KIFBP

Chr 10AR

kinesin family binding protein

Also known as: KBP, KIAA1279, KIF1BP, TTC20

NCBI Gene: 26128 ENSG00000198954 UniProt: Q96EK5 OMIM: 609367

This gene encodes a kinesin family binding protein that activates KIF1B microtubule motor activity and is required for axonal microtubule organization, axonal outgrowth, and maintenance during nervous system development. Mutations cause Goldberg-Shprintzen megacolon syndrome, which involves both gastrointestinal and neurological systems. The condition follows autosomal recessive inheritance.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a kinesin family member 1 binding protein that is characterized by two tetratrico peptide repeats. The encoded protein localizes to the mitochondria and may be involved in regulating transport of the mitochondria. Mutations in this gene are associated with Goldberg-Shprintzen megacolon syndrome. [provided by RefSeq, Mar 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.511 OMIM phenotype

Clinical Summary— KIFBP

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Gene-Disease Validity (ClinGen)

Goldberg-Shprintzen syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.

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ClinVar Variants

17 unique Pathogenic / Likely Pathogenic· 150 VUS of 255 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — KIFBP

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.51LOEUF

pLI 0.076

Z-score 3.42

OE 0.27 (0.15–0.51)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.45Z-score

OE missense 0.77 (0.70–0.86)

255 obs / 329.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.27 (0.15–0.51)

0≤0.351.4

Missense OE?0.77 (0.70–0.86)

0≤0.61.4

Synonymous OE?0.82

0≤1.21.6

LoF obs/exp: 7 / 25.7Missense obs/exp: 255 / 329.1Syn Z: 1.57

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveKIFBP-related Goldberg-Shprintzen megacolon syndromeLOFAR

This gene — mechanism propensity

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

0.6065th %ile

GOF

0.6344th %ile

LOF

0.2969th %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.

ClinVar Variant Classifications

255 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10

Likely Pathogenic7

VUS150

Likely Benign52

Benign20

Conflicting10

Pathogenic

Likely Pathogenic

150

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	9	0	1	0	10
Likely Pathogenic	7	0	0	0	7
VUS	2	129	14	5	150
Likely Benign	0	6	21	25	52
Benign	0	1	16	3	20
Conflicting	—				10
Total	18	136	52	33	249

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap KIFBP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →