Short-rib thoracic dysplasia 17 with or without polydactyly

Summary

Short-rib thoracic dysplasia 17 with or without polydactyly (MONDO:0054565) is a disease caused by DYNLT2B (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: DYNLT2B (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	short-rib thoracic dysplasia 17 with or without polydactyly
Mondo ID	MONDO:0054565
OMIM	617405
UMLS	C4479416
MedGen	1372794
GARD	0025950
Is cancer (heuristic)	no

Also known as: SRTD17

Data availability: 9 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 › ciliopathy › Jeune syndrome › short-rib thoracic dysplasia 17 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 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 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, 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

9 retrieved; paginated sample, class counts are floors:

4 pathogenic, 2 uncertain significance, 1 benign, 1 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
266107	NM_152773.5(DYNLT2B):c.317+4A>T	DYNLT2B	Pathogenic	criteria provided, single submitter
417792	NM_152773.5(DYNLT2B):c.262C>T (p.Arg88Ter)	DYNLT2B	Pathogenic	criteria provided, single submitter
417793	NM_152773.5(DYNLT2B):c.100delinsCT (p.Val34fs)	DYNLT2B	Pathogenic	no assertion criteria provided
417791	NM_152773.5(DYNLT2B):c.113+2C>G	TM4SF19-DYNLT2B	Pathogenic	no assertion criteria provided
813328	GRCh37/hg19 3q29(chr3:196033814-196033883)	DYNLT2B	Likely pathogenic	criteria provided, single submitter
732953	NM_152773.5(DYNLT2B):c.114-1G>A	DYNLT2B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3064198	NM_152773.5(DYNLT2B):c.113+6T>C	DYNLT2B	Uncertain significance	criteria provided, single submitter
2437026	NM_152773.5(DYNLT2B):c.35G>A (p.Gly12Asp)	TM4SF19-DYNLT2B	Uncertain significance	criteria provided, single submitter
1290749	NM_152773.5(DYNLT2B):c.113+17C>G	DYNLT2B	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
DYNLT2B	Strong	Autosomal recessive	short-rib thoracic dysplasia 17 with or without polydactyly	3

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
DYNLT2B	HGNC:28482	ENSG00000213123	Q8WW35	Dynein light chain Tctex-type protein 2B	gencc,clinvar
TM4SF19-DYNLT2B	HGNC:49190	ENSG00000273331		TM4SF19-DYNLT2B readthrough (NMD candidate)	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DYNLT2B	Dynein light chain Tctex-type protein 2B	Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 2 complex (dynein-2 complex), a motor protein complex that drives the movement of cargos along microtubules within cilia and flagella in concert with the i…

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DYNLT2B	Other/Unknown	no		Tctex-1-like, Tctex-1-like_sf
TM4SF19-DYNLT2B	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
olfactory segment of nasal mucosa	1
right uterine tube	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DYNLT2B	135	ubiquitous	marker	right uterine tube, cortical plate, olfactory segment of nasal mucosa
TM4SF19-DYNLT2B	117	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DYNLT2B	830
TM4SF19-DYNLT2B	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DYNLT2B	Q8WW35	2

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
Intraflagellar transport	1	200.3×	0.005	DYNLT2B

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 intraciliary retrograde transport	1	8426.0×	6e-04	DYNLT2B
intraciliary retrograde transport	1	1123.5×	0.002	DYNLT2B
regulation of cilium assembly	1	601.9×	0.003	DYNLT2B
microtubule-based movement	1	295.6×	0.004	DYNLT2B
cilium assembly	1	73.6×	0.014	DYNLT2B

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
DYNLT2B	0	0
TM4SF19-DYNLT2B	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	2	DYNLT2B, TM4SF19-DYNLT2B

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)
DYNLT2B	0	—
TM4SF19-DYNLT2B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.