KIF22

Chr 16AD

kinesin family member 22

Also known as: A-328A3.2, KID, KNSL4, OBP, OBP-1, OBP-2, SEMDJL2

NCBI Gene: 3835ENSG00000079616UniProt: Q14807

The protein encoded by this gene is a member of the kinesin-like protein family. The family members are microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. The C-terminal half of this protein has been shown to bind DNA. Studies with the Xenopus homolog suggests its essential role in metaphase chromosome alignment and maintenance. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

Primary Disease Associations & Inheritance

Spondyloepimetaphyseal dysplasia with joint laxity, type 2MIM #603546
AD
758
ClinVar variants
120
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— KIF22
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
120 Pathogenic / Likely Pathogenic· 198 VUS of 758 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.85LOEUF
pLI 0.000
Z-score 2.24
OE 0.59 (0.41–0.85)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.14Z-score
OE missense 0.98 (0.90–1.06)
398 obs / 406.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.59 (0.41–0.85)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.90–1.06)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.18
0≤1.21.6
LoF obs/exp: 20 / 34.2Missense obs/exp: 398 / 406.0Syn Z: -1.82

ClinVar Variant Classifications

758 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic111
Likely Pathogenic9
VUS198
Likely Benign125
Benign24
Conflicting14
111
Pathogenic
9
Likely Pathogenic
198
VUS
125
Likely Benign
24
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
110
0
111
Likely Pathogenic
0
2
7
0
9
VUS
9
162
26
1
198
Likely Benign
1
19
52
53
125
Benign
0
14
5
5
24
Conflicting
—14
Total1019820059481

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

KIF22 · protein map & ClinVar variants

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

Gene2Phenotype Curations

KIF22-related spondyloepimetaphyseal dysplasia with joint laxity

definitive
ADGain Of FunctionAltered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spondyloepimetaphyseal dysplasia with joint laxity, type 2

MIM #603546

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
KIF22 Promotes Development of Pancreatic Cancer by Regulating the MEK/ERK/P21 Signaling Axis.
Zhang R et al.·Biomed Res Int
2022
Suppression of KIF22 Inhibits Cell Proliferation and Xenograft Tumor Growth in Colon Cancer.
Li B et al.·Cancer Biother Radiopharm
2020
KIF22 promotes multiple myeloma progression by regulating the CDC25C/CDK1/cyclinB1 pathway.
Zhai M et al.·J Cancer Res Clin Oncol
2024
Suppression of KIF22 Inhibits Cell Proliferation and Xenograft Tumor Growth in Tongue Squamous Cell Carcinoma.
Liu Y et al.·Biomed Res Int
2020
High Expression of KIF22/Kinesin-Like DNA Binding Protein (Kid) as a Poor Prognostic Factor in Prostate Cancer Patients.
Zhang Z et al.·Med Sci Monit
2018Cohort
KIF22 promotes bladder cancer progression by activating the expression of CDCA3.
Li K et al.·Int J Mol Med
2021
Bioinformatics analysis: relationship between adrenocortical carcinoma and KIFs.
Li X et al.·Biotechnol Genet Eng Rev
2023
Whole-exome sequencing identifies mutations of KIF22 in spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type.
Min BJ et al.·Am J Hum Genet
2011
Identification of kinesin family member (KIF22) homozygous variants in spondyloepimetaphyseal dysplasia with joint laxity, lepdodactylic type and demonstration of proteoglycan biosynthesis impairment.
Dubail J et al.·J Bone Miner Res
2024
Identification of Key Genes Involved in Pancreatic Ductal Adenocarcinoma with Diabetes Mellitus Based on Gene Expression Profiling Analysis.
Zhou W et al.·Pathol Oncol Res
2021Meta-analysis
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools