KIAA1217

Chr 10

KIAA1217

Also known as: ETL4, SKT

NCBI Gene: 56243 ENSG00000120549 UniProt: Q5T5P2 OMIM: 617367

KIAA1217 encodes a centrosome-localized protein required for normal development of intervertebral disks and embryonic skeletal system development. Mutations cause skeletal dysplasia with severe spinal malformations, following autosomal recessive inheritance. The gene is highly constrained against loss-of-function variants, indicating its critical role in development.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in embryonic skeletal system development. Located in centrosome. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.42

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.42LOEUF

pLI 0.000

Z-score 5.55

OE 0.29 (0.21–0.42)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.29Z-score

OE missense 0.98 (0.93–1.02)

1095 obs / 1122.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.29 (0.21–0.42)

0≤0.351.4

Missense OE?0.98 (0.93–1.02)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 21 / 71.8Missense obs/exp: 1095 / 1122.7Syn Z: -1.01

Background carrier burden — how many people carry a rare variant somewhere in KIAA1217?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 20

2,666 rare PASS variants

Rare truncating (LoF)

1 in 660

245 rare PASS variants

Rare synonymous (reference)

1 in 35

956 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KIAA1217. 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 25	1 in 620
South Asian	~43k	1 in 17	1 in 550
Remaining (unassigned)	~30k	1 in 18	1 in 1,300
European (Finnish)	~27k	1 in 68	1 in 590
Admixed American	~22k	1 in 19	1 in 830
African / African American	~21k	1 in 17	1 in 860
East Asian	~20k	1 in 23	1 in 410
Ashkenazi Jewish	~13k	1 in 83	1 in 1,000
Middle Eastern	~2,884	1 in 20	none seen

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): 20 of 21 coding exons well covered in gnomAD exomes; exon 5 marginal. Genomes: all 21.? see exons ↓