KIF14

Chr 1AR

kinesin family member 14

Also known as: MCPH20, MKS12

NCBI Gene: 9928 ENSG00000118193 OMIM: 611279

KIF14 encodes a microtubule motor protein with ATPase activity that is essential for cytokinesis, chromosome alignment during mitosis, and regulation of cell cycle progression. Mutations cause autosomal recessive primary microcephaly and Meckel syndrome, both reflecting severe developmental abnormalities with early onset. The gene is highly constrained against loss-of-function variants (LOEUF 0.429), consistent with its critical role in fundamental cellular processes including neurogenesis.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the kinesin-3 superfamily of microtubule motor proteins. These proteins are involved in numerous processes including vesicle transport, chromosome segregation, mitotic spindle formation, and cytokinesis. In human HeLa-S3 and 293T cells, this protein is localized to the cytoplasm during interphase, to the spindle poles and spindle microtubules during mitosis, and to the midbody during cytokinesis. An internal motor domain displays microtubule-dependent ATPase activity, consistent with its function as a microtubule motor protein. Knockdown of this gene results in failed cytokinesis with endoreplication, which results in multinucleated cells. This gene has been identified as a likely oncogene in breast, lung and ovarian cancers, as well as retinoblastomas and gliomas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2015]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.432 OMIM phenotypes

Clinical Summary— KIF14

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

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ClinVar Variants

43 unique Pathogenic / Likely Pathogenic· 253 VUS of 523 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.43LOEUF

pLI 0.000

Z-score 5.63

OE 0.30 (0.22–0.43)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.77Z-score

OE missense 0.92 (0.87–0.98)

762 obs / 824.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.30 (0.22–0.43)

0≤0.351.4

Missense OE?0.92 (0.87–0.98)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 23 / 76.0Missense obs/exp: 762 / 824.1Syn Z: 1.01

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongKIF14-related severe microcephaly and short statureLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.75top 25%

GOF

0.5758th %ile

LOF

0.3648th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

523 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16

Likely Pathogenic27

VUS253

Likely Benign135

Benign66

Conflicting8

Pathogenic

Likely Pathogenic

253

VUS

135

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	14	2	0	0	16
Likely Pathogenic	24	2	0	1	27
VUS	11	234	5	3	253
Likely Benign	1	29	40	65	135
Benign	1	6	52	7	66
Conflicting	—				8
Total	51	273	97	76	505

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap KIF14 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →