KIF18A

Chr 11

kinesin family member 18A

Also known as: MS-KIF18A, PPP1R99

KIF18A encodes a microtubule-depolymerizing kinesin that regulates chromosome movement during mitosis by reducing chromosome oscillations and stabilizing kinetochore complexes. Mutations cause autosomal recessive microcephaly, intellectual disability, and seizures. The gene is highly constrained against loss-of-function variants, indicating that complete loss of function is likely not tolerated.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
25
Pubs (1 yr)
19
P/LP submissions
0%
P/LP missense
0.48
LOEUF
DN
Mechanism· predicted
Clinical SummaryKIF18A
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
19 unique Pathogenic / Likely Pathogenic· 108 VUS of 150 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.48LOEUF
pLI 0.001
Z-score 4.36
OE 0.31 (0.200.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.54Z-score
OE missense 0.93 (0.861.01)
433 obs / 466.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.31 (0.200.48)
00.351.4
Missense OE0.93 (0.861.01)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 14 / 45.9Missense obs/exp: 433 / 466.1Syn Z: -0.28
DN
0.76top 25%
GOF
0.6052th %ile
LOF
0.3647th %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

150 submitted variants in ClinVar

Classification Summary

Pathogenic19
VUS108
Likely Benign7
Conflicting1
19
Pathogenic
108
VUS
7
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
0
0
0
VUS
0
104
4
0
108
Likely Benign
0
6
0
1
7
Benign
0
0
0
0
0
Conflicting
1
Total0110231135

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

View in ClinVar →

Protein Context — Lollipop Plot

KIF18A · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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