KNDC1

Chr 10

kinase non-catalytic C-lobe domain containing 1

Also known as: C10orf23, RASGEF2, Very-KIND, bB439H18.3, v-KIND

The protein is a Ras guanine nucleotide exchange factor that negatively regulates dendritic growth in neurons and may be involved in cellular senescence. Mutations cause autosomal recessive spastic paraplegia, intellectual disability, nystagmus, and obesity (SPINOBY syndrome), typically presenting in early childhood. The gene is highly constrained against loss-of-function variants (LOEUF 0.398), suggesting intolerance to protein disruption.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.40
Clinical SummaryKNDC1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.40LOEUF
pLI 0.002
Z-score 5.76
OE 0.27 (0.190.40)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.89Z-score
OE missense 0.92 (0.870.97)
968 obs / 1049.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.27 (0.190.40)
00.351.4
Missense OE0.92 (0.870.97)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 20 / 73.1Missense obs/exp: 968 / 1049.5Syn Z: -0.07

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KNDC1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗