_001375405.1(CEP120):c.1861-2A>G	CEP120	Likely pathogenic	criteria provided, single submitter
2142446	NM_001375405.1(CEP120):c.2014-2A>G	CEP120	Likely pathogenic	criteria provided, single submitter
2847852	NM_001375405.1(CEP120):c.2580+2T>A	CEP120	Likely pathogenic	criteria provided, single submitter
2870301	NM_001375405.1(CEP120):c.1255+1G>A	CEP120	Likely pathogenic	criteria provided, single submitter
2904858	NM_001375405.1(CEP120):c.321+1G>A	CEP120	Likely pathogenic	criteria provided, single submitter
2960162	NM_001375405.1(CEP120):c.2013+1G>A	CEP120	Likely pathogenic	criteria provided, single submitter
446142	NM_001375405.1(CEP120):c.451C>T (p.Arg151Ter)	CEP120	Likely pathogenic	criteria provided, single submitter
4845802	NM_001375405.1(CEP120):c.85del (p.Leu28_Val29insTer)	CEP120	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 3 · 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
CEP120	Strong	Autosomal recessive	short-rib thoracic dysplasia 13 with or without polydactyly	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CEP120	Orphanet:220493	Joubert syndrome with ocular defect
CEP120	Orphanet:474	Jeune syndrome
CEP120	Orphanet:475	Isolated Joubert 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
CEP120	HGNC:26690	ENSG00000168944	Q8N960	Centrosomal protein of 120 kDa	gencc,clinvar
UCP3	HGNC:12519	ENSG00000175564	P55916	Putative mitochondrial transporter UCP3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CEP120	Centrosomal protein of 120 kDa	Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome.
UCP3	Putative mitochondrial transporter UCP3	Putative transmembrane transporter that plays a role in mitochondrial metabolism via an as yet unclear mechanism.

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
Transporter	1	38.9×	0.051
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CEP120	Other/Unknown	no		C2_dom, DUF3668, C2_domain_sf
UCP3	Transporter	yes		MCP, MCP_transmembrane, MCP_dom_sf

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
calcaneal tendon	1
epithelial cell of pancreas	1
mucosa of paranasal sinus	1
gastrocnemius	1
hindlimb stylopod muscle	1
muscle of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CEP120	254	ubiquitous	yes	calcaneal tendon, epithelial cell of pancreas, mucosa of paranasal sinus
UCP3	224	tissue_specific	marker	gastrocnemius, hindlimb stylopod muscle, muscle of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CEP120	1,928
UCP3	1,442

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CEP120	Q8N960	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
UCP3	P55916	62.65

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
The fatty acid cycling model	1	2284.0×	4e-04	UCP3

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
lipid hydroperoxide transport	1	4213.0×	0.003	UCP3
response to fenofibrate	1	4213.0×	0.003	UCP3
response to superoxide	1	1685.2×	0.003	UCP3
positive regulation of centrosome duplication	1	1685.2×	0.003	CEP120
interkinetic nuclear migration	1	1685.2×	0.003	CEP120
positive regulation of establishment of protein localization	1	1404.3×	0.003	CEP120
positive regulation of centriole elongation	1	1203.7×	0.003	CEP120
mitochondrial transmembrane transport	1	842.6×	0.004	UCP3
astral microtubule organization	1	648.1×	0.004	CEP120
adaptive thermogenesis	1	526.6×	0.005	UCP3
positive regulation of cilium assembly	1	383.0×	0.006	CEP120
respiratory gaseous exchange by respiratory system	1	312.1×	0.007	UCP3
response to cold	1	280.9×	0.007	UCP3
cellular response to hormone stimulus	1	191.5×	0.009	UCP3
centrosome cycle	1	168.5×	0.009	CEP120
response to activity	1	162.0×	0.009	UCP3
response to glucocorticoid	1	162.0×	0.009	UCP3
proton transmembrane transport	1	156.0×	0.009	UCP3
response to nutrient	1	147.8×	0.009	UCP3
response to insulin	1	115.4×	0.011	UCP3
neurogenesis	1	104.0×	0.011	CEP120
cerebral cortex development	1	102.8×	0.011	CEP120
fatty acid metabolic process	1	96.8×	0.011	UCP3
response to hypoxia	1	47.9×	0.022	UCP3
lipid metabolic process	1	45.8×	0.022	UCP3

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
CEP120	0	0
UCP3	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	1	UCP3
E	Difficult family or no structure, no drug	1	CEP120

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)
CEP120	0	—
UCP3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.