IFT140

Chr 16ADAR

intraflagellar transport 140

Also known as: CED5, MZSDS, PKD9, RP80, SRTD9, WDTC2, c305C8.4, c380F5.1

NCBI Gene: 9742 ENSG00000187535 UniProt: Q96RY7

This gene encodes one of the subunits of the intraflagellar transport (IFT) complex A. Intraflagellar transport is involved in the genesis, resorption and signaling of primary cilia. The primary cilium is a microtubule-based sensory organelle at the surface of most quiescent mammalian cells, that receives signals from its environment, such as the flow of fluid, light or odors, and transduces those signals to the nucleus. Loss of the corresponding protein in mouse results in renal cystic disease. [provided by RefSeq, Jun 2012]

Primary Disease Associations & Inheritance

{Polycystic kidney disease 9, susceptibility to}MIM #621164

Cranioectodermal dysplasia 5MIM #621180

Retinitis pigmentosa 80MIM #617781

Short-rib thoracic dysplasia 9 with or without polydactylyMIM #266920

462

ClinVar variants

Pathogenic / LP

0.00

pLI score

Active trials

Clinical Summary— IFT140

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Gene-Disease Validity (ClinGen)

IFT140-related recessive ciliopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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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

77 Pathogenic / Likely Pathogenic· 208 VUS of 462 total submissions

Some data sources returned errors (1)

pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

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.

0.82LOEUF

pLI 0.000

Z-score 2.87

OE 0.64 (0.51–0.82)

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.

-0.81Z-score

OE missense 1.07 (1.02–1.13)

997 obs / 927.5 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.0.64 (0.51–0.82)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.07 (1.02–1.13)

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.1.14

0≤1.21.6

LoF obs/exp: 49 / 76.0Missense obs/exp: 997 / 927.5Syn Z: -2.16