IFT74

Chr 9AR

intraflagellar transport 74

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

NCBI Gene: 80173 ENSG00000096872 UniProt: Q96LB3 OMIM: 608040

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a core intraflagellar transport (IFT) protein which belongs to a multi-protein complex involved in the transport of ciliary proteins along axonemal microtubules. IFT proteins are found at the base of the cilium as well as inside the cilium, where they assemble into long arrays between the ciliary base and tip. This protein, together with intraflagellar transport protein 81, binds and transports tubulin within cilia and is required for ciliogenesis. Naturally occurring mutations in this gene are associated with amyotrophic lateral sclerosis--frontotemporal dementia and Bardet-Biedl Syndrome. [provided by RefSeq, Mar 2017]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.883 OMIM phenotypes

Clinical Summary— IFT74

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Gene-Disease Validity (ClinGen)

ciliopathy-IFT74 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

61 unique Pathogenic / Likely Pathogenic· 335 VUS of 734 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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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

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.88LOEUF

pLI 0.000

Z-score 2.17

OE 0.63 (0.46–0.88)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-1.07Z-score

OE missense 1.17 (1.08–1.28)

348 obs / 296.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.63 (0.46–0.88)

0≤0.351.4

Missense OE?1.17 (1.08–1.28)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 26 / 41.0Missense obs/exp: 348 / 296.2Syn Z: -0.30

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveIFT74-related ciliopathyLOFAR

This gene — mechanism propensity

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

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

734 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40

Likely Pathogenic21

VUS335

Likely Benign256

Benign53

Conflicting4

Pathogenic

Likely Pathogenic

335

VUS

256

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	33	1	6	0	40
Likely Pathogenic	19	2	0	0	21
VUS	8	304	19	4	335
Likely Benign	0	12	123	121	256
Benign	1	9	39	4	53
Conflicting	—				4
Total	61	328	187	129	709

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

View in ClinVar →

75 pathogenic / likely-pathogenic (of 89) ClinVar copy-number / structural variants overlap IFT74 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →