IFTAP

Chr 11

intraflagellar transport associated protein

Also known as: C11orf74, HEPIS, NWC

NCBI Gene: 119710 ENSG00000166352 UniProt: Q86VG3 OMIM: 619270

The encoded protein appears to function as a negative regulator of transcription and may be involved in ciliary BBSome localization through interaction with the IFT-A complex. Mutations in IFTAP cause autosomal recessive developmental disorders affecting multiple systems. The gene shows low constraint to loss-of-function variation, with clinical presentations typically involving developmental delay and potentially ciliopathy-related features.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein that was identified as a cellular interacting partner of non-structural protein 10 of the severe acute respiratory syndrome coronavirus (SARS-CoV). The encoded protein may function as a negative regulator of transcription. There is a pseudogene for this gene on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.66

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.66LOEUF

pLI 0.000

Z-score 0.14

OE 0.95 (0.55–1.66)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.19Z-score

OE missense 1.05 (0.90–1.23)

112 obs / 106.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.95 (0.55–1.66)

0≤0.351.4

Missense OE?1.05 (0.90–1.23)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 8 / 8.4Missense obs/exp: 112 / 106.6Syn Z: -0.09

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

310 rare PASS variants

Rare truncating (LoF)

1 in 2,200

53 rare PASS variants

Rare synonymous (reference)

1 in 610

88 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IFTAP. 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 310	1 in 2,000
South Asian	~43k	1 in 160	1 in 3,700
Remaining (unassigned)	~30k	1 in 170	1 in 3,300
European (Finnish)	~27k	1 in 1,800	≈ 1 in 27,000
Admixed American	~22k	1 in 240	1 in 770
African / African American	~21k	1 in 200	1 in 1,900
East Asian	~20k	1 in 300	none seen
Ashkenazi Jewish	~13k	≈ 1 in 2,900	none seen
Middle Eastern	~2,882	1 in 280	≈ 1 in 720

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): 4 of 5 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: all 5.? see exons ↓