Short-rib thoracic dysplasia 21 without polydactyly

Summary

Short-rib thoracic dysplasia 21 without polydactyly (MONDO:0030356) is a disease caused by KIAA0753 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: KIAA0753 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 23

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	short-rib thoracic dysplasia 21 without polydactyly
Mondo ID	MONDO:0030356
OMIM	619479
UMLS	C5561961
MedGen	1794171
GARD	0025550
Is cancer (heuristic)	no

Also known as: short-rib thoracic dysplasia 21 without polydactyly · SRTD21

Data availability: 23 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 21 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 13 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 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

23 retrieved; paginated sample, class counts are floors:

9 benign, 4 pathogenic, 4 pathogenic/likely pathogenic, 2 likely pathogenic, 2 benign/likely benign, 1 conflicting classifications of pathogenicity, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1196005	NM_014804.3(KIAA0753):c.1830-2A>G	KIAA0753	Pathogenic	no assertion criteria provided
2427871	NM_014804.3(KIAA0753):c.757C>T (p.Arg253Ter)	KIAA0753	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
428613	NM_014804.3(KIAA0753):c.970C>T (p.Arg324Ter)	KIAA0753	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
428614	NM_014804.3(KIAA0753):c.1271del (p.Pro424fs)	KIAA0753	Pathogenic	no assertion criteria provided
428615	NM_014804.3(KIAA0753):c.943C>T (p.Gln315Ter)	KIAA0753	Pathogenic	criteria provided, single submitter
439846	NM_014804.3(KIAA0753):c.1571_1572del (p.Arg524fs)	KIAA0753	Pathogenic	criteria provided, multiple submitters, no conflicts
620530	NM_014804.3(KIAA0753):c.2656C>T (p.Arg886Ter)	KIAA0753	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
808212	NM_014804.3(KIAA0753):c.661C>T (p.Arg221Ter)	KIAA0753	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3377254	NM_014804.3(KIAA0753):c.2675del (p.Pro892fs)	KIAA0753	Likely pathogenic	criteria provided, single submitter
4526596	NM_014804.3(KIAA0753):c.1722del (p.Trp574fs)	KIAA0753	Likely pathogenic	criteria provided, single submitter
558755	NM_014804.3(KIAA0753):c.810C>T (p.Tyr270=)	KIAA0753	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1183823	NM_014804.3(KIAA0753):c.69C>T (p.Ser23=)	KIAA0753	Benign	criteria provided, multiple submitters, no conflicts
1221496	NM_014804.3(KIAA0753):c.507T>C (p.Ser169=)	KIAA0753	Benign	criteria provided, multiple submitters, no conflicts
1236419	NM_014804.3(KIAA0753):c.2687A>G (p.Gln896Arg)	KIAA0753	Benign	criteria provided, multiple submitters, no conflicts
1238793	NM_014804.3(KIAA0753):c.1697C>T (p.Pro566Leu)	KIAA0753	Benign	criteria provided, multiple submitters, no conflicts
1252198	NM_014804.3(KIAA0753):c.1125A>T (p.Glu375Asp)	KIAA0753	Benign	criteria provided, multiple submitters, no conflicts
1259547	NM_014804.3(KIAA0753):c.*21A>G	KIAA0753	Benign	criteria provided, multiple submitters, no conflicts
1278062	NM_014804.3(KIAA0753):c.1397T>C (p.Leu466Pro)	KIAA0753	Benign	criteria provided, multiple submitters, no conflicts
1280830	NM_014804.3(KIAA0753):c.1330G>A (p.Asp444Asn)	KIAA0753	Benign	criteria provided, multiple submitters, no conflicts
1284038	NM_014804.3(KIAA0753):c.1716T>C (p.Ala572=)	KIAA0753	Benign	criteria provided, multiple submitters, no conflicts
376793	NM_014804.3(KIAA0753):c.1756A>G (p.Lys586Glu)	KIAA0753	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
445434	NM_014804.3(KIAA0753):c.2338C>T (p.Arg780Cys)	KIAA0753	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
713011	NM_014804.3(KIAA0753):c.236T>C (p.Val79Ala)	KIAA0753	Likely benign	criteria provided, multiple submitters, no conflicts

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
KIAA0753	Strong	Autosomal recessive	short-rib thoracic dysplasia 21 without polydactyly	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KIAA0753	Orphanet:2754	Orofaciodigital syndrome type 6
KIAA0753	Orphanet:474	Jeune syndrome
KIAA0753	Orphanet:475	Isolated Joubert 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
KIAA0753	HGNC:29110	ENSG00000198920	Q2KHM9	Protein moonraker	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KIAA0753	Protein moonraker	Involved in centriole duplication.

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)
KIAA0753	Other/Unknown	no		MNR

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
cortical plate	1
lower esophagus	1
lower esophagus muscularis layer	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KIAA0753	243	ubiquitous	marker	cortical plate, lower esophagus, lower esophagus muscularis layer

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KIAA0753	1,062

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KIAA0753	Q2KHM9	59.08

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
cytosolic ciliogenesis	1	3370.4×	0.001	KIAA0753
centriole replication	1	732.7×	0.002	KIAA0753
protein localization to centrosome	1	674.1×	0.002	KIAA0753
cilium assembly	1	73.6×	0.014	KIAA0753

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
KIAA0753	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	KIAA0753

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)
KIAA0753	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.