KIF4A

Chr XXLR

kinesin family member 4A

Also known as: KIF4, KIF4G1, MRX100, TMDI, XLID100

NCBI Gene: 24137 ENSG00000090889 UniProt: O95239 OMIM: 300521

This protein is an ATP-dependent motor protein that transports membranous organelles along microtubules and plays essential roles in chromosome segregation and cytokinesis during cell division. Mutations cause X-linked intellectual developmental disorder and dental abnormalities including taurodontism, microdontia, and dens invaginatus. The gene follows X-linked recessive inheritance and is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the kinesin 4 subfamily of kinesin related proteins. The encoded protein is an ATP dependent microtubule-based motor protein that is involved in the intracellular transport of membranous organelles. This protein also associates with condensed chromosome arms and may be involved in maintaining chromosome integrity during mitosis. This protein may also be involved in the organization of the central spindle prior to cytokinesis. A pseudogene of this gene is found on chromosome X.[provided by RefSeq, Mar 2010]

OMIM ResearchGenerating clinical summary…

LOFmechanismXLRLOEUF 0.202 OMIM phenotypes

Clinical Summary— KIF4A

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Gene-Disease Validity (ClinGen)

complex neurodevelopmental disorder with or without congenital anomalies · XLLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

7 unique Pathogenic / Likely Pathogenic· 185 VUS of 337 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.20LOEUF

pLI 1.000

Z-score 6.08

OE 0.10 (0.05–0.20)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.56Z-score

OE missense 0.66 (0.60–0.73)

300 obs / 453.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.10 (0.05–0.20)

0≤0.351.4

Missense OE?0.66 (0.60–0.73)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 5 / 52.5Missense obs/exp: 300 / 453.3Syn Z: 0.74

ClinVar Variant Classifications

337 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic2

VUS185

Likely Benign27

Benign14

Conflicting4

Pathogenic

Likely Pathogenic

185

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	4	0	0	5
Likely Pathogenic	0	1	1	0	2
VUS	1	178	6	0	185
Likely Benign	0	7	8	12	27
Benign	0	3	4	7	14
Conflicting	—				4
Total	2	193	19	19	237

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

View in ClinVar →

53 pathogenic / likely-pathogenic (of 63) ClinVar copy-number / structural variants overlap KIF4A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →