KIF3B

Chr 20AD

kinesin family member 3B

Also known as: FLA8, HH0048, KLP-11, OTSC12, RP89

The KIF3B protein is a microtubule-based molecular motor that transports intracellular cargos such as vesicles and organelles, and plays a role in cilia formation and photoreceptor integrity. Mutations cause retinitis pigmentosa 89, inherited in an autosomal dominant pattern. This gene is highly constrained against loss-of-function variants (LOEUF 0.45), suggesting that such mutations are likely pathogenic.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Retinitis pigmentosa 89MIM #618955
AD
0
Active trials
9
Pubs (1 yr)
17
P/LP submissions
12%
P/LP missense
0.45
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryKIF3B
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 76 VUS of 111 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.45LOEUF
pLI 0.084
Z-score 4.06
OE 0.26 (0.150.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.00Z-score
OE missense 0.60 (0.540.66)
259 obs / 435.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.26 (0.150.45)
00.351.4
Missense OE0.60 (0.540.66)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 9 / 34.9Missense obs/exp: 259 / 435.0Syn Z: 0.15
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedKIF3B-related ciliopathyOTHERAD
DN
0.83top 10%
GOF
0.6443th %ile
LOF
0.3357th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

111 submitted variants in ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic4
VUS76
Likely Benign5
Benign2
13
Pathogenic
4
Likely Pathogenic
76
VUS
5
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
11
0
13
Likely Pathogenic
0
0
4
0
4
VUS
0
69
7
0
76
Likely Benign
1
1
1
2
5
Benign
0
0
1
1
2
Total172243100

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

View in ClinVar →

Protein Context — Lollipop Plot

KIF3B · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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