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…

Primary Disease Associations & Inheritance

?Al-Gazali-Bakalinova syndromeMIM #607131

?Hydrolethalus syndrome 2MIM #614120

Acrocallosal syndromeMIM #200990

Joubert syndrome 12MIM #200990

UniProtBardet-Biedl syndrome

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Acrocallosal syndrome; Joubert syndrome 12; no ClinGen or GenCC tier

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.93

LOEUF

LOF

Mechanism· G2P

📖

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

Background carrier burden — how many people carry a rare variant somewhere in KIF7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 22

2,225 rare PASS variants

Rare truncating (LoF)

1 in 460

297 rare PASS variants

Rare synonymous (reference)

1 in 41

972 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KIF7. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 33	1 in 480
South Asian	~43k	1 in 22	1 in 460
Remaining (unassigned)	~30k	1 in 19	1 in 400
European (Finnish)	~27k	1 in 110	1 in 390
Admixed American	~22k	1 in 19	1 in 400
African / African American	~21k	1 in 21	1 in 350
East Asian	~20k	1 in 23	1 in 360
Ashkenazi Jewish	~13k	1 in 92	1 in 570
Middle Eastern	~2,884	1 in 25	≈ 1 in 890

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 17 of 18 coding exons well covered in gnomAD exomes; exon 5 marginal. Genomes: 16 of 18 (exons 14, 18 below).? see exons ↓