IFT88

Chr 13

intraflagellar transport 88

Also known as: D13S1056E, DAF19, TG737, TTC10, hTg737

NCBI Gene: 8100 ENSG00000032742 UniProt: Q13099

The protein positively regulates primary cilium biogenesis and is involved in autophagy through trafficking of ATG16L and expansion of autophagic compartments. Mutations cause autosomal recessive ciliopathy syndromes including nephronophthisis and Bardet-Biedl syndrome, affecting the kidneys, retina, and other organ systems. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.708).

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the tetratrico peptide repeat (TPR) family. The encoded protein is involved in cilium biogenesis. Mutations of a similar gene in mouse can cause polycystic kidney disease. Several transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2017]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.71

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.71LOEUF

pLI 0.000

Z-score 3.21

OE 0.51 (0.37–0.71)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.34Z-score

OE missense 0.95 (0.88–1.04)

394 obs / 413.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.51 (0.37–0.71)

0≤0.351.4

Missense OE?0.95 (0.88–1.04)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 25 / 49.3Missense obs/exp: 394 / 413.2Syn Z: 0.98

Background carrier burden — how many people carry a rare variant somewhere in IFT88?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 69

1,038 rare PASS variants

Rare truncating (LoF)

1 in 930

192 rare PASS variants

Rare synonymous (reference)

1 in 150

302 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IFT88. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 89	1 in 1,100
South Asian	~43k	1 in 44	1 in 630
Remaining (unassigned)	~30k	1 in 64	1 in 610
European (Finnish)	~27k	1 in 310	1 in 2,000
Admixed American	~22k	1 in 62	1 in 1,500
African / African American	~21k	1 in 66	1 in 690
East Asian	~20k	1 in 68	1 in 1,500
Ashkenazi Jewish	~13k	1 in 240	1 in 1,400
Middle Eastern	~2,884	1 in 63	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 25 coding exons well covered in gnomAD exomes; exon 13 poorly covered; exons 2, 4, 5, 6, 8 and 12 more marginal. Genomes: all 25.? see exons ↓