IFT74

Chr 9AR

intraflagellar transport 74

Also known as: BBS22, CCDC2, CMG-1, CMG1, JBTS40, SPGF58

The protein is a core component of the intraflagellar transport complex B that binds and transports tubulin within cilia, essential for ciliogenesis and flagellogenesis during spermatogenesis. Mutations cause autosomal recessive ciliopathies including Bardet-Biedl syndrome 22, Joubert syndrome 40, and spermatogenic failure 58. The gene is not highly constrained against loss-of-function variants, consistent with its recessive inheritance pattern.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.883 OMIM phenotypes
Clinical SummaryIFT74
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Gene-Disease Validity (ClinGen)
ciliopathy-IFT74 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — IFT74
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.88LOEUF
pLI 0.000
Z-score 2.17
OE 0.63 (0.460.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-1.07Z-score
OE missense 1.17 (1.081.28)
348 obs / 296.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.63 (0.460.88)
00.351.4
Missense OE1.17 (1.081.28)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 26 / 41.0Missense obs/exp: 348 / 296.2Syn Z: -0.30
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveIFT74-related ciliopathyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.83top 10%
GOF
0.5268th %ile
LOF
0.2092th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold
Clinical Literature
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