KIF7

Chr 15AR

kinesin family member 7

Also known as: ACLS, AGBK, HLS2, JBTS12, MMEDF, UNQ340

NCBI Gene: 374654 ENSG00000166813 UniProt: Q2M1P5 OMIM: 611254

This gene encodes a kinesin family protein that regulates sonic hedgehog signaling by controlling GLI transcription factors at the primary cilium, acting as both a negative regulator to prevent inappropriate GLI2 activation and a positive regulator to prevent GLI3 processing into its repressor form. Mutations cause autosomal recessive ciliopathies including Joubert syndrome 12, acrocallosal syndrome, and potentially hydrolethalus syndrome 2 and Al-Gazali-Bakalinova syndrome. The pathogenic mechanism is predicted to involve gain-of-function effects that disrupt normal hedgehog pathway regulation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a cilia-associated protein belonging to the kinesin family. This protein plays a role in the sonic hedgehog (SHH) signaling pathway through the regulation of GLI transcription factors. It functions as a negative regulator of the SHH pathway by preventing inappropriate activation of GLI2 in the absence of ligand, and as a positive regulator by preventing the processing of GLI3 into its repressor form. Mutations in this gene have been associated with various ciliopathies. [provided by RefSeq, Oct 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.934 OMIM phenotypes

Clinical Summary— KIF7

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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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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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GeneReview available — KIF7

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.93LOEUF

pLI 0.000

Z-score 2.02

OE 0.72 (0.56–0.93)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.69Z-score

OE missense 1.07 (1.01–1.13)

876 obs / 820.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.72 (0.56–0.93)

0≤0.351.4

Missense OE?1.07 (1.01–1.13)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 43 / 59.9Missense obs/exp: 876 / 820.4Syn Z: -1.07

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveKIF7-related acrocallosal syndromeLOFAR

This gene — mechanism propensity

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

0.6648th %ile

GOF

0.6638th %ile

LOF

0.3745th %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.