GeneBe

IFT80

protein-coding

intraflagellar transport 80, the group of WD repeat domain containing|IFT-B2 complex

Gene summary

The protein encoded by this gene is part of the intraflagellar transport complex B and is necessary for the function of motile and sensory cilia. Defects in this gene are a cause of asphyxiating thoracic dystrophy 2 (ATD2). Three transcript variants encoding two different isoforms have been found for this gene.[provided by RefSeq, Jun 2010]

Previous symbols:
  • WDR56

MANE transcript

NM_020800.3

Inheritance

AR

ClinVar variants

P:69U:316B:138

Top phenotype

Craniofacial; Musculoskeletal; Neurologic; Renal

gnomAD constraint

pLI —, LoF o/e 0.75

Max pathogenic AF

—

Genomic locus

chr3:160,256,986-160,399,880

External References & Databases

Ensembl (ENSG00000068885)NCBI Gene (57560)OMIM (611177)HGNC:29262GenCCUniProt (Q9P2H3)AlphaFoldClinVar (IFT80)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~142.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Beemer-Langer syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0010024

Submitter: Orphanet

asphyxiating thoracic dystrophy 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012644

Submitter: Labcorp Genetics (formerly Invitae)

short rib-polydactyly syndrome, Verma-Naumoff typeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019664

Submitter: Orphanet

asphyxiating thoracic dystrophy 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012644

Submitter: PanelApp Australia

asphyxiating thoracic dystrophy 2DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012644

Submitter: ClinGen

*IFT80* was first reported in relation to autosomal recessive *IFT80*-related short-rib thoracic dysplasia (SRTD) in 2007 (Beales et al., PMID: 17468754). SRPS is characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanisms or inheritance pattern, with lethality dependent on the size of the thoracic cage being the primary difference in phenotypic variability. Therefore, the following disease entities have been lumped into one disease entity, short-rib thoracic dysplasia 2 with or without polydactyly (OMIM:611263), short-rib thoracic dysplasia (SRTD), asphyxiating throracid dystrophy (ATD), and Jeune syndrome. 16 variants (missense, in-frame indel, nonsense, frameshift, canonical splice site) that have been reported in 12 probands in 6 publications (PMIDs: 17468754, 19648123, 23339108, 29068549, 30767363, 33452237) are included in this curation. The mechanism of pathogenicity is known to be loss of function. This gene-disease relationship is also supported by models replicating human phenotypes and ciliary alterations in Tetrahymena thermophila, zebrafish, and mice (PMIDs: 17468754, 17468754, 21227999). In summary, there is definitive evidence supporting the relationship between *IFT80* and autosomal recessive *IFT80*-related short-rib thoracic dysplasia. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Skeletal Disorders GCEP on the meeting date August 5, 2024 (SOP Version 10).

asphyxiating thoracic dystrophy 2MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0012644

Submitter: Ambry Genetics

Jeune syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018770

Submitter: Orphanet

asphyxiating thoracic dystrophy 2DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012644

Submitter: G2P

Clinical Genomic Database (CGD)

Craniofacial; Musculoskeletal; Neurologic; RenalAR

Manifestation: Musculoskeletal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 17468754; 19610081; 19648123; 30767363Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IFT80 variants in ClinVar

11 Conditions Cataloged
Jeune thoracic dystrophyTotal: 558
Asphyxiating thoracic dystrophy 2Total: 165
Inborn genetic diseasesTotal: 89
not providedTotal: 55
not specifiedTotal: 30
IFT80-related disorderTotal: 22
Connective tissue disorderTotal: 15
IFT80-related skeletal disordersTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020800.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
9
clinvar
123
clinvar
2
clinvar
 134
missense
2
clinvar
8
clinvar
298
clinvar
11
clinvar
1
clinvar
 320
nonsense
11
clinvar
7
clinvar
1
clinvar
 19
start loss
1
clinvar
1
clinvar
 2
frameshift
14
clinvar
9
clinvar
1
clinvar
 24
splice donor/acceptor (+/-2bp)
1
clinvar
16
clinvar
6
clinvar
1
clinvar
 24
Total28413161353523

Highest pathogenic variant AF is 0.00007310322

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_020800.3RefSeqNP_065851.119MANE Select
ENST00000326448.12EnsemblENSP00000312778.719MANE Select
NM_001190241.2RefSeqNP_001177170.116Standard
NM_001190242.2RefSeqNP_001177171.116Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
ift80Danio rerio

Structure: photoreceptor cell

Quality: degeneration

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Intraflagellar transport
  • Cilium Assembly
  • Organelle biogenesis and maintenance

Biological Process

  • osteoblast differentiation
  • chondrocyte differentiation
  • smoothened signaling pathway
  • intraciliary transport involved in cilium assembly
  • positive regulation of smoothened signaling pathway

Cellular Component

  • cytoplasm
  • centrosome
  • cilium
  • intraciliary transport particle B
  • ciliary tip

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000326448
Coding exons
19
Length
142895
Individuals with no LoFs
125653
Homozygous LoFs
0
Heterozygous LoFs
95
Defined
125748
p
0.000378
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.513204060.7890.00001985104
Missense (PolyPhen)8096.0320.833061207
Synonymous-0.2761411371.030.000006961419
Loss of Function1.603648.00.7500.00000246565

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000560.00055rare
Latino/Admixed American0.000530.00052rare
Ashkenazi Jewish00.0absent
East Asian0.00110.0011notable
Finnish0.0000530.000046rare
European (Non-Finnish)0.000300.00030rare
South Asian0.000400.00039rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Component of the intraflagellar transport (IFT) complex B, which is essential for the development and maintenance of motile and sensory cilia. {ECO:0000269|PubMed:17468754}.;

Recessive Scores

pRec
0.102

Intolerance Scores

LoFtool
0.568
RVIS EVS
-0.29
RVIS percentile EVS
33.47

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.252

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.