KIF7

Chr 15AR

kinesin family member 7

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

NCBI Gene: 374654ENSG00000166813UniProt: Q2M1P5

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]

Primary Disease Associations & Inheritance

?Al-Gazali-Bakalinova syndromeMIM #607131
AR
?Hydrolethalus syndrome 2MIM #614120
AR
Acrocallosal syndromeMIM #200990
AR
Joubert syndrome 12MIM #200990
AR
UniProtBardet-Biedl syndrome
685
ClinVar variants
42
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— KIF7
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
42 Pathogenic / Likely Pathogenic· 473 VUS of 685 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.93LOEUF
pLI 0.000
Z-score 2.02
OE 0.72 (0.56–0.93)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.69Z-score
OE missense 1.07 (1.01–1.13)
876 obs / 820.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.72 (0.56–0.93)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.07 (1.01–1.13)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 43 / 59.9Missense obs/exp: 876 / 820.4Syn Z: -1.07

ClinVar Variant Classifications

685 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic15
VUS473
Likely Benign146
Benign3
Conflicting21
27
Pathogenic
15
Likely Pathogenic
473
VUS
146
Likely Benign
3
Benign
21
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
1
14
0
27
Likely Pathogenic
10
0
5
0
15
VUS
6
441
25
1
473
Likely Benign
0
18
36
92
146
Benign
0
1
1
1
3
Conflicting
—21
Total284618194685

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

View in ClinVar →

Protein Context — Lollipop Plot

KIF7 · protein map & ClinVar variants

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

Gene2Phenotype Curations

KIF7-related acrocallosal syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeSkeletal
G2P ↗

KIF7-related intellectual developmental disorder

definitive
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Al-Gazali-Bakalinova syndrome

MIM #607131

Molecular basis of disorder known

Autosomal recessive

?Hydrolethalus syndrome 2

MIM #614120

Molecular basis of disorder known

Autosomal recessive

Acrocallosal syndrome

MIM #200990

Molecular basis of disorder known

Autosomal recessive

Joubert syndrome 12

MIM #200990

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — KIF7
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical and genetic spectrum from a prototype of ciliopathy: Joubert syndrome.
Aksu Uzunhan T et al.·Clin Neurol Neurosurg
2023
MOLAR TOOTH SIGN AND ACROCALLOSAL SYNDROME--A REPORT ON A POLISH FAMILY AND REVIEW OF KIF7 SYNDROMOLOGY.
Krajewska-Walasek M et al.·Genet Couns
2015Review
Mutations in KIF7 implicated in idiopathic scoliosis in humans and axial curvatures in zebrafish.
Terhune EA et al.·Hum Mutat
2021Functional
Genetic Variants in KIF7 May Contribute to Supernumerary Tooth Formation.
Chainaphaphorn P et al.·Int Dent J
2025
Co-occurrence of mutations in KIF7 and KIAA0556 in Joubert syndrome with ocular coloboma, pituitary malformation and growth hormone deficiency: a case report and literature review.
Niceta M et al.·BMC Pediatr
2020Review
Construction of a novel copper-induced-cell-death-related gene signature for prognosis in colon cancer, with focus on KIF7.
Li H et al.·BMC Cancer
2024
Clinical and experimental evidence suggest a link between KIF7 and C5orf42-related ciliopathies through Sonic Hedgehog signaling.
Asadollahi R et al.·Eur J Hum Genet
2018
Expanding the Phenotypic Spectrum of Pathogenic KIAA0586 Variants: From Joubert Syndrome to Hydrolethalus Syndrome.
Deconte D et al.·Int J Mol Sci
2024Case report
Expansion of Phenotyping and Genotypic Spectra of KIF7 -Related Intellectual Disability: Case Report and Review of Literature.
Wongong R et al.·Am J Med Genet A
2026Review
Low expression of KIF7 indicates poor prognosis in epithelial ovarian cancer.
Yao Y et al.·Cancer Biomark
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Morbid ObesityBariatric SurgeryTelerehabilitation

Exercise to Fight Obesity

RECRUITING
NCT06934681Phase NAInstituto de Investigacion Sanitaria La FeStarted 2025-05-19
Usual Care GroupControlled exercise with telerehabilitation

External Resources

Links to major genomics databases and tools