KIF21A

Chr 12AD

kinesin family member 21A

Also known as: CFEOM1, FEOM1, FEOM3A

NCBI Gene: 55605 ENSG00000139116 UniProt: Q7Z4S6 OMIM: 608283

This gene encodes a member of the KIF4 subfamily of kinesin-like motor proteins. The encoded protein is characterized by an N-terminal motor domain a coiled-coil stalk domain and a C-terminal WD-40 repeat domain. This protein may be involved in microtubule dependent transport. Mutations in this gene are the cause of congenital fibrosis of extraocular muscles-1. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2010]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Fibrosis of extraocular muscles, congenital, 1MIM #135700

Fibrosis of extraocular muscles, congenital, 3BMIM #135700

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · congenital fibrosis of extraocular muscles · AD · ClinGen 2021

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.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.46

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — KIF21A

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.46LOEUF

pLI 0.000

Z-score 5.88

OE 0.34 (0.25–0.46)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.65Z-score

OE missense 0.75 (0.70–0.80)

650 obs / 870.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.34 (0.25–0.46)

0≤0.351.4

Missense OE?0.75 (0.70–0.80)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 31 / 91.8Missense obs/exp: 650 / 870.2Syn Z: 0.26

Background carrier burden — how many people carry a rare variant somewhere in KIF21A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 46

1,812 rare PASS variants

Rare truncating (LoF)

1 in 610

226 rare PASS variants

Rare synonymous (reference)

1 in 75

710 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KIF21A. 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 56	1 in 590
South Asian	~43k	1 in 41	1 in 380
Remaining (unassigned)	~30k	1 in 37	1 in 610
European (Finnish)	~27k	1 in 160	1 in 660
Admixed American	~22k	1 in 43	1 in 940
African / African American	~21k	1 in 38	1 in 860
East Asian	~20k	1 in 48	1 in 1,400
Ashkenazi Jewish	~13k	1 in 160	1 in 1,800
Middle Eastern	~2,884	1 in 41	≈ 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): 28 of 38 coding exons well covered in gnomAD exomes; exon 10 poorly covered; exons 4, 7, 12, 17, 18 and 4 more marginal. Genomes: all 38.? see exons ↓