IFT74

Chr 9AR

intraflagellar transport 74

NCBI Gene: 80173ENSG00000096872UniProt: Q96LB3

Component of the intraflagellar transport (IFT) complex B: together with IFT81, forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium (PubMed:23990561). Binds beta-tubulin via its basic region (PubMed:23990561). Required for ciliogenesis (PubMed:23990561). Essential for flagellogenesis during spermatogenesis (PubMed:33689014)

Primary Disease Associations & Inheritance

Bardet-Biedl syndrome 22MIM #617119
AR
Joubert syndrome 40MIM #619582
AR
Spermatogenic failure 58MIM #619585
AR
820
ClinVar variants
39
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— IFT74
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 207 VUS of 820 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.88LOEUF
pLI 0.000
Z-score 2.17
OE 0.63 (0.46–0.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.07Z-score
OE missense 1.17 (1.08–1.28)
348 obs / 296.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.63 (0.46–0.88)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.17 (1.08–1.28)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.04
0≤1.21.6
LoF obs/exp: 26 / 41.0Missense obs/exp: 348 / 296.2Syn Z: -0.30

ClinVar Variant Classifications

820 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic11
VUS207
Likely Benign151
Benign3
28
Pathogenic
11
Likely Pathogenic
207
VUS
151
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
0
20
0
28
Likely Pathogenic
10
0
1
0
11
VUS
5
186
14
2
207
Likely Benign
0
8
68
75
151
Benign
0
1
2
0
3
Total2319510577400

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

IFT74 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

IFT74-related ciliopathy

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Bardet-Biedl syndrome 22

MIM #617119

Molecular basis of disorder known

Autosomal recessive

Joubert syndrome 40

MIM #619582

Molecular basis of disorder known

Autosomal recessive

Spermatogenic failure 58

MIM #619585

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
IFT74 variants cause skeletal ciliopathy and motile cilia defects in mice and humans.
Bakey Z et al.·PLoS Genet
2023
Disrupted intraflagellar transport due to IFT74 variants causes Joubert syndrome.
Luo M et al.·Genet Med
2021
Defective airway intraflagellar transport underlies a combined motile and primary ciliopathy syndrome caused by IFT74 mutations.
Fassad MR et al.·Hum Mol Genet
2023
A missense mutation in IFT74, encoding for an essential component for intraflagellar transport of Tubulin, causes asthenozoospermia and male infertility without clinical signs of Bardet-Biedl syndrome.
Lorès P et al.·Hum Genet
2021
Analysis of IFT74 as a candidate gene for chromosome 9p-linked ALS-FTD.
Momeni P et al.·BMC Neurol
2006
Genetic studies of GRN and IFT74 in amyotrophic lateral sclerosis.
Xiao S et al.·Neurobiol Aging
2008
Second case of Bardet-Biedl syndrome caused by biallelic variants in IFT74.
Kleinendorst L et al.·Eur J Hum Genet
2020Case report
Phenotypic and genotypic analysis of 11 fetal cases with Bardet-Biedl syndrome.
Yu QX et al.·Prenat Diagn
2024Cohort
Third case of Bardet-Biedl syndrome caused by a biallelic variant predicted to affect splicing of IFT74.
Mardy AH et al.·Clin Genet
2021Case report
Compound heterozygous IFT81 variations in a skeletal ciliopathy patient cause Bardet-Biedl syndrome-like ciliary defects.
Tasaki K et al.·Hum Mol Genet
2023Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Morbid ObesityBariatric SurgeryTelerehabilitation

Exercise to Fight Obesity

RECRUITING
NCT06934681Phase NAInstituto de Investigacion Sanitaria La FeStarted 2025-05-19
Usual Care GroupControlled exercise with telerehabilitation

External Resources

Links to major genomics databases and tools