IFT57

Chr 3AR

intraflagellar transport 57

Also known as: ESRRBL1, HIPPI, MHS4R2, OFD18

IFT57 encodes a protein required for cilia formation and plays a role in sonic hedgehog signaling and localization of specific G protein-coupled receptors to primary cilia. Biallelic mutations cause orofaciodigital syndrome XVIII, inherited in an autosomal recessive pattern. The gene shows high constraint against loss-of-function variants, with a very low pLI score and LOEUF of 1.096.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 1.101 OMIM phenotype
Clinical SummaryIFT57
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Gene-Disease Validity (ClinGen)
ciliopathy · ARModerate

Moderate evidence — consider for supplementary testing

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.10LOEUF
pLI 0.000
Z-score 1.19
OE 0.74 (0.511.10)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.30Z-score
OE missense 0.94 (0.841.06)
217 obs / 229.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.74 (0.511.10)
00.351.4
Missense OE0.94 (0.841.06)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 18 / 24.4Missense obs/exp: 217 / 229.9Syn Z: -0.16
DN
0.6355th %ile
GOF
0.5367th %ile
LOF
0.3551th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

IFT57 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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