KIF22

Chr 16AD

kinesin family member 22

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

NCBI Gene: 3835 ENSG00000079616 UniProt: Q14807 OMIM: 603213

KIF22 encodes a kinesin family motor protein that binds microtubules and DNA to facilitate spindle formation and chromosome movement during cell division. Mutations cause spondyloepimetaphyseal dysplasia with joint laxity, type 2, an autosomal dominant skeletal dysplasia affecting the spine and growth plates. The gene is highly intolerant to loss-of-function variants (pLI ~1.0), indicating complete loss of function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

GOFmechanismADLOEUF 0.851 OMIM phenotype

Clinical Summary— KIF22

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

9 unique Pathogenic / Likely Pathogenic· 225 VUS of 466 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.85LOEUF

pLI 0.000

Z-score 2.24

OE 0.59 (0.41–0.85)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.14Z-score

OE missense 0.98 (0.90–1.06)

398 obs / 406.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.59 (0.41–0.85)

0≤0.351.4

Missense OE?0.98 (0.90–1.06)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 20 / 34.2Missense obs/exp: 398 / 406.0Syn Z: -1.82

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveKIF22-related spondyloepimetaphyseal dysplasia with joint laxityGOFAD

This gene — mechanism propensity

0.7131th %ile

GOF

0.6249th %ile

LOF

0.3649th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

466 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic6

VUS225

Likely Benign151

Benign44

Conflicting24

Pathogenic

Likely Pathogenic

225

VUS

151

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	2	1	0	3
Likely Pathogenic	0	6	0	0	6
VUS	17	197	9	2	225
Likely Benign	2	29	56	64	151
Benign	0	18	19	7	44
Conflicting	—				24
Total	19	252	85	73	453

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

View in ClinVar →

276 pathogenic / likely-pathogenic (of 297) ClinVar copy-number / structural variants overlap KIF22 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →