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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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IFT74
intraflagellar transport 74
Chromosome 9 Β· 9p21.2
NCBI Gene: 80173Ensembl: ENSG00000096872.18HGNC: HGNC:21424UniProt: Q96LB3
75PubMed Papers
23Diseases
0Drugs
56Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingcentriolar satelliteciliary basal bodyintraciliary transport particle AJoubert syndrome 40Bardet-Biedl syndrome 22spermatogenic failure 58Bardet-Biedl syndrome
✦AI Summary

IFT74 is a core component of the intraflagellar transport (IFT) complex B that mediates ciliary protein assembly and trafficking. As part of the IFT74-IFT81 heterodimer, it forms a tubulin-binding module essential for transporting tubulin into cilia and flagella 1. The N-terminal 40 amino acids are particularly critical for tubulin binding, though they are dispensable for IFT subunit interactions 2. IFT74 also functions as an unconventional GTPase-activating protein for RabL2, facilitating IFT initiation at the ciliary base 3. Dysfunction of IFT74 causes diverse ciliopathies reflecting allele-specific severity. Biallelic splice site mutations cause lethal skeletal chondrodysplasia, while exon 2 deletions produce milder skeletal ciliopathy with motile cilia defects 2. IFT74 mutations underlie Bardet-Biedl syndrome, Joubert syndrome, and primary ciliary dyskinesia through impaired cooperation with IFT25-IFT27 4 and disrupted ciliogenesis and ciliary signaling 5. A hypomorphic exon 2 deletion manifests as combined motile and primary ciliopathy with short-rib thoracic dysplasia, demonstrating that tubulin transport demands differ between ciliary types 6. These findings establish IFT74 as essential for ciliogenesis, ciliary maintenance, and proper skeletal and neurological development.

Sources cited
1
IFT74-IFT81 forms a tubulin-binding module mediating tubulin transport within cilia; required for ciliogenesis
PMID: 23990561
2
IFT74 exon 2 deletion and splice site variants cause allele-specific skeletal ciliopathy and motile cilia defects; N-terminal 40 amino acids important for tubulin binding but dispensable for IFT subunit binding
PMID: 37315079
3
Impaired IFT74-IFT81 interaction with IFT25-IFT27 causes Bardet-Biedl syndrome ciliary defects
PMID: 34888642
4
IFT74 variants cause Joubert syndrome through disrupted ciliogenesis and altered ciliary membrane protein distribution
PMID: 33531668
5
IFT74 exon 2 deletion causes combined motile and primary ciliopathy with short-rib thoracic dysplasia and PCD features
PMID: 37555648
6
IFT81-IFT74 complex acts as unconventional RabL2 GTPase-activating protein during intraflagellar transport
PMID: 37606072
Disease Associationsβ“˜23
Joubert syndrome 40Open Targets
0.73Strong
Bardet-Biedl syndrome 22Open Targets
0.69Moderate
spermatogenic failure 58Open Targets
0.52Moderate
Bardet-Biedl syndromeOpen Targets
0.50Moderate
genetic disorderOpen Targets
0.45Moderate
Male infertility due to large-headed multiflagellar polyploid spermatozoaOpen Targets
0.38Weak
Joubert syndromeOpen Targets
0.37Weak
ciliopathyOpen Targets
0.37Weak
ciliopathy-IFT74Open Targets
0.37Weak
Jeune syndromeOpen Targets
0.27Weak
sign or symptomOpen Targets
0.19Weak
Retinal dystrophyOpen Targets
0.14Weak
microcephalyOpen Targets
0.14Weak
optic atrophyOpen Targets
0.14Weak
neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomaliesOpen Targets
0.12Weak
retinopathyOpen Targets
0.12Weak
HeterotaxiaOpen Targets
0.07Suggestive
azoospermiaOpen Targets
0.06Suggestive
heterotaxy, visceral, 12, autosomalOpen Targets
0.05Suggestive
ciliary dyskinesia, primary, 52Open Targets
0.05Suggestive
Bardet-Biedl syndrome 22UniProt
Joubert syndrome 40UniProt
Spermatogenic failure 58UniProt
Pathogenic Variants56
NM_025103.4(IFT74):c.1024C>T (p.Gln342Ter)Pathogenic
not provided|IFT74-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 342
NM_025103.4(IFT74):c.1685-1G>TPathogenic
Bardet-Biedl syndrome 22|not provided|IFT74-related disorder
β˜…β˜…β˜†β˜†2025
NM_025103.4(IFT74):c.535C>G (p.Gln179Glu)Pathogenic
Joubert syndrome 40|not provided|Inborn genetic diseases|IFT74-related disorder|Bardet-Biedl syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 179
NM_025103.4(IFT74):c.358G>T (p.Glu120Ter)Pathogenic
not provided|Joubert syndrome 40|IFT74-related disorder|Bardet-Biedl syndrome 22
β˜…β˜…β˜†β˜†2024β†’ Residue 120
NM_025103.4(IFT74):c.853G>T (p.Glu285Ter)Pathogenic
Joubert syndrome 40|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 285
NM_025103.4(IFT74):c.1153C>T (p.Arg385Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 385
NM_025103.4(IFT74):c.525+2T>GLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_025103.4(IFT74):c.1348C>T (p.Gln450Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 450
NM_025103.4(IFT74):c.952G>T (p.Glu318Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 318
NM_025103.4(IFT74):c.1054G>T (p.Gly352Cys)Likely pathogenic
Jeune thoracic dystrophy|Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 352
NM_025103.4(IFT74):c.974+1G>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_025103.4(IFT74):c.988A>T (p.Lys330Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 330
NM_025103.4(IFT74):c.256+1G>CLikely pathogenic
not provided|IFT74-related disorder|Acute myeloid leukemia
β˜…β˜†β˜†β˜†2025
NM_025103.4(IFT74):c.991G>T (p.Glu331Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 331
NM_025103.4(IFT74):c.915del (p.Glu306fs)Pathogenic
not provided|IFT74-related disorder
β˜…β˜†β˜†β˜†2025β†’ Residue 306
NM_025103.4(IFT74):c.789+2T>GLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_025103.4(IFT74):c.818dup (p.Ala274fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 274
NM_025103.4(IFT74):c.1570del (p.Asn523_Ile524insTer)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 523
NM_025103.4(IFT74):c.1135_1136del (p.Lys379fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 379
NM_025103.4(IFT74):c.843_844del (p.Leu281_Tyr282insTer)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 281
View on ClinVar β†—
Related Genes
BBS4Protein interaction100%ANKRD55Protein interaction100%IFT140Protein interaction100%IFT38Protein interaction100%IFT54Protein interaction100%UBQLN1Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
80%
Heart
73%
Liver
55%
Brain
47%
Lung
36%
Gene Interaction Network
Click a node to explore
IFT74BBS4ANKRD55IFT140IFT38IFT54UBQLN1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q96LB3
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.51LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.07 [0.77–1.51]
RankingsWhere IFT74 stands among ~20K protein-coding genes
  • #6,336of 20,598
    Most Researched75
  • #1,231of 5,498
    Most Pathogenic Variants56 Β· top quartile
  • #15,214of 17,882
    Most Constrained (LOEUF)1.51
Genes detectedIFT74
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
PMID: 20301537
1.00
2
Structure of a human replisome shows the organisation and interactions of a DNA replication machine.
PMID: 34694004
EMBO J Β· 2021
0.90
3
IFT74 variants cause skeletal ciliopathy and motile cilia defects in mice and humans.
PMID: 37315079
PLoS Genet Β· 2023
0.80
4
PMID: 36865301
medRxiv Β· 2023
0.70
5
Impaired cooperation between IFT74/BBS22-IFT81 and IFT25-IFT27/BBS19 causes Bardet-Biedl syndrome.
PMID: 34888642
Hum Mol Genet Β· 2022
0.60